Volume 49

Endocrine Abstracts

May 2017

19th European Congress of

Endocrinology 2017

20 - 23 May 2017

EDITORS

The abstracts were marked by the Abstract marking Panel selected by the Programme Organising Committee

Programme Organising Committee

Bulent Yildiz (Turkey) Chair

Evi Diamanti-Kandarakis (Greece)

Djuro Macut (Serbia)

Guillaume Assié (France) Co-chair

Andrea Giustina (Italy)

Rod Mitchell (UK)

Riccarda Granata (Italy) Co-chair

Ilpo Huhtaniemi (Finland/UK)

Barbara Obermayer-Pietsch (Austria)

Joa˜o Jácome de Castro (Portugal)

Irena Ilovayskaya (Russia)

Pedro Oliveira (Portugal)

Carlo Acerini (UK)

Tatjana isailovic (Serbia)

Robin Peeters (The Netherlands)

Richard Bergman (USA)

Gregory Kaltsas (Greece)

Duarte Pignatelli (Portugal)

Charlotte Bevan (UK)

Beata Kos-Kudla (Poland)

Matti Poutanen (Finland)

Heike Biebermann (Germany)

Cesar Luiz Boguszewski (Brazil)

Manuel Puig (Spain)

Local Organising Committee (LOC)

Joa˜o de Castro (Lisbon, Portugal) (Chair)

José Silva Nunes (Lisbon, Portugal)

Maria Joa˜o Oliveira (Porto, Portugal)

Duarte Pignatelli (Porto, Portugal)

Leonor Gomes (Coimbra, Portugal)

Mário Mascarenha (Lisbon, Portugal)

Jorge Dores (Porto, Portugal)

Mafalda Marcelino (Lisbon, Portugal)

Miguel Melo (Coimbra, Portugal)

Abstract Marking Panel

T Battelino Slovenia

C Dayan UK

F Kelestimur Turkey

G Raverot France

K Chatterjee UK

W de Herder Netherlands

R Kineman USA

M Reincke Germany

D Cuthbertson UK

W Dhillo UK

M Korbonits UK

S Rice UK

E de Koning The Netherlands

G Di Dalmazi Germany

B Kos-Kudla Poland

M Robledo Spain

M Dentice Italy

E Diamanti-Kandarakis Greece

N Krone UK

P Rodien France

D Fuhrer Germany

F Dotta Italy

H Krude Germany

H Romijn The Netherlands

R Gartner Germany

J Drouin Canada

M Laan Germany

C Ronchi Italy

J Jacome de Castro Portugal

L Duntas Greece

E Lalli France

R Ross UK

C Jazdzewski Poland

G Eisenhofer Germany

J Laven The Netherlands

G P Rossi Italy

C Kanaka-Gantenbein Greece

F Fallo Italy

G Lavery UK

M Ruchala Poland

S Pearce UK

P Farahani Canada

J Leger France

E Rutten Belgium

G Roman Romania

S Farooqi UK

T Links The Netherlands

D Salvatore Italy

E Stener-Victorin Sweden

M Fassnacht Germany

P Lips Netherlands

S Sanlioglu Turkey

E Visser The Netherlands

R Feelders The Netherlands

S Llahana UK

P Saunders UK

M-C Zennaro Spain

U Feldt-Rasmussen Denmark

A Luger Austria

S Schmid Germany

C Acerini UK

E Fliers The Netherlands

C Luiz Boguszewski Brazil

J Schopohl Germany

M Alevizaki Greece

C Flueck Switzerland

R M Luque Spain

D Schulte Germany

W Arlt UK

C Follin Sweden

M Luster Germany

M Sherlock Ireland

G Assié France

S Franks UK

D Macut Serbia

M Simoni Italy

S Aylwin UK

W Fraser UK

M Maggi Italy

J Smit The Netherlands

S Babajko France

J Frystyk Denmark

J Magre France

A Spada Italy

K Badenhoop Germany

L Fugazzolla Italy

M Mannelli Italy

G Stalla Germany

P Beck-Peccoz Italy

F Gabalec Czech Republic

F Mantero Italy

C Stratakis USA

R Bergman USA

A Gimenez-Roqueplo France

D Marks USA

T Tankova Bulgaria

J Bertherat France

F Giorgino Italy

G Mastorakos Greece

M Tena-Sempere Spain

F Beuschlein Germany

A Giustina Italy

C McCabe UK

M Terzolo Italy

C Bevan UK

J Gomez-Ambrosi Spain

R Mitchell UK

M Theodoropoulou Germany

H Biebermann Germany

R Granata Italy

J Mittag Germany

C Thompson Ireland

M Bluher Germany

A Grossman UK

L Morin-Papunen Finland

H Timmers The Netherlands

K Boelaert UK

R Hampl Czech Republic

N Morton UK

J Toppari Finland

A Boelen The Netherlands

M Heikinheimo Finland

A Mukherjee UK

M Toth Hungary

R Bouillon Belgium

C Hoefig Sweden

E Nagy Hungary

S Tsagarakis Greece

J-P Bourguignon Belgium

A Hoeflich Germany

J Newell-Price UK

M Tzanela Greece

G Brabant Germany

W Hoegler UK

B Obermayer-Pietsch Austria

E Valassi Spain

M L Brandi Italy

L Hofland Netherlands

P Oliveira Portugal

E van den Akker Netherlands

K Briot France

I Huhtaniemi UK

U Pagotto Italy

A van der Klaauw UK

G Brunetti Italy

E Husebye Norway

J J Palvimo Finland

A J van der Lelij Netherlands

C Buchanan UK

P Igaz Hungary

R Peeters The Netherlands

J van Eck The Netherlands

P Burman Sweden

I Ilovayskaya Russia

L Persani Italy

W van Hul Belgium

S Cannavo Italy

S Inzucchi USA

T Pieber Austria

J Visser The Netherlands

J Cap Czech Republic

T Isailovic Serbia

V Pirags Latvia

V Volke Estonia

G Carmeliet Belgium

E R Isenovic Serbia

N Pitteloud Switzerland

R Voutilainen Finland

J Castano Spain

M Jaffrain-Rea Italy

M Poutanen Finland

I Wilkinson UK

P Chanson France

B Jarzab Poland

D Power Portugal

Z Wu Germany

F Chiarelli Italy

D Jezova Slovakia

V Prevot France

P Yeoh UK

B Chini Italy

A Kalsbeek Netherlands

S Radian UK

B Yildiz Turkey

J Chowen Spain

G Kaltsas Greece

N Rahman Finland

J Young France

C Daousi UK

A Karlsson Sweden

B Rainey USA

M Zatelli Italy

M Dattani UK

M Keil USA

E Rajpert-De Meyts Denmark

19th European Congress of Endocrinology 2017

CONTENTS

19th European Congress of Endocrinology 2017

PRIZE LECTURES AND BIOGRAPHICAL NOTES

The European Journal of Endocrinology Prize Lecture

EJE1

The Geoffrey Harris Prize Lecture

GH1

European Hormone Medal Lecture

EHM1

Clinical Endocrinology Trust Lecture

CET1

IPSEN1

PLENARY LECTURES

The fantastical world of hormones

The secret life of FGF21

. . . . . P2

Update on regulation of steroidogenesis by aberrant hormone receptors

The role of brain insulin resistance for the development of prediabetic phenotypes

Browning of adipose tissue and metabolic regulation

Thyroid oncology in the crossroads of precision and narrative medicine

SYMPOSIA

Clinical Updates in Hypoparathyroidism

S1.1 - S1.3

Evolving diagnostics in adrenal and neuroendocrine tumours

S2.1 - S2.3

From the pituitary to the periphery

S3.1 - S3.3

2nd Joint Global Symposium on Obesity - The Many Dimensions of the Childhood Obesity Problem

S4.1 - S4.3

Turn your face to the sunshine

S5.1 - S5.3

Treatment of hypothyroidism: what have we learned?

S6.1 - S6.3

Crosstalk between bone & other organ(ism)s

S7.1 - S7.3

Predictors of therapeutic response in functioning pituitary tumours

S8.1 - S8.3

Novel type 2 diabetes treatment: Beyond glycaemic control

S9.1 - S9.3

The Challenges of Male Fertility

S10.1 - S10.3

New Roles for Nuclear Receptors

S11.1 - S11.3

New development in Graves’ Orbitopathy

S12.1 - S12.3

Challenging pituitary diseases

S13.1 - S13.3

Searching for the cause and approach in ectopic hormone syndromes

S14.1 - S14.3

Metabolic surgery mechanisms to clinical results (Endorsed by the European Journal of Endocrinology)

S15.1 - S15.3

Late-breaking: the PCSK9 revolution

S16.1 - S16.3

What endocrinologists should know about the genomics of endocrine tumors

S17.1 - S17.3

Hyperandrogenism: challenges in clinical management

S18.1 - S18.3

How to incorporate the new guidelines for thyroid cancer in my clinical practice

S19.1 - S19.3

Beta cell replacement and plasticity (Endorsed by Endocrine Connections)

S20.1 - S20.3

Environmental influences on endocrine systems

S21.1 - S21.3

Rare bone diseases (Endorsed by the European Journal of Endocrinology)

S22.1 - S22.3

Endo Oncology: prolactin, GH and metabolic hormones in oncology pathogenesis

(Endorsed by Endocrine Connections)

S23.1 - S23.3

Obesity: Pharmacological solutions

S24.1 - S24.3

HPA axis regulation during a woman’s life: impact on metabolic outcomes

S25.1 - S25.3

Tissue specific defects in thyroid hormone action

S26.1 - S26.3

Vitamin D beyond bone (Endorsed by Endocrine Connections)

S27.1 - S27.3

Sleep, love and reproduction (Endorsed by Endocrine Connections)

S28.1 - S28.3

Novel predictors of diabetes

S29.1 - S29.3

Moving away from old-fashioned steroidogenesis: what are the clinical implications?

S30.1 - S30.3

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Guided session 1

. . GS1.1-GS1.6

Guided session 2

. . GS2.1-GS2.6

NEW SCIENTIFIC APPROACHES

NSA1 - NSA6

DEBATES

Is there a role for medical therapy for non-functioning pituitary adenomas?

. . . D1.1-D1.2

Incidentally discovered nonfunctioning pancreatic NETs: Surgery or not?

(Endorsed by the European Journal of Endocrinology)

D2.1 - D2.2

Drug holiday in osteoporosis (Endorsed by the European Journal of Endocrinology)

D3.1 - D3.2

Is cardiovascular risk increased in women with PCOS?

D4.1 - D4.2

Should we still ablate all patients undergoing total thyroidectomy for thyroid cancer?

. . . D5.1-D5.2

Is it time for initial combination in type 2 diabetes?

. . . D6.1-D6.2

MEET THE EXPERT SESSIONS

. MTE1 - MTE16

MTNE1 - MTNE2

MTBS1 - MTBS3

NURSE SESSIONS

. . . N1.1-N1.4

. . . N2.1-N2.4

. . . N3.1-N3.3

ORAL COMMUNICATIONS

Adrenal - Basic & Clinical

OC1.1 - OC1.5

Diabetes Prediction and Complications

. . OC2.1-OC2.5

Receptors & Signalling

OC3.1 - OC3.5

Thyroid Disease 1

OC4.1 - OC4.5

Cardiovascular Endocrinology

OC5.1 - OC5.5

Diabetes therapy and complications . .

. . OC6.1-OC6.5

Cardiovascular endocrinology

OC7.1 OC7.5

Neuroendocrinology

OC8.1 - OC8.5

Thyroid Disease 2

OC9.1 - OC9.5

Bone & Calcium Homeostasis

OC10.1 - OC10.5

Obesity

OC11.1 - OC11.5

Pituitary Clinical

OC12.1 - OC12.5

Reproduction & Endocrine Disruption .

OC13.1 - OC13.5

Thyroid Cancer

OC14.1 - OC14.5

Guided Posters

Adrenal 1

GP1 - GP10

Adrenal 2

GP11 - GP20

Adrenal 3

GP21 - GP32

Bone & Calcium Homeostasis 1

. . GP33-GP42

Bone & Calcium Homeostasis 2

. . GP43-GP51

Cardiovascular & Lipid Endocrinology

. . GP52-GP61

Developmental & Protein Endocrinology

. . GP62-GP70

Diabetes & complications 1

. . GP71-GP82

Diabetes & complications 2

. . GP83-GP92

Diabetes therapy & complications 1

GP93 - GP102

Diabetes therapy & complications 2

GP103 - GP112

Endocrine Nursing

GP113 - GP117

Endocrine Tumours

GP118 - GP130

Female Reproduction

GP131 - GP142

Male Reproduction and Endocrine Disruptors

. GP143 - GP150

Neuroendocrinology & Growth Hormones . .

GP151 - GP160

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Obesity

GP161 - GP172

Pituitary

GP173 - GP184

Pituitary & endocrine Tumours

GP185 - GP196

Thyroid 1

GP197 - GP205

Thyroid 2

GP206 - GP216

Thyroid 3

GP217 - GP224

Thyroid Cancer

GP225 - GP235

Thyroid Cancer & Thyroid Case Reports

GP236 - GP245

EPOSTER PRESENTATIONS: ADRENAL AND NEUROENDOCRINE TUMOURS

Adrenal cortex (to include Cushing’s)

EP1 - EP86

Adrenal medulla

EP87 - EP107

Cardiovascular Endocrinology and Lipid Metabolism

EP108

Clinical case reports - Pituitary/Adrenal

EP109 - EP140

Clinical case reports - Thyroid/Others

EP141 - EP145

Endocrine tumours and neoplasia

EP146 - EP195

Neuroendocrinology

EP196 - EP204

Paediatric endocrinology

EP205 - EP206

Pituitary - Clinical

EP207

Steroid metabolism + action

EP208

Thyroid cancer

EP209

EPOSTER PRESENTATIONS: CALCIUM AND BONE

Bone & Osteoporosis

EP210 - EP246

Calcium & Vitamin D metabolism

EP247 - EP311

Cardiovascular Endocrinology and Lipid Metabolism

EP312 - EP313

Clinical case reports - Pituitary/Adrenal

EP314

Clinical case reports - Thyroid/Others

EP315 - EP342

Developmental endocrinology

EP343

Endocrine tumours and neoplasia

EP344 - EP350

Endocrine tumours and neoplasia

EP351

Paediatric endocrinology

EP352

Steroid metabolism + action

EP353

EPOSTER PRESENTATIONS: DIABETES, OBESITY AND METABOLISM

Calcium & Vitamin D metabolism

EP354

Cardiovascular Endocrinology and Lipid Metabolism

EP355 - EP383

Clinical case reports - Pituitary/Adrenal

EP384

Clinical case reports - Thyroid/Others

EP385 - EP400

Developmental endocrinology

EP401 - EP402

Diabetes (to include epidemiology, pathophysiology)

EP403 - EP497

Diabetes complications

EP498 - EP578

Diabetes therapy

EP579 - EP630

Endocrine Disruptors

EP631 - EP632

Endocrine tumours and neoplasia

EP633 - EP634

Female Reproduction

EP635 - EP637

Growth hormone IGF axis - basic

EP638 - EP640

Neuroendocrinology

EP641

Nuclear receptors and Signal transduction

EP642

Obesity

EP643 - EP723

Paediatric endocrinology

EP724 - EP726

Steroid metabolism + action

EP727 - EP730

EPOSTER PRESENTATIONS: ENVIRONMENT, SOCIETY AND GOVERNANCE

Cardiovascular Endocrinology and Lipid Metabolism

EP731

Clinical case reports - Thyroid/Others

EP732

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Developmental endocrinology

EP733 - EP734

Diabetes (to include epidemiology, pathophysiology)

EP735

Diabetes complications

EP736 - EP737

Endocrine Disruptors

EP738 - EP745

Endocrine tumours and neoplasia

EP746

Female Reproduction

EP747

Pituitary - Clinical

EP748

Thyroid (non-cancer)

EP749

EPOSTER PRESENTATIONS: INTERDISCIPLINARY ENDOCRINOLOGY

Adrenal cortex (to include Cushing’s)

EP750

Calcium & Vitamin D metabolism

EP751 - EP752

Cardiovascular Endocrinology and Lipid Metabolism

EP753 - EP761

Clinical case reports - Thyroid/Others

EP762 - EP774

Developmental endocrinology

EP775

Diabetes (to include epidemiology, pathophysiology)

EP776 - EP777

Diabetes complications

EP778

Endocrine Disruptors

EP779 - EP783

Endocrine tumours and neoplasia

EP784 - EP792

Female Reproduction

EP793 - EP795

Growth hormone IGF axis - basic

EP796

Male Reproduction

EP797

Neuroendocrinology

EP798 - EP800

Nuclear receptors and Signal transduction

EP801 - EP807

Obesity

EP808 - EP810

Paediatric endocrinology

EP811 - EP818

Pituitary - Basic

EP819

Steroid metabolism + action

EP820 - EP824

Thyroid (non-cancer)

EP825 - EP829

EPOSTER PRESENTATIONS: PITUITARY AND NEUROENDOCRINOLOGY

Adrenal cortex (to include Cushing’s)

EP830 - EP831

Clinical case reports - Pituitary/Adrenal

EP832 - EP872

Developmental endocrinology

EP873

Endocrine tumours and neoplasia

EP874 - EP877

Growth hormone IGF axis - basic

EP878 - EP887

Male Reproduction

EP888

Neuroendocrinology

EP889 - EP921

Paediatric endocrinology

EP922 - EP923

Pituitary - Basic

EP924 - EP936

Pituitary - Clinical

EP937 - EP1081

Steroid metabolism + action

EP1082

EPOSTER PRESENTATIONS: REPRODUCTIVE ENDOCRINOLOGY

Bone & Osteoporosis

EP1083

Cardiovascular Endocrinology and Lipid Metabolism

EP1084

Clinical case reports - Pituitary/Adrenal

EP1085 - EP1089

Clinical case reports - Thyroid/Others

EP1090 - EP1091

Developmental endocrinology

EP1092

Endocrine tumours and neoplasia

EP1093 - EP1094

Female Reproduction

EP1095 - EP1156

Male Reproduction

EP1157 - EP1182

Neuroendocrinology

EP1183 - EP1184

Obesity

EP1185 - EP1187

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

European Journal of Endocrinology Prize Winner

The European Journal of Endocrinology Prize is awarded to a candidate who has contributed

significantly to the advancement of knowledge in the field of endocrinology through publication. This

year’s recipient is Dr Miguel Lopez who will receive his prize and deliver his lecture as part of the ECE

2017 Opening Ceremony on Saturday 20 May 2017. Further information on the prize can be found at

http://www.ese-hormones.org/prizes/.

Dr. Miguel López received his PhD in Molecular Biology (2002) from the

University of Santiago de Compostela (USC, Spain) and made his postdoctoral

training (2002-2006) in the Department of Clinical Biochemistry in the University

of Cambridge (UK). Currently, Dr. Miguel López is Associate Professor in

Department of Physiology at the School of Medicine and the Research Centre of

Molecular Medicine and Chronic Diseases (CIMUS) of USC. Since the beginning

of his PhD, he has focussed his research on the regulation of energy balance and

obesity, with his current interest on hypothalamic energy sensors in the modulation

of energy balance and metabolism. He has published around 150 peer-reviewed

papers. He currently serves on the editorial board of Endocronology, Journal of

Molecular Endocrinology, Molecular Metabolism, Journal of Endocrinology, several Frontiers journals

and PLoS ONE, and as a reviewer for several international biomedical journals and funding agencies.

For his work in this area, Dr. López received the awards for Basic Research in Obesity from Spanish

Endocrinology and Nutrition Society (SEEN, 2006 and 2009) and the Spanish Society for the Study of

Obesity (SEEDO, 2009), Spanish Award on Neuroendocrinology (2012), as well as the European

Association for the Study of Obesity (EASO) Young Investigator Award for Basic Science (2008; first

Spanish citizen to be awarded with that price) and the European Journal of Endocrinology Prize for the

European Society of Endocrinology (2017). He has been PI of 12 national and international grants,

among them an ERC Starting Grant. He teaches Endocrinology in the Schools of Medicine and

Pharmacy of USC. He has supervised 14 Master Thesis and 10 PhD Thesis.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Geoffrey Harris Prize Winner

The prestigious Geoffrey Harris Prize is awarded to an established researcher in the field of

neuroendocrinology and is the first of its kind in Europe. This years recipient is Professor Matthias

Tschop who will receive his prize and deliver his lecture as part of the ECE 2017 Opening Ceremony on

Saturday 20 May 2017. Further information on the prize can be found at http://www.ese-hormones.org/

prizes/.

Professor Matthias H. Tschop received his M.D. from Ludwig-Maximilians

Universität in Munich, where he also trained as a physician in internal medicine.

In 1998 he accepted an invitation for a postdoctoral fellowship at the Eli Lilly

Research Laboratories in Indianapolis, USA before returning to Europe in 2002 to

establish his independent research laboratory at the German Institute of Human

Nutrition (DIfE) Potsdam. He later returned to the United States where he

joined the University of Cincinnati to ultimately serve as the Director of the

Diabetes and Obesity Center of Excellence and Arthur Russell Morgan Endowed

Chair of Medicine. In 2011 Prof. Tschop accepted the position as Scientific

Director of the Helmholtz Diabetes Center at Helmholtz Center Munchen and was

named Chair of the Division of Metabolic Diseases at Technische Universität

Munchen. Prof. Tschop is the first German physician to receive the prestigious Alexander-von-

Humboldt Professorship (2012). He was elected into the German National Academy of Science

(Leopoldina) in 2013 and one year later was named adjunct Professor at Yale University, USA.

He started the peer-reviewed open access journal Molecular Metabolism, which he leads as the

Editor-in-Chief (first impact factor 2016: 5.4). In 2016 Matthias Tschop received an honorary doctorate

of the University of Leipzig and was named Director for Biomedicine of the Helmholtz Pioneer Campus

in Munich, which he co-founded.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

The Geoffrey Harris Prize Lecture

a few compound mixtures has set the precedent for combinatorial treatment of

obesity. On the other hand, double or triple therapeutic combinations are more

GH1

difficult to advance to regulatory approval. Following an improved understanding

Toward hormone-based precision medicines for metabolic diseases

of the molecular basis for metabolic benefits following bariatric surgery

Matthias Tschop

interventions, several classes of novel unimolecular or independent combination

Germany.

therapeutics were discovered. These new classes of drug candidates are based on

gastrointestinal hormones, offer efficacy superior to currently prescribed options

and seem to have potential to fully reverse human obesity and type 2 diabetes.

After decades of research unraveling complex metabolic control networks,

Moreover, gut peptide-based cell-specific targeted delivery of small molecules

medicines capable of a safe reversal of morbid human obesity and type 2 diabetes

offer additional potential for novel metabolic precision medicines and reduced

are still not available. Historically, complex diseases have repeatedly proven to be

systemic side effects. In this presentation the discovery, pre-clinical validation

defiant to the best mono-therapeutic approaches. Several examples of

and first clinical test of peptide hormone poly-agonist drug candidates as well as

combination therapies have largely overcome such challenges, notably for the

of combinatorial single molecule therapeutic candidates will be summarized,

treatment of severe hypertension and tuberculosis. Obesity and its consequences,

including previously unpublished observations.

such as type 2 diabetes, have proven to be equally resistant to therapeutic

approaches based on single medicines. Appropriate management of type 2

DOI: 10.1530/endoabs.49.GH1

diabetes often requires adjunctive medications, and the recent registration of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Clinical Endocrinology Trust Lecture

androgen excess may play a crucial role in disrupting the metabolic pathway, in

favouring aberrant visceral fat morphology and function, in favouring the

CET1

development of insulin resistance and in increasing the susceptibility to develop

Prospects for a new assessment of polycystic ovarian syndrome

glucose intolerance states and type 2 diabetes. Hirsutism is common in PCOS,

Renato Pasquali

however its correlation with blood androgen levels is weak or absent. Apart from

Italy.

the opportunity to use more objective methodologies to define it, much more

research is needed on the potential role of cutaneous androgens. Finally, due to

the relevant impact of obesity on PCOS and the fact that in many developed

PCOS is the most common hyperandrogenic disorder, with a high prevalence of

countries most PCOS women are obese, it can be suggested that a secondary form

metabolic comorbidities, including obesity and central fat distribution, insulin

of PCOS related to obesity may exist. The concept of secondary PCOS can be

resistance and the metabolic syndrome. With this background, it should be

extended to other pathological entities, particularly to the severe insulin resistant

accepted that androgen excess must be present in all women with PCOS. Thanks

states, but also to other endocrinopathies and, finally, to specific drugs

to the advance in measuring blood androgen levels by LC-MS/MS, it has become

(particularly antiepileptics). As with other endocrine syndromes, we should

clear that almost all typical cases of PCOS have a variable pattern of androgen

therefore consider that PCOS, precisely because it is a ‘syndrome’, may include

excess. An androgen profile including all major androgens should therefore be

many different phenotypes, ranging from the classic to milder forms, and that a

used for research purposes and clinical practice. The phenotype characterized by

secondary PCOS may occur. Additional mild phenotypes without well defined

menses abnormalities and polycystic ovarian morphology but without androgen

androgen excess may have different pathophysiological mechanisms.

excess should be regarded as a separate entity. The presence of a dysmetabolic

profile should also be used in the characterization of PCOS, specifically insulin

DOI: 10.1530/endoabs.49.CET1

resistance, which is commonly present in obese PCOS women but can also be

detected in their normal-weight counterpart. In fact, there is evidence that

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

The Fantastical World of Hormones

by the aberrant adrenal expression of several hormone receptors, particularly

G-protein coupled hormone receptors (GPCR) and their ligands. Screening for

aberrant expression of GPCR in bilateral macronodular adrenal hyperplasia

The fantastical world of hormones

(BMAH) and unilateral adrenal adenomas of patients with overt or subclinical CS

John Wass

demonstrates the frequent co-expression of several aberrant receptors. In addition,

USA.

the aberrant GPCR can also exert their activity by regulating the paracrine

secretion of ACTH or other ligands for those receptors in BMAH or unilateral

tumors. The molecular mechanisms underlying the abnormal tissue-specific

We all know that endocrinology is the most amazing specialty. However although

expression of the aberrant GPCR remains unclear but may be secondary to

some of the discoveries in the last 3-400 years have been amazing, some of the

dedifferentiation of progenitor cells at the origin of hyperplasia or tumors or to

wrong turns have exhibited opportunism and quackery. Perhaps we should start

specific genetic alterations. The aberrant expression of hormone receptors is not

with testosterone and the effects of castration. We know that removal of the testes

limited to primary adrenal CS but can be implicated in other endocrine tumors

before puberty has irreversible affects and that in 16th and 17th centuries these

including primary aldosteronism (aldosteronoma or bilateral idiopathic hyper-

were exploited for music. Popes did not come out of this covered in glory and the

aldosteronism) and Cushing’s disease. Targeted therapies to block the aberrant

last papal castrato was singing in the Sistine Chapel choir in the early 1900s. In

receptors or their ligands have been effective in selected limited cases to date, but

the late 1840s Berthold a German physiologist in Gottingen experimented on

development of novel specific antagonists could become useful in the future.

capons showing that if he removed their testes and transplanted them into the

abdomen, where they regained their blood supply, the effects of castration were

DOI: 10.1530/endoabs.49.P3

not seen. He did not recognize the importance of his observation. Later in the late

1880s Brown-Séquard, the famous French neurologist, reported at the French

Royal Society injecting himself with a mixture of the bloods from the testes of

dogs and guinea pigs. His reported marked improvement in strength and stamina

was a placebo effect because of the shorter half-life of testosterone. Thyroxine

from sheep given to patients with hypothyroidism, again in the late 1880s had a

remarkable effect in women with hypothyroidism because of the longer half-life

of thyroxine. In the late 1880s the ovary was thought to be part of the nervous

The Role of Brain Insulin Resistance for the Development

system. Oophorectomy at that time was used to treat conditions in women

including hysteria and anorexia and anxiety and even nymphomania. Ernest

of Prediabetic Phenotypes

Starling was the first person to coin the term ‘hormone’ and ‘Ormao’ is the Greek

word to ‘excite or stir up’. This was the founding of endocrinology. We have then

The role of brain insulin resistance for the development of prediabetic

gone from strength to strength with the discovery of insulin and more recent

phenotypes

leptin, pioneered amongst others by Steve O’Rahilly and Sadaf Farooqi in

Hans-Ulrich Häring

Cambridge.

Germany.

DOI: 10.1530/endoabs.49.P1

Abstract Unavailable

The Secret Life of FGF21

The secret life of FGF21

David Mangelsdorf

Browning of Adipose Tissue and Metabolic Regulation

USA.

Browning of adipose tissue and metabolic regulation

Fibroblast growth factor 21 (FGF21) is an endocrine and paracrine factor that is

Jan Nedergaard

produced in many tissues in response to metabolic stress, including several

Sweden.

nutrient and dietary conditions. In addition to its physiologic role in regulating the

adaptive response to these conditions, pharmacologic administration of FGF21 to

In most countries in the world, an increasing number of people suffer from the

obese animals causes weight loss and improves insulin sensitivity. The diverse

metabolic syndrome, normally defined as obesity, high blood sugar, high blood

actions of FGF21 are mediated through a unique receptor complex that is

fats and high blood pressure. The new understanding that adult humans possess

composed of a classic FGF receptor and the novel co-receptor, beta-Klotho.

active brown adipose tissue has led to hope that a (re)activation of this tissue

Investigation of the tissue-specificity of this FGF21

signaling pathway has

(browning) may be helpful in ameliorating the metabolic syndrome. Brown

revealed the existence of a complex peripheral and neural endocrine circuit that

adipose tissue has the ability to combust (extra) food intake in a direct way, due to

regulates metabolism, nutrient preference, and reward behaviors. We have also

the unique presence in this tissue of the UnCoupling-Protein-1 (UCP1). Thus, if

found an unexpected role for FGF21 in the exocrine pancreas as a secretagogue

activated - normally through the release of norepinephrine from the sympathetic

that protects acinar cells from proteotoxicity.

nervous system - the tissue will burn away food energy, leaving only heat, water

DOI: 10.1530/endoabs.49.P2

and CO₂. Thus, it protects against the development of obesity. When the tissue is

chronically activated, the stored lipid reserves in the tissue will not suffice for

continued heat production, and the tissue will take up large amounts of sugar from

the circulation, through a unique adrenergic mechanism, leading to lowering of

blood sugar levels through a large glucose disposal. It will similarly activate the

synthesis of lipoprotein lipase, leading in parallel to a large increase in lipid

uptake from the circulation, diminishing blood triglyceride levels. During

prolonged stimulation, the constant burning of food in the tissue will lead to the

Update on Regulation of Steroidogenesis by Aberrant

mobilization of the body’s lipid reserves (the white adipose tissue) that will be

Hormone Receptors

broken down and the released fatty acids will be transported to the brown adipose

tissue for combustion, i.e. the brown adipose tissue is slimming (and all these

effects together will likely also result in lowering of blood pressure). Although the

Update on regulation of steroidogenesis by aberrant hormone receptors

acute activity of the tissue is determined by norepinephrine, it would seem that

Andre Lacroix

sex hormones (positively) and glucocorticoids (negatively) can affect the tissue.

Canada.

The tendency to a worsening of the metabolic syndrome with age could then

partly be explained by a diminished sex hormone stimulation and an unaltered but

The mechanisms regulating cortisol production when ACTH of pituitary origin is

increasingly dominating negative effect of glucocorticoids, together leading to

suppressed in primary adrenal causes of Cushing’s syndrome (CS) include diverse

brown adipose tissue inactivity, and thus to obesity.

genetic and molecular mechanisms. These can lead either to constitutive

DOI: 10.1530/endoabs.49.P5

activation of the cAMP system and steroidogenesis or to its regulation exerted

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Clinical Updates in Hypoparathyroidism

hypoparathyroidism may be associated with the presence of anti-parathyroid

gland antibodies, and some patients harbor antibodies against the calcium-sensing

S1.1

receptor

(CaSR). Acquired hypoparathyroidism may also be caused by

Congenital hypoparathyroidism

hypomagnesaemia, which impairs PTH secretion; and can rarely be due to

Agnes Linglart

exposure to ionizing radiation, or result from infiltrative diseases affecting the

France.

parathyroids such as metastases or iron/copper overload.

DOI: 10.1530/endoabs.49.S1.2

The most common causes of hypoparathyroidism in children are the lack of or the

impaired development of the parathyroid glands due to genetic/chromosomal

alterations and the abnormal signaling of the Ca(^2C)-sensing receptor (CaSR).

The latter refers to autosomal dominant hypocalcemia (ADH) mainly caused by

heterozygous activating mutations in CASR encoding CaSR (ADH type 1), and

exceptionally caused by activating mutations of GNA11 encoding the Gq/11

S1.3

protein (ADH type 2). Hypoparathyroidism can also be caused by an autoimmune

Clinical updates in hypoparathyroisism

process, mainly in the context of AIRE mutations. However, in many children, the

Erik Fink Eriksen

origin of the hypoparathyroidism remains undiscovered. In a recent national

Norway.

French survey gathering

142

children affected with hypoparathyroidism

performed by MAC, 43% of the patients were diagnosed before the age of

1 year. The main causes of the PTH insufficiency were 22q1.1 deletion (31%),

The spectrum of symptoms associated with hypoparathyroidism span from

ADH1 (13%), AIRE mutations (10%) and cervical surgery (7%). The etiology is

virtually none to severely debilitating fatigue, memory loss, muscle cramps, and

still unknown in 23% of the children. Due to the high calcium needs of the

paresthesia. Until recently disease management has focused on securing stable

skeleton during infancy and childhood, hypoparathyroidism in children is often

serum calcium values at the lower end of the reference range using potent active

symptomatic and is diagnosed because of the clinical symptoms of hypocalcemia

vitamin D analogues like Etalpha and Rocaltrol, together with calcium

(muscle spasms, laryngospasm, seizures). Children may present with unspecific

supplementation. Recently maintenance of adequate levels of 25(OH)D have

features such as cognitive and or motor delay, slowness, ungueal, dental and skin

also been mentioned as being important. Adequate intracellular magnesium levels

anomalies. In addition, clinical characteristics due to the disease itself causing the

seem to be pivotal for PTH secretion and action at the receptor level, and should

hypoparathyroidism may be present such as candidosis, conotruncal cardiac

therefore be kept at the upper end of the normal range if possible. It is one few

defect, renal and/or uterine malformation. Once hypoparathyroidism has been

endocrine diseases where supplementation of missing hormone was impossible

diagnosed in a child, a comprehensive work-up should be performed to identify

about

10 years ago. Now we have access to recombinant PTH(1-34) and

the disease-causing defect. The investigations depends on the age of the child

PTH(1-84), and I will review the potential use of and differences between these

(neonate, child, adolescent), and on the clinical features associated with the

analogues in the treatment of hypoparathyroidism. In terms of symptomatic relief

hypocalcemia. The diagnosis is of importance for the management of follow-up

the results of controlled studies using these analogues as sc. injections have been

and treatment. The management of hypoparathyroidism in children relies upon

disappointing. A more physiological pattern can be achieved with continuous

calcium supplements and vitamin D analogs. Following the initial period of

subcutaneous infusion using insulin pumps, and I will review the results obtained

profound hypocalcemia which may require IV infusion of calcium and high doses

with this technique so far.

of vitamin D analogs (up to 4 mg/day of alfacalcidol), the conventional therapy

DOI: 10.1530/endoabs.49.S1.3

should aim at absence of clinical symptoms, low-normal level of serum calcium

(2-2.2 mmol/l), avoiding hyperphosphatemia and having normal urinary calcium

excretion. In some children, this may be a challenging management requiring the

use of thiazide diuretics, phosphate binders, calcium supplements and in

refractory cases, recombinant PTH. It has become obvious in the past ten years

that we need to i- obtain more data on the long-term evolution of children affected

with hypoparathyroidism, ii- adjust our decision rules for the identification of the

Evolving Diagnostics in Adrenal and Neuroendocrine

cause of hypoparathyroidism in the context of next generation sequencing and

Tumours

gene panels or whole exome sequencing, and iii- develop guidelines for the

S2.1

management of hypoparathyroidism in children including the specificity of ADH.

Role of genetic and biomarker tests for diagnosis of neuroendocrine

DOI: 10.1530/endoabs.49.S1.1

tumours (NETs)

Raj Thakker

UK.

Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms that

S1.2

occur in different organs and give rise to tumours including carcinoids, pancreatic

Acquired hypoparathyroidism

tumours

(PNETs), pituitary adenomas, medullary thyroid carcinoma, and

Fadil Hannan

phaeochromocytomas. NETs usually occur as isolated non-familial tumours,

Uk.

but can also occur as hereditary and syndromic disorders, such as multiple

endocrine neoplasia

(MEN types 1-4), Von Hippel Lindau

(VHL) and

Hypoparathyroidism is characterized by absent or low circulating concentrations

phaeochromocytoma/paraganglioma. Patients with NETs such as PNETs that

of parathyroid hormone

(PTH), which results in hypocalcaemia, hyperpho-

do not secrete hormones (referred to as non-secreting or non-functioning PNETs)

sphataemia and impaired renal reabsorption of calcium. Hypoparathyroidism has

are often asymptomatic, and this may result in late diagnosis and presentation

a prevalence of w20-40 cases per 100 000 individuals, and anterior neck surgery

with metastases. Thus, there is an unmet need for new, reliable and specific

accounts for around 75% of cases. Postsurgical hypoparathyroidism may arise in

biomarkers for early diagnosis that would improve patient survival and quality of

patients undergoing total thyroidectomy, radical neck dissection for head and

life. Biomarkers, which are defined by the World Health Organisation as a

neck malignancies, and after total parathyroidectomy. Hypoparathyroidism

substance, structure or process that can be measured in the body or its products

following surgery is caused by intraoperative trauma, and inadvertent gland

and influence or predict the incidence of outcome or disease, for non-secreting

removal or devascularisation. Transient postsurgical hypoparathyroidism, defined

NETs include pancreatic polypeptide, chromogranins, carcinoembryonic antigen,

as lasting !6 months, affects 25-30% of patients following total thyroidectomy;

a-foetoprotein, neuron specific enolase and synaptophysin. However, these

whilst permanent postsurgical hypoparathyroidism, defined as lasting O6

current biomarkers have poor sensitivity and specificity for non-secreting NETs

months, affects up to 3% of patients after total thyroidectomy. Decreases in

thereby limiting their use for clinical decision making. Recently, detection of

pre-operative serum calcium and 25-hydroxyvitamin D concentrations, reduced

germline mutations of the MEN1 and VHL genes have been established as useful

intraoperative PTH concentrations, and longer duration of surgery represent

predictive biomarkers for the development of PNETs in families with these

independent predictors of transient hypoparathyroidism. Permanent hypopar-

disorders. However, such familial mutations account for only approximately 3%

athyroidism following thyroid surgery is associated with: inability to identify R2

of NETs. Additional biomarker development has also focussed on studying

parathyroid glands during surgery; hypocalcaemia at 24-h post-surgery; and

altered expression of the epigenome, transcriptome, proteinome and metabolome,

reoperation for bleeding. Occasionally, postsurgical hypoparathyroidism may

as well as circulating DNA, microRNAs and tumour cells that can be released

have a delayed-onset and present several years after neck surgery. Autoimmune-

from tumours into the vasculature. These advances will be reviewed. Dr Kate E

mediated destruction of the parathyroids represents the next most common cause

Lines, Dr Mark Stevenson & Professor Rajesh V Thakker.

of acquired hypoparathyroidism and is considered in patients with a personal

DOI: 10.1530/endoabs.49.S2.1

or family history of autoimmune diseases. Autoimmune acquired

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

S2.2

S3.2

Current status in morphological imaging in adrenal and

GHR: are there benefits of endocrine defects?

gastrointestinal neuroendocrine tumours

John Kopchick

Sundin Anders

USA.

Sweden.

The effects of conditional mouse growth hormone receptor gene disruption or

Computed Tomography (CT) constitutes the basic technique for imaging of

‘knock-out’ on metabolic parameters and longevity will be presented. Tissues

adrenal tumours and neuroendocrine tumours (NETs). The major work-load in

investigated include muscle, adipose, heart, and liver. Also, data on adult onset

adrenal imaging is characterisation of adrenal incidentalomas, i.e. adrenal

growth hormone gene disruption will be presented.

tumours diagnosed on imaging performed for other reasons than adrenal disease.

DOI: 10.1530/endoabs.49.S3.2

Myelolipomas, which have a typical appearance with areas of macroscopic fat,

and simple cysts are easy to characterize and require no follow-up.

Morphologically benign adrenal tumours (rounded, sharply delineated, hom-

ogenous internal structure) with an attenuation of %10HU in the native CT

images are characterized as benign adrenocortical adenomas and require no

additional imaging. With an attenuation R10HU, follow-up of tumour size is

S3.3

recommended for 6 months. In young (!40 years) patients this should preferably

Somatostatin receptors: news in the pituitary, lessons for the periphery

be performed by MRI. Calculation of contrast medium wash-out is no longer

Justo Pastor Casta

˜o

applied. For tumours O4 cm surgical resection is recommended unless in cases of

Spain.

a typical myelolipoma or cyst. CT is for NETs used for the initial localization of

the primary tumour, for staging of the disease, detection of recurrence and for

The pituitary has been classically considered the ‘Master Gland’, owing to its

monitoring of therapy. It is also used in hybrid imaging in conjunction with PET

ability to regulate the function of the other endocrine glands of the body.

(PET/CT) and SPECT (SPECT/CT). MRI is superior for imaging of liver,

However, the hypophysis also served over the years as a master, guiding example

pancreas, brain and bone. In metastatic NETs,

68Ga-DOTA-somatostatin

to enlighten multiple fields of experimental biology and medicine, from classic

analogue PET/CT generally shows several additional lesions as compared to

physiology to modern cell biology, biochemistry and molecular biology.

CT/MRI and small lesions such as lymph nodes may be characterized as

Somatostatin and its receptors (sst1-5) comprise a classic regulatory system,

metastatic/not metastatic lesions. Contrast-enhanced US is excellent for

initially discovered and characterized at the hypothalamo-pituitary interface,

diagnosis and characterization of liver lesions and to guide the biopsy needle

which subsequently expanded to influence multiple bodily functions, from

for the histopathological NET diagnosis. Endoscopic US is the best method

neurotransmission to digestive function and metabolic homeostasis, and also

for detection of pancreatic NETs.

tumour biology. In this scenario, our group discovered an aberrantly spliced

DOI: 10.1530/endoabs.49.S2.2

variant of sst5, sst5TMD4, which lacks 3 of the typical 7 transmembrane domains

of GPCRs, but retains unique functional abilities and tisular and subcellular

distribution. Initial studies revealed sst5TMD4

overexpression in pituitary

tumors, particularly in acromegaly, where its presence is associated to a reduced

response to somatostatin analogues, both in vitro and in vivo, and is linked to

enhanced aggressiveness features, such as cell proliferation in vitro and tumor

invasion in vivo. These findings led us to explore the possible presence and

activity of sst5TMD4 in other hormone-related tumors. Interestingly, a series of

collaborative studies demonstrated that this truncated receptor is overexpressed

S2.3

in multiple tumors and cancers, including, so far, breast cancer, pancreatic

Current status in functional imaging

neuroendocrine tumors, poorly differentiated thyroid cancer, medullary thyroid

Vickas Prassad

carcinoma, and prostate cancer. In these pathologies, studies on patient samples

Germany.

and clinical features, an on tumor-derived primary cells or model cell lines have

demonstrated that sst5TMD4 presence is directly linked to enhanced aggressive-

ness features, such as increased cell proliferation, migration and invasion,

Abstract unavailable.

hormonal secretion, etc. Further analysis on the molecular underpinnings of these

observed features have revealed a number of activated oncogenic or inactivated

tumor-suppressing pathways and molecular players, some of which seem to be

shared by most tumor types studied, whereas others seem to be unique for a given

type of tumor/cancer. These results, coupled to our observation that other

misspliced variants related to pituitary pathophysiology (namely, In1-grelin and

GHS-R1b) are also present in the same tumors prompted us to study the splicing

machinery. Of note, ongoing studies have revealed that the splicing machinery is

dysregulated in these pathologies. Thus, the pituitary served, once again, to pave

the way to scientific discovery for the periphery.

DOI: 10.1530/endoabs.49.S3.3

From the Pituitary to the Periphery

S3.1

Implication of the prolactin receptor in humans

Nadine Binart

France.

2nd Joint Global Symposium on Obesity - The Many

Dimensions of the Childhood Obesity Problem

While prolactin

(PRL) is known as the pituitary hormone of lactation,

S4.1

accumulating evidence shows that PRL acts on many tissues and in many

Efficacy and effectiveness of physical activity and nutrition

pathophysiological conditions. The major isoform, 23 kDa PRL, acts via a

interventions in childhood obesity treatment

membrane receptor, the prolactin receptor

(PRL-R), a member of the

Hollie Raynor

hematopoietic cytokine superfamily, and for which the mechanism of activation

USA.

has been elucidated. The aim of this symposium is to present and discuss data

supporting actions of PRL in hyperprolactinemia in the context of gonadotropic

deficiency. High levels of PRL in humans may interfere with reproductive

While several organizations have recommended that multicomponent, behavioral

function mainly by actions at the hypothalamus. Our data suggest that Kisspeptin

family-based programs delivered at a moderate- to high-intensity contact

neurons appear to be the missing link between hyperprolactinemia and GnRH

frequency have a moderate to high rating of efficacy for improving weight status

deficiency. Otherwise, germline PRLR mutations have been suspected to be a

in children, these types of programs are difficult to translate into many practice-

specific genetic cause of prolactinoma in humans. This will be discussed in light

based settings. This presentation will review areas that have been identified within

of our recent results.

childhood obesity treatment programs that may assist with translation to practice-

DOI: 10.1530/endoabs.49.S3.1

based settings, and discuss research that has been conducted that examine these

factors. An example of a current randomized trial translating a multi-component,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

behavioral family-based program into an integrated primary care setting in the

S5.2

USA will be provided.

Vitamin D and rickets in African children

DOI: 10.1530/endoabs.49.S4.1

Vickie Braithwaite

UK.

Rickets is the most common non-communicable disease in low and middle

income countries and is re-emerging in countries such as the UK where it was

once thought to be eradicated. Rickets is a bone disease which affects growing

children and is caused by the undermineralisaton of the growth plate of long

bones. Rickets can lead to osteomalacia, disabling bone deformities of the lower-

S4.2

limbs, stunting, increased fracture risk and in severe cases circulating bone

The hunger genes: pathways to obesity

mineral disturbances can result in hypocalcaemic seizures and death. The

Sadaf Farooqi

majority of nutritional rickets worldwide is thought to be driven by vitamin D

deficiency due to inadequate skin exposure to UVB-containing sunshine. In many

countries in Africa however, 25-hydroxyvitamin D concentrations (the status

Abstract unavailable.

marker for vitamin D) are above those generally associated with vitamin D

deficiency thus indicating alternative causes of rickets. This presentation will

explore some of our work on the role of the vitamin D-calcium-phosphate axis on

nutritional rickets in a selection of African countries; highlighting the potential

roles of calcium and iron deficiency. This presentation will also explore whether

aetiology may differ depending on setting i.e. urban vs rural and the various

treatment methods for rickets including surgical correction of bone deformities,

nutritional supplementation and prophylactic treatment strategies for rickets

prevention.

Funded by MRC programmes U105960371, U123261351, MC-A760-5QX00 and

S4.3

DfID under the MRC/DfID Concordat.

Can we prevent childhood obesity?

DOI: 10.1530/endoabs.49.S5.2

Tim Lobstein

UK.

Childhood obesity prevalence continues at a high level in most developed

economies and is rising strongly in emerging middle-income countries. This rise

in prevalence shows strong links to the exposure of populations to mass-marketed

S5.3

foods and beverages and the use of motorised transport. In Europe the prevalence

Carbohydrate metabolism in patients with Cushing disease: a glance at

tends to be higher, and rising faster, among children from lower-income

the incretin system

households. The prevention of obesity is essential but clearly we are not doing

Lubov Matchekhina

very well - no country in Europe has successfully and sustainably reduced

Russia.

childhood obesity prevalence. We need to ask: What are the major social,

commercial and political barriers which need to be overcome? What steps can we

take to overcome these barriers and create a truly health-promoting society?

The relevance of carbohydrate metabolism studying in patients with Cushing

disease (CD) and acromegaly can be explained by frequent occurrence of glucose

DOI: 10.1530/endoabs.49.S4.3

metabolism disturbances on the one hand, and difficulties in glucose-lowering

therapy in these patients on the other. The effectiveness of hyperglycaemia

treatment may be reduced due to difficulties in remission/cure of the underlying

disease, as well as to the use of specific drug-therapy, leading to hyperglycaemia.

There is a growing interest in research aimed at studying the role of incretin

system in the pathogenesis of secondary hyperglycemia associated with

neuroendocrine diseases recently.

Aim of the study

Turn Your Face to the Sunshine

To analyze the rhythm and levels of incretins and neuropeptides secretion in

S5.1

patients with CD and acromegaly and therefore to specify the pathogenesis of

carbohydrate metabolism disturbances.

Effects of maternal thyroid function on infant neurodevelopment

Methods

Tim Korevaar

42 patients with Cushing disease and acromegaly were included; the mean age

The Netherlands.

was 37.5 years. All of the patients were newly diagnosed with Cushing disease

(using urinary free cortisol levels, evening saliva cortisol levels and low-dose

In this talk I aim to provide a helicopter view of clinical studies on maternal

dexamethasone suppression test) and acromegaly (in absence of GH suppression

thyroid function and child neurodevelopment and use this to pinpoint out how

during OGTT and high IGF1 levels); none of them had a history of previous drug

different viewpoints on the results can help to interpret the clinical relevance of

therapy, radiotherapy or pituitary surgery. All patients underwent OGTT, during

the currently available data and provide handles to make personal but informed

which glucose, glucagon, GLP1, GLP2, GIP, ghrelin were measured at 0, 30 and

clinical decisions. It is well-established that thyroid hormone plays an important

120 min respectively.

role during early stages of fetal brain development. Thyroid hormone-dependent

Results

stages of brain development occur from the 5th week of pregnancy onwards while

During OGTT glucose levels were not significantly different in all groups. The

the fetal thyroid is not functionally matured until week 18-20. This implicates

mean HbA1c level was 5.8% (5.3-6.2). However the relevance of prediabetes was

that adequate maternal thyroid hormone concentrations are important for

higher in CD patients. In CD patients glucagon levels were significantly higher at

achieving optimal early fetal brain development. After the initial link between

all cut off points compared to controls (PZ0.001). In acromegaly patients, no

iodine deficiency and cretinism was first identified, a wide range of experimental

significant differences were found. GIP secretion was slightly lower in CD

studies further established underlying (patho)physiological mechanisms. Sub-

patients; in acromegaly patients, no differences were found. Acromegaly group

sequently, clinical studies were set-up to translate these findings and quantify the

was characterized by inverse rhythm of GIP secretion, with no peak level at 30’:

extent of effects in humans. During this presentation I aim take the audience

GIP 0 min - 194.2 pg/ml, GIP 30 min - 178.8 pg/ml. GLP-1 levels were

through a brief timeline of clinical studies published since the late 1990s until this

significantly higher in CD patients

(PZ0.047). In acromegaly group, no

year. The interpretation of clinical outcomes used to study the hypothesis that

significant differences in GLP-1

secretion were found. GLP-2

levels were

maternal thyroid hormones are important for fetal brain development, such as

significantly higher in CD patients compared to acromegaly and controls

child IQ, will be discussed. The timeline of clinical studies together with the

(PZ0.001). Ghrelin levels were significantly higher in CD (PZ0.013) and

interpretation of the results of recent studies, including clinical trials, could help

acromegaly (PZ0.023) patients.

to weigh the potential clinical benefits and harms, and make for a better informed

Conclusion

decision making.

More pleotropic actions of glucocorticoids can possibly explain higher relevance

DOI: 10.1530/endoabs.49.S5.1

of carbohydrate metabolism disturbances in CD patients. This can be also

explained by higher levels of glucagon secretion, which does not depend on type

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

of carbohydrate metabolism disorder and is stimulated by a direct action of

field may lead to new therapeutic options in congenital or post-surgical

glucocorticoids on glucagon receptor. GIP and GLP-1 secretion in CD and

hypothyroidism.

acromegaly patients are characterized by inverse rhythm with no peak levels

DOI: 10.1530/endoabs.49.S6.3

which means that these hormones are not playing the crucial role in carbohydrate

disturbances development in these patients. On the contrary, GLP-2 and ghrelin

seem to influence and potentially regulate glucose homeostasis in CD and

acromegaly patients.

DOI: 10.1530/endoabs.49.S5.3

Crosstalk between Bone & Other Organ(ism)s

S7.1

Immune system

Patrizia D’Amelio

Italy.

Treatment of Hypothyroidism: What Have We Learned?

The immune system has been recognized as one of the most important regulators

S6.1

of bone turnover and its de-regulation is implicated in several bone diseases as

What is the clinical relevance of deiodinase polymorphisms?

post-menopausal osteoporosis and inflammatory bone loss. The study of the

Antonio Bianco

relationship between immune system and bone metabolism is generally indicated

USA.

under the term ‘osteoimmunology’, the vast majority of these studies have been

performed in animal models, however several data have been confirmed also in

humans. Post-menopausal osteoporosis (PMO) is the most frequent metabolic

Abstract unavailable.

skeletal disease, it is characterized by reduced bone mineral density and micro

architectural deterioration of bone with increased fracture risk. In PMO the

uncoupling between osteoblast (OB)-mediated bone formation and osteoclast

(OC)-mediated bone resorption results in bone loss. Estrogen deficiency is the

main driver of post-menopausal bone loss: during estrogen depletion OCs

formation and activity are increased, this increase is partially mediated trough the

effect of estrogen deficiency on immune system. Estrogen deficiency influences

immune response, in particular T cells, become more active and able to produce

S6.2

inflammatory and pro-osteoclastogenic cytokines as TNFa and RANKL. Despite

T4/T3 combination therapy: is there a true effect?

of some inverse reports, the main body of literature firmly supports the essential

Wilmar Wiersinga

role of activated T cells in regulating bone loss induced by estrogen deficiency,

The Netherlands.

both in animal models and in humans. We recently demonstrated that immune

system, and in particular T cells mediate the effect of PTH on bone turnover, in

particular we demonstrated that during treatment with teriparatide for PMO T

L-T4 monotherapy remains the standard treatment of hypothyroidism, as RCTs

cells mediates osteoblastogenesis trough the production of Wnt10b, whereas

comparing T4 and T4CT3 did not indicate superiority of the combination

primary hyperparathyroidism do not increase this molecule. Moreover we

therapy. However, the issue is far from settled, as these RCTs can be criticized

demonstrated that, both in mice and humans, continuous infusion of PTH and

and 5-10% of patients on T4 have persistent complaints.

primary hyperparathyroidism increases the differentiation of T helper (TH) cells

i) Has T4CT3 therapy a true effect on serum thyroid hormones? Under T4

in TH17. These cells are responsible for increased OCs formation and activity

monotherapy serum FT4 is higher and serum FT3 is lower than in healthy

both in inflammatory diseases and in PMO. In conclusion The interactions

subjects, giving rise to abnormal T3/T4 ratio’s in 29% of patients. T4CT3

between immune system and bone are complex and play significant role in both

therapy produces lower FT4 and higher FT3 values, and thereby T3/T4 ratio’s are

health and disease, nevertheless not all the pathways discovered in animal models

closer to normal values. There is conflicting data whether T3/T4 ratio’s are related

have been fully demonstrated in humans, and several challenging questions

to SNPs (e.g. in DIO2) and to persistent complaints.

remains unsolved.

ii) Has T4CT3 therapy a true effect on thyroid-hormone dependent actions?

There is emerging but weak evidence that markers of thyroid hormone action

DOI: 10.1530/endoabs.49.S7.1

(such as LDL-cholesterol, SHBG, bone alkaline phosphatase) are closer to normal

under T4CT3 therapy than under T4 monotherapy.

iii) Has T4CT3 therapy a true effect on the clinical condition? Patients were

asked for their preference in 4 RCTs. Preference for T4 was 25% and for T4CT3

48%; no preference was expressed by 27%. Preference has been related to loss of

S7.2

body weight and to combined SNPs in MCT10 and DIO2.

iv) Has T4CT3 therapy a true effect on clinical practice? Yes, absolutely. Many

Osteocalcin signaling in myofibers is necessary and sufficient to increase

patients demand T4CT3 therapy, sometimes in a aggressive manner. Prescription

exercise capacity

of T3 tablets have increased, and pharmacy has discovered the potentially big

Gerard Karsenty

market for T3, among others resulting in a steep price increase of T3 tablets but

USA.

also in availability of 5 microgram T3 tablets. Only the ETA published detailed

guidelines how to start the still experimental T4CT3 regimen (Eur Thyroid J

The observation that circulating osteocalcin levels double during exercise in

2012;1:55). The many unresolved issues call for many more clinical trials.of

young mice suggests that this hormone might be a long sought after endocrine

different designs.

regulator of exercise capacity. We addressed this question by analyzing mice

DOI: 10.1530/endoabs.49.S6.2

lacking either osteocalcin or its receptor in myofibers only. This analysis showed

that osteocalcin signaling in myofibers enhances adaptation to exercise because it

increases uptake and utilization of glucose into the tricarboxylic acid cycle and

promotes fatty Osteocalcin signaling in myofibers favors adaptation to exercise

through a second mechanism. Indeed it up-regulates the expression of Interleukin-

6 a myokine that favors adaptation to exercise in part by signaling in bone to

S6.3

promote the production of bioactive osteocalcin. Acids utilization. In the course

of these studies we noticed that circulating osteocalcin levels decline sharply

Rebuilding your own thyroid from stem cells; the future therapy of

before mid-life and do not increase during exercise in older mice. This

hypothyroidism?

observation raised the prospect that osteocalcin may also be sufficient to correct

Anthony Hollenberg

the age-related decline in muscle function. In support of this hypothesis, our

USA.

experiments show that exogenous osteocalcin increases the exercise capacity of

young wilt-type mice and confers to 15 month-old mice the exercise capacity of

Advances in stem cell biology and thyroid development have opened up the

3 month-old mice. This study uncovers an osteocalcin-interleukin-6 axis that

possibility of developing tissue replacement therapy for hypothyroidism. Indeed,

increases muscle function during exercise and can reverse the age-induced

in this session the development from stem cells of functioning thyroid tissue in

decline in exercise capacity.

mice will be reviewed. In addition new insight into the development of this

DOI: 10.1530/endoabs.49.S7.2

technology in human cells will also be discussed. Importantly, advances in this

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

S7.3

levels of GH-hypersecretion (Fig. 1). Treatment with somatostatin analogues,

both before and after surgery, leads to different responses of T2-hypointense

Gut microbiota and bone metabolism

adenomas versus non-hypointense tumours. The T2-hypointense adenomas have

Klara Sjogren

higher GH and IGF1 decreases and more important tumour shrinkage rates (1). It

Sweden.

is therefore interesting to have high quality T2-weighted MRI images at the

diagnosis of acromegaly, as it allows to estimate disease evolution and to orient

The gut microbiota (GM), the commensal bacteria living in our intestine,

the management strategy.

performs numerous useful functions, including modulating host metabolism and

Reference

immune status. Our recent studies demonstrate that the GM is also a regulator of

1. Potorac, J et al. T2-weighted MRI signal predicts hormone and tumor responses

bone mass and we propose that the effect of the GM on bone mass is mediated via

to somatostatin analogs in acromegaly. Endocr Relat Cancer 23(11):871-881.

effects on the immune system, which in turn regulates osteoclastogenesis. A role

DOI: 10.1530/endoabs.49.S8.2

of the GM in bone metabolism is further supported by studies demonstrating that

antibiotic, probiotic, and prebiotic treatments that impact GM composition

regulate bone metabolism. Collectively, these studies suggest that the GM may be

a novel therapeutic target for osteoporosis. Treatment with probiotics has already

been shown to improve bone mass in rodent models of bone loss, but future

randomized clinical trials are required to determine the possible effect of

S8.3

probiotics and other novel therapies modulating the GM composition on bone

Predictors of therapeutic response in functioning pituitary tumours

mass and fracture risk in patients with osteoporosis. Access to cheaper sequencing

Marek Bolanowski

and improved bioinformatics tools will allow metagenomic sequencing for the

Poland.

analysis of the GM composition in large prospective clinical cohort studies. This

can be used to evaluate the predictive value of the GM composition as a

biomarker for low bone mass and fracture risk. In addition, metatranscriptomics

Therapeutic response for medical therapy in hormonally functioning pituitary

and metaproteomics will most likely be used to identify the microbial genes and

tumours is different in various types of tumours. While majority of prolactinomas

proteins that have an impact on bone mass and fracture risk. We propose a new

respond well for medical therapy using dopamine agonists, in other tumours like

cross-disciplinary GM-bone research field called ‘osteo-microbiology’, bridging

somatotropinoma or corticotropinoma their response is significantly lower. In

the gaps between bone physiology, gastroenterology, immunology, and

some case therapy resistance can occur. There are various factors determining the

microbiology. Future studies are clearly warranted in this new research field to

efficacy of medical therapy in patients harboring functioning pituitary adenomas.

determine if the GM composition might be used as a biomarker for fracture risk

They are different for certain type of tumour. Among clinical aspects, gender, age

prediction and to validate the GM as a possible novel therapeutic target for

and extent of hormonal hypersecretion are important factors. In general, response

osteoporosis.

for the therapy in acromegaly is poor in younger male patients with larger

DOI: 10.1530/endoabs.49.S7.3

tumours and greater GH hypersecretion. Pituitary imaging using MRI can show

tumour size and invasiveness, together with T2

intensity. Histological and

molecular analyses assess granulation pattern, somatostatin and dopamine

receptors number and expression, Ki-67 index, mitotic activity, p53 immunor-

eactivity, AIP expression, genetic mutations and polymorphisms. The knowledge

of possible factors influencing therapeutic response is important and may be

Predictors of Therapeutic Response in Functioning

helpful in the choice of optimal individualized therapy.

Pituitary Tumours

DOI: 10.1530/endoabs.49.S8.3

S8.1

Molecular profiling

Monica Gadelha

Brazil.

Novel Type 2 Diabetes Treatment: Beyond Glycaemic Control

Abstract unavailable.

S9.1

Experimental models

Jens Holst

Denmark.

S8.2

One of the most surprising and inspiring experimental models for type 2 diabetes

therapy is gastric bypass surgery. Recent

5-year results have demonstrated

MRI predictors of therapeutic response in GH-secreting pituitary

massive improvements in glycaemic control and body weight, lipids and quality

tumours

of life after surgery compared to intensive medical therapy (the Stampede trial).

Jean Francois Bonneville

Therefore, it is imperative to identify the responsible factors with a view to utilize

Belgium.

this knowledge for future therapy without surgery. Substantial evidence suggests

that increased secretion of gut hormones plays an important role for both weight

The T2-weighted characteristics of GH-secreting pituitary adenomas have

loss

(inhibition of appetite C food intake) and glucose metabolism

(by

recently received particular attention from the research community. It now

stimulating glucose-induced insulin secretion). The appetite inhibition seems to

appears that somatotropinomas can be divided into groups with different behavior

involve hypersecretion of PYY, GLP-1 and perhaps CCK, oxyntomodulin, and

according to their T2-weighted signal. T2-hypointense adenomas are generally

neurotensin. Decreased secretion of ghrelin may also play a role. The improved

smaller, invade the cavernous sinus less frequently and are responsible for higher

glycaemic control is due to a combination of (i) dramatically improved insulin

sensitivity (initially improved hepatic sensitivity in parallel with reduction in

steatosis) and secondly peripheral sensitivity in parallel with general weight loss -

and (ii) improved postprandial insulin secretion due to improved beta cell glucose

sensitivity as well as a stronger glycaemic stimulus caused by accelerated glucose

absorption. The latter is also the major driving force for postprandial release of the

insulinotropic hormone GLP-1, whereas lipids

(bile salts) may explain

neurotensin secretion while protein derivatives drive CCK secretion. Further

experiments using isolated primary gut cells and perfused gut preparations have

identified certain bile salts to potently stimulate secretion while amino acids

transporters including Pept-1

and basolateral calcium-sensing receptors are

important for protein-induced secretioin. The most important lesson so far is that

stimulated secretion predominantly depends on absorption of nutritional

elements. Some of these elements may form the basis for new therapeutic

approaches.

Figure 1 Hyperintense (a) and hypointense (b) GH-secreting

DOI: 10.1530/endoabs.49.S9.1

adenomas on T2 W MRI.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

S9.2

survivors. Male sterility is a relative common side effect of cancer treatment. This

adverse fertility effect is caused by gonadotoxic effects as the cancer treatments

Clinical studies on GLP1 - cardiovascular outcomes

not only effectively kill cancer cells but also destroy the progenitors of sperm.

Baptist Gallwitz

Spermatogenesis is the process of sperm production starting from spermatogonial

Germany.

stem cells that are extremely sensitive to treatments with alkylating agents or

irradiation. Damage to these stem cells results in temporary or permanent sterility

The incretin hormone Glucagon-like peptide-1

(GLP-1) has various non-

depending on the doses. For this reason, adult men diagnosed with cancer are

glycaemic properties. Among those, cardiovascular effects have been described

offered cryopreservation of semen before starting cancer treatment. However, for

in animal studies and in clinical studies in patients with type 2 diabetes that have

pre-pubertal and young boys, this is not an option as sperm is not yet produced in

been treated with GLP-1 receptor agonists (GLP-1RA). In animal studies, GLP-1

these boys. As spermatogonial stem cells are already present in the testis, these

and GLP-1RA have lead to a decrease in ischaemic areas in artificial myocardial

cells are a source for fertility preservation. A potential future clinical application

infarct models. Additionally, in some clinical studies, an improvement in left

to preserve fertility in these boys with cancer is to cryopreserve a small testis

ventricular function was observed as well as a decrease for catecholamine

biopsy prior to cancer treatment for later isolation and propagation of

requirement in post-surgical patients after coronary bypass graft surgery. The

spermatogonial stem cells from this biopsy and transplantation of these cells

pathophysiological explanations for these effects are a possible improvement in

back after cure of cancer. Studies in animal models have provided evidence that

substrate utilization of the myocardium as well as vascular effects mediated by the

this method indeed restores fertility. It is shown that spermatogonial stem cells

activation of cardiovascular GLP-1 receptors and a consecutive amelioration of

can be transplanted to the testis, where they migrate to their niche and colonize the

hypertension. In recent years, randomized, prospective cardiovascular safety

testis, giving full spermatogenesis of which sperm was able of fertilizing eggs and

trials have been initiated or performed with GLP-1RA in patients with type 2

producing offspring. Using this transplantation as readout, spermatogonial stem

diabetes and concomitant cardiovascular disease or cardiovascular risk factors.

cell characteristics could be studied in more detail, resulting in the establishment

Results from three of these studies have been published so far. In the ELIXA-trial,

of a long term in vitro propagation system for mouse spermatogonial stem cells

the short acting GLP-1RA lixisenatide was given as add on to a standard

that upon transplantation could produce sperm to generate offspring. This

antidiabetic therapy in patients after an acute cardiovascular event. In comparison

presentation will give an overview on the state of art of the translation of these

to an established diabetes therapy, lixisenatide demonstrated non-inferiority and

techniques to the human situation to establish a clinical application for fertility

cardiovascular safety. The LEADER-study performed with liraglutide in patients

preservation in young boys suffering from cancer.

with type 2 diabetes and concomitant cardiovascular risk or disease showed a

DOI: 10.1530/endoabs.49.S10.2

highly significant 13% relative risk reduction in the 3-point MACE (MACE Z

multiple adverse cardiovascular events; combined endpoint of cardiovascular

death, non-fatal myocardial infarction and non-fatal stroke) after 54 months. This

result was primarily driven by a significant reduction of cardiovascular death by

22%. Semaglutide, a long-acting GLP-1RA for once weekly injection that is not

approved yet, lead to a significant 26% relative risk reduction in the 3-point

MACE in its clinical phase III study programme. From these data, the hypothesis

S10.3

that the activation of the GLP-1 receptor has beneficial cardiovascular effects, is

strongly supported and it has now been demonstrated in two studies, that patients

Pubertal induction and hormone replacement in young males

with type 2 diabetes and cardiovascular disease may profit from a therapy with

Nelly Pitteloud

GLP-1RA regarding their cardiovascular outcomes.

Congenital gonadotropin-releasing hormone deficiency is a rare disorder

DOI: 10.1530/endoabs.49.S9.2

characterized by incomplete or absent puberty and infertility. This condition is

both clinically and genetically heterogeneous and presents with a broad spectrum

of phenotypes ranging from mild to severe. This presentation will provide a

review of hypogonadotropic hypogonadism, including the clinical presentation of

HH, a rational approach to evaluating HH patients, and an update on treatment

options. In particular, the speaker will focus on the choice of the most appropriate

S9.3

treatment in hypogonadotropic hypogonadism based on clinical presentation

SGLT2 long term protective effects

including the use of rFSH to enhance treatment outcome.

Javier Escalada

DOI: 10.1530/endoabs.49.S10.3

Spain.

Abstract unavaialble.

New Roles for Nuclear Receptors

S11.1

The Challenges of Male Fertility

Identification of nuclear receptors network in male fertility

S10.1

David Volle

France.

Manipulating testicular androgen production to promote lifelong male

health

Lee Smith

Male fertility is controlled by complex interactions among the hypothalamus,

UK.

pituitary, and testis. The major functions of the testis include production of

spermatozoa

(male gametes) and synthesis of testosterone. Testosterone is

produced by the testicular Leydig cells and is responsible for the development of

Abstract unavailable.

gonad, the attainment of puberty, and the maintenance of secondary sexual

characteristics. It is also involved in the maintenance of of spermatogenesis and

thus ensuring male fertility. Many studies have highlighted the complexity of the

regulations of testicular homeostasis at both tissue and cellular levels. Among the

involved molecular mechanisms, several nuclear receptors (NRs) have been

identified as key regulators of testicular physiology. NRs are a family of

S10.2

transcription factors with a conserved structure that within testis control

steroidogenesis and germ cell differentiation. Since several years, using both

Fertility preservation in pre-pubertal and young males

genetic and pharmacologic strategies, we have been implicated in the

Ans van Pelt

identification of the multiple roles of particular members of the NR superfamily.

The Netherlands.

Here we will give an overview of our research highlighting the identification of a

complex network showing the interactions of these NRs in the regulation of the

Survival rates for patients with cancer have continuously increased over the past

exocrine and endocrine functions of the testis.

decade as a result of more advanced cancer treatment. As a consequence, adverse

DOI: 10.1530/endoabs.49.S11.1

side effects of cancer therapy becomes an important health issue for these cancer

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

S11.2

orbital fibroblasts fulfil in GO pathogenesis as well as the potential of direct

targeting of the orbital fibroblast in the treatment of GO.

Crosstalk between estrogen signalling and DNA damage repair

Simak Ali

DOI: 10.1530/endoabs.49.S12.1

UK.

Estrogen receptors (ER) are expressed in the majority of breast cancers, are key

drivers of breast cancer development and progression and hence therapies to

inhibit their activities are a mainstay of treatment for breast cancer. A large

proportion of patients develop resistance to these therapies, so determining the

S12.2

mechanisms of ER action is important for improving patient management and for

identifying new therapies. In defining the mechanisms by which ER regulates

Management of Graves orbitopathy

gene expression, we and others find that proteins involved in DNA damage

Luigi Bartalena

recognition and repair (DDR), including components of base excision repair

Italy.

(BER) and non-homologous end-joining (NHEJ) are central to the promotion of

gene expression by ER. Most recently, we have demonstrated that the cytosine

Management of Graves’ orbitopathy (GO) depends on the severity and activity of

deaminase APOBEC3B (A3B) is recruited to the regulatory regions of estrogen-

the disease. Guidelines for the management of GO have recently been published

responsive genes in an ER-dependent manner. We have shown that A3B

by EUGOGO (European Group on Graves’ Orbitopathy) (European Thyroid

recruitment promotes transient C-to-U changes at ER/A3B binding regions,

Journal 2016 5 9-26). Assessment of GO by standardized criteria is fundamental

repaired by BER/NHEJ pathways, with the cytosine deamination and its repair

to determine the type of intervention. General measures for all patients with GO,

facilitating chromatin remodeling that aids expression of ER target genes.

irrespective of the degree of severity and activity, include restoration and stable

Importantly, we have now extended these studies to demonstrate an important

maintenance of euthyroidism, refrain from smoking, use of local measures (e.g.

role for A3B in transcription regulation in ER-negative, as well as ER-positive

artificial tears, ocular gels). All GO patients, except for the mildest cases, should

breast cancer cell lines, indicating that A3B has a general role in regulating gene

be referred to specialists. Mild GO is not treated actively, except for a 6-month

expression in human cells. These findings highlight the therapeutic potential of

course of selenium supplementation, shown in a randomized clinical trial (RCT)

A3B inhibitors for the treatment of ERC and ER-negative breast cancer. Recent

to be more effective than placebo also in terms of prevention of progression to

reports have implicated A3B as the enzyme responsible for acquisition of

more severe forms of GO. Sight-threatening GO, due to dysthyroid optic

mutations and tumour evolution in diverse cancer types, highlighting the inherent

neuropathy and/or corneal breakdown, is an endocrine emergency and should be

dangers associated with the cellular role of DNA damage and repair in the

treated immediately with very high doses of intravenous glucocorticoids (ivGCs)

regulation of gene expression. These findings also raise the question of whether

and measures to protect the corneal surface. If, however, response is absent or

targeting of A3B to gene regulatory regions might promote non-coding mutations

poor within

2 weeks, the patient should be promptly submitted to orbital

that modify gene enhancer function and provide further impetus for the

decompression. Treatment of moderate-to-severe GO depends on disease activity.

development of A3B inhibitors for cancer.

If GO is stably inactive, there is no place for medical treatment, and rehabilitative

DOI: 10.1530/endoabs.49.S11.2

surgery (orbital decompression, squint surgery, eyelid surgery) can be performed,

as needed. For moderate-to-severe AND active GO, ivGCs represent, for the time

being, the first-line treatment. ivGCs are given as 12 weekly, slow infusions of

methylprednisolone (MP). Most commonly, the cumulative dose of MP is 4.5 g,

but the dose should be tailored to the patient conditions, avoiding a cumulative

dose O8 g and a single dose O0.75 g, to minimize the risk of toxicity. If response

is not satisfactory in terms of regression and inactivation of GO, second-line

therapies include a second course of ivGCs, a course of oral glucocorticoids

S11.3

combined with either orbital radiotherapy or cyclosporine, treatment with

The role of androgens in bone

rituximab. The choice of second-line treatments should be part of a shared

Frank Claessens

decision-making process with the informed patient. In addition to rituximab, the

Belgium.

effectivess and safety of which should be confirmed in larger RCTs, ongoing

studies are investigating the effectiveness and safety of other biologics, including

teprotumumab and tolicizumab. Results of these studies are not available yet.

Abstract unavailable.

DOI: 10.1530/endoabs.49.S12.2

S12.3

New Development in Graves’ Orbitopathy

How to predict progression in Graves orbitopathy?

S12.1

Petros Perros

The orbital fibroblast: a key player and target for therapy in graves’

UK.

orbitopathy

Wim Dik

The Netherlands.

Graves’ orbitopathy (GO) is a relatively rare condition, but can cause

significant morbidity, poor quality of life, socioeconomic cost and

Graves’ orbitopathy

(GO) is characterized by orbital tissue inflammation,

occasionally impaired vision. Some studies indicate that nearly all patients

expansion, remodelling and fibrosis. Although the initiating trigger of GO is

with Graves’ hyperthyroidism, even those without overt GO, have

still indistinct, excessive orbital fibroblast activity is at the heart of its

subclinical eye disease. It is becoming increasingly evident that early

pathogenesis. Orbital fibroblasts are activated by cellular interactions with

recognition of GO and early interventions can affect the long-term outcome

immune cells and the soluble factors they secrete as well as autoantibodies (e.g.

favourably. Predicting which patients will develop clinical manifestations of

TSH-receptor autoantibodies). Activated orbital fibroblasts produce inflammatory

GO is therefore important. Clinical tools for early recognition of GO in a

mediators thereby contributing to the inflammatory process in GO. Moreover,

population of patients with Graves’ hyperthyroidism attending endocrine

orbital fibroblasts exhibit robust proliferative activity and extracellular matrix

clinics have been developed and are being further validated. A number of

(especially hyaluronan) synthesizing capacity and can differentiate into

clinical and biochemical parameters have been shown to be associated with

adipocytes and myofibroblasts with disease progression, thereby contributing to

progression of GO and can be used clinically to identify such cases. They

tissue expansion/remodelling and fibrosis in GO. Orbital fibroblasts, especially

include age, gender smoking status, severity of thyrotoxicosis, dysthyroid

those from GO patients, exhibit a hyper-responsive phenotype when compared to

status, use of radioiodine and the level of TSH receptor antibodies.

fibroblasts from other anatomical regions, which may further contribute to GO

DOI: 10.1530/endoabs.49.S12.3

pathogenesis. This presentation will address our current view on the role that

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Challenging Pituitary Diseases

laboratory and morphological evaluation. ES, in fact, represents a complex

syndrome which requires a multidisciplinary and dedicated team, as to ensure

S13.1

integrated therapy charge and as to prevent the occurrence of the severe disease

Hypophysitis

complications.

Niki Karavitaki

DOI: 10.1530/endoabs.49.S13.2

UK.

Hypophysitis is a rare inflammatory condition of the pituitary gland. Its

pathogenesis is poorly understood and new variants have been recently described.

It can be primary

(isolated inflammation of the gland, not related with

medications, systemic inflammatory disorders, infections, or other diseases), or

secondary (associated with systemic inflammatory processes (as sarcoidosis,

Wegener’s granulomatosis, Crohn’s disease, Takayasu’s arteritis, Cogan’s

syndrome), inflammatory cell proliferative disorders (Langerhans cell histiocy-

S13.3

tosis, Erdheim-Chester disease), infections (as tuberculosis, syphilis), tumour-

Imaging of sellar masses

associated inflammatory infiltrate

(as in germinoma), immunotherapy

(as

Michael Buchfelder

medications targeting cytotoxic T-lymphocyte antigen-4

(CTLA-4) or pro-

Germany.

grammed cell death 1 (PD-1)), rupture of sellar cysts (Rathke’s cleft cysts and

craniopharyngiomas)). The histological subtypes are lymphocytic, granuloma-

tous, xanthomatous, and plasmacytic (also termed IgG4-related hypophysitis

To date, magnetic resonance tomography is generally considered the imaging

which is often a manifestation of systemic disease). The inflammation may

method of choice for its premium resolution of lesions and surrounding anatomic

involve the anterior pituitary gland (adenohypophysitis), posterior gland and stalk

structures. This is mainly due to the improved soft tissue contrast this method

(infundibulo-neurohypophystis), or entire gland (pan-hypophysitis). Patients with

offers. Other advantages are the possibility of direct multiplanar imaging in

hypophysitis present with manifestations related to mass effect from the gland

sagittal, coronal, and axial orientations and the avoidance of ionizing radiation.

enlargement and hypothalamo-pituitary dysfunction. The severity of hormone

The goal of all imaging studies in this region is to indicate precisely the location,

deficiencies may be out of proportion to imaging findings. Radiological findings

extent, and size of a sella region tumor. These features, along with signal

include homogenous enhancement of the pituitary, diffuse symmetric gland

characteristics, frequently not only allow us to determine the presence of a lesion

enlargement, midline stalk thickening, and absence of a posterior pituitary bright

but also indicate the nature of the lesion. For this purpose, its extension in relation

spot. The diagnosis is established by biopsy and pathological examination. There

to the various surrounding structures, its structure, and its enhancement pattern

are no prospective controlled studies on the optimal management of hypophysitis

must be recognized in order to help in differential diagnosis and in treatment

and treatment remains controversial; potential options include surgery (if visual

planning. A proper set of images is required. A stepwise analysis of the images is

deterioration), glucocorticoids (at variable dosages and duration), immunosup-

suggested. For various types of lesions, typical examples are shown. In this

pressive agents and radiotherapy. Spontaneous resolution of pituitary enlarge-

context, monitoring of treatment effects is shown by using repeat imaging with

ment has been observed in a number of cases and improvement of pituitary

comparable data acquisitions. The common artifacts are discussed as well as

hormone deficits may occur after the resolution of hypophysitis.

enhancement of depiction of minute tumours. Of course, the common features

DOI: 10.1530/endoabs.49.S13.1

that allow differential diagnosis, are presented.

DOI: 10.1530/endoabs.49.S13.3

S13.2

Empty sella

Laura De Marinis

Italy.

Searching for the Cause and Approach in Ectopic Hormone

Syndromes

Empty Sella (ES) represents a heterogeneous syndrome, with a completely

S14.1

unknown pathogenesis. Defects in the organogenesis or hypoplasia of the sellar

Rare Cushing’s

diaphragm

(associated with stable or intermittent variation of intracranial

Stephen Petersenn

pressure and/or with pituitary volume variation) can facile the herniation of the

Germany.

arachnoid space into pituitary fossa and the consequently pituitary compression.

ES can be the sequel of necrosis of pituitary adenomas, of hypophysitis or of

brain/head trauma. In these condition, ES is defined secondary. In cases with

Ectopic ACTH syndrome accounts for approximately 20% of all cases of ACTH-

unknown aetiology ES is defined Primary. However, actually, obesity, systemic

dependent Cushing’s syndrome. The most common causes are oat cell

hypertension, multiple pregnancies, diabetes mellitus and pseudotumor cerebri

carcinomas, bronchial and foregut carcinoid tumors, pancreatic islet cell tumors

are considerate factor risks for the occurrence of primary ES (PES). In 50% of

and pheochromocytomas. Rarely, ectopic CRH-secretion occurs by peripheral

cases with PES a coexistent intracranial hypertension is associated, with the

tumors, especially carcinoids. Whereas the screening for hypercortisolism

occurrence of neurological signs and symptoms. The clinical manifestation of

followed by analysis of ACTH is well established, the distinction between

PES can be insidious, with subclinical or severe symptoms, as headache or

pituitary adenomas and ectopic sources in ACTH-dependent Cushing’s syndrome

papilledema, as visual disturbance or diplopia or optic neuritis, as partial or

is more challenging. Ectopic tumors producing ACTH with already suppressed

complete hypopituitarism, also associated to hyper-prolactinemia. Pituitary

pituitary ACTH levels do generally not respond even to high doses of

Magnetic Resonance is crucial for the diagnosis and allow to distinguish between

glucocorticoids. Measuring response to CRH or vasopressin may also be useful

partial or complete empty sella. A complete pituitary function clinical and

in the differential diagnosis. Inferior petrosal sinus venous sampling allows

laboratory evaluation is required to identify and diagnose hypopituitarism

definite identification of a pituitary source of ACTH, especially in combination

condition, with basal and, if necessary, dynamic test. Moreover, measurement of

with a CRH-test administered during catheterization. Localization of the source

intracranial pressure is suggested, though direct or indirect test, as lumbar

of ectopic ACTH secretion may be especially difficult. In addition to CT, MRI

puncture or optical nerve ultrasound to evaluate the thickness of the optic nerves.

and endoscopic ultrasound, nuclear medicine techniques can help greatly in

In ES affected patients, hormonal replacement therapy is required for the

identifying the source of ectopic ACTH production. Treatment often requires a

management of hypopituitarism. Moreover, treatment of intracranial hyperten-

combination of different approaches, including surgery, medical therapies to

sion is strongly suggested, though diuretic drugs, as acetazolamide. In cases of

control hypercortisolism and/or proliferation, local ablation techniques, and

drug-resistant intracranial hypertension or in cases of neurological emergencies,

PRRT. As hypercortisolism may cause more clinical problems than the

intracranial hypertension neurosurgery treatment, as ventricular shunt placement,

underlying tumor itself, bilateral adrenalectomy is performed in selected cases.

is recommended. A semestral or at least annual follow-up is suggested in these

DOI: 10.1530/endoabs.49.S14.1

patients, with endocrinological, ophthalmological and neurosurgical clinical,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

S14.2

bioavailability modification is causal since a bile acid sequestrant suppresses

the beneficial effects of bile diversions on glucose control. In agreement with the

Searching for the cause and approach in ectopic hormone syndromes:

inhibitory role of bile acids on gluconeogenesis, bile diversions promote a

rare acromegaly

blunting in HGP, whereas IGN is increased in the gut segments devoid of bile. In

Franc¸oise Borson-Chazot

obese rats fed a high fat-high sucrose diet, bile diversions improve glucose control

France.

and dramatically decrease food intake. This is due to an acquired disinterest for

fatty food, leading the animals to prefer starch-enriched diet. These data suggest a

Acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) is

key role of bile and of gluconeogenesis in the favorable outcomes of metabolic

rare accounting for less than 1% of cases of acromegaly. Less than 100 cases have

surgery.

been reported in the literature mainly as case reports, except for a nationwide

DOI: 10.1530/endoabs.49.S15.2

French series of 21 cases. Ectopic acromegaly occurs more frequently in women

who represent 2/3 of cases. Median age at diagnosis is 41 years but ranges from

adolescence to elderly. GHRH secreting neuroendocrine tumors are usually well

differentiated, originating in 90% of cases from pancreas or lung. Pheochromo-

cytomas or paragangliomas have been reported in a small proportion of cases.

Positive immunoexpression for GHRH is found in most tumors. Clinical and

hormonal features of ectopic acromegaly are very similar to that of somatotropic

S15.3

adenomas and differentiating between both may be challenging. Pituitary may be

normal or enlarged at MRI which may be difficult to interpret especially in MEN1

Long term effects of metabolic surgery

patients where the association of a microprolactinoma to a pancreatic tumor

Josep Vidal

secreting GHRH may be misleading. GHRH plasmatic measurement has an

Spain.

excellent specificity for the diagnosis. Tumors are usually large and easy to

localize by conventional imaging or somatostatin receptor scintigraphy.

Abstract unavailable.

Prognosis is usually favorable, even in metastatic forms which represent 50%

of cases. Surgical approach is recommended and, when a complete tumoral

resection is feasible, results, in most patients, in long-lasting remission. In such

cases, GHRH concentration is normalized and its increase is an accurate indicator

of recurrence. In uncured patients, somatostatin analogs control GH secretion but

inhibit, only partially, GHRH secretion. MEN1 mutation should be systematically

investigated in patients with a pancreatic tumor.

DOI: 10.1530/endoabs.49.S14.2

Late-breaking: The PCSK9 Revolution

S16.1

Beyond LDL lowering: the pleiotropic roles of PCSK9

Bertrand Cariou

S14.3

France.

Rare hypoglycemia

Kimberley Kamp

Abstract unavailable.

The Netherlands.

Abstract unavailable.

S16.2

New strategies for inhibiting PCSK9

Metabolic Surgery Mechanisms to Clinical Results (Endorsed

TBC

by the European Journal of Endocrinology)

Abstract unavailable.

S15.1

The upper gut anti-incretin theory

Geltrude Mingrone

France.

Abstract unavailable.

S16.3

PCSK9 inihibition in clinical practice: present and future

Alberico Catapono

Italy.

Abstract unavailable.

S15.2

The role of bile in metabolic surgery

Gilles Mithieux

France.

Gastric bypass surgery (GBP) promotes early benefits in energy homeostasis in

What Endocrinologists Should Know about the Genomics of

obese diabetic patients, including decreased hunger and improved glucose

Endocrine Tumors

control. A suggested mechanism associates a decrease in hepatic glucose

production (HGP) with an enhanced intestinal gluconeogenesis (IGN), the latter

S17.1

promoting metabolic benefits in energy homeostasis. In addition, bile acids (BA)

Clinical consequences of the recent genomics findings in thyroid cancer

have emerged as key metabolic regulators, which might account for several anti-

Thomas Giordano

diabetic effects. Moreover, plasma bile acids are elevated after GBP and are

known to inhibit gluconeogenesis. Bile diversions mimicking GBP in lean rats

Abstract unavailable.

(re-insertion of bile in the mid-jejunum or the mid-ileum) promote an increase in

plasma bile acids and a marked improvement in glucose control. Bile

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

S17.2

pathways, and production of oncogenic proteins. As regards the neoplasms

morphologically classified as poorly differentiated neuroendocrine carcinomas,

Clinical implications of SDHx mutations

concurrent results show that they might be associated with three different

Anne-Paule Gimenez-Roqueplo

molecular signatures:

(a) typical

‘high grade neuroendocrine’ signatures,

France.

characterized by mutations in TP53

and Rb, and corresponding to

‘true’

neuroendocrine carcinomas; (b) ‘adenocarcinoma-like’ signatures, corresponding

Paragangliomas and pheochromocytomas (PPGL) are neuroendocrine tumors

to aggressive carcinomas maskerading as neuroendocrine neoplasms, (c) ‘well

with a very strong genetic component. A germline mutation in one of the different

differentiated NET’ signatures, corresponding to highly proliferative well

susceptibility genes identified so far explains about 40% of all cases. Genetic

differentiated neuroendocrine neoplasms with an aggressive behavior. The

testing is recommended in every affected patient and next-generation sequencing

molecular tools now available will clearly help to refine the classification of

(NGS) is the ideal technology to screen the high number of PPGL susceptibility

aggressive, high grade neuroendocrine malignancies, but their clinical and

genes (1). The interpretation of genetic variants identified by NGS can be guided

therapeutic impact remains to be evaluated. As for low grade neuroendocrine

by the clinical presentation as well as by the secretory phenotype and by the

malignancies, the main interest of molecular profiling will probably be prognostic

immunohistochemical analysis of tumors (2). The diagnosis of an inherited form

and predictive.

drives clinical management and tumor surveillance of the patient and relatives (1).

DOI: 10.1530/endoabs.49.S17.3

While whole-exome sequencing studies showed that PPGL is characterized by a

low mutation rate of 0.3 mutations per megabase similar to other neural crest-

derived tumors, the first integrative genomic analysis of a large collection of 202

PPGL, carried out by the French COMETE network, demonstrated that mutation

status in PPGL susceptibility genes is strongly correlated with multi-omics data

and revealed the crucial role of predisposing mutations as being the main drivers

Hyperandrogenism: Challenges in Clinical Management

of PPGL (3). PPGL subtypes can be defined by a set of unique genomic alterations

S18.1

that represent different molecular entities. Transcriptomic studies identified two

Hyperandrogenic states: pitfalls in diagnostic approach

main molecular pathways, activating either the hypoxic pathway (cluster C1) or

Michel Pugeat

the MAPkinase/mTOR signalling (cluster C2). This comprehensive analysis

France.

illustrated the functional interdependence between genomic and epigenomic

dysregulations. Indeed, DNA methylation profiling uncovered a hypermethylator

phenotype specific to the tumors related to a mutation in one of the PPGL

Measuring total testosterone level is the first line approach to assess androgen

susceptibility genes encoding for a protein of the tricarboxylic cycle. Besides, we

excess in women. Most laboratories in Europe use direct testosterone

demonstrated that succinate is acting as an oncometabolite, inhibiting

immunoassay without prior extraction. In the near future, liquid chromatography

2-oxoglutarate-dependent dioxygenases, such as HIF prolyl-hydroxylases and

coupled with tandem mass spectrometry (LC-MS/MS) will be commonly used for

histone/DNA demethylases, explaining noradrenergic secretory and metastatic

measuring testosterone, providing the best accuracy with low limit of detection. In

phenotypes of PPGL classified in cluster 1A (4). A recently published novel

all cases, testosterone norms must be standardized for normal premenopausal

comprehensive multi-platform analysis of

173

PPGLs led by TCGA has

women values. Where testosterone is twice the upper limit of normal, it is

confirmed the COMETE data and identified recurrent fusions genes by RNA

recommended that DHEAS assay be performed. DHEAS is primarily of adrenal

sequencing. Altogether those data suggested new therapeutic targets for patients

origin in women. Thus, a DHEAS level of over 600 mg/dl indicates a diagnosis of

with a metastatic PPGL as well as novel diagnostic and prognostic biomarkers.

androgen-secreting adrenal carcinoma (often associated with hypercorticism). In

New ‘omics’-based tests for PPGL are likely to be transferred from research

this case, abdominal scan must be performed rapidly. Where testosterone is just

laboratories to clinical practice in order to give the access to a precise molecular

above the normal upper limit, the most likely diagnosis is polycystic ovary

classification of every PPGL, after surgery, to practicing clinicians with the goal

syndrome (PCOS). However, screening should be performed for the nonclassic

of establishing a personalized medical management.

form of 21-hydroxylase deficiency (assay of 17OH-progesterone) and depending

References

on the clinical setting, Cushing disease must be ruled. Normal testosterone levels

1. Favier, Nat Rev Endocrinol, 2015.

in patients with clear clinical symptoms of hyperandrogenism must be interpreted

2. Toledo, Nat Rev Endocrinol, 2017.

with care. Indeed, T circulates in the blood tightly bound to sex-hormone binding-

3. Castro-Vega, Nat Commun, 2015.

globulin (SHBG). Low SHBG is typically observed in overweight PCOS patients,

4. Letouzé, Cancer Cell, 2013.

in association to inflammatory state and metabolic syndrome, and contributes to

5. Fishbein, Cancer Cell, 2017.

lower total testosterone by increasing its clearance from the blood. Therefore, it is

DOI: 10.1530/endoabs.49.S17.2

recommended, to measure SHBG for correct interpretation of total testosterone by

calculating free testosterone index, awaiting direct free-T assay that is still not

available. D4-androstenedione

(A) has been studied comparatively with

testosterone, and dissociations exist, with isolated elevation of A but no elevation

of testosterone, particularly in the incident of reduced SHBG. In unusual

circumstances, dexamethasone test to suppress androgens arising from a

S17.3

functional adrenal source and gonadotropin-releasing hormone (GnRH) agonist

Will genomics help to finally classify NET’s?

in identifying ovarian androgen secreting tumor and hyperthecosis, could be

Jean Yves Scoazec

helpful. All these pitfalls should not discourage endocrinologist to challenge the

diagnosis of hyperandrogenic states. Decision trees for evaluating the origin of

France.

androgen excess will be suggested and discussed during the session.

DOI: 10.1530/endoabs.49.S18.1

The genetic landscape of neuroendocrine tumors

(NETs) is being rapidly

uncovered. It has long been known that, like other endocrine tumors, NETs might

occur in the context of familial predisposition syndromes, involving genes like

MEN1, VHL, TSC1/TSC2, NF1 and CDKN1B. Recently, several seminal papers

have described the main molecular abnormalities underlying sporadic or

apparently sporadic NETs. The results confirm that:

(a) well differentiated

S18.2

NETs from various sites are genetically distinct; (b) well differentiated and poorly

Metabolic perspectives for the non-classical CAH (NCAH)

differentiated neuroendocrine neoplasms are genetically distinct and likely

Fahrettin Kelestimur

correspond to different entities. Pancreatic and lung well differentiated NETs are

Turkey.

mainly associated with abnormalities in genes encoding proteins involved in

chromatin regulation and telomere control (such as MEN1, DAXX and ATRX

in pancreatic NETs, MEN1 again and a number of genes of the SWI/SNF pathway

Congenital adrenal hyperplasia (CAH) is one of the most common autosomal

in lung NETs); in addition, recent results have revealed the occurence of fusion

recessive inherited endocrine diseases and is characterized by complete or partial

transcripts involving EWSR in pancreatic NETs, uncovering a new perspective in

impairment of adrenal steroidogenesis.

21-hydroxylase deficiency and

11b-

the molecular mechanisms underlying pancreatic and perhaps other NETs. In

hydroxylase deficiency account for 90% and 6-8% of cases of CAH, respectively.

contrast, in well differentiated small intestinal NETs, the molecular landscape

NCAH is the mild form of CAH and occurs in approximately 0.1-0.2% in the

appears to be heterogeneous, with a high frequency of chromosomal changes and

general population. The worldwide prevalence of NCAH among hyperandrogenic

a wide spectrum of mutations involving various signalling pathways (mTOR,

women is approximately 4.0%. Adrenal androgen secretion and its response to

SMAD). Taken together, these results suggest that in well differentiated NETs,

ACTH is increased in these cases. Patients with NCAH generally present with

several oncogenic mechanisms might be involved: epigenetic dysregulations due

manifestations due to high androgen levels including hirsutism, acne and

to chromosomal and genomic instability, alterations in intracellular signalling

alopecia. Ovulatory and menstrual dysfunction are seen in more than 30-50% of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

patients with NCAH. Polycystic ovarian morphology is recorded in at least 25%

demonstrated a good outcome in more than 1,300 patients with biopsy-proven

of the patients. The data regarding insulin resistance, diabetes, obesity and

mPTC who were not submitted to TX. Thus, since only a minority of mPTC

abdominal visceral adiposity in NCAH patients is scarce. Chronic androgen

progress to a clinically overt disease, it is critical to re-evaluate the current

excess around puberty may favor abdominal visceral adiposity, insulin resistance

management strategy that indiscriminately recommends thyroid surgery that is,

and its metabolic consequences. Hyperinsulinemia and insulin insensitivity

although infrequently, burdened by complications. We retrospectively evaluated

associated with high androgen levels were reported in untreated newly diagnosed

clinical data of 293 consecutive patients with mPTC, surgically treated at our

patients with NCAH. Chronic glucocorticoid administration in a limited number

Department. After 6 years of follow-up no patient had evidence of structural

of patients may also favor metabolic abnormalities. The frequency of type 2

disease. This prompted us to obtain the approval by the ethical committee to offer

diabetes was reported to be increased in NCAH patients. It seems that NCAH is

patients an active surveillance instead of immediate surgery, when they had an

associated with increased cardiovascular and metabolic morbidity. Therefore,

intrathyroid nodule with a Thy4 or a Thy5 cytology, less than 1.3 cm of diameter,

screening metabolic abnormalities may be required in patients with NCAH.

with no evidence at US of extrathyroid extension and cervical lymphnodes

DOI: 10.1530/endoabs.49.S18.2

suspicious for metastasis. Out of 163 patients who choose active surveillance, 97

(59.5%) did not satisfied the inclusion criteria and 66 (40.5%) were enrolled in the

protocol. With a median follow-up of 12 months (6-28) only 3/66 (4.5%) were

addressed to surgery for the appearance of neck metastatic lymphnodes or an

enlargement of the nodule. 7/66 (10.6%) patients withdrew from the study. In

conclusion, the results of prospective studies will provide more precise data to

S18.3

build up a patient tailored approach for the management of mPTC.

Hyperandrogenism and cardiometabolic risk

DOI: 10.1530/endoabs.49.S19.1

Marija Pfeifer

Slovenia.

Hyperandrogenism is the main characteristic of PCOS therefore hyperandrogen-

ism in women is best addressed when studying this highly prevalent syndrome.

S19.2

Besides the clinical features of oligomenorrhea, hirsutism and infertility, PCOS

When and how should we perform extensive surgery?

patients are often insulin resistant (IR), obese, they have arterial hypertension,

Electron Kebebew

dyslipidemia, an increased pro-thrombotic state, impaired glucose tolerance or

USA.

frank type 2 diabetes (T2D). The prevalence of metabolic syndrome is doubled as

compared to non-PCOS population. Obesity, particularly of visceral origin, plays

a crucial role in both the development and maintenance of PCOS and significantly

Thyroid cancer is one of the most rapidly increasing cancer diagnoses worldwide.

influences the severity of cardiovascular risk profile. At least 30% of women with

Thyroid cancers exhibit the full range of cancer behavior from the relatively

PCOS are obese, and in some series, up to 75% are obese. About 50-60% of

indolent occult papillary thyroid cancer to the uniformly aggressive and lethal

women with PCOS have central body fat distribution. Metabolic disease in PCOS

undifferentiated thyroid cancers. Surgical resection is the principal treatment for

should be considered as a continuous variable, with metabolic dysfunction

thyroid cancer and there are several important areas of controversy in the surgical

worsening with severity of androgen excess. Increasing androgen burden is

management of thyroid cancer. Some of these controversies have arisen due to the

associated with an adverse metabolic phenotype. Androstenedione (A) has been

increasing incidence of thyroid cancer, the variable biologic behavior of low-risk

shown to be in better correlation with IR than testosterone (T) in PCOS women.

differentiated thyroid cancer, and because of the improved detection of

Recent data suggest that biochemical androgen excess poses a higher risk of liver

persistent/recurrent disease. International Surgical and Medical Societies and

disease, IR, and subclinical atherosclerosis in PCOS compared with those women

Association have proposed guidelines to the surgical management of thyroid

with anovulation and polycystic ovaries alone. Serum A is a more sensitive

cancer and the level of evidence for these guidelines will be reviewed. Three

indicator of PCOS-related androgen excess than serum total T concentrations.

critical areas in the surgical management of differentiated thyroid cancer remain

Concurrent measurement of both A and T discovers a PCOS cohort that appears to

controversial: the extent of thyroidectomy for differentiated thyroid cancer, need

be at the highest metabolic risk. The analysis of 2543 pre- and perimenopausal

for prophylactic central neck lymph node dissection in patients with papillary

women in their 40s originally included in the SWAN study indicated that

thyroid cancer, and the need for completion thyroidectomy in patients who

hyperandrogenemia but not oligomenorrrhoea was independently associated with

initially undergo hemithyroidectomy. A clinical, pathologic and molecular based

the risk of prevalent metabolic syndrome. High prevalence of cardiovascular risk

approach to address these three controversial areas in the surgical management of

factors in PCOS is assumed to be associated with accelerated cardiovascular

differentiated thyroid cancer will be proposed to personalize surgical manage-

disease

(CVD). However, clear data from large end point trials about

ment decisions in patients with differentiated thyroid cancer.

cardiovascular morbidity and mortality in PCOS is currently lacking. Though,

DOI: 10.1530/endoabs.49.S19.2

there is plenty of data on early occurrence of subclinical, potentially reversible

atherosclerosis in women with PCOS. Endothelial dysfunction is associated with

higher levels of androgens and with insulin resistance. This was observed even at

very early ages, and with a trend of deterioration of endothelial function from lean

to overweight and obese PCOS women. Recent systematic review has confirmed

that carotid intima-media thickness was thicker in women with PCOS in

S19.3

comparison to controls. PCOS women have a greater prevalence and extent of

Dynamic risk stratification in low-risk vs high-risk patients

coronary artery calcification, and that is independent of age and BMI.

Miguel Melo

DOI: 10.1530/endoabs.49.S18.3

Portugal.

In recent years, an increasing interest in an individualized approach for the care of

patients with differentiated thyroid cancer has occurred. The cornerstone of

individualized treatment is the existence of a proper risk stratification system that

supports physicians’ options regarding the treatment and follow-up of patients.

How to Incorporate the New Guidelines for Thyroid Cancer

Considering that the initial risk stratification systems account for only about 15-

in my Clinical Practice

20% of the variability in the outcome they are trying to predict, it is now well

S19.1

recognized that risk stratification is a dynamic process. The input of clinical,

biochemical and imaging data collected during follow-up, notably the response to

Thyroid microcarcinoma: to treat or not to treat?

the initial treatment, can dramatically change risk estimation and significantly

Paolo Vitti

improve its accuracy in predicting long-term outcomes. The use of this approach

Italy.

faces different problems in patients with low/intermediate risk and in patients

with high risk of recurrence. Regarding the low/intermediate risk group, dynamic

In the last 20 years, the incidence of thyroid cancer (TC) has more than doubled.

risk stratification was based in the assessment of response to an initial treatment

Since 50% of the increase is related to papillary microcarcinomas (mPTC,

that consisted in total thyroidectomy followed by radioiodine (RAI) treatment.

!1 cm), it appears that an increased detection, due to the wide use of neck

However, lobectomy is now considered a reasonable approach for some low risk

ultrasound (US), is the major factor driving this dramatic rise. Autoptic and

patients and the role of postsurgical RAI in the low/intermediate risk group is

histological studies after thyroidectomy (TX) show that 10 to 30% of adults

currently under debate. As a consequence, there are no well-established

harbor an undiagnosed mPTC. The disease-specific mortality of patients treated

thyroglobulin (Tg) cut-off points to define categories (e.g. excellent response,

by surgery for mPTC is !1% and loco-regional and distant recurrence rates are

biochemical incomplete response) in patients treated with lobectomy or total

2-6 and 1-2%, respectively. Furthermore, 2 Japanese prospective clinical trials

thyroidectomy without postsurgical RAI treatment. Nonetheless, different

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

thresholds for patients submitted to lobectomy or total thyroidectomy without

S20.3

RAI treatment have been included in clinical recommendations and recently

Induction of pancreatic beta-like cell neogenesis

validated in the low risk group. Apart from static Tg levels, the trend of both Tg

Patrick Collombat

and Tg-antibodies levels over time, with similar TSH values, has proven to be an

France.

effective way of assessing response to treatment. An increase of 20% seems to

accurately predict structural disease recurrence. High-risk patients require a very

individualized follow-up because most of the patients are expected to have

The recent discovery that genetically-modified a-cells can regenerate and convert

persistent disease after the initial treatment. For these patients, the initial follow-

into b-like cells in vivo holds great promise for diabetes research. However, to

up is mainly aimed at identifying those with progressive disease despite initial

eventually translate these findings to human, it is crucial to discover compounds

treatment. Nonetheless, most impact of dynamic risk stratification in this group

with similar activities. Herein, we report the identification of GABA as an inducer

occurs when an excellent response is found, precluding patients from an

of a-to-b-like cell conversion in vivo. This conversion induces a-cell replacement

unnecessary aggressive follow-up strategy. In this session, different ways of

mechanisms through the mobilization of duct-lining precursor cells that adopt an

implementing and refining dynamic risk stratification will be discussed,

a-cell identity prior to being converted into b-like cells, solely upon sustained

addressing the low, intermediate and high risk groups.

GABA exposure. Importantly, these neo-generated b-like cells are functional and

DOI: 10.1530/endoabs.49.S19.3

can repeatedly reverse chemically-induced diabetes in vivo. Similarly, the

treatment of transplanted human islets with GABA results in a loss of a-cells and

a concomitant increase in b-like cell counts, suggestive of a-to-b-like cell

conversion processes also in humans. This newly discovered GABA-induced

a-cell-mediated b-like cell neogenesis could therefore represent an unprece-

dented hope towards improved therapies for diabetes.

DOI: 10.1530/endoabs.49.S20.3

Beta Cell Replacement and Plasticity (Endorsed by

Endocrine Connections)

S20.1

Stem cells for b cell replacement in type 1 diabetes

Valeria Sordi

Italy.

Pluripotent stem cells (PSC), both embryonic and induced (iPSC), are the most

promising cell sources for replacement therapies. In particular for a disease like

type 1 diabetes (T1D), caused by the loss of a single specific cell type that does

not need to be transplanted back in its originating site to perform its function, a

stem cell-based cell replacement therapy seems to be the ideal cure. At present,

Environmental Influences on Endocrine Systems

however, a successful strategy for the use of PSC in patients with diabetes has still

S21.1

to overcome several important hurdles, including i) the development of in vitro

Lifestyle and environmental factors in metabolic diseases; endocrine

differentiation protocol for b cell generation, efficient and reproducible in

disruptors: new diabetogens?

different cell lines in different labs, ii) the possible tumorigenicity of PSC-derived

Patrick Fenichel

b cells, iii) the risk of allo- and auto-immune rejection upon transplantation into a

France.

subject with T1D and iv) the regulatory/economic issues associated to the use of

iPSC in humans, starting from production of GMP iPSC lines. At present, the

major challenge is how to avoid immune-rejection of stem cell-derived b cells. To

The prevalence of metabolic syndrome, obesity and type

diabetes has

overcome the risk of an alloimmune response we could (i) use autologous iPSC,

dramatically increased worldwide during the last few decades and exceeds

but personalized cell therapy has big economic and safety limits or (ii) iPSC from

World Health Organisation’s predictions. It is not possible anymore to explain

a cell bank with a limited number of highly selected cell donors with homozygous

this real pandemic only by genetic predisposition and/or by classical lifestyle

HLA types, to enable HLA matching for a majority of potential recipients. These

changes such as sedentary lifestyle or energy-dense diet. There is increasing

strategies, however, would not eliminate the recurrence of autoimmunity after a

experimental and epidemiological evidence suggesting that exposure to

new exposure to b cell antigens of the immune system of the T1D recipient. The

environmental factors such as noxy foods, dysbiosis or endocrine disrupting

only possible solution consists into trying to ‘hide’ the transplanted cells from the

chemicals (EDCs) may also contribute to the prevalence of DT2. EDCs are

immune system: we and others are exploring the possibility to achieve this goal

natural or synthetic chemical compounds, present in the everyday domestic

through i) the setup of a new immunosuppressive regimen for PSC-derived b

environment, interfering with hormonal regulation systems critical for energy

cells, able to contrast autoimmune response; ii) the microencapsulation of cells

homeostasis. Many are present in the food chain and after absorption are

into inert biomaterials, iii) the macroencapsulation of cells into specific devices

sequestred in adipose tissue. They may represent after low-doses exposure during

able to protect them from allo- and auto-immune response while allowing oxygen,

sensitive windows or via chronic exposure to cumulative doses, one aspect of the

nutrients, and insulin exchange and iv) the genetic manipulation of the cells to

genetic/environment interface, involved in the pathophysiology of DT2. In

escape immune recognition. If the limit of immune rejection is solved, a

humans, some epidemiologic reports suggested a strong link between exposure to

successful translation to the clinical practice of stem cell therapy for diabetes will

some persistent EDCs

(pesticides, polychorinated biphenyls, bisphenol A,

be closer.

phthalates, dioxins, polycyclic aromatic hydrocarbons) and DT2, especially

DOI: 10.1530/endoabs.49.S20.1

after acute and accidental releases of EDCs (Seveso plant explosion, Vietnam war

veterans). Other cross-sectional studies around the world reported suggestive to

strong association between diabetes and obesity and EDCs exposure, especially

for persistent organic pollutants, which should be considered as insulin-resistance

risk factors. In rodents, exposure to bisphenol A is responsible for modifications

of insulin synthesis and secretion in pancreatic beta cells but also for

modifications of insulin signaling in liver, skeletal muscle and adipose tissue,

which both lead to insulin-resistanc. In vivo and in vitro experimental studies have

shown that EDCs may act through nuclear receptors (ERs, AhR, PPARg, ERRg)

involved in metabolic control and are able to induce in specific windows of

exposure

(fetal, perinatal, pre-pubertal periods) epigenetic changes

(DNA

S20.2

methylation, histone modifications, miRNA dysregulation) programming later

obesity, insulin resistance, and/or b cell failure. It is still necessary to better

New Strategies for beta cell replacement

understand the involved molecular mechanisms, to develop additional human

Stefan Bornstein

prospective, longitudinal case/control epidemiological studies, and to identify

Germany.

early biomarkers of exposure, in order to improve assessment of chronic exposure

to mixture of EEDs in order to determine the real implication of EEDs in DT2

Abstract unavailable.

highly susceptible patients.

DOI: 10.1530/endoabs.49.S21.1

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

S21.2

Rare Bone Diseases (Endorsed by the European Journal of

Evidence on reproductive disorders through endocrine disruption

Endocrinology)

in-utero

S22.1

Jorma Toppari

Finland.

Approach for clinicians

Maria-Luisa Brandi

Italy.

Differentiation of male reproductive system is guided by testicular hormones and

growth factors secreted during fetal development under gonadotropin control.

Disruption of testicular hormone production or action leads to gonadal dysgenesis

Rare skeletal metabolic diseases comprise a group of diseases commonly

and maldevelopment of external genitalia. Cryptorchidism and hypospadias are

associated with severe clinical consequences. In recent years, the description of

the most common birth defects in boys, and both conditions can arise as a

the clinical phenotypes and radiographic features of several genetic bone disorders

consequence of anti-androgenic disturbance during development. Both of them

was paralleled by the discovery of key molecular pathways involved in the

are also associated with poor semen quality and testicular cancer, suggestion

regulation of bone and mineral metabolism. Including this information in the

similar pathogenetic pathways. Animal experiments show robust evidence that

description and classification of rare skeletal diseases may improve the recognition

inhibition of androgen synthesis or action causes abnormalities in testicular and

and management of affected patients. In a recent effort to recognize the rare skeletal

genital development. Chemicals with different mechanisms of action towards

diseases based on their metabolic pathogenesis 116 OMIM phenotypes with 86

declined androgen activity work in an additive fashion. Therefore even small

affected genes related to bone and mineral homeostasis were recognized. The

diseases were divided into four major groups, namely, disorders due to altered

amounts of anti-androgens can add a critical dose to the total anti-androgenic

osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix

load. While this is well documented in experimental animals, there is limited

proteins; disorders due to altered bone microenvironmental regulators; and

evidence on human harm. This is due to challenges in epidemiology to

disorders due to deranged calciotropic hormonal activity. This publication

demonstrate causal relationships, albeit there are many examples of associations

provides the first comprehensive taxonomy of rare metabolic skeletal diseases

of chemical exposures with reproductive disorders.

based on deranged metabolic activity. This classification will help in the

DOI: 10.1530/endoabs.49.S21.2

development of common and shared diagnostic and therapeutic pathways for

these patients and also in the creation of international registries of rare skeletal

diseases, the first step for the development of genetic tests based on next generation

sequencing and for performing large intervention trials to assess efficacy of orphan

drugs. For their metabolic nature, the interest of endocrinologists towards this

disorders is very high. The clinical management of these diseases from a metabolic

point of view will be illustrated during the presentation.

DOI: 10.1530/endoabs.49.S22.1

S22.2

S21.3

Osteogenesis imperfecta & Ehlers-Danlos Syndrome

Euthyroid: towards a euthyroid Europe

Anna Maria Formenti

Henry Volzke

Italy.

Germany.

Abstract unavailable.

Despite the fact that iodine deficiency (ID) can easily be prevented by iodine

fortification of table salt, industrial salt and cattle food, Europe belongs to the

worst regions in terms of access to iodized salt and is seriously iodine deficient,

resulting in the perpetuation of the single most important, preventable cause of

brain damage. Up to an estimated 360 million European citizens are exposed to

ID, which is not only due to variable iodine provision, it is also rooted in

significant heterogeneity of prevention and monitoring activities, leading to

S22.3

inappropriate interventions, health inequalities and increased disease burden with

Fibrous dysplasia of bone/McCune-Albright syndrome

substantial impact on health-care costs. A major concern remains the large

Roland Chapurlat

number of pregnant women exposed to ID, which results in a measurable decrease

France.

in cognitive potential of their children. The effects of ID in total cause significant,

preventable costs in health-care systems of affected regions. More than

countries contribute to the EUthyroid consortium, which is funded by the EC

Fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS) is due to a

Horizon2020 programme. The overall aims of EUthyroid are to evaluate IDD

somatic activating GNAS mutation. Patients may be asymptomatic in monostotic

prevention programmes in European countries, to initiate capacity building for

forms, which represent two thirds of cases. In those forms, the diagnosis is often

integrated activities in Europe. Coordinated measures at national and EU level are

incidental. But these monostotic FD may also be revealed by bone pain, bone

a long-term goal, which will be worked towards by targeted communication

deformity or fracture. The diagnosis is generally made in childhood or in young

activities of project results. EUthyroid has established a meta-platform for

adults. Polyostotic FD is often more severe, with a higher incidence of fragility

collaborative data collection and use. National and regional registry data are

fracture. It is also commonly associated with renal phosphate wasting. About 5%

collected to gain an overview over prevalent and incident thyroid diseases and

of patients with FD also suffer from endocrine complications, including

treatments in European nations. In parallel, EUthyroid improves the data quality

precocious peripheral puberty, growth hormone excess and hyperthyroidism.

of ID monitoring studies by providing infrastructures for training and

These endocrine conditions have to be treated as early as possible. For example,

standardization of interviews, laboratory measurements and thyroid ultrasound.

the precocious puberty generally responds well to an aromatase inhibitor,

All data will be used to provide a European map of iodine status and subclinical

letrozole. Bisphosphonates have been used to treat bone pain and reduce bone

disorders and to relate the iodine status of populations to thyroid-related outcomes

turnover for more than two decades with satisfactory outcomes in most patients.

for the evaluation of ID prevention programmes. In addition, thyroglobulin, a

This treatment can often be tapered after 2-3 years. Preventive surgery is often

novel and promising biomarker for the iodine status will be evaluated using

advised in children to avoid fracture and deformity of lower limbs. This kind of

biomaterials collected in ID monitoring studies and three mother-child cohorts

approach is also warranted in adults. A multidisciplinary management is

from regions with different iodine status. The latter cohorts will investigate the

necessary, involving specialists of bone diseases, endocrinologists, orthopedic

important association between the iodine status in pregnant women and the

surgeons, and sometimes cranio-facial surgeons along with neurosurgeons, both

neurocognitive function in their children. Combining findings from all studies,

in children and adults. New therapies e.g., denosumab and tocilizumab are

health-economic analyses will be conducted to investigate benefits and harms as

currently being studied to improve bone pain in those patients who do not

well as cost-effectiveness of IDD prevention. Potential barriers against

adequately respond to bisphosphonates. An international collaboration is

harmonized IDD prevention and monitoring programmes will be explored by

currently developing a framework that would be applicable around the world to

collecting information from national and European ministries.

improve the care of this rare disease, in particular to avoid delays in treatment.

DOI: 10.1530/endoabs.49.S21.3

DOI: 10.1530/endoabs.49.S22.3

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Endo Oncology: Prolactin, GH and Metabolic Hormones in

Conclusions

We hypothesize that GH leads to a pro-neoplastic environment and that high

Oncology Pathogenesis (Endorsed by

intracellular GH is a component of the field change enabling colon mucosal

Endocrine Connections)

proliferation. GH-mediated senescence evasion may explain why GH deficiency

S23.1

is protective for cancer.

Prolactin regulation of prostate stem cells: potential implications in

DOI: 10.1530/endoabs.49.S23.2

prostate cancer

Vincent Goffin

France.

Prostate stem cells have been proposed to participate in prostate cancer initiation.

Furthermore, based on their androgen-independence, they are suspected to trigger

prostate cancer recurrence when the tumor is no longer responsive to anti-

androgens. Therefore better understanding the regulation of this particular cell

pool may have important therapeutic relevance. In the human prostate, expression

of prolactin (PRL) and activation of its major downstream signaling effector

S23.3

Stat5, have been correlated to prostate cancer progression and relapse. To

Is reducing insulin-resistance relevant to prevent cancer?

understand these effects, we use the probasin (Pb)-PRL transgenic mouse model

Michael Pollak

which involves prostate-specific expression of PRL. Pb-PRL mice recapitulate

Canada.

many pre-neoplastic features of the human prostate including focal areas of

epithelial dysplasia, prostate intra-epithelial neoplasia and moderate inflam-

Abstract unavailable.

mation (‘reactive stroma’), together with hypertrophy and ductal dilatation of all

prostate lobes. Using various cell lineage-specific markers coupled to

immunohistochemistry and cell sorting (FACS), we showed some years ago

that the p63C basal/stem cell compartment (which contains ‘tumor-initiating’

cells) was highly enriched in Pb-PRL prostate tumors (Rouet et al, PNAS 2010).

Subsequent studies revealed enrichment of another cell population that we

discovered and named ‘LSCmed’ based on its FACS profile (Sackmann Sala et al,

Am. J. Pathol 2014). LSCmed are luminal progenitors that exhibit stem-like

properties in vitro (prostasphere assay, gland formation in transplantation assays)

and importantly, resistance to androgen deprivation in vivo. Transcriptomic

profiling showed that LSCmed is a distinct cell entity that differs from the well-

known basal and luminal cell populations and that can be identified using a

Obesity: Pharmacological Solutions

specific gene expression signature. LSCmed are rare in the normal prostate and

their amplification in Pb-PRL prostate tumors more likely results from paracrine

S24.1

signals downstream of PRLR/Stat5 signaling than from a direct PRL effect.

MSH analogs

Strikingly LSCmed represent the major cell component of aggressive, castration-

Peter Kuhnen

resistant prostate tumors driven by Pten loss, both before and after castration. This

Germany.

is particularly relevant since loss of PTEN is frequently observed in the human

prostate oncogenome. In summary, LSCmed represent a newly-identified

The leptin-melanocortin signaling pathway plays a pivotal role in the regulation

prostatic cell population that is a strong candidate for mediating cell resistance

of body weight within the hypothalamus. Leptin, secreted by the adipose tissue,

to androgen-deprivation therapy. Ongoing studies aim to elucidate the

activates the leptin receptor at the arcuate nucleus, which in turn leads to the

mechanisms that that regulate these luminal progenitors and to identify

production of proopiomelanocortin (POMC) derived peptides as melanocyte

LSCmed(-like) cells in the human prostate.

stimulating hormone

(MSH). MSH activates the melanocortin

receptor

DOI: 10.1530/endoabs.49.S23.1

(MC4R), regulating thereby satiety and energy expenditure. Mutations within

this pathway are leading to severe early onset obesity based on severe

hyperphagia. After the discovery of MSH, different approaches have been

made to generate MC4R agonists. Unfortunately, most of the studies were not

successful either due to ineffectiveness of the drug to reduce body-weight or due

to severe side-effects as e.g. increased blood pressure. However, recently the

S23.2

development of new MC4R agonists as setmelanotide (RM-493), which is leading

Is GH a cancer growth factor?

to severe weight loss in POMC deficient patients, has open new perspectives for

Shlomo Melmed

the treatment of monogenic obesity forms. Future studies will elucidate whether

USA.

this new compounds will be of advantage and a new treatment option for obesity

in these rare diseases.

DOI: 10.1530/endoabs.49.S24.1

Acromegaly is associated with increased soft tissue neoplasms, while GH

deficient patients are protected from cancer development. Both environmental

and age-related signals lead to cellular senescence and cell cycle dysregulation.

We have shown that DNA damage-induced cellular senescence increases GH by

inducing p53. GH, in turn, suppresses tumor suppressor proteins in both pituitary

and nonpituitary cells.These observations led us to propose that intracellular

epithelial GH in the mucosal microenvironment may enable neoplastic growth.

Mechanisms underlying pro-neoplastic GH actions include: knockdown or

suppressing either GH or GHR mRNA induces p53; GH suppresses p53 by

S24.2

inhibiting PTEN,a p53 acetylator, which protects p53 from ubiquitination, and

The future drugs to come

up-regulates TRIM29, which also destabilizes p53. Thus, p53 ubiquitination and

Gema Fruhbeck

altered acetylation underlie suppression of p53 mediated by GH. GH also induces

Spain.

mTOR, EMT transcription factors and enhanced cell motility. In vivo epithelial

p53 is markedly induced in GH-deficient Prop1^K/K, and in GH receptor deficient

GHR^K/K mice, and in mutant GH receptor (Laron syndrome) fibroblasts. In

A complex interaction between environmental and genetic/epigenetic factors is

nutlin-treated mice with DNA damage, GH is induced in colon epithelial cells.

driving the escalating obesity and diabetes epidemics together with a multitude of

Doubly mutant Prop1^K/K (GH-deficient) and Apc^minC/K (develop intestinal

associated comorbidities. In the past decades the role of gastrointestinal signals in

tumors) mice exhibit high colon p53 and markedly decreased intestinal tumor

energy homeostasis and glucose control has made tangible progress mainly due to

number and size compared to single mutant APC minC/K mice.GHR blockade

the findings derived from bariatric/metabolic surgery. In particular, incretin-based

induced by pegvisomant treatment of acromegaly patients leads to increased

approaches in relation with glucagon-like peptide 1 and amylin have fostered the

colon mucosal p53 and its transcriptional target p21. Overexpressing intracellular

emergence of new treatment avenues. Interestingly, one of the most challenging

GH, or re-introducing WT GHR to mutant human fibroblasts, suppresses p53

obstacles in obesity treatment is maintaining a lower body weight after weight

thereby evading cellular senescence.

loss. It can be argued that weight loss and its maintenance may be uncoupled

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

biological processes that require different pharmacological approaches. Thus, the

S25.2

reduction in metabolic rate triggered by a high calorie-restriction-induced weight

HPA axis, insulin resistance and adipocytokines in the

loss, contributes to powerful counter-regulatory

‘homeostatic’ mechanisms

fetal-maternal unit

leading to weight regain. Therefore, innovative strategies aimed at effectively

George Mastorakos

minimizing these compensatory adaptations with combinations of drugs (combos)

Greece.

using different mechanisms of action may prove useful. Consequently, targeting

of food hedonics in combination with the archetypical anorectic and thermogenic

pathways will probably provide unparalleled pharmacological efficacy to combat

‘Stress’ is defined as a state of disharmony or threatened homeostasis. Pregnancy

obesity and prevent weight regain. Glucagon has reemerged in weight loss

is a transient period of relative hypercortisolism. Chronic or acute stressors

polypharmacy relevantly complementing thermogenic agents. Fibroblast growth

influence maternal and fetal Hypothalamus-Pituitary-Adrenal Axes (HPA) during

factors (FGFs) are undoubtedly among a plethora of newly identified metabolic

pregnancy. Insulin sensitivity is a feature of normal pregnancy, possibly reflecting

macromolecules. Evidence that brown adipose tissue exists in adult humans and is

an adaptive phenomenon aiming at diverting maternal glucose towards fetal

activated after cold exposure has opened the interest in the potential browning of

needs. We investigated the effect of maternal stress into maternal insulin

adipose tissue and the quantitative contribution of BAT induction/activation

sensitivity during pregnancy by employing state-trait anxiety inventory (STAI)

towards energy expenditure in obesity. Novel insights that facilitate the design of

trait and state questionnaires for stress assessment and we found that in normal

refined polypharmacy that relevantly targets food hedonics at the same time as

pregnant women, enhanced long-term stress is associated with decreased insulin

stimulates energy expenditure without severe off-target effects that are currently

sensitivity. Both long- and short- term stress are associated with enhanced

frequently linked to behavioral pharmacology are being pursued.

maternal HPA axis and increased placental CRH secretion. Furthermore the

DOI: 10.1530/endoabs.49.S24.2

decrease in insulin sensitivity during pregnancy is paralleled by the progressive

increase of maternal adipose tissue deposition. Throughout pregnancy maternal

adipose tissue is metabolically active, producing adipocytokines involved in the

process of insulin resistance. Visfatin concentrations in the

1st trimester

positively predict insulin sensitivity during the 2nd trimester. Body fat mass

during 1st trimester of pregnancy is negatively associated with insulin sensitivity

during the 2nd trimester and should be kept under control. Furthermore, first

trimester maternal BMI and serum visfatin seem to be strongly associated with

fetal insulin secretion and final birth weight, respectively, suggesting a role of

early-pregnancy maternal adipose tissue in the pregnancy metabolic environment.

S24.3

Interestingly, during pregnancy, maternal GLP1

might be involved in

US experience update

mechanisms that compensate for the pregnancy-related increase in glycemia

Mike Lean

and insulin resistance, suggesting a role of this peptide in maternal metabolism

UK.

and weight and fetal growth. In conclusion, both maternal adipose tissue and

stress-induced HPA activation influence directly and/or indirectly the develop-

Abstract unavailable.

ment of insulin resistance during pregnancy.

DOI: 10.1530/endoabs.49.S25.2

HPA Axis Regulation During a Woman’s Life: Impact

on Metabolic Outcomes

S25.1

HPA axis regulation during a woman’s life: impact on metabolic

S25.3

outcomes

11b-hydroxysteroid dehydrogenase activity, androgen excess, and

Svetozar Damjanovic

metabolic outcomes in woman

Serbia.

Jeremy Tomlinson

UK.

Aging in both men and women is linked with a decline in diurnal variations in

cortisol secretion. Cortisol secretion is increased during circadian nadir and

Steroid hormones have potent metabolic effects. Glucocorticoid excess is

possibly in total through the day. Reduced suppressibility of cortisol after

characterized by central adiposity, insulin resistance, type

2 diabetes and

dexamethasone (DEX) administration and increased ACTH secretion with aging

increased cardiovascular risk. Whilst endogenous glucocorticoid excess is rare,

are well documented. It appears that aging associates with the decrease in cortisol

local tissue-specific availability of glucocorticoid is controlled by a series of

negative feedback efficacy on HPA axis due to underexpression of miner-

enzymes that are, at a pre-receptor level, able to regulate cortisol’s ability to bind

alocorticoid receptors (MRs) and imbalance of MRs to glucocorticoid receptors

and activate the glucocorticoid receptor. 11b-hydroxysteroid dehydrogenase type

(GRs) in hippocampus (HC). Chronically elevated glucocorticoids (GCs) in mice,

(11b-HSD1) converts inactive cortisone to active cortisol, and therefore

but not in the other species, lead to neuronal cell loss in the HC. In contrast to

amplifies local glucocorticoid action. It is highly expressed in key metabolic

these results, an age-related decline in peripheral cortisol values from 30 to 60

target tissues including liver, fat and muscle and is dysregulated in metabolic

years of age within the obese subjects has been observed. This may be explained

disease including polycystic ovarian syndrome. It has been a target for therapeutic

by emotional eating which reduce HPA axis activity by CRF suppression. No

intervention and selective

11b-HSD1 inhibitors provide modest metabolic

such correlation was found in healthy individuals with normal body-mass-index

improvements in patients with type 2 diabetes. In parallel, the A-ring reductases,

(BMI). It seems that ‘healthy’ aging does not lead to enhanced HPA axis activity

(5a- and 5b-reductase), inactivate glucocorticoids, but importantly, the isoforms

and peripheral cortisol levels rather decline with aging. Parental regulation of

of 5a-reductase convert testosterone to the more potent androgen, dihydrotes-

hippocampal GR expression as well as the priming effect of high GC

tosterone. 5a-reductase activity is increased in patients with PCOS and may

concentrations on the future responses to stressors imprint life history through

contribute significantly to the androgen excess observed in these patients and fuel

epigenetic changes within HC. Additionally, men and women tend to react

their adverse metabolic phenotype. In addition, adipose tissue is able to generate

differently with stress-both psychologically and biologically. Clinical signi-

androgens through the activity of 17b-hydroxysteroid dehydrogenase type 5

ficance of reduced adrenal androgen production (DHEA and DHEAS) with aging

(AKR1C3), and activity and expression are increased in patients with obesity and

is not well established. Aldosterone secretion appears to be slightly reduced in

PCOS. In vitro data suggest that AKR1C3 may drive lipid accumulation locally

elderly whereas sympathetic tone vary from organ to organ. Altogether aging

within adipocytes through enhanced androgen generation. In conclusion, pre-

associated changes in HPA activity only in a part depends on genetic background.

receptor steroid hormone metabolism has a powerful role to play in the regulation

Individual differences in stress reactivity might be important risk factor for

of metabolic phenotype in patients with PCOS and offers significant potential as a

gender-specific health problems in men and women.

target for therapeutic intervention.

DOI: 10.1530/endoabs.49.S25.1

DOI: 10.1530/endoabs.49.S25.3

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Tissue Specific Defects in Thyroid Hormone Action

Methods

We conduct a world-wide prospective interventional trial in which about 45

S26.1

AHDS patients receive 1 year Triac treatment. The primary end-point is the

Mouse models to study tissue specific hypothyroidism

reduction of serum T3 levels, and secondary end-points include normalization of

Heike Heuer

heart rate (HR), improvement of body weight (BW) and serum parameters that

Germany.

reflect TH action in peripheral tissues. Neuro(psycho)logical functioning is

assessed before and after 1 year of Triac treatment.

Results

Thyroid hormone (TH) actions and metabolism are intracellular events that

Currently,

41 patients (age:

1-66 years) have been enrolled (median (IQR)

require the transport of TH across the plasma membrane in target cells.

follow-up time: 8 (3-12) months) of whom 18 have completed 1 year of follow-

Consequently, impaired uptake of TH can lead to tissue- specific TH deprivation

up. Triac treatment effectively suppressed serum TSH levels (2.3 (1.6-3.9) to 0.9

independent of the TH concentrations in the circulation. A prominent example for

(0.2-1.9) mU/l; P!0.001), resulting in a strong reduction of T3 levels (5.0 (3.9-

such a scenario represents the Allan-Herndon-Dudley syndrome (AHDS). This

6.5) to

1.7

(1.4-2.2) nmol/l; P!0.001). Importantly, BMI, serum HDL

syndrome is caused by inactivating mutations in the X-linked Slc16a2 gene

cholesterol, creatinine and CK levels significantly increased, whereas basal

encoding the monocarboxylate transporter MCT8, a highly specific TH

heart rate and serum SHBG levels significantly decreased.

transporter widely expressed in CNS and peripheral tissues. Patients with

Discussion

inactive MCT8

display severe neurological symptoms and signs of brain

Triac treatment effectively normalizes serum T3 levels. This interim analysis

hypothyroidism despite highly elevated serum T3 concentrations. Likewise, Mct8

suggests that Triac treatment has beneficial effects on the peripheral phenotype of

ko mice exhibit abnormal TH serum values together with complex tissue-specific

AHDS, which will be further substantiated upon completion of the follow-up

changes in the TH status ranging from hypothyroidism (brain, pituitary) to

period by the other participants.

hyperthyroidism (liver, kidney, skeletal muscle). In order to define the tissue-

specific function of Mct8 we recently started to generate mouse mutants that lack

DOI: 10.1530/endoabs.49.S26.3

Mct8 in defined cell types only. In my presentation, I will report on our studies

demonstrating pronounced cell-specific alterations in the TH status upon deletion

of Mct8 at the blood-brain barrier (BBB), in hypothalamic tanycytes as well as in

thyrocytes while absence of Mct8 in forebrain neurons or hepatocytes did not

compromise proper tissue-specific TH action. Overall, our data clearly underscore

the importance of Mct8 and other TH transporters in mediating TH transport

thereby influencing tissue-specific TH homeostasis.

Vitamin D Beyond Bone (Endorsed by

DOI: 10.1530/endoabs.49.S26.1

Endocrine Connections)

S27.1

Heart & Vessels

Klaus Witte

UK.

S26.2

Syndromes of decreased sensitivity to thyroid hormone

Vitamin D is a recognised important factor in bone health but in recent years is

Nadia Schoenmakers

receiving much attention for its role in multiple other systems. The enthusiasm

UK.

with which it is embraced as an elixir vitae especially in cancer, cardiovascular

disease and neurodegenerative diseases is overwhelming and matched only by the

skepticism from other quarters, since solid evidence is largely lacking. I will

Disorders of thyroid hormone action are classified broadly, to encompass

review the pleiotropic effects of vitamin D and how they may be of relevance to

conditions with defective cellular uptake, metabolism or nuclear action of thyroid

the specific syndrome represented by chronic heart failure and the evidence

hormones. Genomic thyroid hormone action is mediated via receptor subtypes

generated to date by, amongst others, the VINDICATE program at Leeds.

(TRalpha, TRbeta) with differing tissue distributions. TRbeta-mediated Resist-

DOI: 10.1530/endoabs.49.S27.1

ance to Thyroid Hormone (RTH) is characterised by elevated thyroid hormones,

raised metabolic rate and cardiac hyperthyroidism but hepatic resistance

(dyslipidaemia, steatosis). In contrast, TRalpha1-mediated RTH patients exhibit

growth retardation, skeletal dysplasia and constipation together with reduced

metabolic rate and cardiac hypothyroidism, with near-normal thyroid hormone

levels. The contrasting phenotypes of TRalpha1

and beta- mediated RTH

S27.2

exemplify the differing importance of receptor subtypes in tissues, providing a

rational basis for receptor-specific drug development. Mutations in SECISBP2

Fertility

and TRU-TCA1-1 cause a multisystem disorder of defective selenoprotein

Elisabeth Lerchbaum

synthesis, with features attributable both to tissue-specific selenoprotein

Austria.

deficiencies (e.g. male infertility, muscular dystrophy) and raised cellular reactive

oxygen species due to lack of antioxidant selenoenzymes (e.g. photosensitivity,

Accumulating evidence from animal and human studies suggests that vitamin D is

increased adipose mass and function). Additionally, patients have a characteristic

involved in many functions of the reproductive system in both genders. In women,

biochemical signature resulting from impaired conversion of T4

to T3 via

vitamin D status has been associated with in vitro fertilization (IVF) outcome,

selenium-containing deiodinases. This presentation will describe clinical features

features of polycystic ovarian syndrome (PCOS), endometriosis, and sex hormone

of these conditions, which increase our understanding of thyroid hormone action

steroidogenesis. In detail, cross-sectional data suggest a regulatory role of vitamin

and inform potential future therapeutic developments.

D in PCOS-related aspects such as ovulatory dysfunction, insulin resistance as

DOI: 10.1530/endoabs.49.S26.2

well as hyperandrogenism. Moreover, results from randomized controlled trials

(RCTs) suggest that vitamin D supplementation may be beneficial for follicular

development and menstrual cycle regulation in PCOS women. Although several

data converge towards a beneficial effect of vitamin D supplementation in

metabolic disturbances in women with PCOS, this remains to be demonstrated in

S26.3

high-quality RCTs. Regarding assisted reproductive techniques, recent studies

suggest that vitamin D supplementation might be beneficial for couples

Restoring TH action in patients with transporter defects: the triac trial

undergoing IVF. In men, vitamin D status has been associated with semen

Stefan Groeneweg

quality and sperm count, motility and morphology as well as with androgen levels

The Netherlands.

in both fertile and infertile men. Further, there is evidence for a favourable effect

of vitamin D supplementation on semen quality, fertility outcomes as well as on

Mutations in the thyroid hormone (TH) transporter MCT8 result in the Allan-

testosterone concentrations. In summary, vitamin D deficiency may be a risk

Herndon-Dudley syndrome

(AHDS), which is characterized by severe

factor for adverse fertility outcomes, there is, however, insufficient evidence to

intellectual and motor disability and high serum T3 levels inducing thyrotoxicity

establish causality. High quality RCTs are needed to further evaluate the effects of

in peripheral organs. At present, no effective treatment is available. Preclinical

vitamin D supplementation on fertility and sex hormone steroidogenesis in

studies suggest that the T3 analogue Triac is a promising candidate to i) normalize

women as well as in men.

serum T3 levels and thus alleviate the thyrotoxicosis and ii) restore TH signaling

DOI: 10.1530/endoabs.49.S27.2

in the brain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

S27.3

that it was responsible for the strong bonds between mother and child but in the

recent years it was investigated in relation to other types of pair bonding, the

Muscles

development of monogamous relations, and even the relation between different

Roger Bouillon

species like between humans and dogs. It’s role in sexual orgasm was also

Belgium.

recognized. Its secretion can be influenced by a hug or a simple conversation

when feelings of trust are present. Indeed, Oxytocin could be responsible for

The vitamin D endocrine system (D-endo) is essential for calcium and bone

social behaviour as it facilitates the development of trust and empathy between

homeostasis. The vitamin D receptor, VDR, is ubiquitously expressed and about

individuals, strengthening relationships. This neuropeptide seems to facilitate

3% of the mouse or human genome is regulated by D-endo. VDR knock-out mice

security in human relations thus being supportive of positive social interactions.

show impaired striated muscle maturation and selective VDR deficiency in heart

For all of these discoveries it became known as the love hormone. However other

muscle cause cardiomyopathy. Muscle weakness may be severe in patients with

roles have also been attributed to Oxytocin: decreasing levels of stress, fear and

severe chronic renal failure combined with vitamin D deficiency or in subjects

pain, and also a sort of selective influence on memory (allowing the individual to

with congenital CYP27B1 deficiency. Muscle strength and function may be

keep some memories while eliminating others). The therapeutically potential of

impaired in elderly vitamin D deficient elderly subjects and result in increased

oxytocin has already started to be studied in diseases like autism spectrum

risks of falls. The final proof of causality is hotly debated but meta-analyses of

disorder, schizophrenia and depression. Lab tools like measurements of oxytocin

supplementation studies suggest a modest reduction in falls in elderly subjects

in plasma, brain imaging (f-MRI/PET) and genetic/epigenetic assays bring new

with severe vitamin D deficiency. All cells of the immune system express VDR. A

opportunities to explore the oxytocin pathway and will continue to help us to

large number of immune-related genes are coherently controlled by 1,25(OH)₂D.

understand how to live a healthy life in a love ambience.

The native immune system is stimulated by 1,25(OH)₂D. A low vitamin D status

DOI: 10.1530/endoabs.49.S28.2

is associated with an increased risk for all types of infections. Human intervention

studies however are equivocal. The acquired immune system is suppressed by

D-endo. In animal models vitamin D deficiency leads to increased sensitivity to

autoimmune diseases such as inflammatory bowel disease or autoimmune

diabetes after exposure to predisposing factors. In man, epidemiological studies

confirm such associations, but intervention studies till now fail to show preventive

S28.3

effects. The antiproliferative effect of 1,25(OH)2D on cancer cells has been

Kisspeptin and neurokinin B - novel reproductive hormones with

confirmed in most cells with inhibition of the cell cycle. VDR deficient mice are

therapeutic potential

more prone to cancer when exposed to predisposing factors. The association

Waljit Dhillo

between a low vitamin D status and colon cancer is fairly consistent in several

UK.

meta-analyses. A few RCTs however have so far not confirmed beneficial effects

on caner. In conclusion, serum 25OHD levels above 20 ng/ml may convey some

global health benefits beyond bone but ongoing studies will allow confirming or

Kisspeptin and neurokinin B are 2 novel key hypothalamic hormones which are

correcting this conclusion.

vital in normal reproductive function. Inactivating mutations for the gene or the

DOI: 10.1530/endoabs.49.S27.3

receptor for either of these peptides will cause a failure of puberty due to

hypogonadtotrophic hypogondaism. In this talk I will present evidence to suggest

that kisspeptin is important in sexual and emotional processing in humans (1). In

addition I will present evidence which suggests that NK3R (the receptor for NKB

in humans) is important as a mediator of menopausal flushing and this has

potentially practice changing therapeutic potential (2).

Sleep, Love and Reproduction (Endorsed by

References

Endocrine Connections)

1. Comninos AN, et al. Kisspeptin modulates sexual and emotional brain

processing in humans. J Clin Invest. 2017 127 709-719. https://www.jci.org/

S28.1

articles/view/89519

Candidate mechanisms underlying the association between poor sleep

2. Comninos AN, et al. Neurokinin 3 receptor antagonism as a novel treatment for

and obesity

menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled

Christian Benedict

trial. Lancet online on

3^rd April

2017

http://dx.doi.org/10.1016/S0140-

Sweden.

6736(17)30823-1

DOI: 10.1530/endoabs.49.S28.3

An increasing proportion of people living in our 24/7 culture complain about

insomnia symptoms, i.e., they experience problems to fall and/or stay asleep. As

demonstrated by epidemiological studies, chronic sleep loss is correlated with

weight gain. To investigate whether sleep loss would alter energy metabolism in

favour of weight gain, my lab therefore performed a series of sleep loss

Novel Predictors of Diabetes

experiments in metabolically healthy normal-weight subjects. These studies

S29.1

demonstrated that acute sleep loss alters circulating levels of appetite-modulatory

metabolites (e.g. higher levels of the hunger-promoting hormone ghrelin), impairs

Novel predictors of type 1 diabetes

the ability to control food impulses, and increases metabolic efficiency. In the

Mikae Knip

setting of chronically insufficient sleep, such behavioral and metabolic effects

Finland.

may predispose normal-weight individuals to gain weight.

DOI: 10.1530/endoabs.49.S28.1

Islet autoantibodies are strong predictors of type 1 diabetes (T1D), as positivity

for multiple, i.e.is two or more, autoantibodies is associated with a risk of around

70% of progression to clinical disease over the next 10 years. Autoantibodies do

not, however, predict when T1D will present clinically. We have assessed the

utility of signs of dysglycemia for the prediction of the time of disease

S28.2

manifestation and observed that an increase in HbA1c of 10% over 3-12 months

provides a 50% likelihood of disease presentation within 1.1 year after the

Oxytocin: from biology to love

observed increase. When the HbA1c value was 5.9% (41 mmol/mol) in two

Susana Guerreiro

consecutive samples, the median time to diagnosis was 0.9 years. The median

Portugal.

time to diagnosis after the detection of impaired glucose tolerance on OGTT was

0.7

years. After the detection of an increased random plasma glucose

Oxytocin was discovered by Henry Dale in 1906 and synthesized in the early 50’s

(R7.8 mmol/l) the median time to diagnosis was

1.0

years. The omics

by Vincent du Vigneaud and coworkers. It is secreted by axonal terminals in the

technologies have raised the issue, whether there is a possibility to identify

neurohypophysis emanating from the neurosecretory neurons of the supraoptic

high risk individuals before the appearance of the first autoantibodies. We have

and paraventricular nuclei of the hypothalamus. This hormone similarly to others

looked at markers generated by transcriptomics. We observed that genes and

is secreted in a pulsatile way and, classically, in relation to labor

(uterine

pathways related to innate immunity functions, such as the type 1 interferon (IFN)

contractility), lactation and to the maternal behaviour. After the initial

response, were active, and IFN response factors were identified as central

identification of its role in labor induction and lactation it became clear that

mediators of the IFN-related transcriptional changes. In a proteomics study we

Oxytocin plays other very important roles in human life namely in the creation of

found that when including the total observation time from birth to diagnosis we

bonds which gave this hormone the title of social hormone. First it became clear

were able to classify the participants into disease progressors and non-progressors

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

with a success rate of 91%. The classifica-tion was based on the combination of the

novel clinical relevance attributed to steroids previously deemed irrelevant and

relative levels of APOC4 (decreased) and afamin (AFAM, increased). Lipidomics

successful implementation of new anti-cancer treatments. Prostate cancer is a

and metabolomics analyses showed that individuals who developed T1D had

prime example of the latter with the recent confirmation that castration-resistant

reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth,

disease is still androgen-dependent and susceptible to hormonal manipulation

reduced levels of triglycerides and antioxidant ether phospholipids throughout the

with next generation steroidogenic enzyme inhibitors and anti-androgens. In

follow up, and increased levels of proinflammatory lysoPCs several months before

advanced stages of prostate cancer hormonal treatment leads to complex and

seroconversion to autoantibody positivity. The appearance of insulin and glutamic

incompletely understood changes in circulating steroid hormones levels. CYP17

acid decarboxylase autoantibodies was preceded by diminished ketoleucine and

inhibitors like abiraterone acetate lead to accumulation of mineralocorticoid

elevated glutamic acid. Another study focusing on the lipidome/metabolome in

precursors and progesterone metabolites. This ensues a steroid flux into the

cord blood revealed that those children, who progressed quickly to clinical T1D,

alternative pathway to 5a-dihydrotestosterone (DHT) with intermediates such as

were characterized by a distinct cord blood lipidomic profile that includes reduced

allopregnanolone and androstanediol. Our data in parental and abiraterone-

major choline containing phospholipids, including sphingomyelins and phospha-

resistant prostate cancer cells show a functional block at the level of CYP17 in

tidylcholines. Risk children, who progress to clinical T1D are characterized by a

prostate cancer cells, preventing de novo steroid synthesis and local activation of

decreased microbial diversity, an increased abundance of potentially pathogenic

CYP17 precursors. However, accumulation of other steroid hormones intratu-

bacteria and a reduced functional gene content in their intestinal microbiome.

morally could affect nuclear receptor activation. Concurrently, interaction with

These changes, can however, not be seen before seroconversion to autoantibody

supplemented glucocorticoids leads to a complex interaction between wild type,

positivity. To summarize, metabolic markers help in the estimation of time to

mutant and splice variants of nuclear receptors and DNA regulatory elements.

diagnosis in prediabetic individuals. The potential predictive markers generated by

Further research into pre-receptor regulation of steroid hormones combined with

omics technologies have to be validated.

innovative genome-wide receptor-DNA binding analyses will pave the way

DOI: 10.1530/endoabs.49.S29.1

towards comprehensive understanding of their effects. In turn, this could secure

efficient targeting of the detrimental sequelae of steroid hormones in prostate

cancer and other endocrine diseases.

DOI: 10.1530/endoabs.49.S30.1

S29.2

Clinical and genetic indicators for diabetes prediction

Valeriya Lyssenko

Denmark.

S30.2

Clinical relevance of steroid precursors in adrenocortical tumors

Vasileios Chortis

Worldwide diabetes epidemic leads to exponential increase in incidence and

prevalence of associated co-morbidities and mortality. During the last 10 years we

have devoted to investigate how clinical and genetic biomarkers can be used to

facilitate prediction of these life-threatening hazards. Accumulating evidence

Adrenal incidentalomas represent an increasingly common diagnostic problem

from our large prospective studies indicate that decline in insulin secretion

facing clinical Endocrinologists. Swift and accurate differentiation of benign from

adjusted for the degree of insulin sensitivity is the key factor contributing to overt

malignant disease is essential, but the diagnostic performance of current imaging

type 2 diabetes. Furthermore, genetic data indicate that risk alleles in genetic loci

modalities is sub-optimal and often leads to ill-advised management decisions.

for type 2 diabetes influenced changes in pancreatic beta-cell function over time,

Urinary steroid profiling by modern mass spectrometry-based techniques can

while having no effect on changes in body mass index. Presently, genetic

provide a comprehensive profile of steroidogenesis, quantifying both precursor

information has insufficient power to predict common type 2 diabetes. However,

molecules and end products. Adrenocortical carcinomas display a premature

our follow-up studies on variants in TCF7L2, MTNR1B, GIPR, GRB10 genes

pattern of steroidogenesis, dominated by precursor hormone synthesis, which can

unravelled multiple and pleiotropic mechanisms of genetic loci which

be captured in the urinary profile. Emerging evidence highlights the unique

significantly contributed to our understanding of pathogenesis of type 2 diabetes

diagnostic opportunities presented by this feature. The combination of high-

including effects on insular-incretin axis (GIP/GLP-1 and glucagon) and hepatic

sensitivity biochemical analysis and computational data processing is expected to

glucose production in the liver. We and others have also reported

transform the management of adrenal tumours, from the diagnostics of adrenal

a-hydroxybutyrate, linoleoyl glycerophosphocholine, and copeptin as novel

incidentalomas to the post-operative surveillance of adrenocortical carcinomas.

biomarkers to be associated with increased risk of type 2 diabetes. However, these

DOI: 10.1530/endoabs.49.S30.2

new biomarkers require a systematic evaluation and validation across different

studies and populations before their actual diagnostic and prognostic value is

confirmed.

DOI: 10.1530/endoabs.49.S29.2

S30.3

Glucocorticoid production in primary aldosteronism - from

mechanisms to clinical implications

Felix Beuschlein

Germany.

S29.3

Novel predictors of diabetes - NAFLD, diabetes and CVD

Enzo Bonora

Adrenal aldosterone excess is the most common cause of secondary hypertension

Italy.

and is associated with increased cardiovascular morbidity and mortality.

However, adverse metabolic risk in primary aldosteronism extends beyond

hypertension, with increased rates of insulin resistance, type 2 diabetes, and

Abstract unavailable.

osteoporosis, which cannot be easily explained by aldosterone excess but would

rather be associated with oversecretion of glucocorticoids. Over the last years,

exome sequencing has provided new insights into the genetic set-up of adrenal

adenomas highlighting the concept of calcium dependent signalling being the

main driver for aldosterone secretion while the cAMP/PKA pathway can be

considered of particular importance for cortisol production. In rare examples

somatic mutations in genes involved in cAMP signalling could be identified.

Moving Away from Old-fashioned Steroidogenesis:

However, in the majority of cases the contribution of glucocorticoid oversecretion

What Are the Clinical Implications?

in patients with primary aldosteronism has remained uncertain. Recently, we have

S30.1

performed mass spectrometry-based steroid metabolome profiling in 24-h urines

from consecutively recruited patients with primary aldosteronism. Comparisons

Clinical relevance of alternative synthesis of androgens

were made with healthy controls, patients with endocrine inactive adrenal

Hans Hofland

adenoma, and patients with mild subclinical and clinically overt adrenal cortisol

The Netherlands.

excess. Based on these measurements, patients with primary aldosteronism had

significantly increased cortisol and total glucocorticoid metabolite excretion, only

Recent years have seen many exciting developments in the field of

exceeded by glucocorticoid output in patients with clinically overt adrenal

steroidogenesis. These include improved diagnostics through mass spectrometry,

Cushing syndrome. Several surrogate parameters of metabolic risk correlated

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

significantly with glucocorticoid but not mineralocorticoid output. We analysed

GS1.3

the expression of cortisol-producing CYP11B1

and aldosterone-producing

Adult aspects of turner syndrome

CYP11B2 enzymes in adrenal adenoma tissue from patients with primary

Janielle Alfen-van der Velden

aldosteronism, employing immunohistochemistry with digital image analysis.

Intra-tumoral expression of CYP11B1 correlated significantly with glucocorti-

In this session, the adult aspects of Turner syndrome are addressed following the

coid excretion, whereas CYP11B2 expression correlated with aldosterone output.

new Clinical Practice Guidelines for Turner syndrome. The presentation includes

Unilateral adrenalectomy for adenoma removal resolved both mineralocorticoid

both theoretical backgrounds and practical recommendations. Fertility preser-

and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was

vation is discussed and the results of our GRADE evaluation according to the

found in roughly one third of tested patients. These data show that glucocorticoid

outcome of oocyte donation is presented. New insights in health surveillance for

co-secretion is a prevalent feature in primary aldosteronism and significantly

co-morbidities are highlighted. Practical tools for transition from pediatric to

contributes to associated metabolic risk. Mineralocorticoid receptor antagonist

adult care are provided. In addition, a toolbox for neuropsychological and

therapy alone may not be sufficient to counteract adverse metabolic risk in

psychological assessment of women with Turner syndrome is presented and

medically treated patients with primary aldosteronism.

possible options for intervention are discussed.

DOI: 10.1530/endoabs.49.S30.3

DOI: 10.1530/endoabs.49.GS1.3

Guided Session 1

GS1.4

Cardiovascular health issues in turner syndrome

GS1.1

Philippe Backeljauw

New international clinical practice guidelines for the care of girls and

women with turner syndrome

Individuals with Turner syndrome (TS) have an increased risk for congenital and

Claus H Gravholt

acquired cardiovascular disease (23-50%). This results in increased morbidity

Denmark.

and mortality throughout the TS lifespan. There is an increased prevalence of

bicuspid aortic valve malformation, coarctatio of the aorta, elongation of the

transverse aortic arch, and partial anomalous venous return. In addition, TS

Turner syndrome (TS) affects 25-50 per 100 000 females and can involve

females may develop aortopathy that may result in clinically significant aortic

multiple organs through all stages of life, necessitating a multidisciplinary

dilatation, which occasionally leads to dissection or rupture. Other cardiovascular

approach to care. Previous guidelines have highlighted this, but numerous

conditions such as hypertension, coronary heart disease, and cerebrovascular

important advances have been noted since their publication. These advances

disease (stroke) further reduce the lifespan of TS individuals. Because of this high

cover all specialty fields involved in the care of girls and women with TS. This

prevalence of cardiovascular disease, any care provider should have some

new international guideline is based on an international effort that started with

familiarity with the non-invasive cardiac imaging techniques required for

exploratory meetings in 2014 in both Europe and the USA, and culminated with a

diagnosis and management. Imaging modalities include transthoracic echocar-

Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this

diography and cardiac magnetic resonance imaging. Echocardiography is useful

meeting, five groups each addressed important areas in TS care: i) diagnostic and

in the diagnosis of a bicuspid aortic valve and other congenital heart diseases, and

genetic issues, ii) growth and development during childhood and adolescence, iii)

can be used for surveillance of aortic dilatation. Some abnormalities, such as

congenital and acquired cardiovascular disease, iv) transition and adult care, and

elongation of the transverse aortic arch and partially anomalous pulmonary

5) other comorbidities and neurocognitive issues. These groups produced

venous return, are not as readily ascertained by ultrasound however, and cardiac

proposals for the new guidelines. Additionally, four pertinent questions were

magnetic resonance imaging is now commonly used as a screening and

submitted for formal GRADE

(Grading of Recommendations, Assessment,

surveillance tool, especially in adult TS patients. The newly developed clinical

Development and Evaluation) evaluation with a separate systematic review of the

care guidelines for girls and women with TS include very specific recommen-

literature. These four questions related to the efficacy and most optimal treatment

dations on which aortic dimensions may warrant consideration for close

of short stature, infertility, hypertension, and hormonal replacement therapy.

monitoring and possible operative intervention. They also provide guidance in

These guidelines were initiated and developed by the European Society of

decision-making regarding participation in various sports disciplines, and greatly

Endocrinology (ESE) in Europe, and by the Pediatric Endocrine Society (PES) in

clarify when more frequent cardiovascular health monitoring may be beneficial. It

USA, with important contributions from the European Society of Human

is important that both pediatric and adult endocrinologists, as well as reproductive

Reproduction and Embryology

(ESHRE), the Endocrine Society

(ES), the

endocrinologists, are familiar with the updated recommendations for cardiovas-

European Society for Cardiology (ESC), the American Heart Association (AHA),

cular health management in TS, in order to coordinate care with the cardiologists

and the European Society for Pediatric Endocrinology (ESPE). Several delegates

and to facilitate over health maintenance of girls and women with TS.

from other societies also participated. Advocacy groups appointed representatives

DOI: 10.1530/endoabs.49.GS1.4

who participated in pre-meeting discussions and in the consensus meeting. Here,

we will present the most important new advances in the care of Turner syndrome.

DOI: 10.1530/endoabs.49.GS1.1

GS1.5

Abstract unavailable.

GS1.2

Growth and puberty induction

Theo Sas

The Netherlands.

In July

2016, an International Turner Syndrome Meeting was organized in

Cincinnati, Ohio, USA. Today, an updated document concerning the Clinical

Practice Guidelines for the Care of Girls and Women with Turner Syndrome is

finalized. This document gives the summary of the evidence and expert opinions

GS1.6

about several aspects of the treatment and follow-up of individuals with Turner

syndrome. It will be published soon. In this presentation, the main conclusions

and recommendations about growth and induction of puberty will be reported and

discussed.

Abstract unavailable.

DOI: 10.1530/endoabs.49.GS1.2

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

NSA1

NSA4

Identifying molecular signatures for cancer patient stratification via

CRISPR/cas9 cas9-generated mouse models of resistance to thyroid

metabolomics and integrative bioinformatics

hormone due to THRA mutations

Hector Keun

Frederic Flamant

UK.

France.

Altered metabolism in tumor cells is required for rapid proliferation but also can

Resistance to thyroid hormone due to THRA mutations (RTHa) is a recently

influence other phenotypes that affect clinical outcomes such as metastasis and

discovered genetic disease with high variability in its clinical presentation. This

sensitivity to chemotherapy. Integration of metabolome and transcriptome data

variability may result from the fact that patients bear different types of mutations,

for the NCI-60

panel of cancer cells lines allowed us to identify ecto-5⁰ -

which may impact in different ways the functionality of thyroid hormone receptor

nucleotidase

(NT5E or CD73) and miRNA-22 as a major determinants of

a1 (TRa1). Our aim was to understand the relationship between specific

metabolic phenotypes in cancer cells. NT5E expression and associated

THRA mutations and symptoms, using mouse models. CRISPR/Cas9 genome

metabolome variations were also correlated with sensitivity to several

editing was used to generate five new models of RTHa, the human genetic disease

chemotherapeutics including platinum-based treatment. We observed that

caused by mutations in THRA. Like human patients, the mutant mice displayed a

tumor NT5E levels were prognostic for outcomes in ovarian cancer and were

hypothyroid-like phenotype, with altered post-natal development. Phenotype

elevated after treatment with platinum, supporting the translational relevance of

severity varied over a broad range between models, mainly depending on the

our findings. The cancer-associated and cardioprotective miR-22 was shown to

ability of the mutant receptor to interact with the NcoR transcription corepressor

repress fatty acid synthesis and elongation in tumour cells by targeting ATP

in the presence of thyroid hormone. These data illustrate the outstanding

citrate lyase and fatty acid elongase 6, as well as impairing mitochondrial one-

possibilities offered by CRISPR/Cas9 genome editing which allows to rapidly

carbon metabolism by suppression of methylene tetrahydrofolate dehydrogen-

produce mouse models of human genetic disease, and even to model individual

ase/cyclohydrolase (MTHFD2). Importantly, a beneficial effect of miR-22 on

sporadic cases of the disease.

clinical outcomes in breast cancer was shown to depend on the expression levels

DOI: 10.1530/endoabs.49.NSA4

of the identified target genes, demonstrating the relevance of miRNA/mRNA

interactions to disease progression in vivo. These studies illustrate one route

towards patient stratification based the rational combination of different types of

molecular biomarkers for metabolic processes.

DOI: 10.1530/endoabs.49.NSA1

NSA5.1

Methodical tools for the structural elucidation of G-protein coupled

receptors

Patrick Scheerer

NSA2

Germany.

Exosome profiling: potential in cancer diagnosis and stratification

Juan Falcon-Perez

Spain.

In my short methodological talk, I will present why we need a detailed structural

description of membrane proteins such as the TSH receptors (TSHR) of the

endocrine system and how can we succeed to get three-dimensional structures.

In the last decade, cell-secreted extracellular vesicles (EVs) have been isolated

The talk includes a methodical toolbox of protein-production or -stabilization and

from most of the fluids of the body. There are many different types of EVs that

advanced structural biology techniques like protein X-ray crystallography and

include different subpopulations of exosomes, microvesicles and apoptotic bodies,

cryo-electron microscopy for selected examples.

all of them varying in size, composition and intracellular origin. Many laboratories

DOI: 10.1530/endoabs.49.NSA5.1

around the world have shown that its composition of lipids, proteins, messenger

and micro RNAs is cell-type specific, and subject to changes in pathological

scenarios, consequently these vesicles are being actively studied as a source to

identify disease biomarkers. Metabolic syndrome is a clinical condition affecting

up to 25% of all adults worldwide. It influences many cellular systems including

adipose tissue, macrophages and hepatocytes compromising most of the time the

NSA5.2

hepatic function that is essential for homeostasis of the organism. Apart of

Small molecule agonists and antagonists as potential new therapeutics

metabolic syndrome, liver injury ranging from mild infection to life-threatening

targeting the TSH receptor

liver failure constitute by itself a serious worldwide health issue. Consequently, a

Susanne Neumann

major goal in liver pathology is the identification of molecular markers for its early

USA.

detection, i.e. before clinical manifestations are produced. In this context, by

applying metabolomics, proteomics and transcriptomics technologies as well as

specific biochemical tools, our group is studying the physiological role of

Thyroid-stimulating hormone (TSH, thyrotropin) is an activator of the TSH

extracellular vesicles in the hepatic function in normal and pathological conditions

receptor (TSHR) in the hypothalamic-pituitary-thyroid axis leading to biosyn-

to identify novel low-invasive markers for liver injury. During last years, our group

thesis and secretion of thyroid hormones. We have developed an orally available

has demonstrated that hepatocytes are able to secrete exosomes-like vesicles

small molecule, allosteric TSHR agonist, E2, for follow up diagnosis of patients

enriched in metabolic enzymes. Now, we are currently achieving a thorough

with thyroid cancer. This ligand could replace recombinant human TSH (rhTSH,

qualitative and quantitative analysis by proteomics, transcriptomics and

Thyrogen) which is currently used in the clinic. In a mouse model, oral

metabolomics of extracellular vesicles secreted by hepatocytes obtained from

administration of E2 is as efficacious as intraperitoneal injections of rhTSH.

experimental models of drug-induced liver injury and metabolic syndrome. Our

Therefore, E2 represents a next step in the pre-clinical development of an oral

work provides a repertoire of low invasive candidate markers to evaluate hepatic

drug to stimulate radioiodine uptake and/or serum thyroglobulin levels in patients

function in a low invasive manner. Furthermore, our results also support a

with thyroid cancer. Graves’ disease (GD) is caused by persistent, unregulated

physiological role of hepatic exosomes in different patho-physiological processes.

stimulation of thyroid cells by thyroid-stimulating antibodies

(TSAbs) that

activate the TSHR. We identified the first small molecule TSHR antagonist

DOI: 10.1530/endoabs.49.NSA2

(ANTAG3) which inhibits TSH- and TSAb-stimulated signaling. ANTAG3 is

selective for TSHR because it does not inhibit activation of LH or FSH receptors,

the receptors with the highest homology to TSHR within the seven

transmembrane domain in which ANTAG3 binds, and it inhibits TSHR activation

in the thyroid gland of mice in vivo. These findings suggested that ANTAG3

NSA3

could be able to inhibit TSHR signaling in extra-thyroidal tissues that express

Genomic approaches on epigenetics

TSHRs including orbital fibroblasts, which play a role in the pathogenesis of

Salvatore Oliviero

Graves’ ophthalmopathy (GO), a disease of the eye that is associated with GD.

Italy.

None of the treatment regimens for GD and GO used today are directed at the

pathogenesis of these diseases. In an ideal case the same drug would treat

Graves’ hyperthyroidism and GO. ANTAG3, directly acting at the TSHR,

Abstract unavailable.

reduced TSH- and TSAb-stimulated hyaluronan

(HA) production, a major

component of GO, by Graves’ orbital fibroblasts. Crosstalk between the TSHR

and the insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) initiated by

activation of TSHR may play a prominent role in the development GO. We have

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

shown that TSHR activation alone is sufficient to stimulate HA secretion, through

nuclear DNA methylation is a well stablished feature, very little attention has

both IGF-1R-dependent and -independent pathways. ANTAG3 inhibited both

been devoted to mitochondrial epigenetics. Obesity is often associated with a state

IGF-1R-dependent and -independent pathways at all doses of the monoclonal

of mild chronic inflammation characterized by an abnormal production of

stimulating antibody M22; whereas IGF-1R antagonist linsitinib

(a small

proinflammatory and prooxidant mediators. This proinflammatory condition has

molecule kinase inhibitor) and 1H7 (inhibitory antibody) lost efficacy at high

been linked to a mitochondrial dysfuncion. In fact, an energy restriction therapy

M22 doses. We propose that combination therapy targeting TSHR and IGF-1R

devised to lose weight induces an increase in the intracellular ATP content and

may be an effective treatment strategy, especially for GO. We suggest that small

mitochondrial-related gene expression, concomitantly with a decrease oxidative

molecule TSHR antagonists are leads for the development of orally active drugs

stress and inflammatory markers. Mitochondrial dysfunction and the increment of

to treat patients with Graves’ hyperthyroidism and GO.

mitochondrial Reactive Oxygen Species

(ROS) production are important

DOI: 10.1530/endoabs.49.NSA5.2

benchmarks of the aging and metabolic disturbances development. Therefore,

the mitochondrial dysfunction might be critically involved in the pathogenesis of

obesity. However, the molecular mechanisms leading to mitochondrial

dysfunction in metabolic diseases are still unknown. In this context,

mitochondrial epigenetics is a novel mechanism to understand the pathobiology

of diseases with a mitochondrial dysfunction involvement. Epigenetic regulation

NSA6

of mtDNA has received increasing attention in the last years due to its implication

Mitochondrial epigenetics in obesity and its co-diseases

in clinically relevant disease. Variations in mtDNA methylation were associated

Ana Belén Crujeiras

with exposure to pollutants and Nonalcoholic fatty liver disease (NAFLD) and

were proposed to have a role in mitochondrial gene expression regulation.

The biological regulatory system through which the organism responds to

mtDNA methylation was reported to be induced by hyperglycaemia in retinal

environmental pressures is mediated by epigenetic modifications of the genome

endothelial cells and to negatively regulate mitochondrial gene expression.

without altering the DNA sequence. Among the epigenetic processes, DNA

Moreover, mitochondrial epigenetic can modulate nuclear DNA and nuclear

methylation is perhaps the best understood epigenetic adaption and most common

DNA epigenetic may affect mtDNA. Hence, abnormal mtDNA methylation is

DNA modification. This mechanism plays an important role in regulating the

attracting increasing attention as potential biomarker and might have therapeutic

gene expression of many biological processes and has wide-ranging effects on

potential for metabolic diseases management.

health. Aberrant epigenetic regulation has been described in many human

diseases. Concretely, there is growing body of evidence that shows a relevant role

DOI: 10.1530/endoabs.49.NSA6

of epigenetic marks with obesity and its co-disease susceptibility. However, while

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Is There a Role for Medical Therapy for Non- Functioning

Incidentally Discovered Nonfunctioning Pancreatic NETs:

Pituitary Adenomas?

Surgery or Not? (Endorsed by the European Journal of

D1.1

Endocrinology)

Is there a role for medical therapy for non- functioning pituitary

D2.1

adenomas? - FOR

Incidentally discovered nonfunctioning pancreatic NETs: Surgery or

Yona Greenman

not? - FOR

Israel.

Ulrich Knigge

Denmark.

In this debate I will make an overview of outcomes of NFPA patients with post-

operative remnants, who were treated conservatively after surgery. In view of the

Pancreatic incidentalomas are defined as asymptomatic pancreatic lesions,

high rates of tumor progression with consequent need for repeated surgery and

discovered incidentally by imaging for an unrelated indication. A significant

radiation therapy, we propose the use of dopamine agonists in these patients.

proportion of these tumors may be malignant or have a malignant potential. As the

Recent data showing that preventive treatment with dopamine agonists

use of improved cross sectional imaging increases incidentalomas are becoming

significantly reduces the rate of tumor progression and the need for radiation

more common. In the ENETS guidelines it is proposed that selected patients with

therapy or additional surgical interventions will be reviewed.

incidentally found sporadic, asymptomatic, non-functioning

(NF) pancreatic

DOI: 10.1530/endoabs.49.D1.1

neuroendocrine neoplasms (pNEN) less than 2 cm in size may be followed with

repeated imaging instead of resected. However, this conclusion is based on

limited data as only few and retrospective studies with a heterogeneous design

have investigated the safety of active surveillance. Only few patients had

histological or cytological diagnosis and the Ki67 proliferation index, which is the

most powerful prognostic marker in NF pNEN, was only determined in 10% of

the patients. Up to 20% (in a single study 50%) of the patients had significant

tumor growth although regional lymph node metastases developed in few

patients. In a recent study, 38% of pNEN !2 cm displayed malignant features.

Hence, it cannot be predicted which patients will progress during observation.

Accordingly, active surveillance is a doubtful approach and resection should be

offered patients with small NF pNEN, if not contraindicated by age, severe

co-morbidity and poor performance status. Surgical procedures for small NF

pNEN are safe when performed in high-volume centers. In contrast, in MEN-1

D1.2

patients NF pNEN % 2 cm are generally indolent tumors with low malignant

features and surgical treatment is rarely indicated.

Is there a role for medical therapy for non- functioning pituitary

adenomas? - AGAINST

DOI: 10.1530/endoabs.49.D2.1

Stylianos Tsagarakis

Greece.

Non-functioning pituitary adenomas

(NFPA) are the second most common

variant of pituitary tumors. They are presented by compression symptoms,

hypopituitarism and in rec as incidental findings during brain imaging. When

symptomatic, primary therapy for NFPAs is surgery most commonly by the trans-

D2.2

sphenoidal (TSS) approach. Medical therapy is not generally recommended in

Incidentally discovered nonfunctioning pancreatic NETs: Surgery or

this setting, particularly when immediate decompression of the optic chiasm is

not? - AGAINST

needed. Despite the debulking efficacy of TSS, in many occasions only partial

Reza Kiamanesh

tumor resection is achieved. Recurrence rates are high in partially resected

France.

tumors. Although less frequently, even completely resected tumors may also

recur. Therefore, there is a need for post-surgical surveillance and intervention in

Abstract Unavailable.

order to prevent recurrence. The current practice in most centers is to follow-up

the pituitary lesion by MRI-imaging and offer additional therapy, usually in the

form of radiotherapy (RT), in case of recurrence. RT, either conventional or

stereotactic, is effective in controlling further tumor growth but its use is

compromised by significant side effects. Based on findings that many NFPAs

demonstrate expression of dopamine and somatostatin receptors, medical therapy

with dopamine agonists (DA) and somatostatin analogues (SSA) have been used

after surgery in order to prevent recurrence. So far, DAs have been more widely

tested showing some promise in several small-scale case series. In a recent larger

Drug Holiday in Osteoporosis (Endorsed by the European

study, introduction of DA immediately after surgery led to a lower number of

Journal of Endocrinology)

recurrences compared to a control group that did not receive DA therapy.

However, since not all patients will recur, such a strategy exposes a substantial

D3.1

number of patients to unnecessary long-term DA therapy. Unfortunately there are

Drug holiday in osteoporosis - FOR

no robust predictors for tumor recurrence. In fact, the best predictor of tumor

Bente Langdahl

growth is growth itself. However, DA therapy was less effective when introduced

Denmark.

later in patients that already demonstrated a tendency for tumor regrowth.

Surprisingly the beneficial effect of DA therapy does not correlate with dopamine

Abstract Unavailable.

receptor expression. This finding raises concerns about the pathophysiological

background of the observed DA benefit. Moreover, there are no solid data on hard

end points e.g. prevention of visual fields defects and avoidance of second

surgery. Although early initiation of treatment may be preferable, dosage and

duration of treatment are largely empirical. The need for higher doses and long

treatment periods raises some safety concerns. Definitely a well-designed

randomized control trial will resolve many of these issues. However, the lack

D3.2

of industrial interest and the long time-length required to obtain valid data, limits

Drug holiday in osteoporosis - AGAINST

the feasibility of such a perspective. To summarize, the promise of most

Dennis Black

medications is limited by imprecisions regarding the final outcome and

USA.

uncertainties on dosing and duration of preventive therapy. So far, effective

medications have rendered prolactinomas and acromegaly well manageable

disorders. For NFPAs such a possibility still remains elusive.

Abstract Unavailable.

DOI: 10.1530/endoabs.49.D1.2

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Is Cardiovascular Risk Increased in Women with PCOS?

D5.2

D4.1

Should we still ablate all patients undergoing total thyroidectomy for

thyroid cancer? - AGAINST

Is cardiovascular risk increased in women with PCOS? - FOR

Sophie Leboulleux

Harpal Randeva

France.

UK.

Regarding the debate about whether we should still ablate all patients undergoing

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder

total thyroidectomy, the answer is no. Most thyroid cancer patients have an

amongst women of reproductive age and is associated with various cardiometa-

excellent prognosis with a normal life expectancy and among them most of them

bolic perturbations, in addition to chronic anovulation and factors related to

have a low risk of recurrence. The absence of ablation in patients with thyroid

androgen excess. Indeed androgen excess has been associated with increased

cancer of 1 centimeter or less (pT1a) is already widely applied, so, we are used not

cardiovascular risk in women; serum testosterone correlates with indices of

to ablate all thyroid cancer patients treated with total thyroidectomy. The

subclinical atherosclerosis and cardiovascular disease (CVD). Moreover, women

question, indeed, is whether the group of patients not undergoing systemic

with PCOS, as compared with age- and body mass index-matched women without

ablation can be extended beyond pT1aN0/x patients. The selection of patients to

the syndrome, appear to have a higher risk of insulin resistance, hyperinsulinemia,

be spared from ablation can indeed be based on pathology examination, on

glucose intolerance, dyslipidemia, and an increased prothrombotic state, possibly

tumour size, on lymph node involvement and since some of these patients are now

resulting in a higher rate of type 2 diabetes mellitus, fatty liver disease, subclinical

recognized as low risk patients. The selection can also be based on postoperative

atherosclerosis, vascular dysfunction, and potentially cardiovascular disease and

thyroglobulin level because of its excellent negative predictive, whether

mortality. Obesity, an independent risk factor for CVD, is also more prevalent in

measured after TSH stimulation or measured under levothyroxine treatment

PCOS women as compared to age-matched controls, and is aggravated by

with ultrasensitive method, and on neck ultrasonography. However, prospective

androgen excess and has an detrimental android pattern of distribution. Further

randomized trials are needed in order to answer this question of ablation. This will

alterations in PCOS include an increased prevalence of sleep apnoea, as well as

allow reinforcing the strength of recommendation that can be done.

various changes in the secretion and/or function of adipokines and adipose tissue-

derived pro-inflammatory factors, all of them with direct or indirect influences on

DOI: 10.1530/endoabs.49.D5.2

the complex signaling network that regulates metabolism, insulin sensitivity, and

energy homeostasis. The literature is full of conflicting data and this is partly due

to the definition(s) used to identify women with PCOS and also the phenotypic

variability of PCOS, which in itself generates significant influence on the

cardiometabolic risks.

DOI: 10.1530/endoabs.49.D4.1

Is It Time for Initial Combination in Type 2 Diabetes?

D6.1

Is it time for initial combination in type 2 diabetes? - FOR

D4.2

Stefano Del Prato

Is cardiovascular risk increased in women with PCOS? - AGAINST

Italy.

Enrico Carmina

Italy.

Abstract Unavailable.

Young women with PCOS presents a severe risk of developing type II diabetes,

cardiovascular diseases, chronic liver disease and endometrial cancer. However,

in term of events, there is proven evidence only for type II diabetes and for

endometrial cancer. In particular, it is still unclear whether CV events are

increased in women with PCOS. Completely different data have been published

and the quality of many studies is relatively low. Some recent evidence suggests a

larger number of cardiovascular events (4 fold) in young population with PCOS.

However, studies at this age present an inherent difficulty linked to the low

D6.2

number of CV events in young population. In addition, these data are based on

Is it time for initial combination in type 2 diabetes? - AGAINST

hospitalized population and this approach may have some biases because it may

Didac Mauricio

exclude the less affected population. In our large follow up of unselected PCOS

Spain.

patients, no increase of CV events was noted. In aged PCOS patients the data are

also contrasting with some studies showing a slight increase of CV diseases and

others reporting normal prevalence of CV events. Large follow up studies are

missing and are urgently needed to solve this important issue. However, it is clear

Type

diabetes mellitus is a heterogeneous disease with multiple

that the number of events in aged women, who had PCOS during their

pathophysiological pathways contributing to hyperglycemia, and also

reproductive age, is much lower than that expected on the basis of risk calculation

resulting in a variable clinical picture. Thus, individualization of

during young adult age. The mechanisms of the discrepancy between CV risk and

hypoglycemic therapy is a mainstay of current clinical guidelines. Several

late events in PCOS are unclear but a progressive normalization of CV risk during

factors should be considered for a given treatment choice. These include the

late reproductive age may have a main role.

characteristics related to a given medication (efficacy, hypoglycemia, effect

DOI: 10.1530/endoabs.49.D4.2

on weight, other safety issues, the mechanism of action), and other factors,

like costs related to each treatment, convenience for the patient, etc. Initial

combination therapy may be considered as a suitable choice for some

patients/circumstances. However, the evidence favoring this combinatory

initial option has not been clearly established. Different issues concerning

the convenience of using either initial combination therapy vs sequential

Should We Still Ablate all Patients Undergoing Total

addition of hypoglycemic drugs will be addressed during the discussion. The

Thyroidectomy for Thyroid Cancer?

following aspects will be dealt with: long term efficacy of combination

therapy vs sequential titration/addition of hypoglycemic agents; durability;

D5.1

overall cost and cost-effectiveness; safety issues, including hypoglycemia

Should we still ablate all patients undergoing total thyroidectomy for

and weight changes; advantages/disadvantages in terms of treatment

thyroid cancer? - FOR

adherence; effects on patient-oriented outcomes, including long-term

Markus Luster

morbidity and mortality; effect on clinical inertia; what is the best

Germany.

combination of hypoglycemic agents; individualization vs combination for

every patient. To conclude, the question about the implementation of initial

Abstract Unavailable.

combination therapy as a strategy in usual clinical practice is still open.

DOI: 10.1530/endoabs.49.D6.2

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

MTE1

MTE3

How to manage diabetes in the elderly?

Hormone-secreting adrenal tumours in pregnancy

Leocadio Rodriguez-Manas

Catherine Williamson

Spain.

UK.

The prevalence of diabetes and glucose intolerance is close to 50% in people older

Hormone-secreting adrenal tumours are rare occurrences in women or

than 65. At the same time, near 50% of people with type 2 diabetes are R 65 years

reproductive age. The commonest is phaeochromocytoma, followed by primary

old. But being these figures relevant enough to raise a special consideration about

aldosteronism and Cushing’s syndrome. The shared maternal phenotypic feature

how to manage diabetes in this population, there are other reasons supporting the

of these tumours in marked hypertension. They may be difficult to diagnose as

need of that a special consideration. These other needs are not quantitative but

many of the clinical features are mimicked by pregnancy, e.g. flushing, weight

qualitative ones, making older people with diabetes a particular group of patents

gain, palpitations. Furthermore hypertensive disease occurs in approximately 5%

with different characteristics, different aims and, as a consequence, different

of pregnant women. However, there are specific clinical features associated with

management compared to adult non-older patients with type 2 patient and, of

each tumour type that aid diagnosis; the hypertension in phaeochromocytoma may

course, younger patients with both type 1 and type 2 diabetes. These differences

be paroxysmal; primary aldosteronism is often accompanied by hypokalaemia and

range from differences in the pathophysiology of diabetes, that although

the striae in Cushing’s syndrome are usually more purple and marked than in

stemming from insulin resistance have a different origin of this insulin resistance,

normal pregnancy. It is important to know the normal ranges for the specific

to the mechanisms underlying the development of vascular and other

endocrine tests used to diagnose each hormone-producing tumour, and once a

complications of diabetes, the impact of the disease in the several classical target

diagnosis has been made a multidisciplinary team should be involved with clinical

organs (in people older than 80 diabetes does not increase the risk of blindness),

management. This should include endocrinologists with an understanding of

the clinical manifestations of the disease, the diagnostic approach or the general

gestational disease, obstetricians, specialist anaesthetists, midwives and neonatol-

management of the patient. Among all of those, and some others, differences,

ogists. Individualised decisions should be made with regard to treatment with

perhaps the most relevant is the focus on function. While in younger populations,

surgery or drugs. All hormone-secreting adrenal tumours are associated with

the focus is usually centered in preventing or treating vascular disease (both

increased rates of adverse pregnancy outcome, including preterm labour and

micro- and macroangiopathy) and other complications of diabetes, when people is

stillbirth. This talk will summarise current knowledge about the management of

older the main focus is to avoid, delay or, if possible, reverse functional (both

these rare, and potentially life-threatening tumours in pregnant women and will

physical and cognitive) impairment. It is quite clear that diabetes increases less

consider the merits of prospective population cohorts to improve our understanding

significantly the risk of death in this population, reaching relative risks as low as

of the optimal management strategies to improve maternal and offspring outcomes.

1.2 in people older than 80 years. old. However, diabetes is one of the chronic

DOI: 10.1530/endoabs.49.MTE3

diseases increasing the risk of mobility disability, dependency for instrumental or

basic activities of daily living, falls and cognitive impairment/dementia in more

than twice. In addition, the role of functional status in conditioning the prognosis

(both functional and vital, plus other outcomes like hospitalization) is increasingly

higher as patient is getting older, substituting the classical role of the

MTE4

comorbidities (both those related and those non-related to diabetes). Finally, the

functional impact of the disease is also the main factor explaining the costs of

Treatment of congenital hypothyroidism

the disease, reaching figures of

78% of the costs. As a consequence, the

Heiko Krude

management of diabetes in older people should be based in functional status as the

Germany.

main factor in the decision-making process, but also as the main therapeutic

target. This change in the focus is crucial to get the best benefits when facing older

Treatment for congenital hypothyroidism (CH), based on thyroid extracts, was

people with diabetes.

introduced more than 100 years ago and resulted in a compelling improvement of

DOI: 10.1530/endoabs.49.MTE1

impaired growth, obesity, depression and severe delay of motor development.

However, severe mental retardation remained despite treatment. It was only after

the implementation of neonatal screening for CH in 1970s that intellectual

outcomes improved to an average normal IQ. However, whether complete

normalization of cognitive outcome is possible remains controversial, since some

studies have found significant gaps compared to control populations including

healthy siblings. Furthermore, there is some evidence that quality of life (QoL)

scores are lower compared to the general population. To further improve the

outcome, higher starting doses of more than 10 mg/kg and commencement of

treatment within the first two weeks of life were recommended. The most recent

outcome study from New Zealand, reporting patients treated according to a

MTE2

regimen consistent with these recommendations, documented IQ at age 10 years

Diagnosis and management of GH deficiency - from childhood to

that was no longer different from sibling control subjects. Nevertheless treatment

adulthood

with higher starting doses has raised concerns regarding adverse effects of

Jens Jorgensen

supraphysiological T4 levels, with studies in rodents and patients with neonatal

Denmark.

hyperthyroidism suggesting abnormal CNS development. In addition, it has been

repeatedly shown that the recommended high LT4 dose of O10 mg/kg results in

fT4 levels in newborns and infants with CH that exceed the reference ranges in

Pituitary dwarfism has been known for many decades, originally as a component

this age group. However, after decades of neonatal screening and recent confusion

of organic panhypopituitarism. GH for clinical use was purified by Maurice

about an “unfavourable” outcome with a high dose LT4 treatment, we now

Raben from human cadaveric pituitaries and tested for the first time and with

provide strong evidence -based on a recent IQoutcome study- that the present

success in 1957 in a patient with childhood onset disease. Moreover, pivotal short

recommendations of a high initial dose above 10 mg/kg is necessary, efficient and

term studies on the metabolic effects were performed in both healthy and

safe to achieve optimal cognitive development in all CH patients including those

hypopituitary adults. The concomitant introduction of imunnoassays for GH led

who are severely affected.

to the introduction of GH stim tests and recognition of isolated and idiopathic

GHD. But the scarcity of GH for clinical use was a major limitation until the

DOI: 10.1530/endoabs.49.MTE4

1980s when biosynthetic GH became available. This opened the possibility of

novel indications including GHD in adults (GHDA). The two first placebo-

controlled studies in 1989 reported positive effects in both childhood- and adult-

onset GHDA in terms of body composition and exercise capacity. This has since

been corroborated in numerous trials, and it is also documented that

MTE5

discontinuation of GH in the transition from child to adulthood is unfavorable.

Modern spectrum of bone turnover markers - are they clinically useful?

Finally, there is indirect evidence to suggest that GH replacement in adults may

Richard Eastell

reduce mortality and does not associate with increased cancer risk. Still, GH

UK.

therapy in adults is by no means a fountain of youth, and there is no evidence to

suggest that it is of any meaningful use in either normal or frail aging. This MTE

will discuss this exiting journey from a personal point of view.

Bone turnover markers reflect the work of the osteoblast and the osteoclast. They

DOI: 10.1530/endoabs.49.MTE2

can be measured in blood or urine and allow for an inexpensive and non-invasive

way to study bone metabolism. They have been evaluated for their use in

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

predicting risk of fracture, accelerated bone loss or the presence of secondary

the thyroid. Additionally, patients can take b blockers for symptomatic relief.

osteoporosis, but for all these uses they are not yet established. They are useful in

Although all three options are effective, no treatment is ideal and thus indicated in

monitoring the response to treatment of osteoporosis, especially with drugs such

all patients with GD. Selection of therapy depends on multiple considerations,

as oral bisphosphonates. One study focused on the clinical utility of modern

including: patient’s age, severity of thyrotoxicosis, presence of goiter,

spectrum of bone turnover markers for monitoring oral bisphosphonate therapy

orbitopathy, pregnancy, comorbidities. The treatment selection must also take

(alendronate, ibandronate, risedronate) in women with postmenopausal osteo-

into account the patient’s preference. Before deciding on a treatment plan, the

porosis. The study concluded that two approaches could be used to identify

treating physician and patient should discuss each of the treatment options,

response, namely a change beyond the least significant change or a change to

including the logistics, local availability, advantages, disadvantages, potential

below the mean value of bone turnover in healthy young women (1). This

side effects and costs.

approach identified about 90% of women from the study as responding by 12

DOI: 10.1530/endoabs.49.MTE7

weeks on treatment. The International Osteoporosis Foundation and European

Calcified Tissue Society proposed that a bone marker measurement made after 12

weeks was a good way to identify patients who are not adhering to therapy, as

non-adherence is the commonest reason for non-response (2). The meet-the-

expert session will examine the evidence for the use of bone turnover markers in

treatment monitoring and give case examples of this approach in practice.

MTE8

References

How best to manage neuroendocrine tumours? - Towards a new

1. Naylor KE, Jacques RM, Paggiosi M, Gossiel F, Peel NF, McCloskey EV,

algorithm

Walsh JS, & Eastell R. Response of bone turnover markers to three oral

Alicja Hubalewska-Dydejczyk

bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study.

Poland.

Osteoporosis International 2016 27 21-31.

2. Diez-Perez A, Naylor KE, Abrahamsen B, Agnusdei D, Brandi ML, Cooper C,

During the last couple of years an essential increase of newly diagnosed NENs has

Dennison E, Eriksen EF, Gold DT, Guan˜abens N, et al. Recommendations for the

been observed, however it should be underlined that many cases represent new

screening of adherence to oral bisphosphonates. Osteoporosis International 2017

challenges for the medical staff. Development of personalized approach to NEN

28 767-774.

patients on the basis of knowledge rapidly coming from genetic/molecular

DOI: 10.1530/endoabs.49.MTE5

research, improvement of biochemical/imaging diagnostic methods and

availability of more efficient therapeutic options, means that existing guidelines

are still being changed. However, the questions: ‘what of the future hold for

NEN?’ and ‘how will future achievements influence the new algorithm?’ remain

open. In the majority of patients the overall prognosis depends on the grade (G)

MTE6

and stage (TNM) of the tumour. Recently proposed classification of NENs divides

How best to utilise technology in diabetes?

additionally G3 NENs into NET G3a and G3b neuroendocrine cancers. Ki-67 is

Hans DeVries

currently the main prognostic index which drives the management of all NENs,

The Netherlands.

nevertheless it should be stressed that very often patient outcomes are difficult to

foresee and the lack of response to therapeutic treatment regiments remains

unpredictable so the identification of other prognostic factors would be of great

More and more devices are becoming available for people with diabetes. Should

help and it would make diagnostic and therapeutic decisions more appropriate. At

you advise your patients to use a pedometer? How can insulin pumps be of help?

present chromogranin A, urinary 5-HIAA and tumour specific hormones in

An insulin pump is the best way to accommodate the changing insulin needs over

secreting NENs are widely used as biomarkers. One should bear in mind that

the 24 hours of the day and gives one the opportunity to temporarily stop insulin

surgery is the only possible curative method in NENs however, half of the patients

administration in case of unanticipated exercise, which is impossible when using

have metastases at presentation and unknown primary focus can also be

injection therapy. Trials have mainly been done in Type 1 diabetes, but a recent

challenging. Therefore, the development of fast and accurate imaging procedures

trial also shows beneficial effects in a selected group of people with Type 2

(endoscopies, USG, CT/MRI and the implementation of the different radiolabelled

diabetes. The evidence for Continuous Glucose Monitors Continuous has recently

compounds targeting various membrane/intracellular receptors/metabolic

been brought to higher level, both for insulin pump and injection therapy users.

pathways (PET/SPECT-CT/MRI) is necessary. Antiproliferative therapy with

Both a lower HbA1c and less severe hypoglycemia have now convincingly been

SSA, TKI, PRRT and cytotoxic therapy should be given rather as sequential

shown in people with Type 1 diabetes. The role of continuous glucose monitoring

monotherapy than a combination one. Based on clinical cases of patients with

in diabetic pregnancy on the other hand is unclear. The newest kid on the block is

NENs in different locations and at a different stage of the disease the different

Flash Glucose Monitoring, for which the evidence is mixed and scarce, but it does

diagnostic/therapeutic options will be discussed during the Meeting.

herald the end of finger pricks. And how are we going to implement the holy grail

of diabetes technology, the artificial pancreas or closed loop? A first generation

DOI: 10.1530/endoabs.49.MTE8

closed loop is now on the market in the US, EU to follow early 2018. What can it

do and what not? Together we will cover a number of the above questions in an

interactive way.

DOI: 10.1530/endoabs.49.MTE6

MTE9

Sarcopenia - why should we care?

Franz Jakob

MTE7

When and which treatment to use in Graves disease?

Tomasz Bednarczuk

Abstract Unavailable.

Poland.

Graves’ disease (GD) is a heterogeneous autoimmune disorder affecting, with

varying degrees of severity, the thyroid, eyes and skin. GD is the most common

cause of hyperthyroidism. The incidence peaks between 30 and 50 years of age,

but people may be affected at any age. Hyperthyroidism is caused by

autoantibodies stimulating the TSH receptor on thyroid cells. The severity of

thyrotoxicosis in GD is variable and the response to anti-thyroid drugs is difficult

MTE10

to predict. Graves’ orbitopathy

(GO) is the most common and serious

Contraception in women with obesity, metabolic syndrome and diabetes

extrathyroidal manifestation of GD, significantly impairing the quality of life of

Phillippe Bouchard

affected patients. Clinically apparent orbitopathy occurs in 25%-50% of patients.

France.

Pretibial myxedema and acropachy are much less common, occurring in less than

2% of patients. The reasons for this variation in the clinical presentation of GD are

Abstract Unavailable.

largely unclear. There are three treatment options for Graves’ hyperthyroidism:

(1) blocking of hormone synthesis by antithyroid drugs (ATD), (2) destruction of

the thyroid by radioactive iodine (RAI) and (3) partial or total surgical ablation of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

MTE11

been approved for advanced thyroid cancers either from follicular or

parafollicular origin. A judicious use of different treatment modalities in

Drug induced osteoporosis

advanced thyroid carcinoma may improve patients’ outcome and prolong

Gherardo Mazziotti

survival. Illustrative cases of some advanced thyroid cancer patients will be

Italy.

presented and discussed in this MTE session.

DOI: 10.1530/endoabs.49.MTE14

Abstract Unavailable.

MTE15

Gaucher disease: interdisciplinary management

Milan Patakov

MTE12

Serbia.

A modern approach for treatment PCOS

Hector Escobar-Morreale

Gaucher disease (GD) is a rare, genetic, autosomal recessive lysosomal storage

Spain.

disease with multi-system manifestations caused by a deficiency of the lysosomal

enzyme glucocerebrosidase, which leads to an accumulation of its substrate

glucosylceramide (glucocerebroside) in macrophages of various tissues with an

Abstract Unavailable.

inflammatory response and a release of cytokines. In general population its

incidence is approximately 1/40 000 to 1/60 000, rising to 1/800 in Ashkenazi

Jews. Clinical features comprise cytopenias, splenomegaly, hepatomegaly, and

bone lesions. Non-neuronopathic type-1

Gaucher disease, which affects the

majority of patients (90% in Europe and USA), is characterized by visceral

effects, whereas neuronopathic types 2 and 3 are dominantly associated with

neurological impairment. The diagnosis of GD can be confirmed by the deficient

MTE13

acid glucocerebrosidase activity in peripheral blood leukocytes. Patients with

What can new insulins provide for management of diabetes?

type 1 GD, and even carriers of one gene mutation have predisposition to develop

Jean François Gautier

Parkinson’s disease, and there is increased risk of some neoplasia in GD patients.

France.

Disease-specific treatment of type

GD consists of intravenous enzyme

replacement therapy (ERT) with one of the available enzymes (imiglucerase,

velaglucerase, or taliglucerase) or oraly administered substrate reduction therapy

The major abnormality in type 1 diabetes is insulin deficiency. Type 2 diabetes is

(SRT) with inhibitors of glucosylceramide biosynthesis (miglustat or eliglustat).

also characterized by an insulin secretory defect so that many patients are on

Currently there is no treatment for type 2 disease which is lethal early in the life.

insulin therapy. Methods of replacing insulin have improved throughout the

decades, but there are still limiting factors that prevent the achievement of a better

DOI: 10.1530/endoabs.49.MTE15

HbA1c levels such as hypoglycaemic events and glycaemic variability, weight

gain and fatty liver. Additionally, most patients wish to do less insulin injections

and less blood glucose self-monitoring! New insulins and newer delivery systems

are being developed that can improve some of the limitations of current insulins

or make the delivery of insulins more acceptable for some patients. Extending the

MTE16

duration of action of basal insulins (glargine U300, Insulin degludec, PEGylated

New treatment approaches in dyslipidemia

insulin Lispro) may have advantages in reducing risk of hypoglycemia (and

Luis Masana

especially nocturnal hypoglycemia) and weight gain. PEGylated insulin Lispro is

no more in development for safety reasons (high triglycerides and liver enzymes)

The introduction of PCSK9 inhibitors has changed the paradigm of dyslipidemia

and there is still no head-to-head comparison between glargine 300 U/ml and

treatment. These monoclonal antibodies produce an incremental LDL reduction

degludec. Shortening the peak of fast-acting insulins in order to mimic the

of about 60% add-on current therapy. Achieving LDL concentrations below

physiological first phase insulin secretion (bioD-090, rHuPH20, Ultra-fast-acting

40 mg/dl is usual. The recent publication on the effect of very low LDL

insulin aspart, BioChaperone lyspro) may also have advantages. However, peer-

concentrations on atherosclerotic plaque burden

(Glagov study) and on

reviewed evidence to date remains scarce. Biosimilars are developed to minimize

cardiovascular outcomes (Fourier and Spire) show the impact of this therapy in

insulin cost but do not bring something new for the patients. Combination of new

cardiovascular prevention. In the other hand these treatments seem to be pretty

long acting insulins with a short acting insulin or with a GLP-1 analogue are

safe. Ebbinhouse study has demonstrated no impact on neurocognitive function.

available in some countries. These combinations reduce the number of injections.

Price of therapy is the main limiting factors and several scientific societies have

Different delivery systems may make insulin more acceptable to patients.

issued recommendation for use. The aim of this meeting is discussing about the

Whether these innovations permit a better glycemic control will be discussed.

new approaches of dyslipidemia therapy.

Lastly, we will see whether ‘smart’ insulin, that is glucose-responsive insulin, the

DOI: 10.1530/endoabs.49.MTE16

Holy Grail promise, will be available in the next future.

DOI: 10.1530/endoabs.49.MTE13

MTNE1

A paediatric perspective of endocrine late complications following

MTE14

childhood cancer

Thyroid carcinoma: complicated cases

Tanya Urquhart

Valeriano Leite

UK.

Portugal.

Dramatic improvements in cancer survival over the past four decades means that

Thyroid neoplasias show a wide range of biological behaviours from indolent to

greater than 80% of children diagnosed with cancer can expect to survive for

highly aggressive, invasive and metastatic cancers. The great majority of thyroid

more than five years. For some cancers, such as acute lymphoblastic leukaemia

carcinomas are successfully treated with surgery, radioactive iodine and TSH

and Hodgkin’s disease, cure rates exceed 90%. Currently, there are over 26000

suppressive therapy. However, a subset of tumors can behave aggressively, with

young adults living in the UK,

600 000 across France, Italy, Switzerland,

distant metastasis and/or local invasion. These patients have a poor prognosis and

Netherlands and the Nordic countries and 363 000 in the US, who are survivors of

a shorter survival, remaining a challenging task in treatment options. Cytotoxic

childhood cancer (CCS). A late effect (LE) is the term used to describe any

chemotherapy has only limited effect, without clear evidence that benefit

physical, psychological or social consequence of the disease itself or the disease

outweighs risk of toxicity. Radiotherapy is an option for surgically unresectable

treatment. The consequence of cytotoxic effects on maturing tissues may only

neck recurrences and for bone and brain metastases. Recently, interest rose on

become apparent many years following completion of treatment and with

tyrosine kinase inhibitors (TKI) and, currently, there are several TKIs that have

subsequent development, hence the term LE. Treatment for childhood cancer

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

usually involves chemotherapy, radiotherapy

(including radiosurgery) and

MTBS1

surgery. These treatments can occur in isolation or in any combination, and can

Unravelling the role of transient receptor potential channels in

affect almost any system in the body. The most common effect of these treatments

endocrine regulation and metabolism

is on growth, endocrine function, fertility, neuropsychology and the cardiac

Thomas Gudermann

systems. Two-thirds of childhood cancer survivors will experience at least one LE

Germany.

and the endocrine system is commonly involved. Another third of patients will

develop two or more LE which may be severe or life threatening. Therefore this

session will explore the endocrinopathies associated with the treatment for cancer

Abstract Unavailable.

in childhood using case studies to provide examples from practice. Knowledge of

oncology and endocrinology are paramount for nurse specialists working with this

patient cohort to ensure accurate education for young people about their past

treatment and its implications for their future health. Transition will also be

considered as these young people grow, develop and require continuing care from

adult healthcare professionals.

MTBS2

DOI: 10.1530/endoabs.49.MTNE1

Regulation and dysregulation of appetite and satiety

Patricia Iozzo

Italy.

The modulation of appetite, satiation and food intake stems from the interplay of

central mechanisms of homeostasis, hedonism and cognitive control, receiving

and integrating information on energy balance and feeding status of the body from

peripheral organs, including dietary and gut-related signals. Obesity is a

phenotype, likely resulting from the dysregulation of one or more of the above

mechanisms. Different mechanisms may prevail in different people, though

leading to a similar phenotype. The recognition of such diversity would offer

opportunities for personalized treatment. This lecture will present data from a

study conducted in well characterized overweight women, undergoing brain

imaging of glucose metabolism to detect cerebral reactions to sensory food

stimuli. The study suggests that women with food addictive behavior have a

specific pattern of activation, which implicates cognitive control and diet-related

factors (hormones, substrates, and possibly microbiota) in their food seeking

MTNE2

behavior. This hypothesis is supported by the characterization of feeding behavior

Providing nursing care for the adult patient with endocrine late effects

and brain and brown adipose tissue (BAT) metabolism in mice models of

of cancer treatment

neurodegenerative disease and/or high-fat feeding, also in combination with

Cecilia Follin

intranasal insulin therapy. In order to better define the sequence of events linking

Sweden.

brain function and feeding behavior, studies in the offspring of obese mothers are

addressed, since maternal obesity represents a preventable condition, in which the

factors above are affected since early life in the offspring. Results in humans, and

Survival rates of childhood cancer have improved markedly and today more than

animal models will be presented. Cumulatively, our studies suggest that a

80% of those diagnosed with a pediatric malignancy will become

5-year

hypermetabolic brain, deriving from metabolic disturbances or high-fat dietary

survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at

exposure may be an early detrimental factor, and a hypometabolic brain reflecting

particularly high risk for long-term morbidity, such as endocrine insufficiencies,

neuronal loss may enhance food intake, but also BAT browning. Substrates,

metabolic complications and cardiovascular morbidity. Deficiencies of one or

hormones and gut microbes can promote a vicious cycle.

more anterior pituitary hormones have been described following therapeutic CRT

for primary brain tumours, nasopharyngeal tumours, and following prophylactic

DOI: 10.1530/endoabs.49.MTBS2

CRT for childhood acute lymphoblastic leukemia

(ALL). Studies have

consistently shown a strong correlation between the total radiation dose and the

development of pituitary deficits. Further, age at treatment and also time since

treatment has strong implications on pituitary hormone deficiencies. Studies have

shown that childhood cancer survivors

(CCS) need information regarding

psychosocial support and social advocacy. Thus, the challenge is to guide the

MTBS3

survivors through the potential late complications and offer care designed to meet

MicroRNAs and the regulation of glucose and lipid metabolism

their specific needs in order to optimise their quality of life. Information about late

Markus Stoffel

complications is essential in order to achieve an independent life and to engage in

Switzerland.

healthy behaviour, such as regular physical activity. Thus, having a holistic

approach, tailored to their specific needs is crucial for their future well-being and

quality of life.

Abstract Unavailable.

DOI: 10.1530/endoabs.49.MTNE2

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

N1.1

as envisioned future directions. At the conclusion of this session participants will

be able to:

Clinical practice overlap and seamless care - diagnosis and

† describe the interrelationship between hypogonadism and MetS/T2DM

management of hypothyroidism in patients with diabetes mellitus

† identify those patients who warrant screening for androgen deficiency

Elena Shelestova

† recognize barriers to providing integrated care for these patients

Today diabetes (DM) is one of the largest global health emergencies. Each year a

† examine how their nursing care for these patients may be improved

large number people live with this condition. Currently there are more than 422

DOI: 10.1530/endoabs.49.N1.2

mln people with DM worldwide. DM is one of the major public health problems

in Georgia. Number of people with DM is on the rise, though no exact statistical

data for Georgia exist. Diabetes Atlas (International Diabetes Federation, 2015)

gives diabetes prevalence for Georgia of 7.9%, though these data are extrapolated

from other countries. On the other hand, hypothyroidism (HOT) is believed to be

a common health issue worldwide. The prevalence of HOT in the developed

world is about 4-5%, and the prevalence of subclinical HOT is about 4-15%.

N1.3

Both HOT and subclinical HOT are thought to be risk factors for T2DM

Clinical practice overlap and seamless care - challenges in the

development. In our patients approximately 30% of women and 15% of men have

management of patients with Cushing’s syndrome and diabetes

both conditions. Prevalence of both conditions increases with the age of the

Mies Kerstens

patients (age 35-74 years, prevalence range 7-5%).

The Netherlands.

Materials and methods

Herein, 2 clinical cases (coexisting T2DM and HOT) are discussed. Both patients

(pt) were diagnosed and are managed at the National Centre for Diabetes

This lecture focuses on, a patient with Cushing’s syndrome cased by bilateral

Research. Case #1 - pt. E.G., 49 years old, female. T2DM since 2008, HOT -

adrenal hyperplasia. After adrenal surgery, there are major challenges in the care

since 2015. Pt. was treated with oral hypoglycaemic agents (OHAs) - SU and

for this patient, that will be addressed: challenges in medical treatment (cortisol

Metformin (Met), in 2017 pt. was transferred to DPP-4 and Met. DM control is

withdrawal and change of medication in hypertension en diabetes mellitus) as

satisfactory. In 2015 pt addressed the Centre with typical signs and symptoms -

well as challenges in coaching (misconceptions in diabetes mellitus treatment,

weight gain, dyspeptic symptoms, cognitive impairment, constipation. Ultra-

fears, educational needs with respect to hypercortisolisme and hypocortisolisme,

sound examination was performed and thyroid hormones (TSH, F₄, anti-TPO)

withdrawal complains).

were tested. L-thyroxine therapy was initiated (50 mg, then elevated to 100 mg).

DOI: 10.1530/endoabs.49.N1.3

Since treatment initiation pt. condition is satisfactory, clinical and laboratory tests

have improved. Pt is control every 3 months. Prescribed treatment is continued,

Case # - pt. K.N., 65 years old, female, HOT and goiter with thyroid nodules (no

biopsy performed) were diagnosed in 2010. Treatment with L-thyroxine was

initiated. No follow-up was carried out though the drug (50 mg) was used

regularly. In 2017 pt. came to our Centre for the 1-st time. Ultrasound of the

thyroid gland and hormone tests was performed that revealed thyroid nodules

(TSH was within the n range). Nodule biopsy was carried out, colloid goiter was

N1.4

diagnosed. Pt had following DM risk factors - family history of DM, obesity,

Clinical practice overlap and seamless care - at risk of two endocrine

arterial hypertension, HOT. Thus, she was screened for DM. HbA1c was 7.0%

emergencies: the patient with type 1 diabetes and Addison’s disease

indicating to T2DM. Met. (500 mg) was initiate. Treatment with L-thyroxine at

Sofia Sjoberg

selected dose is continued. Diet and physical activity recommendations were

Sweden.

selected individually. At present both pts are regularly followed-up (every 3

months). Doses and treatment are adjusted based on the results achieved.

Patients diagnosed with Addison’s disease and diabetes mellitus type1, has a rare

Conclusion

combination of two autoimmune conditions. Two diagnosis that requires a great

Combination of the conditions is globally widely spread, it needs serious

deal of self-care. Patients have a potential risk to induce endocrine emergencies

attention, knowledge and experience to manage. Proper management permits pts

such as diabetic hypoglycemia, adrenal crisis and diabetic ketoacidosis. The lack

to live long and productive life and avoid complications caused by the conditions.

of lifesaving hormones can put the patient in potential life threatening situations.

DOI: 10.1530/endoabs.49.N1.1

I’ll share my experience in meeting these patients. Brief physiology how the lack

of hormones affects the glucose metabolism and what aid the patient need to

handle the two disorders in daily life.

DOI: 10.1530/endoabs.49.N1.4

N1.2

Clinical practice overlap and seamless care - links between

hypogonadism, the metabolic syndrome and type 2 diabetes

N2.1

Andrew Dwyer

Nurses professional development and networking session - obstructive

Switzerland.

sleep apnea and comorbidities in patients with pituitary adenomas

Christine Yedinak

USA.

There is a bi-directional relationship between hypogonadism and type 2 diabetes

and the metabolic syndrome (T2DM/MetS). Studies show that up to 50% of men

with MetS/T2DM have testosterone deficiency. Moreover, both hypogonadism

Short sleep duration and insomnia have been linked to higher risk of

and MetS confer increased health risk for morbidity and mortality. Men with

cardiovascular disease and CVD related mortality. Likewise, obstructive sleep

MetS are twice as likely to develop cardiovascular disease and have a fivefold

apnea has been shown to confer a higher cardiovascular risk and is reported to be

higher risk for developing T2DM. Notably, the inverse relationship between

associated with 52-70% of acute myocardial infarctions and strokes. Hyperten-

testosterone and MetS is consistently observed across racial and ethnic groups.

sion (HTN), diabetes (DM), weight gain, sleepiness, fatigue and depression have

Therefore, in the setting of ever increasing obesity rates, the relationship between

all been correlated with obstructive sleep apnea (OSA). Patients with pituitary

the reproductive endocrine axis and metabolism warrants renewed attention.

adenomas (PA), particularly those with Cushing’s disease and acromegaly, often

Using a case-based approach, this presentation will provide an overview of the

present with reported sleep dysfunction, fatigue and metabolic risk factors,

pathophysiologic basis for the relationship between hypogonadism and

diabetes, hypertension and cardiovascular disease and depression. The prevalence

MetS/T2DM. Male patients may be trapped in the vicious cycle of

of sleep apnea in patients with pituitary hypersecretion at diagnosis has not been

hypogonadism-obesity-insulin resistance. We will review an evidence-based

clearly quantified in patients as it may not be recognized and may go undiagnosed

approach to the patient including the appropriate evaluation and treatment based

at the time of presentation. Additionally, the correlation with diabetes and other

on existing guidelines and recommendations. This presentation will have a

cardiovascular risk factors is not clear in these disorders. There is little data

particular focus on the role of the endocrine nurse in managing patients who

regarding the impact of treatment and disease remission on both OSA and

present with this confluence of endocrine disorders. Current challenges in the field

persistent risk factors. The aim of this presentation is to explore the prevalence

will be highlighted and we will touch on some yet unanswered questions as well

and correlation between sleep disturbance (SD), depression, BMI, HTN, diabetes

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Mellitus (DM), pituitary deficiencies (PD), tumor size, diagnosis and risk of OSA

N3.1

for patients with PA pre and post treatment remission. Data from one institution

Update on diet and lifestyle throughout lifespan to improve health -

will be presented.

prevalance and treatment of vitamin D deficieny in children

DOI: 10.1530/endoabs.49.N2.1

Pauline Musson

UK.

A number of factors have been associated with the apparent increase in children

with vitamin D deficiency (VDD) in developed countries: increased awareness,

N2.2

increased migration, children living with chronic illness or disabilities, effects of

Nurses professional development and networking session - utilising the

medication (e.g. glucocorticoids, anticonvulsants), use of sunscreen, changes in

competence framework to develop the role of endocrine nurses in

lifestyles and a rise in childhood obesity. The clinical features of VDD vary with

adrenal insufficiency

age and degree of deficiency and importantly, calcium deficiency is now

Janina Kirchner

recognized as a key factor in symptomatic VDD. At presentation, children may be

Germany.

asymptomatic or, have musculoskeletal pain; and in severe cases hypocalcaemic

seizures, rickets and life threatening cardiomyopathy may occur. Evaluation of

children should include careful assessment of dietary intake, previous medical

The competence of endocrine nurse in the treatment of adrenal insufficiency (AI)

history, medication review

(including use of complementary alternative

is defined by the competence framework. Here is distinguished into Competent,

medicines), growth and puberty, and systemic enquiry of symptoms suggestive

proficient and expert. In these points, the nurse’s knowledge is presented and

of malabsorption. Biochemical investigations are merited in symptomatic cases

gives a good overview of already acquired knowledge and things to be learned.

and there are important rare diagnoses that should be considered when

With the acquired knowledge the endocrine nurse is intended to treat, train and

interpreting results. There are a variety of treatment regimens for VDD. Typically

support patients with AI as far as possible. Due to differences in the health

treatment is with cholecalciferol, administered in daily, weekly, monthly or 12

systems of the countries in Europe, not all approaches are possible. Here the

weekly doses. Oral doses are considered as effective as intramuscular injections in

example of Germany is shown how patients with AI are provided with a national

children with normal intestinal absorption. Potential side effects from treatment

training program and the competence framework is also applied.

should be communicated to the family and are rare. Calcium supplements should

DOI: 10.1530/endoabs.49.N2.2

be considered in those with inadequate dietary intake. The family should be made

aware of the reasons for intervening, the differences between treatment versus

supplement doses of vitamin D, and how to optimize diet and adverse lifestyle

factors. Some licensed products are not palatable for children and achieving

adherence can be challenging. Poor medicine adherence may be further

N2.3

aggravated by confusion regarding the doses required and inconsistent

information given to families by health care professionals. I will review the

Nurses professional development and networking session - hybrid

contemporary multidisciplinary approach to the child presenting with vitamin D

training of nurses in/for the endocrinology; train the trainer with help

deficiency with illustrative clinical cases.

of e-learning modules

Johan Beun

DOI: 10.1530/endoabs.49.N3.1

The Netherlands.

Adrenal insufficiency is a rare adrenal disorder that can be made more

complicated by an adrenal crisis even to a life-threatening situation. An adrenal

crisis occurs when the body has a shortage of the hormone cortisol. If the patient

does not receive the correct treatment an adrenal crisis can be fatal. This can be

N3.2

avoided by correctly and carefully following the ‘stress instructions’ (also known

Update on diet and lifestyle throughout lifespan to improve health -

‘sick day rules’). A significant percentage of patients have insufficient

sexual hormones and bone, a close link throughout lifespan

knowledge of these stress instructions or are not able to put them into practice

Georgios Papadakis

themselves. In addition, it has become evident that the stress instructions vary

Switzerland.

between the different hospitals. For that reason, AdrenalNET has drawn up

uniform stress instructions. These form part of the Quality of Care Standard for

Adrenal Disorders, which sets out quality criteria

(as applicable in the

Bone health is increasingly recognized as a crucial factor for quality of life.

Netherlands) for the care of patients with adrenal insufficiency. One important

Osteoporosis, defined as bone impairment leading to an increased risk of fracture,

quality criterion for the proper care of patients with adrenal insufficiency is that

is an important source of morbidity and even mortality in later life. Both male and

the hospital must have a nurse who has successfully completed this training

female achieve the peak bone mass at around the age of 25 years. This peak is

course.

significantly lower in case of puberty and/or growth disorders, thus increasing the

Objective

risk of osteoporosis later in life.

The objective of this training course is to offer nurses the essential theoretical and

Discussion

practical knowledge that they need if they are to provide adrenal patients with

Our Reproductive Division of Endocrinology in Lausanne University Hospital

optimum care and instruct them how to apply the stress instructions for

specializes in Congenital Hypogonadotropic Hypogonadism (CHH), a disorder

themselves. Indirectly, this will also help to promote the principle of

characterized by absent puberty and infertility due to complete or partial

co-management when patients with adrenal insufficiency find themselves in

deficiency of GnRH, the hypothalamic hormone that initiates the reproductive

stressful situations. We are, in fact, training the trainers first via e-learning

cascade. When CHH is accompanied by anosmia, it is called Kallmann syndrome

modules (4!) later one day at the university incl. a test at the end.

(KS). In our cohort of KS and CHH patients, there is an important decrease of

DOI: 10.1530/endoabs.49.N2.3

bone density, which is more significant when the disease was diagnosed late in

life, resulting in long periods without hormonal replacement. On the contrary, as

our clinical cases illustrate, when diagnosis of these rare disorders is performed

promptly and adequate treatment is followed, the patients maintain a near-normal

bone density and avoid fractures later in life. In a different approach to the relation

between bone and sexual hormones, using data from the OsteoLaus population-

N2.4

based study, a large cohort of post-menopausal women, we recently showed that

Nurses professional development and networking session - developing a

menopausal hormone treatment (MHT) is associated with enhanced bone density

European position statement for endocrine nurses providing care for

and structure. Interestingly, the bone benefit seems to persist for at least 2 years

patients with adrenal insufficiency

after its withdrawal. These results corroborate other studies outlining that in

Sofia Llahana

young postmenopausal women aged 50 to 60 years old the ratio benefit/risk is

UK.

clearly in favor of the benefits in terms of bone health, cardiovascular outcomes

and even mortality. We should reconsider MHT for recently postmenopausal

women with menopausal symptoms such as hot flushes and/or increased risk of

Abstract unavailable.

fractures. In new unpublished data, we detected that MHT users have significantly

lower visceral fat mass, an important element with potential bone and systemic

implications.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

lifestyle, pharmacological therapy, and patient education. Changes to the patient’s

Sexual hormone deficiency throughout lifespan severely impairs bone quantity

diet and lifestyle typically involve: optimizing calcium and vitamin D intake and

and quality leading to bone fragility. Increased awareness of the link between

exercise levels, cessation of smoking and reducing alcohol consumption.

bone and gonadal function is mandatory among endocrine physicians and nurses

Pharmacological therapies used to treat osteoporosis by reducing the fracture

in order to promote early diagnosis and avoid lack of treatment. The risk of bone

risk include bisphosphonates or the RANK ligand inhibitor denosumab. Nurses

morbidity later in life can be an important argument to increase patient’s

have an important role in educating patients about fracture risk, the benefits of

adherence to therapy.

lifestyle modifications for maintaining bone health and the treatment options

DOI: 10.1530/endoabs.49.N3.2

available, including side effects and the importance of adherence. In the current

Dutch osteoporosis guidelines, it is recommended that hospitals appoint a

specialised fracture nurse for the organisation and coordination of osteoporosis

care. These specialised nurses provide care relating to case finding, risk

evaluation, prevention, diagnosis, treatment and follow up. Each of these steps

is essential and an insufficient implementation can result in suboptimal fracture

N3.3

prevention. Their main area of expertise is the recognition of risk factors. These

Update on diet and lifestyle throughout lifespan to improve health -

risk factors can be related to the bone itself, a fall or the patient’s lifestyle. Some

osteoporosis and prevention of fractures: nurses can a play key role

of these factors can be influenced, some cannot. Patients need to have a good

Marsha Van Ooswaard

understanding of their diagnosis and fracture risk to make informed choices with

The Netherlands

regard to pharmacological treatment and/or lifestyle change.

DOI: 10.1530/endoabs.49.N3.3

Treatment of osteoporosis is all about prevention of fractures. It relies on a

combination of approaches, including adjustments to the patient’s diet and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Adrenal - Basic & Clinical

EZH2 in the control of stress progenitors homeostasis through WT1 and GATA4

and adrenal cortex zonation, which rely on a novel interaction between EZH2 and

OC1.1

PKA signalling pathway.

High resolution tissue mass spectrometry imaging: a new tool for

DOI: 10.1530/endoabs.49.OC1.2

identification of prognostic markers in adrenocortical carcinoma

Thomas Kunzke¹, Na Sun¹, Silviu Sbiera^2,3, Vanessa Wild³,

Michaela Aichler¹, Cristina Ronchi², Nicolas Schlegel²,

Andreas Rosenwald³, Martin Fassnacht^2,3, Axel Walch¹ &

Matthias Kroiss^2,3

¹Helmholtz-Center Munich, Munich, Germany;²University Hospital

OC1.3

Wurzburg, Wurzburg, Germany;³University of Wurzburg, Wurzburg,

Steroid metabolomics for accurate and rapid diagnosis of inborn

Germany.

steroidogenic disorders

Elizabeth Baranowski^1,2, Kerstin Bunte^3,4, Cedric H L Shackleton¹,

Angela E Taylor^1,2, Beverley A Hughes¹, Michael Biehl³, Peter Tino^1,4,

Adrenocortical carcinoma (ACC) is an orphan tumor entity the pathogenesis of

Tulay Guran⁵ & Wiebke Arlt^1,2

which is poorly understood. In advanced tumour stages, prognosis is unfavorable,

¹Institute of Metabolism and Systems Research, University of Birmingham,

but biomarkers for early diagnosis are lacking. MALDI-Mass Spectrometry

Birmingham, UK;²Centre for Endocrinology, Diabetes and Metabolism,

Imaging (MALDI-MSI) enables semi-quantitative detection of a broad spectrum

Birmingham Health Partners, Birmingham, UK;³Johann Bernoulli Institute

of analytes including endogenous cell metabolites in tissue sections. MALDI-MSI

for Mathematics and Computer Science, University of Groningen,

was used as a discovery approach to analyse tissue specimens of 72 ACC patients

Groningen, The Netherlands;⁴School of Computer Science, University of

in FFPE tissue arranged in tissue microarrays to identify pathways of

Birmingham, Birmingham, UK;⁵Department of Pediatric Endocrinology

pathophysiological relevance and histologic markers related to patient prognosis.

and Diabetes, Marmara University, Istanbul, Turkey.

We focused on steroid hormones and their metabolites which might also serve as

tumour-derived blood biomarkers in the future. 3843 individual endogenous m/z

species were obtained of which five were identified as known components of

Background

steroid hormone synthesis and metabolism. 2/5 steroid hormone metabolites

Urinary steroid metabolite profiling is an accurate reflection of adrenal and

showed differential abundance between ACC samples. Their low abundance in 5

gonadal steroid output and metabolism in peripheral target cells of steroid action.

and 6 of the 72 ACC samples was associated with poor overall survival in Kaplan-

Measurement of steroid metabolite excretion by gas chromatography--mass

Meier analyses (Log rank PZ0.0030 and 0.0045, respectively). Based on the type

spectrometry

(GC-MS) is considered reference standard for biochemical

of the steroid hormone modification present, mass spectra were screened for

diagnosis of steroidogenic disorders. However, performance of GC-MS analysis

related m/z species. An unusual steroid hormone metabolite (M) was identified

and interpretation of the resulting data requires significant expertise and age- and

and validated by tandem mass spectrometry. After multivariable adjustment for

sex-specific reference ranges. Here we developed novel computational

age, tumor stage and sex by using the Cox proportional hazards model, presence

approaches for rapid interpretation of GC-MS data for diagnosis of inborn

of M was associated with poor overall survival (HR 4.54, 95%CI 1.56-13.22;

steroidogenic disorders

PZ0.0056). By using immunohistochemistry we analysed protein expression of

Methods

two related enzymes which was correlated with metabolites abundance. In

We analysed the urinary steroid metabolome by GC-MS in 829 healthy controls

conclusion, we demonstrated the utility of MALDI-MSI in detecting and

(302 neonates and infants, 167 children and 360 adults) and 118 untreated patients

identifying small molecule markers in FFPE tissue samples of ACC. A limited

with genetically confirmed inborn disorders

(21-hydroxylase deficiency,

number of compounds related to steroidogenesis with strong prognostic value

17-hydroxylase deficiency, POR deficiency,

11b-hydroxylase deficiency,

could be detected. One steroid hormone metabolite and related enzymes were of

3b-HSD2 deficiency, 17b-HSD3 deficiency, 5a-reductase type 2 deficiency,

outstanding prognostic value. The potential of these metabolites as blood

cytochrome b5 deficiency). We calculated age-related normative values for

biomarkers remains to be investigated.

established metabolite ratios representing distinct enzymatic functions. We

DOI: 10.1530/endoabs.49.OC1.1

developed a novel interpretable machine learning technique, Angle Learning

Vector Quantisation (ALVQ), which looks at all possible metabolite ratios,

computationally reduces these to the most relevant for discrimination, and

differentiates disease states by comparison to a representative prototype. The

method runs independent of sex and age information, units of measurement and

method of urine collection.

OC1.2

Results

EZH2: a master regulator of adrenal cortex homeostasis and zonation

Conventional biochemical ratios had

100% sensitivity but only very poor

Mickael Mathieu¹, Coralie Drelon², Houda Tabbal¹, Stéphanie Rodriguez¹,

specificity. By contrast, ALVQ predicted ‘affected urine’ vs ‘healthy urine’ with

Amandine Septier¹, Annabel Berthon³, David Sainte-Catherine¹,

100% sensitivity and 97% specificity. For our three most prevalent conditions

David Breault⁴ & Antoine Martinez¹

(PORD, SRD5A2 and CYP21A2), the specific condition was identified correctly

¹Laboratoire GReD, Clermont-Ferrand, France;²Albert Einstein College of

in 96% of cases.

Medicine, Bronx, New York, USA;³National Institutes of Health, Bethesda,

Conclusion

Maryland, USA;⁴Harvard Stem Cell Institute, Boston, Massachusetts, USA.

We developed a novel Steroid Metabolomics approach to automatically diagnose

inborn steroidogenic disorders with very high sensitivity and specificity, superior

to current methods, and with high potential for implementation in routine clinical

In adult mice the adrenal cortex is divided, in two distinct functional zones,

care.

outermost zona glomerulosa

(ZG) and innermost zona fasciculata

(ZF),

encapsulated by a thin layer of mesenchymal cells (capsule). The adrenal cortex

DOI: 10.1530/endoabs.49.OC1.3

undergoes constant centripetal cell renewal, reliying on recruitment of

progenitors located within an outer cortex niche. Progenitors initially differentiate

as ZG cells and undergo lineage conversion to ZF as they move within the cortex.

This relies on a subtle balance and trans-inhibition between WNT and PKA

signalling pathways. Epigenetic histone modifiers are prototypical factors that

OC1.4

play essential roles from embryonic development to carcinogenesis. We have

The epidemiology of pheochromocytoma: increasing incidence and

recently shown that the histone methyl-transferase EZH2 is overexpressed in

changing clinical presentation. A population-based retrospective study

adrenal cortex carcinomas where is it associated with poor prognosis and tumour

1977-2015

aggressiveness. In order to understand EZH2 function in adrenal physiology, we

Andreas Ladefoged Ebbehoj^1,2, Esben Sondergaard¹, Christian Trolle¹,

have developed a mouse model of EZH2 inactivation relying on a floxed allele of

Kirstine Stochholm¹ & Per Logstrup Poulsen¹

EZH2 and the Sf1:Cre driver (EZH2KO). Our analyses show adrenal hypoplasia

¹Department of Endocrinology and Internal Medicine, Aarhus University

and primary corticosterone insufficiency, associated with expansion of ZG at the

Hospital, Aarhus, Denmark;²Department of Clinical Medicine, Aarhus

expense of ZF and aberrant mixed ZG/ZF differentiation. Consistent with the role

University, Aarhus, Denmark.

of PKA and WNT signalling in establishment and maintenance of zonation, WNT

pathway is increased whereas PKA activity is decreased in EZH2KO adrenals. In

addition to zonation defects, EZH2KO present abnormal accumulation of ‘stress

Pheochromocytoma is a rare disease but frequently poses a diagnostic dilemma

progenitors’. Recruitment of these particular progenitors is under control of WT1

due to the unspecific symptoms and its potentially life-threatening nature. There is

and GATA4. Our in vivo ChIP and expression data show that these two

a perception of an increase in the incidence of pheocromocytomas in recent years,

transcription factors are direct targets of the inhibitory action of EZH2 in the

but no data on time trends exist. We obtained data from The Danish National

adrenal. Altogether, these data suggest completely unanticipated functions of

Registry of Patients, The Danish Registry of Causes of Death, and The National

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Pathology Registry for all persons registered with pheochromocytoma in 1977-

¹Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil;²Postgraduation

2015. Health records were reviewed to validate the diagnosis for all patients in the

Program in Medical Sciences: Endocrinology, Faculdade de Medicina,

Northern and Central Regions of Denmark (population 1.75 million). Incidence

Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;³Instituto

rates were calculated using Poisson regression and time trends were analysed with

da Crianc¸a com Diabetes, Porto Alegre, Brazil;4Institute of Informatics,

year as a continuous explanatory variable. As incidence increased significantly in

Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

2007-2015, we compared the clinical characteristics of patients diagnosed in this

time interval with patients diagnosed in 1977-2006 in a secondary analysis using

the Wilcoxon-Mann-Whitney test. We identified

183

confirmed cases of

Context

pheochromocytoma. A significant increasing trend (P!0.001) was observed in

Since the exact cause of type 1 diabetes mellitus (T1DM) remains unclear, the

incidence rates from 2.06 (CI95% 1.68-2.49) per million person-years 1977-

detection of novel biomarkers is necessary to complement the information

obtained from the presence of autoantibodies together with genetic and

2006

4.65

(CI95% 3.72-5.82)

2007-2015. In

1977-2006

paroxysmal

environmental risk factors. MicroRNAs (miRNAs) are a class of small noncoding

symptoms and secondary hypertension were the primary causes leading to the

RNA molecules that negatively regulate gene expression. Changes in their

diagnosis (34 and 21%, respectively), while incidentalomas were the leading

expression were described in several pathological conditions, including

cause of diagnosis 2007-2015 (57%). Patients diagnosed 2007-2015 were older

autoimmune diseases. Circulating miRNAs are attractive biomarker candidates

(P!0.001), less symptomatic (PZ0.003) and had smaller tumours (PZ0.033),

as they can be easily collected, are stable under different storage conditions and

compared to 1977-2006. No changes were observed in duration of symptoms or

can be measured using specific assays.

level of catecholamines. The incidence of pheochromocytoma has increased

Objective

significantly in recent years, presumably due to increased use of imaging studies.

To investigate a miRNA expression profile in plasma from patients with T1DM

It is unlikely that earlier diagnosis or lead-time bias accounts for the increasing

and nondiabetic controls and suggest their targets using bioinformatics analysis.

incidence since patients are getting older. Therefore, these incidentaloma patients

Design

appear to represent a new group of pheochromocytomas not previously

Expressions of 48 miRNAs were investigated in the plasma from 33 T1DM

diagnosed. Whether surgical treatment provides a health benefit in this group

patients and 26 age-and-gender-matched controls using Stem-loop RT-PreAmp

remains unknown.

Real-time PCR and TaqMan Low Density Array cards (Thermo Scientific Inc).

DOI: 10.1530/endoabs.49.OC1.4

Five dysregulated miRNAs were chosen for validation using RT-qPCR in an

independent sample (27 T1DM patients and 14 age-and-gender-matched controls).

Results

Nine miRNAs were differentially expressed between controls and T1DM patients

with !5 years of diagnosis: 1 miRNA was downregulated (has-miR-146a-5p)

OC1.5

while 8 miRNAs were upregulated (hsa-miR-101-3p, hsa-miR-103a-3p, hsa-miR-

Diagnostic accuracy of three confirmatory tests for primary

1275, hsa-miR-146a-5p, hsa-miR-148b-3p, hsa-miR-155-5p, hsa-miR-200a-3p,

aldosteronism: a prospective study and systematic review

hsa-miR-210-5p and hsa-miR-21-5p) in patients with

!5 years of T1DM

Qifu Li, Ying Song, Shumin Yang & Aipin Zhang

diagnosis compared to controls. In contrast, no differences were detected between

Department of Endocrinology, Chongqing, China.

controls and T1DM patients with O5 years of diagnosis. Bioinformatics analysis

evidenced that hsa-miR-103a-3p, hsa-miR-146a-5p, hsa-miR-155-5p, hsa-miR-

200a-3p and hsa-miR-210-3p participate in pathways associated with T1DM

Background

pathogenesis, such as apoptosis, insulin and immune system.

Confirmatory tests, including saline infusion test (SIT), captopril challenge test

Conclusions

(CCT) and fludrocortisone suppression test

(FST) are commonly used for

Our data demonstrate that 9 miRNAs are differentially expressed in T1DM

diagnosis of primary aldosteronism (PA). Each test has its advantages and

patients in the first years of the diagnosis. Our study also provided novel

disadvantages, but which one should be preferentially performed is controversial.

information about biological pathways implicated in T1DM. Ongoing studies will

We aimed to evaluate the diagnostic accuracy of three tests in a prospective study.

further explore the role of these miRNAs as possible novel biomarkers for T1DM

Methods

prediction.

Five hundred and thirty-one hypertensive patients with high risk of PA were

DOI: 10.1530/endoabs.49.OC2.1

enrolled. Plasma aldosterone-renin ratio

(ARR) was used for screening.

Hypertensive patients tested positive at PA screening

(ARRR3.7 ng/dl per

mIU/ml), one in every three consecutive patient tested negative (ARR!3.7 ng/dl

per mIU/ml) and patients who tested negative but PA was strongly suspected

proceeded to three confirmatory tests. Area under receiver operator characteristics

curve (AUC), sensitivity and specificity were calculated. A systematic review and

meta-analysis of relevant studies were performed to place our results in context.

OC2.2

Findings

Finally,

132

patients diagnosed as PA and

104

diagnosed as essential

Effectiveness of complex therapy in patients with comorbidity

hypertension completed three tests. AUC of CCT, SIT and FST were 0.97

of type 2 diabetes and essential hypertension depending on genetic

(95% CI 0.95-0.99), 0.97 (0.95-0.99) and 0.98 (0.97-0.99), respectively, when

polymorphism PPARg2

post-test plasma aldosterone concentration (PAC) was used to confirm PA. But

Anna Shalimova, Oleksandr Bilovol & Lesya Bobronnikova

AUC of CCT significantly decreased to 0.76 (0.69-0.82) if PAC suppression ratio

Kharkiv National Medical University, Kharkiv, Ukraine.

was used to confirm PA. When PAC cutoffs of SIT and FST was set at 8 ng/dl, and

CCT at 11 ng/dl, the sensitivity were 87.9%, 93.2%, 92.4% and specificity were

The aim

93.3%, 90.4%, 90.4% respectively. No significant difference of synthetic AUC,

To evaluate effectiveness of complex therapy in patients with comorbidity of type

pooled sensitivity or specificity between SIT and CCT was found in the meta-

diabetes

(DM2) and essential hypertension

(EH) depending on genetic

analysis. Only one study of FST fulfilling the criteria of the systematic review was

polymorphism peroxisome proliferator-activating receptor-g2 (PPARg2). Before

included, reporting a sensitivity of 0.87 and a specificity of 0.95.

and after 3 months of treatment we examined 145 patients with EH stage II, grade

Interpretation

and DM2 moderate, subcompensated aged 45-60 years: group 1 (71 patients)

CCT, SIT and FST has comparable diagnostic accuracy. Based on their pros and

received standart therapy

(telmisartan, indapamide, metformin, gliclazide,

cons, it is reasonable to recommend CCT as the first choice to confirm PA in

atorvastatin, acetylsalicylic acid) and group 2 (74 patients) additionally received

clinical practice. When interpreting the results of CCT, PAC post-CCT is

a-lipoic acid (a-LA). Both groups were matched for age, sex, EH stage and grade,

recommended.

the degree of compensation DM2. Methods: biochemical blood analysis,

DOI: 10.1530/endoabs.49.OC1.5

echocardiography evaluation of mitral diastolic blood flow and tissue Doppler

spectral modes, reactive hyperemia, color Doppler mapping, enzyme immu-

noassay. We conducted genotyping of Pro12Ala polymorphism of PPARg2.

Results

Patients with genotype Pro/Pro of PPARg2 had significantly higher levels of total

cholesterol, LDL, proinflammatory cytokines (TNF-a and IL-6), the values of

Diabetes Prediction and Complications

intima-media thickness and significantly lower degree of endothelium-dependent

OC2.1

vasodilatation as compared to genotype Pro12Ala/Ala12Ala. After standart

microRNA expression profile in plasma from patients with type 1

therapy in patients with EH and concomitant DM2 (in all PPARg2 genotypes)

diabetes: a case-control study and bioinformatics analysis

metabolic and hemodynamic parameters were improved. More pronounced

Tais Silveira Assmann^1,2, Mariana Recamonde-Mendoza⁴, Marcia Punales³,

dynamics was in patients with genotype Pro12Ala/Ala12Ala. Additional

Balduino Tschiedel³, Luis Henrique Canani^1,2 & Daisy Crispim^1,2

appointment of a-LA impacted more to vascular remodeling and levels of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

proinflammatory cytokines as compared to standard therapy. Decrease HbA1c

A total of 53 patients met the criteria for inclusion. They were randomly assigned

and triglyceride levels in patients with additional appointment of a-LA was

to receive multiprobiotic

‘Symbiter’

(concentrated biomass of

14 probiotic

significantly more pronounced as compared to standard therapy only in genotype

bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium)

Pro12Ala/Ala12Ala.

or placebo for 8-weeks administered as a sachet formulation in double-blind

Conclusions

treatment. The primary main outcome was the change HOMA-IR (homeostasis

Effectiveness of complex therapy in comorbidity of DM2 and EH depends on

model assessment-estimated insulin resistance) which calculated using Matthews

PPARg2 genotype. Dynamics of metabolic and hemodynamic parameters was

et al.’s equation. Secondary outcomes were the changes in glycemic control-

more pronounced in additional appointment of a-LA, especially in genotype

related parameters, anthropomorphic variables and cytokines (TNF-a, IL-1b,

Pro12Ala/Ala12Ala.

IL-6, IL-8, INF-g) levels. ANCOVA was used to assess the difference between

DOI: 10.1530/endoabs.49.OC2.2

groups.

Results

Supplementation with alive multiprobiotic for 8 weeks was associated with

significant reduction of HOMA-IR from 6.85G0.76 to 5.13G0.49 (PZ0.047),

but remained static in the placebo group (7.24G0.74 to 7.95G1.01; PZ0.573).

With respect to our secondary outcomes, HbA1c insignificant decreased by 0.09%

(PZ0.383) and 0.24% (PZ0.068) respectively in placebo and probiotics groups.

However, in probiotic responders (nZ22, patient with decrease in HOMA-IR)

OC2.3

after supplementation a significant reduction in HbA1c by 0.39% (PZ0.022) as

GLP-1 based multi-agonists-induced signaling includes profound TRP

compared to non-responders was observed. In addition, from markers of chronic

channel involvement in insulin secretion

systemic inflammatory state only TNF-a (15.8%, P!0.001), and IL-1b (14.4%,

Noushafarin Khajavi¹, Brian Finan², Oliver Kluth^3,4, Stefan Mergler⁵,

PZ0.001) and IL-6 (22.1%, PZ0.027) changes significantly after treatment with

Timo Muller², Gunnar Kleinau¹, Annette Schurmann^3,4, Matthias

probiotics.

H Tschop², Richard DiMarchi⁶, Heiko Krude¹ & Heike Biebermann¹

Conclusion

¹Institute for Experimental Pediatric Endocrinology, Charite, University-

Probiotic therapies modestly improved insulin resistance in patients with type 2

Medicine Berlin, Berlin, Germany;²Institute for Diabetes and Obesity,

diabetes. Modulation of the gut microbiota represents a new treatment for

Helmholtz Center Munich, German Research Center for Environmental

diabetes and should be tested in larger studies.

Health (GmbH) and Technical University Munich, Munich, Germany;

DOI: 10.1530/endoabs.49.OC2.4

³Department of Experimental Diabetology, German Institute of Human

Nutrition Potsdam-Rehbruecke, Nuthetal, Germany;⁴German Center for

Diabetes Research, Neuherberg, Germany;⁵Department of Ophthalmology,

Charite, University-Medicine Berlin, Berlin, Germany;⁶Department of

Chemistry, Indiana University, Bloomington, Indiana, USA.

Promiscuous multi-agonists that simultaneously activate two or three key

receptors (incretin- and/or glucagon receptor) were recently shown to improve

OC2.5

glycemic control in mice. Here we investigated the underlying mechanisms of

Urinary peptidomics for the detection of diabetic kidney disease

multi-agonists to enhance insulin secretion in murine islets and human pancreatic

Leticia A Brondani, Ariana A Soares, Angelica D’Allagnol,

b-cells. These mixed agonists display a greater potency in cAMP signaling as

Joíza L Camargo, Karina Monteiro & Sandra P Silveiro

compared to the native incretins. However, pharmacological blockade of cAMP

Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

signaling only partially inhibited the increases in insulin secretion. Therefore,

additional mechanisms independent from Gs signaling-coupled Ca^2C influx

appear to mediate insulin secretion. Here, we showed multi-agonists evoked

Background

significant increases in Ca^2C influx through activation of both voltage-dependent

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease It is

Ca^2C channels (VDCCs) and transient receptor potential channels (TRPs). These

defined by glomerular filtration rate

(GFR) impairment and/or presence of

responses were more rapid and larger after multi-agonist stimulation than those

increased urinary albumin excretion (UAE). However, these parameters are

after mono-agonists. Pharmacological blockade of TRP channels suppressed

nonspecific and somewhat delayed manifestations of renal damage. Thus, earlier

Ca^2C transients induced by multi-agonists to a greater degree than exposure to

DKD new biomarkers are strongly warranted.

VDCC blocker. TRP blockers also blunted cAMP accumulation and abolished

Objective

increases in whole-cell currents that are evoked with multi-agonists. These

To investigate the urinary peptidomics profile of type 2 diabetes mellitus (DM)

observations argue for a direct TRP channel activation by ligand-engaged incretin

patients with different stages of DKD.

receptors. Collectively, direct activation of adenylyl cyclase through GPCR/

Methods

channel constellations and concomitant rapid Ca^2C influx likely contribute to the

Casual urine samples were collected from 66 type 2 DM patients matched by age,

increases in insulin secretion induced by multi-agonists.

gender and time of diabetes duration. Urine natural occurring peptides were

DOI: 10.1530/endoabs.49.OC2.3

purified by ultrafiltration under denaturing conditions and analyzed by

LC-MS/MS. UAE was assessed by immunoturbidimetry and GFR was estimated

by CKD-EPI equation. Kruskall-wallis, Mann-Whitney and c2 tests were

performed when appropriate; Perseus software was used to perform hierarchical

clustering of significantly up- and down-regulated proteins.

Results

Type 2 DM patients (mean ageZK61.5G9.7 years; malesZ47.1%) were

stratified by the levels of albuminuria (normal (nZ27), moderately increased (MI,

OC2.4

nZ18) and severely increased (SI, nZ21)). A total of 116 urinary proteins were

Effect of alive probiotic on insulin resistance in type 2 diabetes patients:

detected by LC/-MS/MS. A distinct proteomic profile was identified in patients

randomized clinical trial

with SI albuminuria, represented by

11 proteins. When GFR values were

Nazarii Kobyliak¹, Kateryna Kondratiuk¹, Dmytro Kyriienko² &

analyzed, we observed that 13 urinary proteins differed significantly in the

Galyna Mykhalchyshyn¹

9 patients with GFR !60 ml/min per 1.73 m² when compared to 57 patients with

¹Bogomolets National Medical University, Kyiv, Ukraine;²Kyiv City

GFR R60 ml/min per 1.73 m². Among the most remarkably different urinary

Endocrinology Center, Kyiv, Ukraine.

protein profile, alpha-1 type I collagen was around 10% less expressed in SI

patients, while alpha-1 antitrypsin, plasma protease C1 inhibitor and apolipopro-

Background

tein-1 were wtwofold increased in these patients.

Probiotics have beneficial effect on obesity related disorders in animal models.

Conclusions

Despite a large number of animal data, randomized placebo-controlled trials

LC-MS/MS analysis revealed that at least 11 urinary proteins were differentially

(RCT) concluded that probiotics have a moderate effect on glycemic control-

expressed in type 2 DM patients according to DKD severity. This study confirms

related parameters. However, effect of probiotics on insulin resistance are

the previously described findings in other populations and also detected novel

inconsistent.

proteins commonly altered in patients with GFR impairment and increased

Aim

albuminuria.

In a double-blind single center RCT, effect of alive multistrain probiotic vs

DOI: 10.1530/endoabs.49.OC2.5

placebo on insulin resistance in type 2 diabetes patient were assessed.

Methods

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Receptors & Signalling

P!0.01) in Lxra/b DKO. Androgen biosynthesis genes (Cyp17a1, Hsd3b2,

Hsd17b3), triglyceride synthesis (Acsl, Acot7) as well as genes involved in

OC3.1

sphingolipid metabolism were altered correlating with lipidomic data.

Epigenetic regulation of aldosterone synthase gene, CYP11B2 by

Discussion

potassium

Our integrative approach using lipidomic analysis with mRNA transcript studies

Yoshiyu Takeda, Masashi Demura, Takashi Yoneda, Yoshimichi Takeda,

provides novel data, implicating LXRs in pathways such as sphingolipid

Mitsuhiro Kometani, Seigo Konishi & Toshitaka Sawamura

metabolism, critical for successful spermatogenesis.

Kanazawa University, Kanazawa, Japan.

DOI: 10.1530/endoabs.49.OC3.2

Purpose

We found the hypomethylation status of CYP11B2 gene in the aldosterone-

producing adenomas compared with normal adrenal glands or non-functioning

adrenal adenomas and reported that the methylation of promoter region of this

gene influenced the mRNA expression in the adrenal cells. Angiotensin II or

OC3.3

potassium regulates CYP11B2 gene expression in the adrenal cells. In order to

AKR1C3-mediated adipose androgen generation drives lipotoxicity in

clarify the acute effect of potassium on the methylation status of CYP11B2 gene,

polycystic ovary syndrome

Human adrenal cells rats were treated with potassium and the methylation status

Michael O’Reilly¹, Punith Kempegowda¹, Mark Walsh³, Angela Taylor¹,

of CYP11B2 gene in the adrenal cells was examined.

Konstantinos Manolopoulos¹, William Allwood¹, Robert Semple⁴,

Methods

Daniel Hebenstreit³, Warwick Dunn¹, Jeremy Tomlinson² & Wiebke Arlt¹

H295R cells were treated with potassium for 28 days. The gene expression of

¹University of Birmingham, Birmingham, UK;²University of Oxford,

CYP11B2 was measured by real time quantitative PCR in the adrenal cells. ChiP

Oxford, UK;³University of Warwick, Coventry, UK;⁴University of

assay and methylation activity were measured. Isolated DNAs from adrenal cells

Cambridge, Cambridge, UK.

were treated with bisulfite and amplified using primers specific for the human

CYP11B2 promoter regions.

Polycystic ovary syndrome (PCOS) is prevalent metabolic disorder in women,

Results

associated with androgen excess and insulin resistance. These two major features

CYP11B2 mRNA levels were increased from 4th day to 7th day by the treatment

are closely correlated, but the direction of causality remains unclear.

with potassium. The methylation ratio was decreased from

4th day. The

Aldoketoreductase type

1C3 (AKR1C3) converts the androgen precursor

expression of CREB1 and NR4A1 were increased from 4th day. The methylation

androstenendione to testosterone (T), and is highly expressed in subcutaneous

activity was increased from 7th day. The chromatin accessibility was increased

(SC) adipose tissue. We hypothesised that adipose tissue represents an important

from 4th day to 7th day

site linking androgen activation and metabolic dysfunction in PCOS. We

Conclusions

undertook metabolic phenotyping in 10 PCOS women and 10 age- and BMI-

Aldosterone biosynthesis may be reversibly regulated by the epigenetic

matched controls. Participants underwent an oral challenge with the androgen

mechanism.

precursor DHEA, alongside adipose tissue microdialysis, with measurement of

DOI: 10.1530/endoabs.49.OC3.1

metabolic markers and adipose androgens in microdialysate fluid. Non-targeted

serum metabolome analysis was performed before and after androgen exposure.

SC adipose tissue biopsies were collected for RNA-sequencing. Complementary

in vitro experiments in primary SC adipocytes and a preadipocyte cell line were

performed to examine the effects of insulin and androgens on AKR1C3

expression and de novo lipogenesis, respectively. PCOS women had higher

adipose T (P!0.0006) and dihydrotestosterone (DHT, PZ0.01) than controls as

OC3.2

measured by liquid chromatography-tandem mass spectrometry. Non-targeted

Elucidating the role of Liver X receptors (LXRs) in the testis using lipid

serum metabolomics and adipose microdialysis revealed pro-lipogenic effects of

systems biology

androgens at baseline and after DHEA in PCOS. AKR1C3 mRNA expression was

Sheba Jarvis¹, Lee Gethings², Raffaella Gadaleta^3,1, Lord Robert Winston¹,

increased in PCOS SC adipose tissue

(PZ0.04). Transcriptional profiling

Catherine Williamson⁴ & Charlotte Bevan¹

revealed dysregulation of mitochondrial and inflammatory pathways in PCOS SC

¹Department of Surgery and Cancer, Imperial College London, Hammer-

adipose tissue. In vitro studies showed that insulin upregulates adipose AKR1C3

smith Hospital, London, UK;²Waters Corporation, Wilmslow, UK;

expression and activity, and androgens enhance adipose de novo lipogenesis.

Pharmacological inhibition of AKR1C3

decreased adipose tissue androgen

³Dipartimento Interdisciplinare di Medicina, University of Bari, Bari, Italy;

generation and androgen-mediated de novo lipogenesis. Complementary in vivo

⁴Womens Health Clinical Academic Group, Kings College London, Guys

and in vitro studies highlight that AKR1C3-mediated intra-adipose androgen

Campus, London, UK.

activation drives lipotoxicity and adverse metabolic risk in PCOS, fuelling a

vicious circle of androgen generation and insulin resistance. Selective inhibition

Introduction

of AKR1C3 holds promise as a novel therapeutic approach in PCOS.

The importance of the liver-X receptors (LXRs) in the maintenance of cholesterol

DOI: 10.1530/endoabs.49.OC3.3

homeostasis within the testis has yet to be fully characterised. By 7 months of age,

Lxra/b double knockout male mouse (Lxra/b DKO) develops sterility with

aberrations in testosterone production and lipid homeostasis. However, the

underlying testicular LXR-regulated pathways are not well understood.

Aim

The aim of this study was to further understand the importance of LXRs in the

OC3.4

testis by investigating disruption of candidate genes and networks of cellular

Treatment with thyroid hormone metabolite 3,5-T2 alters cholesterol

lipids and steroid metabolites in Lxra/b DKO mice.

and sex steroid metabolism in mouse liver

Methods

Julika Lietzow¹, Janine Golchert², Georg Homuth², Wenke Jonas³,

We used RNA-seq and quantitative mass spectrometry to study whole testicular

Claes Ohlsson⁴, Andreas Landin⁴, Matti Poutanen⁵ & Josef Kohrle¹

tissues from 6-month old Lxra/b DKO mice alongside age-matched littermate

¹Institute of Experimental Endocrinology, Charité Universitatsmedizin

controls. cDNA libraries were prepared followed by sequencing using NextSeq-

Berlin, Berlin, Germany;²Interfaculty Institute for Genetics and Functional

500. Lipid extracts from mouse testis were prepared for LC-MS analysis using

Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald,

SONAR acquisition, based on an m/z isolation range of the quadrupole. Results

Germany;³Department of Experimental Diabetology, German Institute of

were analysed using LipidMaps and Progenesis QI for normalized quantitation.

Human Nutrition, Nuthetal, Germany;⁴Institute of Medicine,

Results

The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden;

Histological assessment of testicular tissues from Lxra/b DKO mice confirmed

⁵Department of Physiology, Institute of Biomedicine, University of Turku,

abnormal seminiferous tubules, germ-cell loss and lipid deposition. Quantitative

Turku, Finland.

lipidomic analysis confirmed statistically significant differences in

53 lipid

species including triglycerides and cholesterol esters (notably 20:4 cholesteryl

ester) in the Lxra/b DKO mice. Sphingolipid species (e.g. ceramide t18:0/20:0)

Recent findings revealed

3,5-diiodo-L-thyronine

(3,5-T2) as a metabolically

were also altered. The retrieved curated targets were mapped onto KEGG

active iodothyronine affecting hepatic energy and lipid metabolism. Therefore,

pathway analysis, identifying key changes in steroid hormone biosynthesis and

3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of

sphingomyelin metabolism. RNA-seq analysis revealed

1161

differentially

obesity and its hepatic aftermath. So far only limited data exists relating to the

expressed genes (log2 fold change in gene expression of K3.49 to C2.17,

effects of 3,5-T2 on metabolism in euthyroid mammals maintained on high-fat

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

diet from the day of weaning onwards. Therefore, we performed a study in which

Furthermore, unbiased GMLVQ analysis of the urinary steroid metabolome

20-week old diet-induced obese male mice in comparison to lean animals

appears robust in differentiating healthy controls from cirrhosis and warrants

received either 3,5-T2 (2.5 mg/g body weight) or saline over a four-week period.

further exploration as a novel non-invasive biomarker tool to assess the severity

To identify new target genes and signaling mechanisms of 3,5-T2 which are

of NAFLD.

distinct from established hepatic T3

action we performed microarray-based

DOI: 10.1530/endoabs.49.OC3.5

transcriptome analyses of liver tissue. The transcriptome as well as qPCR data

demonstrated higher hepatic expression of genes involved in cholesterol

biosynthesis (e.g. Sqle 4.8-fold, Cyp51 2.8-fold, Hsd17b7 1.8-fold) and bile

acid formation (Cyp7a1 2.0-fold, Cyp39a1 2.9-fold) in obese but not in lean mice

treated with

3,5-T2. In contrast to the elevation of hepatic cholesterol

biosynthesis, serum cholesterol concentration was reduced by up to 57% with

Thyroid Disease 1

3,5-T2

administration. In addition,

3,5-T2

modulated expression of genes

OC4.1

important for sex steroid biosynthesis and inactivation (e.g. Cyp17a1 3.5-fold,

Hypothyroidism in pregnancy is associated with twin pregnancies and

Hsd17b6 -7.8-fold). GC MS/MS analysis of the hepatic sex steroid hormone

with adverse obstetric outcome: Analysis of 142,277 deliveries data

profile indicated higher progesterone and androstenedione content in livers of

from a single center

obese mice treated with 3,5-T2, whereas no such changes were observed in

Orit Barenholz-Goultschin^1,2, Rivka Farkash^1,2, Arnon Samueloff^1,2 &

3,5-T2-treated lean mice. These results suggest a diet-dependent role of 3,5-T2 in

Gabriel Munter^1,2

modulating local cholesterol as well as sex steroid biosynthesis and androgen

¹Shaare Zedek Medical Center, Jerusalem, Israel;²Hebrew University,

homeostasis in mouse liver. Such actions of thyroid hormone metabolites have

Jerusalem, Israel.

not been reported elsewhere up to date and might help to explain liver-targeting

effects of T3-receptor beta-selective ligands.

DOI: 10.1530/endoabs.49.OC3.4

Introduction

Many studies have examined maternal and fetal complication rates in treated and

untreated overt and subclinical hypothyroidism. Maternal hypothyroidism may

adversely affect the development of the fetal pituitary-thyroid axis. It has also

been reported to be closely related to adverse pregnancy outcome.

Aim

To study the prevalence and outcome of hypothyroidism in pregnancy during the

OC3.5

last decade in a high volume obstetric center in Jerusalem.

Accurate staging of non-alcoholic fatty liver disease through analysis of

Methods

the urinary steroid metabolome

A retrospective study of the obstetric database between August

2005 and

Ahmad Moolla¹, Amin Amin², Beverly Hughes², Wiebke Arlt²,

December 2015 in Shaare Zedek Medical Center, Jerusalem.

Zaki Hassan-Smith², Lorna Gilligan², Matt Armstrong³, Philip Newsome³,

Results

Tahir Shah³, Luc Van Gaal⁴, An Verrijken⁴, Sven Francque⁴, Jane Grove⁵,

During the study period there were 142,277 deliveries of singleton or twin

Neil Guha⁵, Guruprasad Aithal⁵, Ellie Barnes⁶, Michael Biehl⁷ &

pregnancies (1.9% twin deliveries). The medical files of 4042 (2.8%) deliveries

Jeremy Tomlinson¹

(group A) included a diagnosis of maternal hypothyroidism. Women giving birth

¹Oxford Centre for Diabetes, Endocrinology and Metabolism, University of

with the diagnosis of hypothyroidism were older (31.1G6 years 28.8G5.6 y.

Oxford, Oxford, UK;²Centre for Endocrinology, Diabetes & Metabolism,

P!0.0001). Gestational diabetes was more prevalent (7.3% vs 3.3%, P!0.0001)

University of Birmingham, Birmingham, UK;³Centre for Liver Research,

in group A as were hypertensive disorders (3.7% vs 2.3%, P!0.0001). Higher

University of Birmingham, Birmingham, UK;⁴University of Antwerp,

rate of assisted reproduction techniques were used in group A (8.5% vs 3.7%,

Antwerp, Belgium;⁵NIHR Nottingham Digestive Diseases Biomedical

P!0.0001). Although not previously reported, the incidence of twin pregnancies

Research Unit, Nottingham University Hospitals NHS Trust and University

was higher in group A (3.8% vs 1.8% P!0.0001) and this association remained

of Nottingham, Nottingham, UK;⁶Translational Gastroenterology Unit,

significant in a multivariate analysis with IVF as a co-variate

(OR 1.43

University of Oxford, Oxford, UK;⁷University of Groningen, Groningen,

95%CI[1.20-1.71], P!0.001). Obstetric complications including preterm

The Netherlands.

deliveries

(7.8% vs 5.2%, PO0.0001), cesarean sections (20.6% vs 11.4%,

PO0.0001), any obstetric hemorrhage and prolonged hospitalization were more

frequent in group A. The incidence of adverse neonatal outcome including low

Introduction

birth weight (7.3% vs 5.4%, PO0.0001) and NICU admission (5.1% vs 3.6%,

Non-alcoholic fatty liver disease

(NAFLD) is associated with dysregulated

PO0.0001) was higher in group A but there was no difference in fetal

glucocorticoid metabolism. Advanced stages of NAFLD are associated with

macrosomia and apgar scores.

adverse outcome and current strategies to stage disease severity are still reliant

Conclusions

upon liver biopsy. We have previously described changes to enzymatic pathways

In this large database, hypothyroidism is associated with adverse obstetric

that regulate cortisol bioavailability; 11b-hydroxysteroid dehydrogenase type-1

outcome. This is the first study to describe a higher incidence of hypothyroidism

(11b-HSD1) regenerates cortisol from inactive cortisone, and A-ring reductases,

in twin pregnancies. TSH screening should be considered in twin pregnancies.

5a- and

5b-reductase

(5aR/5bR), inactivate cortisol to tetrahydrocortisol

DOI: 10.1530/endoabs.49.OC4.1

metabolites (THF/5aTHF). Changes to these pathways are apparent across the

NAFLD spectrum (simple steatosis, steatohepatitis

(NASH), fibrosis and

cirrhosis). Here we have further validated these observations in a large cohort

of patients with NAFLD and compared these to healthy controls and to patients

with alcoholic cirrhosis.

Methods

OC4.2

Using gas chromatography / mass spectrometry, we analysed steroid metabolites

Inducible thyrocyte-specific Gs alpha-deficient mice as a novel model

in spot urine samples (corrected for creatinine) in patients with biopsy proven

for hypothyroidism

NASH (nZ65), NAFLD cirrhosis (nZ51), alcoholic cirrhosis (nZ48) and in

Konrad Patyra¹, Holger Jaeschke¹, Henriette Undeutsch¹, Christoffer Lof¹,

healthy controls (nZ58). Additionally, we used machine learning-based analysis

Suvi Ruohonen¹, Meeri Jannari¹, Min Chen², Lee S. Weinstein²,

to investigate changes across 32 steroid metabolites.

Ralf Paschke³, Jorma Toppari¹ & Jukka Kero¹

Results

¹Institute of Biomedicine, Turku, Finland;²Metabolic Diseases Branch,

Cortisol regeneration

(11b-HSD1 activity: THFC5aTHF/THE ratio), was

National Institute of Diabetes, Digestive and Kidney Diseases, National

significantly increased in NAFLD cirrhosis (PZ0.0004), and alcoholic cirrhosis

Institutes of Health, Bethesda, MD, USA;³Division of Endocrinology and

(P!0.0001), compared to controls. Cortisol inactivation

(A-ring reductase

Metabolism, Departments of Medicine and Oncology and Arnie Charbon-

activity: THF/5aTHF ratio) was significantly reduced in NAFLD cirrhosis

neau Cancer Institute, Cummings School of Medicine, University of

compared to controls (PZ0.0004), but not between controls and alcoholic

Calgary, Calgary, Canada.

cirrhosis (PO0.99) nor NASH (PZ0.332). Machine learning-based analysis by

generalised matrix-learning vector quantisation (GMLVQ) achieved excellent

separation of control and NASH groups (AUC-ROCZ0.87). Furthermore, there

The thyroid gland produces thyroid hormones, which are essential regulators of

was near perfect separation of controls from NAFLD cirrhosis (AUC-ROCZ

growth, development and metabolism of the body and is mainly regulated by the

0.99) and controls from alcoholic cirrhosis (AUC-ROCZ0.98).

thyroid stimulating hormone (TSH)/TSH receptor (TSHR) interplay. The TSHR

Conclusion

couples to all four G protein families in vitro but only for the Gs and Gq signaling

This data is consistent with our previous findings that identified differentially

cascade a role has been identified in vivo. To gain further insights into the

regulated steroid metabolic pathways across the spectrum of NAFLD.

complex signaling networks mediated by G proteins in the thyroid, we generated

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

a thyrocyte-specific tamoxifen-inducible Gs deficient mouse line (iTGsKO). Mice

Whereas G-protein coupled receptors (GPCRs) have long been believed to signal

were injected with tamoxifen at P28 and phenotypic characterization was carried

via cyclic AMP (cAMP) exclusively at the cell surface, our group has shown that

out by performing thyroid function tests at different ages. iTGsKO mice showed

GPCRs also stimulate cAMP production from the cell interior once internalized

hypothyroidism at P56, four weeks after induction with tamoxifen. Furthermore, a

together with their ligands. This phenomenon, which we originally described for

decrease in thyroid weight and an increased pituitary weight support the

the thyroid stimulating hormone receptor (TSHR) in thyroid follicles, has now

conclusion of hypothyroidism in these mice. Morphometric analysis of the

also been shown for several other GPCRs. However, the involved subcellular

thyroid histology of iTGsKO mice with an age of 6 months (P168) showed that

compartment(s) and the mechanisms linking signalling by internalized GPCRs to

the thyrocyte layers between adjacent follicles and the follicle areas were

downstream biological effects are largely unknown. The aim of this study was to

significantly reduced when compared with controls. Interestingly, despite of an

follow the trafficking of internalized TSHRs and involved signalling proteins in

identical thyroid hormone status we observed a clear sex difference. In iTGsKO

living primary thyroid cells by highly inclined thin illumination

(HILO)

males, the body weight was significantly decreased at P70 when compared with

microscopy as well as to monitor cAMP production and protein kinase A

control males but no weight difference was seen in females over the investigated

(PKA) activation by real-time fluorescence resonance energy transfer (FRET)

time period of 6 months (P168). The lower body weight in iTGsKO males was

microscopy. Importantly, using a biosensor nanobody that is specific for the

associated with reduced fat mass. In summary, we show that iTGsKO mice are a

active Gs-protein, we were able to directly demonstrate that the internalized

useful tool for understanding the role of G-protein signaling in the thyroid as well

TSHR activates an endogenous pool of Gs-protein located on membranes of the

as investigating the metabolic consequences in hypothyroidism.

Trans Golgi Network (TGN). Direct monitoring of PKA activation with a Golgi-

DOI: 10.1530/endoabs.49.OC4.2

localized FRET sensor (AKAR2) showed a delayed PKA activation (approx.

10 min) after TSH stimulation, which is compatible with the time required for

TSH/TSHR complexes to reach the Golgi/TGN. Moreover, our results also

indicate that Gs-protein mediated signalling by internalized receptors at the TGN

and the resulting PKA activation at a critical position near the nucleus are

required for the efficient induction of CREB phosphorylation and gene

OC4.3

transcription. These findings provide a mechanism to explain the biological

A novel variant in the SERPINA7 gene causing partial TBG deficiency

relevance of GPCR signalling at intracellular sites, which might help explaining

in a women and two male siblings: molecular and protein structural

the pathogenesis of endocrine disorders such as Graves’ disease and might pave

analysis

the way to innovative pharmacological therapies.

Cristiane Lima¹, Andressa Maciel¹, Sarah Caixeta Cardoso¹,

DOI: 10.1530/endoabs.49.OC4.4

Matheus Andrade¹, Vinicius Cunha¹, Lucas Bleicher², Juliana mazzeu³

& Adriana Lofrano-Porto¹

¹University of Brasília, Faculty of Health Sciences, Molecular Pharma-

cology Laboratory, Brasilia, DF, Brazil;²Federal University of Minas

Gerais, Department of Bichemistry and Imunology, Belo Horizonte, MG,

Brazil;³Univeristy of Brasilia, Faculty of Medicine, Medical Genetics

OC4.5

Laboratory, Brasilia, DF, Brazil.

Levothyroxine replacement therapy: once treatment is started, should it

last indefinitely?

Sarantis Livadas¹, Christina Bothou¹, Ioannis Androulakis¹,

Background

Anastasios Boniakos¹, Nicholas Angelopoulos¹ & Leonidas Duntas²

Thyroxine-binding globulin (TBG) is the major human thyroid hormone transport

¹Endocrine Unit, Metropolitan Hospital, Athens, Greece;²Unit of

protein. It is encoded by the SERPINA7 gene, located on the long arm of the X

Endocrinology, Diabetes and Metabolism, Evgenideion Hospital, University

chromosome (Xq22.2). Inherited TBG abnormalities result in complete (TBG-

of Athens, Athens, Greece.

CD) or partial (TBG-PD) TBG deficiency. We performed a comprehensive

molecular analysis of the SERPINA7 gene in a Brazilian family with TBG-PD.

Methods

Background

Genomic DNA was extracted from the female proband, her father, dizygotic twin

Levothyroxine (LT4) is one of the most prescribed drugs worldwide. Once

sister and two brothers, and the coding region of the SERPINA7 gene was

started, about 90% of patients continue LT4 treatment long-term.

sequenced. The proband’s X-chromosome inactivation pattern was evaluated by

Aim of the study

methylation analysis using the human androgen receptor (AR) gene, located next

To evaluate the necessity of long-term thyroxine supplementation and to

to SERPINA7 (Xq11.2). Structural analysis of the Serpin protein family was

determine the prognostic factors that could identify which patients may

performed using PFSTATS, and was also used to map equivalent positions in all

discontinue LT4 treatment.

human homologs. Molecular modeling was done as described by Feyfant et al.

Design and methods

Results and Discussion

LT4 replacement therapy was paused for at least six weeks in all patients

A novel missense mutation in the SERPINA7 gene (p.R35W; c.163COT) was

consecutively visiting our department, excluding those who have a definite need

found in heterozygosity in the proband and in hemizygosity in her brothers.

for L-thyroxine use (replacement after total thyroidectomy), those on thyroid-

They presented low serum levels of total T4, total T3 and TBG, compatible with

altering medication, women wishing to conceive and those who gave birth last

TBG-PD. The proband expressed an X-chromosome inactivation ratio of 20:80.

year. 231 individuals were assessed (84% females), aged 48 years (SDZ16.5),

The substitution of an arginine by a tryptophan is predicted to disrupt the protein

who were categorized into the following categories: a) unknown reason for

surface and main electrostatic interactions. The conservation and correlation

thyroxine supplementation (nZ62), b) presence of thyroid nodules (nZ90),

patterns showed that tryptophans are extremely rare (0.1%) in this position, and

normal TSH before thyroxine administration (nZ44), over 10 years’ use (nZ10),

there is no significant (P!10-10) pairwise.

therapy initiated post-pregnancy (nZ20). Thyroid function was evaluated before

Conclusion

and after the thyroxine pause. A value of TSH R4.5 IU/ml post treatment

We report a new variant of the SERPINA7 gene associated with TBG-PD in three

discontinuation was considered as ‘relapse’ and LT4 was reinstituted in those

siblings. The proband’s X-chromosome inactivation pattern may have accounted

individuals. The potential prognostic factors analyzed were family history of

for the rare phenotypic expression in a heterozygous woman. The hydrophobic

thyroid dysfunction, sex, age, dose per BMI and dose per kg, thyroid volume,

nature of the mutant is predicted to create an apolar patch at the protein surface,

thyroid ultrasound characteristics, positivity of thyroid autoantibodies, basal TSH

which would be significantly exposed to the solvent, and result in protein

values and reason for the initial treatment indication.

aggregation and/or misfolding with consequent thyroxin transport defect.

Results

DOI: 10.1530/endoabs.49.OC4.3

25.54% (83% females) of the studied subjects relapsed. Of the above-described

factors, only diffuse inhomogeneous echogenicity was tentatively identified as the

only predictive factor for relapse (71% vs 57%, P:001). The age (47.27G15.45 vs

48.17G16.98 years, P:0.72), the positivity of TPOAb (69%% vs 54%, P:0.064)

and basal TSH values (1.51G0.96 US. 1.57G0.84, P:0,81) did not differ

significantly among the two groups.

OC4.4

Conclusions

The TSH receptor reaches the trans-Golgi network to induce PKA

One out of four individuals evaluated required thyroxine treatment. The need for

activation and trigger gene transcription

a patient-centered approach regarding L-thyroxine supplementation and for a

Amod Godbole^1,2, Sandra Lyga^1,2, Martina Leo^1,2 & Davide Calebiro^1,2

thorough review of patient history was evident.

¹Institute of Pharmacology and Toxicology, University of Wurzburg,

DOI: 10.1530/endoabs.49.OC4.5

Wurzburg, Germany;²Bio-Imaging Center/Rudolf Virchow Center,

University of Wurzburg, Wurzburg, Germany.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Cardiovascular Endocrinology

Materials and methods

Visceral and subcutaneous adipose tissues were obtained from 97 non-diabetic

OC5.1

subjects (41 non-obese, 18 obese, and 38 morbid obese), who underwent open

Polarized epithelial cells release exosomes loaded with miRNAs capable

abdominal surgery with minimal impact on dietary intake. Intake of hydrogenated

of interacting with HSD11B2 and MR genes

and non-hydrogenated vegetable oils and butter was collected using a valid and

Eric Barros¹, David Ortiz¹, Carmen Campino¹, Carolina Valdivia¹,

reliable food frequency questionnaire. The gene expressions of PPAR-gamma in

Alejandra Tapia-Castillo^1,2, Jaime Lizama¹, Fidel Allende¹, Sandra Solari¹,

visceral and subcutaneous adipose tissue were assessed by Real-Time PCR.

José Vicente Gonzalez¹, Alejandro Martínez-Aguayo¹, Andrea Vecchiola¹,

Findings

Gabriela Repetto^1,2, Marlene Aglony¹, Rene Baudrand¹, Carlos

After adjustment for total energy intake and age, visceral adipose tissue PPAR-

F Salomon^1,3, Carlos E Fardella¹ & Cristian Carvajal¹

gamma gene expression was correlated with total fat and oil intake (bZK0.531,

¹Pontificia Universidad Católica de Chile, Santiago, Chile;²Universidad del

PZ0.014) in total population. Among non-obese subjects, visceral adipose tissue

Desarrollo, Santiago, Chile;³University of Queensland, Brisbane, Australia.

PPAR-gamma gene expression was correlated with non-hydrogenated oil

(bZ0.621, PZ0.017). PPAR-gamma gene expression in subcutaneous adipose

tissue was correlated with non-hydrogenated oil (bZ0.481, PZ0.026) among

obese subjects. Moreover, among morbid obese subjects we found significant

Arterial hypertension is a major health problem affecting 1.13 billion people

correlations between visceral adipose tissue PPAR-gamma expression and total

worldwide, of which 10% could be due to endocrine pathologies related

fat and oil intake (bZ0.417, PZ0.020).

to the mineralocorticoid receptor

(MR) (i.e. primary aldosteronism,

Conclusions

11b-hydroxysteroid dehydrogenase type 2 enzyme (HSD11B2) deficiency).

Expression of adipose tissue PPAR-gamma mRNA negatively correlates with

The MR pathway is expressed mainly in placenta, kidney and colon

total fat and oil intake mostly in visceral fat. In addition, non-hydrogenated oil

epithelial cells. Current research highlights potential epigenetic regulatory

positively correlates with PPAR-gamma expression.

mechanisms for the MR pathway. Here, specific miRNAs are being studied

as epigenetic regulators, either present in cells or exosomes (nanovesicles of

DOI: 10.1530/endoabs.49.OC5.2

40-150 nm diameter) carrying miRNA, RNA, lipids and proteins. Those

miRNAs could dynamically influence the onset and progression of the

mineralocorticoid arterial hypertension (AH).

Aim

To isolate exosomes from polarized epithelial cells and to identify in their cargo

miRNAs affecting HSD11B2 and MR gene expression.

Methods

OC5.3

The bioinformatic tool mirWalk2.0 was used to determine miRNAs capable to

interact with HSD11B2 and MR RNAs. The cell line derived from colon epithelia

Cardio metabolic assessment of lamin A/C mutation carriers according

(Caco-2) cells was cultured and polarized in Transwells. MR pathway genes and

to R482 or Non-R482 mutation

miRNAs targeting the MR and HDS11B2 were measured by qPCR. Exosomes

Maxime Kwapich¹, Kenza Benomar¹, Stéphanie Espiart¹, Eric Van Belle²,

from apical and basolateral culture medium were isolated at 24 h of incubation in

Pascal Pigny³, Gisèle Bonne⁴, Corinne Vigouroux^5,6, Dominique Lacroix²

basal conditions, quantified with NanoSight-NS300 and their specific miRNA

& Marie-Christine Vantyghem^1,7

content was determined.

¹Service d’Endocrinologie et Métabolisme, Hôpital C Huriez Centre

Results

Hospitalo-universitaire de Lille, 1 rue Polonovski, 59 037 Lille Cedex,

We identified bioinformatically that miRNA 135b, 644a and miRNA 488, 1205

France;²Service de Cardiologie, Institut Cœur-poumon, Centre Hospitalo-

could interact with the MR and HSD11B2, respectively. Caco-2 cells polarize

universitaire de Lille, 1 rue Polonovski, 59 037 Lille Cedex, France;

after

days of culture

(trans-epithelial resistance

(TEER):

114.18 cm²),

³Service de Biochimie et Biologie Moléculaire, Centre de Biologie-

expressing polarization genes (SLC11A2, SLGT1, ALPI), genes associated to

Pathologie, Centre Hospitalo-universitaire de Lille, 1 rue Polonovski,

MR pathway (NR3C2, HSD11B2, SCNN1A, SLC12A2, SGK1, ATP1A1) and

59 037 Lille Cedex, France; ⁴Sorbonne Universités, UPMC Univ Paris 06,

pre-miRNAs (135b,

644a,

488,

1205). We identified that Caco-2

release

INSERM UMRS974, CNRS FRE3617, Center for Research in Myology,

21!109G0.69!109 (apical) and 4.1!109G0.0029!109 (basolateral) extra-

Institut de Myologie, G.H. Pitié Salpêtrière, F-75651 Paris Cedex 13,

cellular vesicles per ml of which a 36.8 and 38.5% are exosomes with a modal

France;⁵Saint-Antoine Research Center, Institute of Cardiometabolism and

range in 124-125 nm diameter respectively. Preliminary results show expression

Nutrition, INSERM UMR, Pierre-and-Marie Curie University, Université

of miRNA 135b, 644a, 488 and 1205 in apical and basolateral exosomes.

Paris, Sorbonne Universités, Paris, France;⁶Departments of Molecular

Conclusion

Biology and Endocrinology, Assistance Publique-Hopitaux de Paris,

Caco-2 cells release five-times more exosomes in the apical than basolateral side,

Hôpital Saint-Antoine, Paris, France;⁷Equipe INSERM 1190 Prise en

both carrying miRNAs that could interact HSD11B2 and MR gene.

charge translationnelle du diabète Institut EGID (European Genomic

Institute for Diabetes), Lille, France.

DOI: 10.1530/endoabs.49.OC5.1

Background

Lamin A/C mutations show heterogeneous phenotypes expanding from

cardiopathies to lipodystrophies. LMNA-related heart disease has recently been

shown to be associated with a high incidence of phenotypic progression and

OC5.2

adverse arrhythmic and non-arrhythmic events. Anticipatory planning to prevent

sudden death has been recommended in a multicentric cardiologic recruitment.

Association of PPAR gamma gene expression with dietary intake of fat

Nevertheless the specific cardiac prognosis of R482-LMNA mutated patients, the

and oil among non-diabetic subjects

hot-spot for partial lipodystrophic syndromes, has not been well studied.

Emad Yuzbashian^1,2, Maryam Zarkesh³, Golaleh Asghari¹,

Objectives

Azita Zadeh-Vakili³, Behnaz Mahmoodi¹, Mehdi Hedayati³,

To compare the cardio-metabolic complications of R482-LMNA mutated

Parvin Mirmiran¹ & Alireza Khalaj⁴

patients, and carriers of other LMNA mutations.

¹Nutrition and Endocrine Research Center, Research Institute for Endocrine

Methods

Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran;

This retrospective study included 29 R482-LMNA mutated patients and 29

²Student Research Committee, Biochemistry of Nutrition Research Center,

carriers of another lamin A/C mutation (non-R482 group) followed at a single

School of Medicine, Mashhad University of Medical Sciences, Mashhad,

university hospital for a median of

5.5 years. The cardiac and metabolic

Iran;³Cellular and Molecular Endocrine Research Center, Research

phenotypes were compared between the two groups.

Institute for Endocrine Sciences, Shahid Beheshti University of Medical

Results

Sciences, Tehran, Iran;⁴Obesity Treatment Center, Department of Surgery,

The non-R482 carriers showed more electrocardiographic anomalies and wore

Shahed University, Tehran, Iran.

more cardiac devices than the R482-carriers (P!0.001). The ultrasound cardiac

examinations of non-R482 patients showed a higher frequency of left auricular

Background and Objective

dilatations

(P!0.05) and a lower mean left ventricular ejection fraction

Several animal studies showed the expression of peroxisome proliferator

(P!0.01) than in R482-carriers. A family history of medical devices

activated receptor-gamma (PPAR gamma) in adipocytes among rats fed with

(P!0.001) or sudden death (P!0.01) was more frequent in non-R482 than in

high-fat diet was higher than those fed with normal diet. However, there are no

R482-carriers. The prevalence of diabetes (P!0.01) and hypertriglyceridemia

human studies to support this. The objective of the present study was to

(P!0.05) and coronaropathy was higher in R482 than in non-R482 carriers.

investigate the association between the PPAR gamma expression in adipose tissue

The R482 carriers had a lower leptin (P!0.01) and BMI (P!0.05) level than the

and intake of hydrogenated and non-hydrogenated vegetable oils and butter.

non-R482.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

¹INSERM 1185, Le Kremlin Bicetre, France;²Service d’endocrinologie

The non-R482 presented more arrhythmias than the R482-carriers, who were

pédiatrique, hôpital Robert Debré, APHP, Paris, France;³INSERM UMR-S

twice more often diabetic with more coronaropathies. The frequency of diabetes

938, Paris, France;⁴Prem Up foundation, Paris, France.

reached, however 40% in non-R482 mutations. The follow-up of laminopathies

should be adjusted to the genotype. Arrythmias, especially associated to diabetes

or medical device family history should lead to LMNA genetic testing.

Sex differences have been demonstrated in various biological processes such

DOI: 10.1530/endoabs.49.OC5.3

as arterial blood pressure. However, the potential sex dimorphism of the

renin-angiotensin-aldosterone system and, by extension, the mineralocorti-

coid receptor (MR) signaling pathway, major regulators of blood pressure,

has only been poorly studied, notably in the kidney. Basal systolic blood

pressure (SBP) and heart rate (HR) were measured in adult male and female

mice. Renal gene expression studies of major players of MR signaling were

performed at different developmental stages in male and female mice using

OC5.4

RT-qPCR, and were compared to that of the same genes in the lung, another

Food history characterization of Portuguese centenarians, nutritional

mineralocorticoid epithelial target tissue. The potential role of sex hormones

biomarkers and cardiovascular risk: case control study

in the regulation of these genes was also investigated in differentiated

Alda Pereira da Silva^1,2, Catarina Chaves³, Andreia Matos^1,5, Angela Gil^1,5,

KC3AC1 renal cells. Additionally, renal expression of the

11bHSD2

Carolina Santos^1,5, Ana Valente⁴, Manuel Bicho^1,5 & João Gorja˜o Clara2

protein, a regulator of mineralocorticoid specificity, was measured by

¹Genetics Laboratory, Environmental Health Institute - ISAMB, Faculty of

immunoblotting and its activity was indirectly assessed in the plasma using

Medicine, University of Lisbon, Lisbon, Portugal;²Geriatric Universitary

LC-MSMS method. SBP (91.7 G1.1 vs 99.2 G1.0 mmHg, P!0.0001) and

Unit of Faculty of Medicine, University of Lisbon, Lisbon, Portugal;

HR (662 G3 vs 687 G 4 bpm, P!0.0001) were significantly lower in

³Centro Hospitalar de Lisboa Central, Lisbon, Portugal;⁴Department of

females compared to males. This was accompanied by a sex and tissue-

Nutritional Science, Atlantica University, Barcarena, Portugal;⁵Instituto de

specific expression of MR signaling pathway from fetal stage (E18) to

Investigação Científica Bento da Rocha Cabral, Lisbon, Portugal.

adulthood, most notably for GR (Nr3c1) and Gilz renal mRNA expression

which was twofold-lower in adult females mice compared to males

(P!0.01). Moreover, 11bHSD2 mRNA and protein expression was found

Introduction

significantly increased in females (P!0.05), with a statistically different

Eating habits may contribute to longevity. Consumption of red meat, source of

ratio of corticosterone/dehydrocorticosterone between both sexes

saturated fatty acids and cholesterol may be associated with increased risks of

(PZ0.012). Finally, the implication of sex hormones in this sex-specific

diabetes, cardiovascular disease (CVD), and mortality risk.

expression profile was confirmed in vitro, most notably for Gilz mRNA

Methods

expression. We demonstrate a tissue-specific, sex-dependent and develop-

We studied 521 subjects, both genders, 253 centenarians (CENT) (100.26G1.98

mentally-regulated pattern of expression of MR signaling that could have

age) and 268 controls (67.51G3.25 age), both low (LCR) and high cardiovascular

important implications in physiology and pathology, particularly in the

risk

(HCR), calculated based on QRISKw2-2016. Anthropometric and body

development of essential hypertension in men.

composition analysis were evaluated by bioimpedance. The abdominal obesity

DOI: 10.1530/endoabs.49.OC5.5

(cm), BMI (kg/m²) and the cut-off for fat mass (FM) by gender, defined according

WHO. Sarcopenia defined by muscle-mass index cut-off%16.7 kg/m². Statistical

methods were chi-square test, ANOVA and binary logistic regression.

Results

There were differences in the distribution of food frequency history between

centenarians and controls concerning food groups except oilseeds. The daily

intake of red meat, adjusted for age and gender, was a protective factor for

sarcopenia (ORZ0.25, CI 95%Z0.096-0.670, PZ0.006), but contributes for FM

Diabetes therapy and complications

excess (ORZ4.946, CI 95%Z1.471-16.626, PZ0.01), overweight and obesity

OC6.1

(ORZ4.804, CI 95%Z1.666-13.851, PZ0.004). Only 2% of the centenarians

A passe-PAR2 for b-cell regeneration and protection

reported this eating habit unlike the 64.3% of the HCR group. The frequency

Ron Piran¹ & Fred Levine²

history of red meat intake was associated with higher cardiovascular risk

¹Bar Ilan University’s Faculty of Medicine, Safed, Israel;²Sanford

(c2Z239,807; dfZ8, P!0.0001), as well as canned food intake (c2Z225.321;

Children’s Health Research Center, Sanford Burnham Prebys Medical

dfZ8, P!0.0001). Basal metabolism (Kcal) was lower in centenarians and

Discovery Institute, La Jolla, California, USA.

higher in HCR group

(CENTZ1176.78G201.98; LCRZ1356.54G170.65;

HCRZ1561.33G267.85; P!0.0001), in the same way as BMI (CENTZ

21,06G3.68; LCRZ28.49G4.69; HCRZ29.56G5.26; P!0.0001), waist

circumference (CENTZ85.29G10.83; LCRZ96.02G11.71; HCRZ104.50G

Cell and tissue damage, particularly to pancreatic b-cells, is an essential

11.84; P!0.0001) and hip-waist ratio (CENTZ0.88G0.07; LCRZ0.92G0.08;

characteristic of diabetes mellitus, triggered by autoimmune destruction of

HCRZ1.01G0.08; P!0.0001).

b-cells in type-1

(T1D) and by obesity associated factors or insulin

Conclusions

resistance in type 2. Thus, stimulating b-cell regeneration has long been a

Centenarians have different food history than the control population. Frequent

most important goal of diabetes research. Recently, we have shown that

consumption of red meat may contribute to obesity and increased cardiovascular

pancreatic injury consisting of acinar cell inflammation and b-cell

risk, since the hemic iron of red meat may catalyze oxidations leading to disease

destruction led to islet cell transdifferentiation. In this work, we report

processes. The low frequency of this consumption, observed in centenarians,

that the molecular mechanism for this process requires the activation of the

although associated with sarcopenia, may be one of the keys to longevity.

protease-activated receptor-2 (PAR2), a G-protein-coupled receptor. PAR2

DOI: 10.1530/endoabs.49.OC5.4

modulation was sufficient to induce islet cell transdifferentiation in the

b-cells ablated animals as PAR2 Knock out mice and mice injected with

PAR2 pharmacological activator showed that it was necessary and sufficient

for the induction of islet cell transdifferentiation in the settings of b-cell

ablation. PAR2 expression was modified in an islet cell type-specific manner

in murine and human T1D. In addition to transdifferentiation, PAR2

OC5.5

regulated b-cell apoptosis in caerulein-mediated pancreatitis, demonstrating

Sex dimorphism of renal corticosteroid signaling during development

that PAR2

was required for b-cell survival and protection during

and long term consequence on blood pressure

inflammation.

Laurence Dumeige¹, Caroline Storey^1,2, Lyvianne Decourtye³,

DOI: 10.1530/endoabs.49.OC6.1

Mélanie Nehlich^1,4, Christophe Lhadj^1,4, Say Viengchareun¹,

Laurent Kappeler³, Marc Lombès¹ & Laetitia Martinerie^1,2

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

OC6.2

differentially methylated CpG regions near the promoters. Five genes,

Insulin-mimetic effects of short-term Rapamycin in type 1 diabetic

considered most likely biologically relevant to have impact in diabetes were

patients prior islet transplantation

those involved in processing of energy molecules, differentiation and

Federica Ermetici¹, Silvia Briganti¹, Stefano Benedini^1,2, Roberto Codella²,

formation of adipocytes and exhibiting GTF-ase activities. Eighteen regions

Paola Maffi³, Rossana Caldara³, Antonio Secchi³, Lorenzo Piemonti³,

included genes with known specific functions that are not directly linkable to

Rodolfo Alejandro⁴, Camillo Ricordi⁴ & Livio Luzi^1,2

influencing diabetic phenotype. Finally 12 genes where either pseudogenes

¹Endocrinology and Metabolism, IRCCS Policlinico San Donato,

or had unknown function. In conclusion this is the first study that shows

San Donato Milanese, Italy;²Department of Biomedical Sciences for

influence of metformin in altering DNA methylation in humans and

Health, Università degli Studi di Milano, Milano, Italy;³Department of

identified markers may prove to be valuable biomarkers for the under-

Internal Medicine, Transplant Medicine Unit, San Raffaele Scientific

standing of the molecular basis of metformin action and may lead to the

identification of new drug targets.

Institute, Milano, Italy;⁴Diabetes Research Institute, University of Miami

Miller School of Medicine, Miami, Florida, USA.

DOI: 10.1530/endoabs.49.OC6.3

It has been suggested that the selective m-TOR inhibitor, Rapamycin, has

been improved the success pancreatic islet allotransplantation (ITx) in type

1 diabetic patients (T1DM). Forty-one ITx were studied. Thirteen T1DM in

OC6.4

poor glycemic control underwent a 45-days Rapamycin before ITx followed

Copeptin and its association to cardiovascular dysfunction in type 2

by standard Edmonton Protocol (EP, group 1, Milan), and they were

diabetes

compared to 28 T1DM patients undergoing EP (group 2, Miami). Outcome

Simona Ioana Chisalita¹, Lee Ti Chong², Fredrik Nystrom¹,

measures were daily insulin requirement (DIR), HbA1c, C-peptide and the

Carl Johan Ostgren³ & Toste Länne⁴

SUITO index of beta-cell function before and 1 year after ITx. Four patients

¹Department of Endocrinology and Department of Medicine and Health

from group 1 underwent euglycemic-hyperinsulinemic clamp with 6,6-d2-

Sciences, Linkoping University, Linkoping, Sweden;²Department of

glucose infusion before and after ITx. We found a significant reduction in

Emergency and Department of Medicine and Health Sciences, Linkoping

DIR after Rapamycin pre-treatment (K8G6 U/day, meanGS.D., P!0.001).

University, Linkoping, Sweden;³Department of Medical and Health

Nine patients from group 1 fulfilled follow-up. One year after ITx, DIR

Sciences (IMH)/Division of Community, Linkoping, Sweden;⁴Department

significantly decreased

(K37G15 U/day, P!0.001) and six patients

of Thoracic and Vascular Surgery, and Department of Medicine and Health

became insulin independent. We observed greater DIR reduction in group

Sciences, Linkoping University, Linkoping, Sweden.

1 as compared to group 2 at 1-year follow-up (K37G15 vs K19G

13 U/day, PZ0.005), which remained significant after adjusting for gender,

Background

age, glucose and baseline HbA1c (beta coefficient of multivariate regression

We aim to test whether plasma copeptin (copeptin), the C-terminal fragment of

analysisGS.E. 18.2G5.9, PZ0.006). In patients from group 1, HbA1c

vasopressin, has predictive value of cardiovascular events in patients with type 2

significantly decreased 1 year after ITx (K2.1G1.4%, PZ0.002), while

diabetes without previous cardiovascular disease who were treated in primary

C-peptide (C1.5G0.9, PZ0.002), and SUITO index increased (C57.4G

care.

39.7, PZ0.016). We did not observe differences in change between group 1

Methods

and 2 as far as HbA1c, C-peptide and SUITO index are concerned before

We measured copeptin in 697 patients who participated in the epidemiological

and after ITx. Hepatic glucose production during the insulin clamp

study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes - a

decreased after Rapamycin pre-treatment

(K1.1G1.1 mg/kg per min,

Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737)

PZ0.04) and after ITx (K1.6G0.6 mg/kg per min, PZ0.015), while no

and who did not have previously known myocardial infarction or stroke. The

changes in peripheral glucose disposal were observed during Rapamycin

outcome variable was a composite endpoint consisting of cardiovascular

treatment. In conclusion, Rapamycin contributes to improve metabolic

mortality, hospitalization for myocardial infarction and hospitalization for stroke.

control also enhancing hepatic insulin sensitivity after ITx. Rapamycin

Results

pre-treatment may improve ITx success rate by reduction of pre-transplant

During a median follow-up time of almost 7 years, the unadjusted HR per each

DIR and increase of hepatic insulin sensitivity.

increment of Copeptin by 1 pmol/l was 3.5 (95% CI 1.7-7.1, P!0.001) for the

DOI: 10.1530/endoabs.49.OC6.2

primary endpoint. Following adjustments for age, sex, HbA1c, arterial stiffness

(PWW) as well as atherosclerosis plaque the adjusted hazard ratio was 2.4 (95%

CI 1.1-5.2, PZ0.03).

Conclusions

In primary preventive patients with type 2 diabetes treated in primary care,

copeptin predicted a composite outcome of incident cardiovascular events

OC6.3

independently of age, sex, HbA1c, arterial stiffness as well as atherosclerosis

Alterations in DNA methylation from peripheral blood cells in humans

plaque.

threated with metformin

DOI: 10.1530/endoabs.49.OC6.4

Janis Klovins¹, Ilze Elbere¹, Raitis Peculis¹, Ineta Kalnina¹,

Linda Zaharenko¹, Ilze Konrade³ & Valdis Pirags^1,2

¹Latvian Biomedical Research and Study Centre, Riga, Latvia;²Department

of Endocrinology, Pauls Stradins Clinical University Hospital, Riga, Latvia,

³Riga Stradins University, Riga, Latvia.

OC6.5

Activation of the Renin-Angiotensin II-Aldosterone-System leads to

increases in extracellular protein disulfide isomerase: role in insulin

Metformin is a biguanide class agent widely used as a first-line treatment

resistance

for type

2 diabetes, however the detailed mode of action and exact

Ricardo Perez-Fuentes⁴, Patricia Pulido^1,4, Joshua Cazares^1,2,

pharmacodynamics has not been clarified. Moreover there is no studies in

Yaritza Inostroza-Nieves¹, Enrique Torres-Rasgado^1,4, Akira Nishiyama³,

humans displaying the effect of metformin on DNA methylation. We

Alicia Rivera¹, Rudy Ortiz² & Jose Romero¹

therefore performed a clinical study involving twelve healthy nondiabetic

¹Division of Endocrinology, Diabetes and Hypertension, Department of

individuals who were subjected to the

week of metformin

(2!

Medicine, Brigham and Women’s Hospital, and Harvard Medical School,

850 mg/day) treatment. Peripheral blood for DNA isolation was drawn at

Boston, Massachusetts, USA;²Department of Molecular and Cellular

three time points during metformin treatment: i) right before metformin

Biology, University of California, Merced, California, USA;³Department of

treatment, ii) 10 hours after the first metformin dose and iii) after a week-

Pharmacology, Kagawa Medical University, Kagawa 761-0793, Japan;

long metformin administration. DNA methylation was estimated using

⁴Universidad Autonoma de Puebla/Instituto Mexicano Seguro Social,

genome-wide Illumina Infinium HumanMethylation450 BeadChip (Illu-

Puebla, Mexico.

mina), which allows interrogation of 485 512 CpG dinucleotides. Analysis

global methylation data displayed predominance of demethylated CpGs

over the methylated as the result of metformin treatment. In order to identify

differentially methylated gene promoter regions we filtered all CpGs located

Insulin resistance and type II diabetes (T2D) are associated with activation

2000 pb proximity of the transcription start site and having median

of the Renin-Angiotensin-Aldosterone-System

(RAAS) in part via

methylation change across all samples larger than 3% with Bonferroni

regulation of its principal effector molecule, Angiotensin II

(AngII).

corrected P values. This stringent approach resulted total in 35 genes with

Endothelial cell activation leads to, among other factors, increased

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

extracellular protein disulfide isomerase (PDI), a multifunctional protein

OC7.2

that is critical to thrombus formation and regulation of reactive oxygen

Targeted molecular markers derived from genomic classification for

species. However, the effects of RAAS on PDI are unknown. We studied the

adrenocortical cancer prognostication

in vitro effects of AngII on EA.hy926 human endothelial cells and measured

Anne Jouinot^1,2, Guillaume Assié^1,3, Martin Fassnacht^4,5, Rossella Libé^1,3,

PDI activity. Our results show that AngII

(10 nM), dose- and time-

Bertrand Dousset⁶, Silviu Sbiera Cristina Ronchi⁴, Matthias Kroiss⁵,

dependently, increased PDI activity (P!0.05, nZ6); an event that was

Esther Korpershoek⁷, Ronald De Krijger^7,8, Jens Waldmann⁹,

blocked by pre-incubation with 0.5 mM losartan, an AngII Type I receptor

Marcus Quinkler¹⁰, Antoine Tabarin¹¹, Olivier Chabre¹²,

antagonist (ARB). Western blot analyses showed increased PDI following

Michaela Luconi¹³, Massimo Mannelli¹³, Lionel Groussin^1,3, Eric Baudin¹⁴,

AngII that was likewise reduced by losartan. In normal in Sprague-Dawley

Laurence Amar¹⁵, Felix Beuschlein¹⁶ & Jérôme Bertherat^1,3

rats, we studied the in vivo effects of exogenous AngII infusion and observed

¹Institut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes

significant increases in plasma PDI levels (P!0.05, nO5) that were blunted

University, Paris, France;²Medical Oncology, Assistance Publique

by ARB treatment. We then studied the obese Otsuka Long Evans

Hôpitaux de Paris, Hôpital Cochin, Paris, France;³Department of

Tokushima Fatty (OLETF) (nZ6/group) rats, a model of naturally increased

Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin,

AngII and RAAS-mediated insulin resistance and hypertension. Our results

Paris, France;⁴Endocrinology and Diabetes Unit, University Hospital,

show that OLETF rats had increased insulin resistance and greater

University of Wurzburg, Wurzburg, Germany;⁵Comprehensive Cancer

circulating PDI activity than lean control rats (P!0.05) and was reduced

Center Mainfranken, University of Wurzburg, Wurzburg, Germany;

by ARB treatment to baseline levels (P!0.05). To assess the clinical

⁶Department of Digestive and Endocrine Surgery, Assistance Publique

relevance of our findings, we measured circulating PDI in subjects with and

Hôpitaux de Paris, Hôpital Cochin, Paris, France;⁷Department of

without T2D. PDI activity correlated with measures of insulin resistance in

Pathology, Erasmus MC University Medical Center, Rotterdam,

our cohort (HOMA2-IR, Spearman PZ0.496, P!0.001, nZ134) and was

The Netherlands;⁸Department of Pathology, Reinier de Graaf Hospital,

significantly greater in T2D patients than healthy controls (P!0.01, nZ56

Delft, The Netherlands;⁹Department of Surgery, University Hospital

vs 78, respectively). Our data in human and animal models suggest that

Giessen and Marburg, Marburg, Germany;¹⁰Department of Medicine,

RAAS activation represents a novel mechanism for PDI secretion. Thus we

Charite University, Berlin, Germany;¹¹Department of Endocrinology,

posit that PDI may contribute to the deleterious effects of RAAS-mediated

Diabetes and Metabolic Diseases, University Hospital of Bordeaux,

vascular disease.

Bordeaux, France;¹²Department of Endocrinology, University Hospital of

DOI: 10.1530/endoabs.49.OC6.5

Grenoble, Grenoble, France;¹³Department of Experimental and Clinical

Biomedical Sciences, University of Florence, Florence, Italy;¹⁴Department

of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy,

Villejuif, France;¹⁵Hypertension Unit, Hôpital Européen Georges Pompi-

dou, Assistance Publique-Hôpitaux de Paris, Paris, France;¹⁶Medizinische

Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen,

Munchen, Germany.

Cardiovascular endocrinology

Background

OC7.1

Adrenocortical cancer

(ACC) is an aggressive tumour with heterogeneous

prognosis. Recently integrated genomics reported distinct genomic alterations:

Estrogens enhance gonadectomy-induced adrenocortical tumor

transcriptome “C1A” (high expression of proliferation/cell cycle-related genes)

progression in mice

vs “C1B”, “CIMP” (CpG islands hypermethylation) vs “non-CIMP”, chromo-

Marcin Chrusciel^1,2, Milena Doroszko¹, Meike Jakobi¹, Michal Brouze¹,

some alterations “Noisy” (numerous and anarchic alterations) vs “Chromosomal”

Donata Ponikwicka-Tyszko³, Piotr Bernaczyk⁴, Slawomir Anisimowicz⁵,

(extended patterns of loss of heterozygosity) and “Quiet” (limited alterations),

Slawomir Wolczynski^2,3, Jorma Toppari^1,6, Ilpo Huhtaniemi^1,7 &

and recurrent somatic mutations in 20 genes. These alterations converge into a

Nafis Rahman^1,2

single three-groups classification, correlating with outcome. The aim was to

¹Department of Physiology, University of Turku, Turku, Finland;

develop and validate targeted molecular markers reflecting these genomic groups.

²Department of Reproduction and Gynecological Endocrinology, Medical

Patients and methods

University of Bialystok, Bialystok, Poland;³Institute of Animal Repro-

Two hundred and forty five ACC were included from 21 ENSAT (European

duction and Food Research, Polish Academy of Sciences, Olsztyn, Poland;

network for the Study of Adrenal Tumors) centers. Tumor RNA was assessed

⁴Department of Pathology, Medical University of Bialystok, Bialystok,

by RT-qPCR for BUB1B-PINK1 expression (nZ135). Tumor DNA was studied

Poland;⁵Center of Gynecology and Reproductive Endocrinology Artemida,

by SNP array for chromosomal alterations (nZ238), targeted NGS for mutations

Bialystok, Poland;⁶Department of Pediatrics, Turku University Hospital,

of 20 driver genes (nZ251), and MS-MLPA for CpG islands methylation of

Turku, Finland;⁷Institute of Reproductive and Developmental Biology,

four genes -PAX5, GSTP1, PYCARD, PAX6- (nZ221).

Imperial College London, London, UK.

Results

Gene expression levels identified “C1A”, “C1B” and “undetermined” ACC in 50,

Prepubertally gonadectomized (GDX) wild-type DBA/2J mice develop adreno-

38 and 12% of cases respectively. Methylation assay identified “CIMP” and “non

cortical neoplasms presenting with small spindle-shaped non steroidogenic

CIMP” ACC in 44 and 56% of cases respectively. Chromosomal alteration

A-cells and large lipid-laden, steroidogenic and mitotically active B-cells.

profiles identified “chromosomal”, “noisy” and “quiet” ACC in 55, 32 and 13%

Neoplastic B-cells overexpress estrogen receptor a (ERa, Ers1) and b (ERb,

of cases respectively. Recurrent mutations or deletions were found in ZNFR3,

Ers2), aromatase (CYP19a1) and produce sex-steroids, resembling gonadal rest

CDKN2A, TP53 and CTNNB1 in 21, 17, 15 and 11% of cases respectively, in

tissue. To test the role of estrogen-ER system in adrenocortical tumor progression,

agreement with previous exome studies. All molecular statuses were available for

GDX 12 months-old DBA/2J females were treated with selective estrogen

107 tumors. 87/107 (81%) concordantly recapitulated the 3 main ACC subgroups

receptor modulator tamoxifen (TMX, 0.4 mg/kg/24 h) and aromatase inhibitor

previously identified by genomic classifications: 37 were “C1A/CIMP”, 18 were

letrozole

(LET, 2 mg/kg/24 h) for 21 days. Both TMX and LET treatments

“C1A/non-CIMP”, and 32 were “C1B/non-CIMP”. Death events occurred in

significantly reduced the adrenal weights, with stronger effect of the latter. Both

34/37, 7/18 and 1/32 patients respectively (Fisher exact P!10-15).

treatments decreased the expression of proliferation marker MKI67 and induced

Conclusion

apoptosis predominantly in the tumorous B-cells. TMX and LET treatments

Targeted molecular measures can recapitulate the genomic classification of ACC,

decreased plasma estradiol (E2) levels significantly decreasing sensitivity of the

giving original and useful prognostication information for patient management.

negative feedback on luteinizing hormone

(LH) secretion. Gene expression

DOI: 10.1530/endoabs.49.OC7.2

profiling showed that TMX and LET downregulated gonadal-like markers Ers2,

LH receptor (Lhcgr) and transcription factor Gata4, but upregulated a negative

regulator of steroidogenesis Nr0b1. Additionally, LET significantly decreased

expression of Esr1, Cyp19a1 and Cyp17a1. Control GDX mouse uteri displayed

endometrial hyperplasia without cellular atypia. TMX- and LET-treated mice

OC7.3

uteri were significantly smaller and showed cystically dilated endometrial glands

and signs of mild chronic inflammation. In summary, we showed that adrenal

High Total 68Ga-DOTATATE-Avid Tumor Volume (TV) is associated

estrogens promote progression of GDX-induced adrenocortical tumors. Our

with low progression-free survival and high disease-specific mortality

findings also support the rationale for TMX- and LET-based therapeutic strategies

rate in patients with neuroendocrine tumors

in treating ERs-positive/estrogen responsive adrenocortical carcinomas in human.

Amit Tirosh^1,2, Georgios Z. Papadakis^1,3, Corina Millo¹,

Samira M. Sadowski⁴, Peter Herscovitch¹, Karel Pacak¹, Stephen J. Marx¹,

DOI: 10.1530/endoabs.49.OC7.1

Lily Yang⁵, Pavel Nockel⁵, Jasmine Shell⁵, Patience Green⁵,

Xavier M. Keutgen⁶, Dhaval Patel⁵, Naris Nilubol⁵ & Electron Kebebew⁵

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

National Institutes of Health, Bethesda, MD, USA;²Sackler Faculty of

expression levels. These effects were totally abolished in QGP-1 cells lacking

Medicine, Tel Aviv University, Tel Aviv, Israel;³Institute of Computer

AIP. In conclusion, metformin acts as anticancer agent in P-NET cells, its activity

Science (ICS), Foundation for Research and Technology Hellas (FORTH),

is mediated by AIP and its interacting proteins, HSP70, AHR and Zac1. These

Crete, Greece;⁴Endocrine and Thoracic Surgery, University Hospitals of

findings provide a novel insight into the antitumorigenic mechanism of

Geneva, Geneva, Switzerland;⁵Endocrine Oncology Branch, National

metformin.

Cancer Institute, National Institutes of Health, Bethesda, MD, USA;

DOI: 10.1530/endoabs.49.OC7.4

⁶Department of Surgery, Rush University Medical Center, Chicago, IL,

USA.

Background

Patients with neuroendocrine tumors (NETs) have divergent survival, even when

OC7.5

having the same site of primary tumor, and tumor stage and grade. 68Gallium

Regulation of steroid receptor signalling by tumor suppressor INPP4B

(68Ga)-DOTATATE positron emission tomography

(PET)/computed

Manqi Zhang¹, Egla Suarez¹, Lubov Nathanson², Michael Ittmann³,

tomography (CT) is a sensitive imaging modality for detecting NETs. The

Nancy Weigel² & Irina Agoulnik^1,3

purpose of this study was to determine whether 68Ga-DOTATATE PET/CT

¹Florida International University, Miami, FL, USA;²Nova Southeastern

imaging has any prognostic utility in patients with NETs.

University, Ft. Lauderdale, FL, USA;³Baylor College of Medicine,

Methods

Houston, TX, USA.

One hundred and eighty-four patients with NETs were enrolled in a prospective

study of 68Ga-DOTATATE PET/CT imaging and comprehensive biochemical

analysis. Total

68Ga-DOTATATE-Avid Tumor Volume (68Ga-DOTATATE

Androgen receptor

(AR) signaling is the main driver for prostate cancer

TV) was measured in all participants. The primary outcome measures were

progression and androgen ablation is the treatment of choice for tumors that

progression-free survival (PFS) and disease-specific mortality (DSM). PFS and

spread beyond the prostate. Efficient at first, androgen ablation fails due in part to

DSM rates were compared according to 68Ga-DOTATATE TV quartiles of the

altered cell signaling and expression of AR spice variants. Cell signaling in

current cohort. Then, specific 68Ga-DOTATATE TV cut-offs were set using a

prostate cancer is regulated by dual specificity phosphatases and tumor

receiver operating characteristic (ROC) curve analysis, and the risks for DSM and

suppressors INPP4B and PTEN that are lost with prostate cancer progression.

PFS were validated with Kaplan-Meyer and Cox regression analyses.

Loss of PTEN destabilizes AR and alters AR transcriptional output. We

Results

investigated how loss of INPP4B affects AR signaling. We have previously

Patients were followed for a median of 18 months (range 4-35 months). 68Ga-

shown that AR induces expression of INPP4B in prostate cancer. Intriguingly, AR

DOTATATE TV quartiles had inverse correlation with PFS (PZ0.001) and

splice variant AR-V7, which also contributes to ADT resistance, was unable to

survival rates

(PZ0.002). Using cut-offs derived from ROC curve analysis,

induce INPP4B expression. We performed microarray analysis of changes in gene

68Ga-DOTATATE TV R7.0 was associated with a lower PFS (HRZ2.0,

expression caused by INPP4B knockdown. Gene expression clustering and GSEA

PZ0.03), and 68Ga-DOTATATE TV R35.8 ml was associated with increased

analysis revealed that the INPP4B loss significantly altered AR transcriptional

(HRZ10.7) disease-specific mortality in multivariate analysis (PZ0.03), as well

activity. Using immunofluorescent labeling with 3D rendering we determined that

as in subgroup analysis of patients with pancreatic NETs.

INPP4B localizes to cellular and endoplasmic membranes. We and others have

Conclusions

shown that INPP4B suppresses PI3K/Akt and PKC pathways. We show that

We show for the first time the prognostic utility of 68Ga-DOTATATE TV in a

INPP4B specifically inhibits PKCz and bII in multiple prostate cancer cells. The

large cohort of patients with NETs, enabling clinicians to determine the need for

analysis of PI3K, Akt and PKC specific inhibitors, LY294002, AZD5363, and

intervention using this non-invasive tool.

BIM-I, showed that Akt and PKC signaling did contribute to the changes in AR

signaling. We investigated INPP4B functions in prostates of Inpp4b^K/K mice.

DOI: 10.1530/endoabs.49.OC7.3

AR expression in mouse prostate was not affected by the loss of INPP4B.

Remarkably, expression of several direct AR target genes like Msmb, Apof, and

Nkx3.1 was significantly reduced in Inpp4b^K/K prostates. We compared Akt and

PKC signaling in the anterior (AP), dorsal/lateral (DLP) and ventral (VP) prostate

lobes of the wild-type and Inpp4b^K/K mice. Loss of INPP4B increased Akt

signaling in DLP and VP and PKC z and b II pathways in AP and DLP. We

determined that levels of PTEN protein were unchanged in Inpp4b^K/K mouse

OC7.4

prostates suggesting that Akt signaling was elevated exclusively due to Inpp4b

A novel insight into the anticancer mechanism of metformin in

loss. Taken together, full length AR, but not AR-V7 induce INPP4B expression.

Pancreatic Neuroendocrine Tumor cells

INPP4B reciprocally modulates AR transcriptional activity without altering AR

Eleonora Vitali¹, Sara Piccinini¹, Ilena Boemi¹, Alberto Tresoldi¹,

protein level in both normal prostate and prostate cancer cells and suppresses

Alessandro Zerbi², Carlo Carnaghi³, Anna Spada⁴ & Andrea Lania^1,5

Akt and PKCz and b II signaling and the suppression is required for optimal AR

¹Laboratory of Cellular and Molecular Endocrinology, IRCCS Humanitas

transcriptional activity.

Research Hospital, Rozzano, Italy;²Pancreas Surgery Unit, IRCCS

DOI: 10.1530/endoabs.49.OC7.5

Humanitas Research Hospital, Rozzano, Italy;³Oncology Unit, IRCCS

Humanitas Research Hospital, Rozzano, Italy;⁴Endocrinology and

Diabetology Unit, IRCCS Ospedale Maggiore Policlinico, Milano, Italy;

⁵Department of Biomedical Sciences, Humanitas University, Rozzano,

Italy.

Neuroendocrinology

Metformin (1.1-dimethylbiguanide hydrochloride), a widely used antidiabetic

OC8.1

drug, has been reported to display potent anticancer properties in various types

Elucidating the molecular mechanisms underlying AIP dependent

of cancers, including neuroendocrine tumors. Recently, a potential synergistic

tumorigenesis

activity between metformin and octreotide (SSA) in Pancreatic Neuroendocrine

Eva-Maria Bogner¹, Adrian F. Daly², Albert Beckers², Michael J. Atkinson³

Tumors (P-NETs) has been proposed. AIP (aryl hydrocarbon receptor-interacting

& Natalia S. Pellegata¹

protein) acts as tumor suppressor gene in neuroendocrine tumors at pituitary level

¹Institute for Diabetes and Cancer, Helmholtz Center Munich, Munich,

and it is up-regulated by SSA. We investigated the effects of metformin on

Germany;²Department of Endocrinology, Centre Hospitalier Universitaire

P-NETs cell proliferation, apoptosis and colony formation, the potential

de Liège, University of Liège, Liège, Belgium;³Institute for Radiation

synergistic effect between metformin and octreotide and the possible role of

Biology, Helmholtz Center Munich, Munich, Germany.

AIP pathway in mediating these effects. We found that in QGP-1 cells metformin

significantly inhibited cell proliferation

(K37G2% P!0.001 vs basal at

10 mM). We showed no additive effect between Metformin and Octreotide on

Pituitary adenomas (PAs) are benign neoplasms that comprise 10-20% of all

P-NETs cell proliferation. Moreover, metformin incubation reduced colony

intracranial tumors. Mutations in the aryl hydrocarbon receptor interacting

formation, cells amount after 7 days (K66G6% P!0.001 vs basal) and it

protein (AIP) have been identified to cause a small subset of hereditary PAs. To

promoted apoptosis (C150G8% P!0.05 vs basal). As expected, octreotide

study the mechanisms of tumor formation in patients with AIP-mutated PAs we

induced AIP up-regulation (C60G11% P!0.05 vs basal), and surprisingly, AIP

conducted a miRNA array analysis comparing AIP-mutated PAs with AIP-wild

expression levels were also increased by metformin (C90G13% P!0.05 vs

type PAs. We found a novel and specific set of miRNAs differentially expressed

basal). In addition, AIP silencing abolished the antiproliferative and proapoptotic

between the two groups of PAs. We selected several candidate miRNAs and

effects of metformin, confirming its involvement in mediating metformin effects.

validated them in the patient tissues. To characterize the candidate miRNAs

Interestingly, metformin decreased HSP70 expression, increased Zac1 and AhR

in vitro and clarify their role in AIP dependent tumorigenesis we performed

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

functional studies using mouse embryonic fibroblasts (MEFs) derived from Aip

¹Section of Specialized Endocrinology, Department of Endocrinology, Oslo

knockout (AIP-KO) mice and a rat somatotroph tumor cell line (GH3). In the

University Hospital, Oslo, Norway;²University of Southern Denmark,

AIP-KO MEFs we saw that transfection of mutant AIP altered the expression of

Odense, Denmark;³Department of Medical Genetics, Oslo University

two of the candidate miRNAs according to the changes observed in the miRNA

Hospital, Oslo, Norway;⁴Faculty of Medicine, University of Oslo, Oslo,

array. Additionally, cell viability and cell migration were increased after

Norway;⁵Research Institute for Internal Medicine, Oslo University

transfection of mutant AIP. Since deregulation of cAMP levels is a common

Hospital, Oslo, Norway;⁶Latvian Biomedical Research and Study Centre,

feature of PAs we also checked cAMP levels upon transfection of mutant AIP. We

Riga, Latvia;⁷Department of Endocrinology and Metabolism, Odense

could observe that mutant AIP increased cAMP levels in AIP-KO MEFs.

University Hospital, Odense, Denmark.

Overexpression of the candidate miRNAs in GH3 cells increased cell migration

and cAMP levels while apoptosis was decreased. To further clarify the role of the

Background

selected miRNAs in tumor development we identified their predicted targets and

Non-functioning pituitary adenomas (NFPAs) necessitate prolonged clinical,

focused on those involved in cAMP signalling. We plan to validate the role of

biochemical and radiological observation, constituting a significant burden in

these predicted targets in PAs in the future. In conclusion, we identified novel

terms of medical resources and societal costs. Reliable biomarkers associated

miRNAs in AIP-mutated PAs and were able to show that these miRNAs promote

with aggressiveness and recurrence of NFPAs are lacking. As the growth of tumor

a tumor-like behaviour in several functional assays in AIP-KO MEFs and GH3

remnants is highly variable, molecular markers that can predict growth potential

somatotroph cells.

and tumor behavior are necessary.

DOI: 10.1530/endoabs.49.OC8.1

Aim

To identify target genes in fast- and slow- growing NFPAs estimated by

postoperative initial tumor volume doubling time (TVDT), and to find reliable

biomarkers predicting the growth potential of the remnant tumor, focusing on the

specific role of epithelial-mesenchymal transition (EMT) process.

Material and methods

RNA sequencing was performed in gonadotroph NFPAs with short TVDT

OC8.2

(median

!30.05 months, fast group, nZ4) and long TVDT

(median

Knocking down/out the prokineticin pathway during zebrafish

O30.05 months, slow group, nZ4). Data was analyzed by tophat2

and

development results in the GnRH neurons axons misguiding

cufflinks/cummeRbund pipeline. Furthermore, genes

(nZ40) were selected

Ivan Bassi¹, Federica Marelli¹, Valeria Vezzoli², Luca Persani^1,2,

based on significance, fold of change and pathway analysis for validation with

Yoav Gothilf³ & Marco Bonomi^1,2

RT-qPCR in a larger cohort of gonadotroph NFPAs (nZ20, 13 male).

¹Laboratory of Experimental Endocrinology, Istituto Auxologico Italiano

Results

IRCCS, Milan, Italy;²Department of Clinical Sciences and Community

RNA sequencing identified 350 genes significantly differentially expressed,

Health, University of Milan, Milan, Italy;³Department of Neurobiology,

between the two groups (285 genes up- and 65 down- regulated in the fast group,

The George S. Wise Faculty of Life Sciences and Sagol School of

P adjusted !0.05). Of the 40 genes chosen for further validation by RT-qPCR, 11

Neuroscience, Tel-Aviv, Israel.

showed significant correlations with TVDT (K0.669%RRK0.466, P!0.05).

These were six genes involved in EMT (PCDH18, SPAG9, SKIL, MTDH,

HOOK1 and CNOT6L), and also UNC5D, EMCN, MYO1B, GPM6A and

Studies conducted using knockout mouse model revealed that defects of PROKR2

PRKACB.

affect the correct ontogeny of GnRH neurons and, by consequence, neuroendo-

Conclusions

crine control of reproduction. Nevertheless its exact role during these processes

Fast- and slow- growing NFPAs show different gene expression profiles. Genes

and in the pathogenesis of congenital hypogonadotropic hypogonadism (CHH)

known as related to EMT have higher expression in fast-growing tumors,

remains elusive due to the phenotypic differences observed between mouse and

suggesting a pathogenic role in tumor growth. The identified genes and their

human. Zebrafish (ZF) has emerged in the last ten years as a reliable model

products could represent useful markers for predicting tumor aggressiveness and

organism for studying the GnRH neuronal development and the neuroendo-

recurrence, and may be potential targets for drug therapy.

crinology of reproduction. Previous results obtained in our lab identified two well-

DOI: 10.1530/endoabs.49.OC8.3

conserved loci in the ZF genome, on chr1 and chr13, respectively named prokr1a

and prokr1b. Whole mount in situ hybridization

(WISH) and qRT-PCR

experiments conducted at different developmental stages of ZF revealed distinct

patterns of expression for prok-receptors suggesting prokr1b as the potential

candidate involved in the GnRH-secreting neurons migration process from

olfactory placode to their final hypothalamic destination. To verify these

OC8.4

indications and better elucidate the function of both prokineticins receptors we

Cerebrovascular stroke incidence in GH-treated adults: experience

recently conducted knockdown experiments using morpholino oligonucleotides

from KIMS (Pfizer International Metabolic Database)

sequences. Our results display an alteration of the GnRH fibers network

Cecilia Camacho-Hubner¹, Jose Cara¹ & Anders Mattsson²

architecture at 48 hours post fertilization (hpf) after downregulation of prokr1b

¹Endocrine Care, Pfizer Inc, New York, NY, USA;²Endocrine Care, Pfizer

that appeared misguided and reduced in numbers especially at level of pallium

Health AB, Sollentuna, Sweden.

commissure and optic chiasm. Moreover, we also generated in ZF the prokr1b

knockout model and our preliminary data are confirming the knockdown model

observations. On the contrary, the downregulation of prokr1a does not affect

Background and aim

GnRH fibers architecture. Taken together these results confirm the role of prokr1b

Patients with GH deficiency (GHD) have increased risk of cerebrovascular

during GnRH neurons migration establishing it as the ZF orthologous of human

events. The aim of this study was to evaluate the rate and factors associated with

PROKR2. A deeper characterization of ZF prokr1b KO model could provide new

the occurrence of stroke, a major cause of death and disability, in adults with

information regarding the early establishment of the forebrain GnRH system, the

GHD.

factors controlling this complex developmental event, and its functional

Patients and methods

significance.

Data from 15,188 GHD patients treated with GH replacement therapy (GHRT)

This work was supported by funds from University of Milan (Dotazione per

enrolled in KIMS were analyzed. Stroke incidence rates were compared to rates

attività istituzionali—Linea 2 azione B Piano di Sviluppo di Ateneo) and IRCCS

from the Oxford Vascular Study (Lancet_2004; 363:1925-33) by standardized

Istituto Auxologico Italiano (Ricerca Corrente Funds: 05C202 and GONAFISH).

incidence ratios (SIRs). Age at first radiotherapy (RT) corrected for attained age

Funds: 05C202 and GONAFISH).

and sex, was analyzed with Poisson regression.

Results

DOI: 10.1530/endoabs.49.OC8.2

Causes of GHD comprised pituitary adenoma 42.9%, craniopharyngioma 10.8%

and idiopathic GHD 15.6%. Mean age at KIMS entry was 43.7 (range 17-75)

years. Mean GH dose was 0.42 mg/day and number of patient treatment-years

was 81,086. Mean age at first radiotherapy (RT) was 34.5 (range 3-72) yrs. First-

ever stroke was reported in 155/7667 (M) and 123/7521 (F) patients. The crude

OC8.3

incidence was 377 (M) and 308 (F) per 100,000 patient- years and overall SIR was

RNA sequencing and RT-qPCR identify different gene expression

2.51

(95% CI: 2.22-2.82). SIR ranged between causes of GHD from 1.02 (0.41-

profiles in fast- vs. slow-growing non-functioning pituitary adenomas

2.1) in patients with Idiopathic GHD and unexposed to RT to 19.3 (11.6-30.1) in

Camilla Maria Falch^1,2, Arvind Y.M. Sundaram³, Kristin Astrid

patients with GHD secondary to a malignant cranial tumor. RT was reported in

Berland Øystese^1,4, Kjersti Ringvoll Normann^1,4, Ivars Silamikelis⁶,

3866 patients and 146 reported a stroke (SIR: 3.96; 3.35-4.66). Rates were

Marianne Andersen⁷, Jens Bollerslev^1,4 & Nicoleta Cristina Olarescu^1,5

increased in all ages at first exposure (P!0.01), especially in younger patients

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

(RRZ2.2 (1.05-4.63) for !18 vs R18 years of age). Among 11,322 patients

the highest prevalence of elevated BP (60%), elevated glucose (22.7%), waist

who did not receive RT, 132 cases were reported, SIR 1.78 (1.49-2.11).

circumference (33.4%) and TG (30.2%), low HDL-cholesterol (26.5%), and MetS

Conclusion

(27.7%). In women, the lowest FT4 quartile was only associated with elevated TG

GHD patients have a significantly increased rate of strokes with considerable

(11.2%), waist circumference (47.4%), and MetS (13.8%). In contrast, higher FT3

variability between causes of GHD. Rates were positively associated with RT in

levels were associated only with low HDL-cholesterol in both sexes, and with a

all studied ages, with younger patients at first RT showing a higher risk.

higher percentage of participants with R3 MetS components (21.6% in men,

DOI: 10.1530/endoabs.49.OC8.4

12.4% in women).

Conclusions

Levels of FT4, but not FT3, were inversely associated with all components of the

metabolic syndrome in men, and with elevated TG, waist, and overall MetS in

women.

DOI: 10.1530/endoabs.49.OC9.1

OC8.5

Ephrin-B2 is required for pituitary development

Fernando Jimenez, Angelica Gualtieri, Valeria Scagliotti &

Carles Gaston-Massuet

WHRI, Queen Mary University of London, London, UK.

OC9.2

Effect of restoration of euthyroidism in patients with hypothyroidism on

The pituitary progenitors are responsible for generating a fully functional

cold induced thermogenesis

endocrine organ during embryonic development. They also preserve potency, to

Claudia Maushart, Rahel Loeliger, Cemile Bathelt, Nina Hutter,

maintain the homoeostasis in the adult pituitary, being able to respond to

Mirjam Christ-Crain & Matthias Betz

endocrine challenges, such as pregnancy or obesity. But the main players of this

Department of Endocrinology, Diabetes and Metabolism, University

complex process remain elusive. Eph-Ephrins have been implicated in an

Hospital Basel, Basel, Switzerland.

increasing number of physiological functions such as axon-guidance, eye field

segregation from neural plate, tissue boundary formation, cell migration,

angiogenesis and more recently stem cell maintenance and differentiation in the

Background

colon and mammary gland. However, the EprhinB:EphB signalling pathway in

Thyroid hormones have been shown to be necessary for proper function of brown

hypothalamic-pituitary function is not known. Using a transgenic line that

adipose tissue (BAT) and cold induced thermogenesis (CIT) in rodent models. In

expresses GFP under the EphrinB2 (Efnb2) genetic locus we observed that cells

humans hyperthyroidism has been demonstrated to activate BAT and increase

expressing Efnb2 are localised in the pituitary progenitor of the anterior pituitary.

thermogenesis. However, the data on CIT in humans in the hypothyroid vs. the

We found Efnb2 co-expressed with known PPSCs markers Sox2/Sox9 during

euthyroid state are limited and conflicting.

embryogenesis and this expression continues in adulthood, suggesting a role in

Methods

adult pituitary homoeostasis. Conditional genetic removal of Efnb2

in the

This was a prospective observational study. We recruited 40 patients presenting

undifferentiated precursor using a Cre-pituitary line, results in significant pituitary

to a University hospital out-patient endocrine clinic with subclinical or overt

abnormalities, comprising multiple bifurcations hyperplasia of the anterior

hypothyroidism, and in whom thyroid hormone replacement was planned.

pituitary gland. These data suggest for the first time, that Efnb2 is a critical

Currently, 24 patients completed the study. Thermogenesis was measured by

regulator of pituitary development and could have an effect on hypothalamic-

indirect calorimetry during warm conditions and after a mild cold stimulus of

pituitary body endocrine regulations. Interestingly a proportion of Efnb2 Knock-

90 min, both during the hypothyroid state and after at least 3 months of sufficient

out animals exhibit features of congenital hypopituitarism, such as dwarfism and

thyroid hormone replacement. CIT was determined as the difference between

eye abnormalities suggesting that, in this physiological context, Efnb2 could be a

resting energy expenditure (REE) during cold (REEcold) and warm (REEwarm)

candidate gene for rare unknown conditions such Septo-Optic Dysplasia.

conditions. Additionally, skin temperature was measured using wireless probes in

DOI: 10.1530/endoabs.49.OC8.5

one-minute intervals in the supraclavicular region adjacent to the major human

BAT depot. The primary endpoint was CIT in the hypothyroid vs euthyroid state.

Data were analysed by non-parametric tests and are given as meanGS.D.

Results

CIT increased from 73(G103) kcal/d during the hypothyroid state (CIThypo) to

160

(G143) kcal/d in the euthyroid state (CITeu), PZ0.0007. REEwarm was

Thyroid Disease 2

1324

(G120) kcal/d during hypothyroidism and rose slightly to 1395(G140)

kcal/d, PZ0.0137. REEcold rose profoundly from

1396(G157) kcal/d to

OC9.1

1555(G178) kcal/d, PZ0.0001. While the inter-individual variability of CIT

Thyroid function and metabolic syndrome: results from the population-

was large, the correlation between CIThypo and CITeu was moderate, rZ0.657,

based LifeLines Cohort study

PZ0.001. The change in supraclavicular skin temperature during cold exposure

Bruce Wolffenbuttel, Hanneke Wouters, Sandra Slagter,

correlated with CIT in the euthyroid

(rZ0.389, PZ0.067), but not in the

Robert van Waateringe, Jana van Vliet-Ostaptchouk, Thera Links &

hypothyroid state (rZ0.041, PZ0.853).

Melanie van der Klauw

Conclusion

University of Medical Center Groningen, Groningen, The Netherlands.

Cold induced thermogenesis is blunted in hypothyroid patients and increases

markedly after restoration of euthyroidism. The difference in CIT is larger than

the difference in resting energy expenditure during warm conditions.

Background

DOI: 10.1530/endoabs.49.OC9.2

The metabolic syndrome (MetS) is a combination of unfavourable health factors

including abdominal obesity, dyslipidaemia, hypertension and impaired fasting

glucose. Several small-scale studies have reported a relationship between thyroid

function and some MetS components or suggested that serum FT3 levels within

the normal range were independently associated with insulin resistance. We

assessed how thyroid function relates to the prevalence of MetS in a large

OC9.3

population-based study.

How much of the genetic predisposition to Hashimoto’s thyroiditis can

Methods

be explained by genes commonly associated with the disease?

Data of 26,719 western European participants aged 18-80 years from the Dutch

Anna Skalniak^1,2, Agata Jabrocka-Hybel^1,2, Jakub Piętkowski²,

LifeLines Cohort study, all with normal TSH, FT4

and FT3

levels

Renata Turek-Jabrocka^1,2, Dorota Pach^1,2, Agnieszka Ludwig-Gałęzowska³,

(electrochemiluminescent immunoassay, Roche Modular E170

Analyzer),

Julita Machlowska³, Przemysław Kapusta³, Paweł Wołkow³ &

were available. MetS was defined with the revised NCEP ATP III criteria. We

Alicja Hubalewska-Dydejczyk^1,2

calculated prevalence of all MetS components according to FT4

and FT3

¹Chair and Department of Endocrinology, Jagiellonian University Medical

quartiles.

College, Krakow, Poland;²Endocrinology Department, University Hospital

Results

in Krakow, Krakow, Poland;³Center for Medical Genomics OMICRON,

At similar TSH levels and age (mean 45 yrs), men had significantly higher levels

Jagiellonian University Medical College, Krakow, Poland.

of FT4, FT3, blood pressure

(BP), heart rate, total and LDL-cholesterol,

triglycerides

(TG), and creatinine, but lower HDL-cholesterol compared to

women (all P!0.001). In total, 9.1% of women and 10.2% of men were treated

Background

with BP-lowering agents. In men, lower FT4 levels were associated with higher

Hashimoto’s thyroiditis (HT) is a common autoimmune disorder of the thyroid

prevalence of all MetS components. The lowest FT4 quartile was associated with

(AITD) which affects about 1-2% of the European population. The disease often

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

clusters in families, which is why many attempts have been undertaken to find the

Conclusions

genetic background that would underly the predisposition to HT. In contrast to

Thyroid dysfunction during the use of PD-1/PD-L1 blockade and its severity

another AITD - Graves’ disease, results of genetic analyses have been ambiguous

predict its favorable disease outcome in NSCLC patients. Therefore, regular

and have failed to find a major genetic locus that would be essential for HT

measurement of thyroid hormone levels during the use of PD-1/PD-L1 blockade

development.

could be the good biomarker of immune monitoring.

Aim

DOI: 10.1530/endoabs.49.OC9.4

To assess the joined impact of disease loci associated in the literature with HT

predisposition.

Methods

One hundred and forty seven HT fully-symptomatic patients and 147 healthy

controls (matched for age, gender, incomes, education, marital status and place of

descent), unrelated to each other, were genotyped for

polymorphisms

(Illumina GoldenGate, custom panel), which were located in genes most often

tested in literature for association with AITD, or typed out by genome-wide

association studies. All polymorphisms were confirmed to be in Hardy-Weinberg

equilibrium in the control group (PO0.05). Variations in the HLA-DRB1 gene

were analyzed by Sanger sequencing. A genetic model for HT predisposition was

OC9.5

obtained with use of stepwise logistic regression. Biostatistical analyses were

Selenium supplementation in the management of thyroid autoimmunity

performed with the programs Statistica v12, Plink v1.9, and GCTA v1.02.

during pregnancy: results of the ‘Serena Study’ a randomized,

Results

double-blind, placebo-controlled trial

The model which best explained the predisposition to HT contained seven

Carla Di Dato¹, Giovanna Mantovani², Costanzo Moretti³, Ermanno Greco⁴,

polymorphisms in the genes PTPN22, IFIH1, CTLA4, RGS6, TNMD, NOX1, and

Marco Bonomi⁵, Antongiulio Faggiano⁶, Stefania Di Sante¹,

the promoter region of FAM155A. The model was able to classify correctly 67%

Vincenzo Giannetta¹, Luisa Petrone⁷, Angela Fumarola¹,

of all cases, similarly for both groups. Such a model explained only 5.12% of the

Annamaria Colao⁸, Andrea Lenzi¹, Andrea M. Isidori¹ & Elisa Giannetta¹

between-group variance. This value is in agreement with a model published lately

¹Department of Experimental Medicine - Sapienza University of Rome,

for another autoimmune disorder.

Rome, Italy;²Endocrine Unit, Department of Clinical Sciences and

Discussion

Community Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore

Our data confirm that there seem to be no genes that are per se crucial for HT

Policlinico, University of Milan, Milan, Italy;³Unit of Endocrinology,

development. Future analyses on HT predisposition should focus on the joined

Section of Reproductive Endocrinology, Department of Systems’ Medicine,

influence of many polymorphisms in different genetic regions.

University of Rome Tor Vergata, Rome, Italy;⁴Centre for Reproductive

DOI: 10.1530/endoabs.49.OC9.3

Medicine, European Hospital, Rome, Italy;⁵Department of Clinical

Sciences and Community Health, University of Milan, Milan, Italy;

Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la

Cura dei Tumori-IRCCS, Fondazione G. Pascale”, Naples, Italy;

Endocrinology Unit, Careggi Hospital and University of Florence,

Florence, Italy;⁸Endocrinology Unit, Department of Clinical Medicine and

Surgery, University of Naples Federico II, Naples, Italy.

Autoimmune thyroiditis and related complications represent a growing concern

during pregnancy. Selenium is frequently present in nutraceuticals recommended

OC9.4

for thyroiditis and pregnancy, given its advocated role in immunity, fertility and

Thyroid dysfunction during the use of PD-1/PD-L1 blockade predicts its

thyroid function. However, most evidences come from non-controlled studies.

therapeutic response in the patients with advanced non-small cell lung

Materials and Methods

cancer

We designed a multicenter, randomized, double-blind, placebo-controlled trial

Hye In Kim¹, Tae Hyuk Kim¹, Hye Won Jang², Young Nam Kim¹,

(Serena Study: NCT01465867) to evaluate the effects of L-selenomethionine (Se)

Hosu Kim¹, So Young Park¹, Sun Wook Kim¹ & Jae Hoon Chung¹

supplementation on antibodies title in euthyroid women with positive anti-thyroid

¹Samsung Medical Center, Seoul, Republic of Korea;²Sungkyunkwan

antibodies that are pregnant or undergoing in-vitro fertilization. Secondary

University School of Medicine, Seoul, Republic of Korea.

outcomes included: implantation rates, pregnancy rate, delivery, obstetrical, fetal

and neonatal complications. Ten endocrinology and gynecology Italian referral

centers participated. The study was promoted and supported by EnGioI Club

Background

(Italian Young Endocrinology).

PD-1/PD-L1 blockade is one of the promising drugs in the treatment of advanced

Results

non-small cell lung cancer (NSCLC). and predicting drug effect is important due

56 women were randomly assigned to placebo (PLB) or Se 83 mcg/die. Thyroid

to unique pattern of response. Immune-related adverse event (IRAE) might be

hormones, TgAb, TPOAb, selenium concentration were measured during

associated with favorable clinical outcome. Thyroiditis is the most common IRAE

pregnancy and after labor (months 38 to 68). All analysis were centralized. Of

which can be easily detected with the measurement of thyroid hormone levels.

the enrolled women,

(80.3%) were pregnant and

(19.6%) embryo

However, the relationship between thyroid dysfunction during the use of

transferred. A significant reduction of TgAb was observed in Se-treated women

PD-1/PD-L1

blockade and its therapeutic response has not been well

after labor: treatment effect dZ108.67 (95%CI:K1.3, 218.6; PZ0.03). The

demonstrated in advanced NSCLC patients.

change in antibodies was paralleled by a significant increase in selenium serum

Methods

concentration measured already at

36G2 weeks:

(PLB:K11G23.76,

A total 53 patients with stage IV NSCLC treated with PD-1/PD-L1 blockade were

Se:C30.5G17.63; treatment effect dZ35.57 95% CI:14.9, 62.3; PZ0.004)

enrolled. Patients were categorized into thyroid dysfunction and euthyroid group.

and confirmed after labor: treatment effect dZ17.56

(95% CI: 3.9,

31.2;

Overall survival (OS) and progression free survival (PFS) of two groups were

PZ0.014). Post-labor rebound in antibodies’ title of PLB treated, as compared to

compared. Hazard ratio (HR) adjusting patients, tumor, and drug factors were

Se-treated women was paralleled by a trend toward TSH rise (PLB:C3.96G

analyzed using Cox proportional hazard model. Response rate (RR) and durable

12.56 vs Se: C1.69G6.00). Safety analysis showed no discontinuation in the

RR were assessed according to thyroid dysfunction and its severity.

Se-treated subjects. Two miscarriage occurred in PLB vs 0 in Se-treated. No

Results

differences were found in fetal and maternal complications. The pregnancy rate

OS (mean 148.5G82.6 vs 82.0G65.1, log-rank PZ0.003) and PFS (143.2G88.2

after embryo transfer was 3/5 (60%) in Se-treated vs 1/6 (16.6%) in PLB.

68.0G50.0, log-rank PZ0.001) were significantly longer in the thyroid

Conclusion

dysfunction group. After adjustment for age, sex, smoking status, tumor stage,

SERENA Study demonstrated a beneficial effect on the title of TgAb with a safety

and drug type, adjusted HR (95% CI) for overall death and progression disease

profile. Larger studies are needed to confirm the trends observed on post-partum

were 0.08 (0.01-0.65) and 0.29 (0.12-0.69) compared with euthyroid group. RR

thyroiditis recurrence and hypothyroidism, miscarriage and pregnancy rate in

(36.0 vs 10.7%, PZ0.028) and durable RR (28.0 vs 0%, PZ0.003) were more

in vitro-fertilization.

frequent in the thyroid dysfunction group. Severity of thyroid dysfunction was

DOI: 10.1530/endoabs.49.OC9.5

also associated with RR (P for trend Z0.018) and durable RR (P for trend Z

0.001).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Bone & Calcium Homeostasis

were collected form clinical records. TBS was calculated by reevaluating the

already existing BMD images. Patients were classified into two different groups

OC10.1

according to their treatment: 1) 13 patients who underwent surgery, in whom TBS

Treatment of 711 patients with hypoparathyroidism: a retrospective

was evaluated before surgery (B-S) and one year after surgery (A-S), and 2) 10

study in 3 German endocrine centres

patients who received standard medical treatment, in whom TBS was evaluated

Martin Grussendorf¹, Bettina Stamm², Niklas Stamm^3,4 &

with a time-lapse of 1 year. Basal age, body mass index (BMI), serum calcium,

Heide Siggelkow^4,5

vitamin 25-OH-D levels and T-Scores were not significantly different between the

¹Endocrine Centre, Stuttgart, Germany;²MVZ Endokrinologikum, Saar-

two groups. Only PTH levels (82 vs 110 pg/ml, PZ0.04) presented differences.

brucken, Germany;³Endocrinology and Metabolism, University Medicine,

We observed a significant improvement of TBS one year after surgery in the first

Mainz, Germany;⁴Clinic of Gastroenterology and Gastrointestinal

group (1.244G 0.11 vs 1.311G0.1 PZ0.08). A subtle deterioration on TBS was

Oncology, University Medical Center, Gottingen, Germany;⁵MVZ

observed one year after standard treatment in the second group (1,249G0.06 vs

Endokrinologikum, Gottingen, Germany.

1.223G0.07 PZ0.124). Overall, surgical patients experienced a TBS increase

5.8% whilst a decrease of K2.04% was observed in the second group (PZ0.02).

In the multivariate correlation analysis, the percentage of variance in TBS was

Care of patients (pts.) with hypoparathyroidism (HypoPT) is a challenge, because

negatively correlated with the level of PTH and calcium at the moment of the

pts. are usually not treated with the absent hormone, but with several forms of

second BMD (0.04 and 0.03 respectively). Bone microarchitecture, measured by

vitamine D. We retrospectively evaluated the data of pts. with HypoPT in three

TBS, improves after surgery in patients with PHH and has shown to be sensitive

endocrine centres in Germany.

to changes developed during only one year time-lapse in bone. This parameter is a

Methods

promising tool in the evaluation of bone status in PHH.

Records of 711 pts. with HypoPT (Centre 1 (C1): nZ381, C2: nZ253, C3:

nZ77) were reviewed (female: 592, male: 119). The following data under

DOI: 10.1530/endoabs.49.OC10.2

treatment (time range 2-199 months) were evaluated: medication, Calcium (Ca) -

values, tingling sensations (paresthesia), and cramps.

Results

Of these 711 pts. 29 had idiopathic HypoPT, 10 HypoPT after parathyroidectomy,

669 after thyroid operation (Tx): subtotal Tx: 471, HemiTx: 12, totalTx: 186 pts.

Age of pts. at first visit (V1): 49.85 years (mean), time between Tx and V1: 76.85

months (mean, range 0-733 months). Mean values of Ca (mmol/l), PO4 (mg/dl)

OC10.3

in serum, Ca in urine (Ca U; mmol/24 h); % of patients with paresthesia (par.) and

High prevalence of radiological vertebral fractures in patients with

cramps under different therapies (mean daily dose in brackets) as follows:

differentiated thyroid carcinoma undergoing L-thyroxine

TSH-suppressive therapy

Anna Maria Formenti¹, Gherardo Mazziotti², Stefano Frara³,

Filippo Maffezzoni¹, Mauro Doga³, Francesco Bertagna⁴, Roberto Maroldi⁵,

Medication

PO4

Ca U par. % cramps %

Maurizio Memo¹, Raffaele Giubbini⁴ & Andrea Giustina³

Department of Molecular and Translational Medicine, University of

Calcium (1462 mg/d)

2.08

1.49

1.67

Brescia, Brescia, Italy;²Department of Internal Medicine, Mantua Hospital,

Vitamine D

2.12

1.46

2.88

Mantua, Italy;³Chair of Endocrinology, Vita-Salute San Raffaele

(11,442 U/d),

University, Milan, Italy;⁴Chair of Nuclear Medicine, University of Brescia,

Ca (1245)

Brescia, Italy;⁵Chair of Radiology, University of Brescia, Brescia, Italy.

1-Alphacalcidol

2.19

1.26

2.65

(2.41 ug/d), Ca (1321)

1-Alphac.(1.26),

2.19

1.44

2.65

Thyroid hormones play a central role in the regulation of bone turnover and

Vit.D (15,949),Ca

thyrotoxicosis is an established cause of secondary osteoporosis. Increased

(1005)

prevalence of reduced bone mineral density (BMD) has been reported even in

Calcitriol (0.64 ug/d),

2.19

1.43

2.52

patients with subclinical thyrotoxicosis such as those with differentiated thyroid

Ca (1354)

carcinoma undergoing long-term L-thyroxine (L-T4) TSH-suppressive therapy.

Calcitr.(0.60),

2.18

1.34

3.27

Morphometric vertebral fractures (VFs) are an early and clinically crucial marker

Vit.D (9845), Ca (1133)

of bone fragility but they have never been investigated so far in this setting. In this

Tachysterin (0.73 mg/d)

2.29

1.35

2.52

cross-sectional study, we evaluated the VF prevalence

(DXA quantitative

Tachysterin (0.77),

2.22

1.43

2.75

morphometry) and BMD (DXA Hologic 4500 W, at lumbar spine, total hip and

Ca (1292)

femoral neck) in 53 consecutive patients with differentiated thyroid carcinoma

(two males, 51 females; median age 61 years, range: 42-82; 45 with papillary

carcinoma and eight with follicular carcinoma; median duration of therapy

Conclusion

5 years, range: 1-45) and 75 control subjects (72 females and three males; median

As expected monotherapy with high doses of calcium was not sufficient. The

age 62 years, range: 42-83) with normal thyroid function attending an outpatient

combination of 1-Alphacalcidol and Calcium was the best regimen for treating

bone clinic. VFs were significantly more prevalent in patients with thyroid

HypoPT and improving complaints. Further correlations between different

carcinoma as compared to the control subjects (30.2 vs 9.3%; PZ0.002) without

treatment regimen and parameters of renal and bone metabolism will be

significant (PZ0.21) differences in BMD at either skeletal sites. BMD was not

calculated.

significantly different between fractured and non-fractured TSH suppressed

patients at either skeletal site. Prevalence of VFs was not significantly (PZ0.29)

DOI: 10.1530/endoabs.49.OC10.1

different among patients with normal BMD (11.1%), osteopenia (39.1%) and

osteoporosis (28.6%). In patients under TSH-suppressive therapy, VFs were

significantly associated with age (OR 1.1, C.I.95% 1.01-1.12; PZ0.03) but not

with duration of L-T4 therapy (OR 1.03; C.I.95% 0.96-1.11; PZ0.34). This is the

first study showing high prevalence of VFs in patients with thyroid carcinoma

OC10.2

undergoing L-T4 TSH-suppressive therapy likely due to an impairment in bone

Evaluation of bone quality, measured by trabecular bone score (TBS) in

quality. Vertebral morphometry should be performed at baseline and during

patients with primary hyperparathyroidism (PHH) with and without

follow-up of TSH-suppressed patients to assess their skeletal health.

surgery

DOI: 10.1530/endoabs.49.OC10.3

Isabel Huguet, Miguel Sampedro-Nú

˜ez, Jose Luis Mun˜ oz De Nova,

Ana Ramos-Levi, Sandra Campos, Eugenio Escolano & Mónica Marazuela

Hospital La Princesa, Madrid, Spain.

Evaluation of bone quality represents a challenge since the analysis by bone

OC10.4

mineral density (BMD), provides useful but incomplete information. New tools

The effect of denosumab or bisphosphonates in women with severe

are arising, and amog them, TBS is emerging as a new surrogate marker of bone

postmenopausal osteoporosis after completion of teriparatide treatment

texture and microarchitecture which may be useful to potentially evaluate the risk

Tomaz Kocjan¹, Antonela Sabati Rajic¹, Mojca Jensterle Sever¹,

of bone fracture and can be obtained from already existing BMD scans.

Gaj Vidmar², Barbara Ostanek³, Janja Marc³, Nina Orehek³ &

Retrospective study of 23 patients with PHH. Clinical, analytical and BMD data

Marija Pfeifer¹

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

University Medical Centre Ljubljana, Ljubljana, Slovenia;²University

identified a novel Ga11

mutation, Phe220Ser, causing FHH2, and have

Rehabilitation Institute, Ljubljana, Slovenia;³Faculty of Pharmacy,

demonstrated the importance of the hydrophobic Phe220 residue, which forms

University of Ljubljana, Ljubljana, Slovenia.

part of a cluster, for G-protein signaling via PLC-Ca2Ci and ERK/MAPK

pathways.

DOI: 10.1530/endoabs.49.OC10.5

The ideal antiresorptive agent to preserve or further increase bone mineral density

(BMD) following teriparatide treatment is not known. We aimed to compare

BMD changes after one year of therapy with denosumab or bisphosphonates in

osteoporotic patients who had completed treatment with teriparatide. We

retrospectively analyzed 140 women (age 74 years, 26 years from menopause,

BMI 27 kg/m² on average) with severe postmenopausal osteoporosis who had

been treated between 2006 and 2014 with teriparatide for 18-24 months at our

outpatient clinic. After stopping teriparatide, they continued with a bispho-

Obesity

sphonate

(alendronate, risedronate, ibandronate or zoledronic acid) or with

OC11.1

denosumab in standard doses per physician’s and/or patient’s preference. All

Role of Extracellular vesicles in the crosstalk between adipocytes and

patients were prescribed with vitamin D3 1000 IU daily and were instructed to

pancreatic beta-cells

ingest 1200 mg of calcium daily. BMD was measured at lumbar spine (LS), total

Iacopo Gesmundo¹, Eleonora Gargantini¹, Enrica Favaro²,

hip (TH) and femoral neck (FN) by DXA when teriparatide was stopped and after

Lorenzo Piemonti³, Giovanni Camussi² & Riccarda Granata¹

12 months of further treatment. The data were analyzed using multiple linear

¹Division of Endocrinology, Diabetology and Metabolism, Department of

regression to adjust the comparison between groups for age, BMD, 25-hydroxy-

Medical Sciences, University of Torino, Torino, Italy;²Department of

vitamin D, serum urate, procollagen type 1 N-terminal propeptide (P1NP) at

Medical Sciences, Torino, Italy;³San Raffaele Diabetes Research Institute,

baseline and BMD gain on teriparatide. Seventy patients continued treatment with

IRCCS San Raffaele Scientific Institute, Milano, Italy.

a bisphosphonate and 70 received denosumab. The results indicate a lower BMD

increase (especially at LS) in patients on bisphosphonates when compared to

denosumab; a lower BMD increase at FN and LS in patients who had a larger

Obesity is characterized by insulin resistance and pancreatic b-cell dysfunction;

BMD increase on teriparatide (i.e. regression to the mean); a lower BMD increase

moreover, secretion of adipokines from adipocytes may affect metabolic

at FN and a higher BMD increase at LS in patients with higher baseline P1NP; and

functions in several tissues, including pancreatic b-cells. Extracellular vesicles

a higher BMD increase at FN in patients with higher baseline serum urate. Twelve

(EVs), released by cells as exosomes or shedding vesicles, play a key role in cell-

months after stopping teriparatide, sequential osteoporosis treatment with

to-cell communication, modifying the phenotype and function of recipient cells

denosumab yields higher additional BMD gain as compared to a bisphosphonate.

by delivering proteins, RNAs and microRNAs. The crosstalk between adipocytes

The effect is more pronounced at LS.

and b-cells in the regulation of glucose and lipid metabolism is still unclear. We

DOI: 10.1530/endoabs.49.OC10.4

hypothesized that EVs derived from adipocytes are able to influence the survival

and function of b-cells in pathophysiological conditions. In this study, the role of

EVs released by murine 3T3-L1 adipocytes was evaluated on cell viability and

proliferation, apoptosis and function of rat INS-1E b-cells and human pancreatic

islets. INS-1E b-cells and human pancreatic islets were treated for

24 and

72 hours, respectively, with EVs in either presence or absence of CKs or palmitic

acid and high glucose (P/G). Our results show that EVs derived from untreated

adipocytes promote cell survival and proliferation, inhibit apoptosis in b-cells and

OC10.5

pancreatic islets treated with CKs and P/G, and stimulate glucose-induced insulin

Ga11-Phe220Ser loss-of-function mutation causes familial

secretion. Conversely, EVs derived from adipocytes treated with CKs enhanced

hypocalciuric hypercalcemia type-2 (FHH2) by disrupting a

the detrimental effects of CKs and P/G. These results suggest a functional

hydrophobic cluster critical for G-protein signaling

crosstalk between adipose tissue and b-cells/pancreatic islets. Furthermore, the

Caroline M. Gorvin¹, Treena Cranston², Fadil M. Hannan^1,3, Helena Valta⁴,

protective effects of EVs derived from adipocytes on survival and function of

Outi Makitie⁴, Camilla Schalin-Jantti⁵ & Rajesh V. Thakker¹

b-cells exposed to stress, such as inflammatory CKs or glucolipotoxicity, suggest

¹Academic Endocrine Unit, Radcliffe Department of Medicine, Oxford

possible therapeutic implications in pathological conditions like diabetes and

Centre for Diabetes, Endocrinology and Metabolism, University of Oxford,

obesity.

Oxford, UK;²Oxford Molecular Genetics Laboratory, Churchill Hospital,

Oxford, UK;³Institute of Ageing and Chronic Disease, University of

DOI: 10.1530/endoabs.49.OC11.1

Liverpool, Liverpool, UK;⁴Children’s Hospital, University of Helsinki and

Helsinki University Hospital, Helsinki, Finland;⁵Division of Endo-

crinology, Abdominal Center, University of Helsinki, Helsinki, Finland.

Mutations of the calcium-sensing receptor (CaSR), G-protein alpha-11 subunit

(Ga11), and adaptor protein-2

sigma subunit

(AP2s) resulting in a loss-

OC11.2

of-function, cause familial hypocalciuric hypercalcemia types 1-3 (FHH1-3),

Three year prospective study in morbidly obese patients between

respectively. We investigated a family with FHH

(four affected and two

longitudinal gastrectomy and gastric bypass based on a composite

unaffected members) for CaSR, Ga11 and AP2s mutations, and identified a

outcome combining weight loss efficacy and surgery related

heterozygous Ga11 missense mutation, Phe220Ser, which is predicted to disrupt

complications (PHRC SLEEVE K060213 / IDRCB2007-A00373-50)

a cluster of hydrophobic residues that are important for G-protein/G-protein

Jean Marc Catheline¹, Marinos Fysekidis², Yasmina Bendacha¹,

coupled receptor interactions. Ga11, which acts downstream of the CaSR,

Najib Bdeoui¹, Vidhya Raghavan³, Sophie Gérard³, Jean Jacques Portal³,

activates phospholipase C (PLC) leading to two predominant signal outputs:

Rami Dbouk¹, Jean Michel Fabre⁴, Gilles Fourtanier⁵, Jean Gugenheim⁶,

intracellular calcium (Ca2Ci) release; and activation of the extracellular-signal

Noël Huten⁷, Maxime Sodji⁸, Simon Msika⁹, Michel Scotté¹⁰, Eric Vicaut³

regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. We

& Regis Cohen¹

assessed the effects of the Ga11 mutation on signalling by expressing Ga11-wild-

¹Centre coordinateur du PHRC, Centre Hospitalier de Saint-Denis, Saint-

type Phe220, and three Ga11-mutants: Ser220, detected in the FHH2 kindred; and

Denis, France;²CHU Bobigny, Bobigny, France;³Unité de Recherche

engineered mutants, Ala220

(a hydrophobic residue); and, Glu220

(a non-

Clinique Lariboisière-St Louis Hôpital Fernand Widal, Paris, France;⁴CHU

hydrophobic residue), in HEK293

cells stably expressing CaSR. Ca2Ci

de Montpellier, Montpellier, France;⁵CHU Toulouse, Toulouse, France;

responses to extracellular calcium

(Ca2Ce) were assessed using a Fluo-4

⁶CHU Nice, Nice, France;⁷CHU Tours, Tours, France;⁸Clinique

fluorescent assay and an NFAT-response element-containing luciferase reporter

Emailleurs, Limoge, France;⁹Hôpital Louis Mourier « APHP », Colombes,

that measures Ca2Ci-induced gene expression; and MAPK responses assessed

France;¹⁰CHU Rouen, Rouen, France.

using a phospho-ERK (pERK) AlphaScreen assay and a serum-response element

(SRE)-containing luciferase reporter that measures ERK-induced gene

expression. Mutation of Phe220 to the non-hydrophobic Ser220 and Glu220

Since its first description in 2000, Longitudinal Gastrectomy (LG) has become the

residues, but not the hydrophobic residue, Ala220, significantly impaired Ga11

first surgical procedure in the treatment of morbid obesity in the world, exceeding

signalling via PLC-Ca2Ci and ERK/MAPK pathways. Thus, Ser220 and Glu220,

in numbers Gastric Bypass

(GB). GB is considered to have better results

when compared to wild-type (Phe220) and Ala220 led to: a rightward shift of the

regarding long-term weight loss and improvement in co-morbidities. We aimed to

dose-response curves of Ca2Ci responses to Ca2Ce with increased mean half-

demonstrate that LG is non inferior to GB for a composite end point that included

maximal concentration (EC50) values; reductions in NFAT reporter responses;

more than 50% excess weight loss from the baseline and surgery related

impaired pERK responses; and reductions in SRE reporter activity. Thus, we have

complications after a mean follow-up of 36 months. This is a prospective study in

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

morbidly obese patients that tested a two hypotheses composite outcome: the first

Weight loss induced with diet and exercise decreases hepatic steatosis and

hypothesis was that after 36 months LG was non-inferior to GB regarding EWL

inflammation, but requires greater efforts to sustain compared to medication. We

(the predefined margin of non-inferiority was G15%), and the second hypothesis

therefore aimed to compare the effects of liraglutide, a glucagon-like peptide-1

was the presence of significant difference in post-operative morbidity and

agonist which induces weight loss, on hepatic steatosis and inflammation in obese

mortality. From February 2008 to March 2015 we included 277 patients (91 GB

Asian adults with NAFLD with intensive lifestyle modification.

vs 186 LG). The mean age was 41.1 years, 19.2% had a previous bariatric

Methods

operation,

85.9% were women and the average pre-intervention BMI was

abdominally obese Asian

(mean BMI

33.6G3.9 kg/m², mean waist

45.3 kg/m². At baseline there were no significant differences between the GB and

circumference WC

108.5G10.6 cm) non-diabetic normotensive adults with

LG for age, sex and BMI. The % of patients with EWL O 50% was at 18 months

NAFLD, as diagnosed by a hepatologist based on elevated serum alanine

for 82.1% (GB) vs 84.5% (LG), and 79.1 vs. 79.5% respectively at 36 months.

transaminase (ALT) and aspartate transaminase (AST) levels and liver fat fraction

The estimated difference in EWL was [K10.5% to 9.8%], confirming the non-

O5% using magnetic resonance imaging (MRI) in the absence of other causes of

inferiority of LG compared to BP. Finally there was a significant less morbidity

hepatic steatosis and transaminitis, were randomized to supervised dieting

and mortality for the LG group (GB vs LG, 12.1 vs. 4.8%, one death for LG,

(restriction by 400 kcal/day) plus moderate-intensity exercise (200 minutes/week)

PZ0.01). This is the first prospective study demonstrating that LG is not inferior

to induce R5% weight loss (DE group, nZ11) or liraglutide 3 mg daily (LI

to GB for an estimated

10% difference in EWL but with less surgical

group, nZ11) for 26 weeks. Insulin resistance was estimated by homeostasis

complications. These results reinforce the choice of LG as surgical procedure

model assessment (HOMA-IR) and liver shear stiffness with MRI elastography.

for obesity.

Results

DOI: 10.1530/endoabs.49.OC11.2

At 26 weeks, both DE and LI groups had significant (P!0.01) and similar

reductions in weight (K3.1G2.9 vs K3.6G2.4 kg), WC (K4.4G3.2 vs K5.7G

3.9 cm), liver fat (K9.5G13.8 vs K7.7G7.3%), liver stiffness (K0.22G0.20 vs

K0.32G0.25 kPa), ALT (K42G34 vs K43G39 U/l), AST (K21G16 vs

K26G25 U/l) and HOMA-IR (K2.87G2.67 vs K3.12G2.40).

Conclusion

Once-daily liraglutide is as effective as intensive lifestyle modification for

decreasing hepatic steatosis, inflammation and stiffness in obese Asian adults

with NAFLD.

OC11.3

DOI: 10.1530/endoabs.49.OC11.4

Interleukin-1 antagonism decreases cortisol levels in obese individuals

Sandrine Urwyler¹, Philipp Schutz², Fahim Ebrahimi¹, Marc Y. Donath¹ &

Mirjam Christ-Crain¹

¹University Hospital Basel, Basel, Switzerland;²Kantonsspital Aarau,

Aarau, Switzerland.

Background

Increased cortisol levels in obesity may contribute to the associated metabolic

syndrome. In obesity, the activated innate immune system leads to increased

interleukin (IL)-1b, which is known to stimulate the release of adrenocortico-

OC11.5

tropin hormone

(ACTH). We therefore hypothesised that in obesity IL-1

Differentiating constitutional thinness from anorexia nervosa in

antagonism would result in downregulation of the hypothalamo-pituitary-adrenal

DSM 5 era

(HPA) axis, leading to decreased cortisol levels.

Bruno Estour^1,2, Nesrine Marouani¹, Torrance Sigaud^2,3, Francois Lang^2,3,

Methods

Eric Fakra^2,3, Aurelie Diamonde², Bogdan Galusca^1,2 & Natacha Germain^1,2

In this prospective intervention study we included 73 patients with obesity (BMI

¹Endocrinology Department, University Hospital of Saint Etienne,

O30 kg/m²) and at least one additional feature of the metabolic syndrome.

Saint Etienne, France;²EA 7423, Jean Monnet University of Saint Etienne,

The primary endpoint was change in morning cortisol from baseline to after

Saint Etienne, France;³Psychiatry Department, University Hospital of Saint

the administration of the IL-1 receptor antagonist (anakinra/Kineretw, total dose

Etienne, Saint Etienne, France.

3!100 mg). Secondary endpoints were effects on salivary cortisol and ACTH.

Results

Introduction

Median morning serum cortisol levels (nmol/l) decreased significantly after IL-1-

antagonism (from baseline 452 to 423, absolute difference K38.7, 95%CI K64 to

Constitutional thinness (CT) is an underweight state characterized by normal

menstruations and no change in feeding behaviour. Thinness is the only

K13.4, PZ0.0019). Similar effects were found for salivary cortisol levels (K2.8,

resemblance between Anorexia Nervosa (AN) and CT. Removal of amenorrhea in

95%CI K4.4 to K1.3, PZ0.0007), ACTH levels (K2.2, 95%CI K4.2 to K0.1,

the new DSM 5 definition of AN might lead to misdiagnosis between these two

PZ0.038), systolic blood pressure (K5.2, 95%CI K8.5 to K1.8, PZ0.0006) and

populations. The objective of this study was to compare CT, AN and Control

heart rate (K2.9, 95%CI K4.7 to K1.0, PZ0.0029).

subjects in terms of biological, anthropometric, and psychological markers in

Conclusion

order to better distinguish AN from CT subjects.

IL-1 antagonism in obese individuals with features of the metabolic syndrome

Patients and method

leads to a decrease in serum cortisol, salivary cortisol and ACTH-levels along

This retrospective study conducted from 2000 to 2015 included three groups of

with a reduction in systolic blood pressure and heart rate. IL-1 antagonism could

young women: fifty-six CT, forty restrictive-type AN and fifty-four control

thus be a novel treatment option to improve cortisol levels and associated

subjects were included in the study. Basal evaluation was made in all groups with

comorbidities in obesity.

any intervention. Body composition, nutritional markers, pituitary hormones,

DOI: 10.1530/endoabs.49.OC11.3

bone markers and psychological scores were evaluated in three groups. For every

markers, a receiver Operator Characteristics (ROC) curve was calculated to

evaluate the accuracy of differentiation between AN and CT groups.

Results

For the majority of the studied parameters, CT subjects were similar to controls

but dramatically different from AN subjects. According to ROC data, while

psychological scores were unsuccessful to differentiate AN from CT, except for

OC11.4

DEBQ Restrained Eating item, free-T3 and Leptin were strong tools for AN and

Comparing effects of weight loss by liraglutide with intensive lifestyle

CT distinction as they displayed high sensitivities and specificities with low P

modification on hepatic steatosis, inflammation and stiffness, and insulin

values (!0.0001).

resistance in obese Asians with non-alcoholic fatty liver disease

Conclusions

(NAFLD)

Taking AN and CT distinction as a major objective, the exclusive use of

Joan Khoo, Ngai-Moh Law, John Hsiang, Jessica Tan & Tiing-Leong Ang

psychological criteria is not sufficient and should be completed by at least a free

Changi General Hospital, Singapore, Singapore.

T3 determination, which is a cheap and an accessible laboratory testing for

general practitioners. The final goal is to avoid social stigmatization and excessive

useless therapies for CT women.

Background and Aims

DOI: 10.1530/endoabs.49.OC11.5

Non-alcoholic fatty liver disease (NAFLD), a leading cause of cirrhosis and liver

cancer, is increasing worldwide due to rising obesity rates, particularly in Asia.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Pituitary Clinical

Design

Cohort study based on an electronic survey open for participation to ESE

OC12.1

members Dec 2015-Nov 2016.

T2-Weighted signal intensity of functional pituitary adenomas:

Results

correlation with clinicopathological findings and response to treatment

Reports on 167 patients, 40 pituitary carcinomas, and 127 aggressive pituitary

Sema Ciftci Dogansen¹, Seher Tanrikulu¹, Gulsah Yenidunya Yalin¹,

tumours were obtained. Median age at diagnosis was 43 (range 4-79) years. 59%

Sakin Tekin¹, Nihan Nizam¹, Bilge Bilgic² & Sema Yarman¹

of tumours were clinically functioning at presentation, and the most frequent were

¹Division of Endocrinology and Metabolism, Department of Internal

corticotroph tumours. TMZ was the first line chemotherapy in 157 patients. At the

Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul,

end of TMZ treatment (mean 9.92 cycles) radiological evaluation showed

Turkey;²Department of Pathology, Istanbul Faculty of Medicine, Istanbul

complete response in 6%, partial response in 31%, stable disease in 33% and

University, Istanbul, Turkey.

progressive disease in

30%. Progression occurred more often in pituitary

carcinomas (40%) than in aggressive adenomas (26%), PZ0.05. Clinically silent

tumours showed less regression compared with secreting tumours, 17 vs 45%,

Purpose

PZ0.01 (overall c² test). Median follow-up after TMZ treatment was 21 months.

Somatotrophinomas have been shown to demonstrate T2-weighted signal

Of patients with complete response, partial response and stable disease 22, 34 and

intensity (WSI) on MRI that is correlated with clinicopathological findings and

40% respectively showed progression during further follow-up. Twenty five

response to treatment. Therefore, we aimed to investigate these correlations in

patients received a second course of TMZ, 3 had a partial response. Overall

functional pituitary adenomas, including prolactinoma and corticotrophinoma.

mortality was 33%, and highest in patients with progression after TMZ treatment

Material and Methods

(54%).

Patients with somatotrophinoma (nZ87), prolactinoma (nZ78) and cortico-

Conclusion

trophinoma (nZ33) were involved in this study. The initial T2-WSI findings

TMZ was accompanied by tumour regression in 37% of patients, documenting its

(grouped into hypo-, iso- and hyperintense) were compared with hormon levels,

value in the management of these aggressive tumours. The high recurrence rate

tumor diameter, granulation patterns and treatment response.

following TMZ cessation highlights the need to identify additional effective

Results

therapies.

While most of somatotrophinomas were hypointense, most of prolactinomas and

corticotrophinomas were hyperintense. Tumor diameter was significantly larger

DOI: 10.1530/endoabs.49.OC12.2

in hyperintense somatotrophinomas than in hypointense group (PZ0.007), but

the tumor diameter in the isointense group did not show any difference when

compared to the others. IGF-1% ULN (upper limit of normal) was higher in

hypointense somatotrophinomas than the other two groups (PZ0.02). Sparsely

granulation pattern in hyperintense somatotrophinomas and densely granulation

pattern in hypointense somatotrophinomas are more frequent

(PZ0.035),

whereas the granulation pattern distribution in isointense group did not differ

from the other two groups. The hormonal response to somatostatin analogs (SSA)

treatment (percentage of IGF-1 reduction) was higher in the hypointense group

OC12.3

than in the other two groups (PZ0.04). The tumor diameter was smaller in the

hyperintense prolactinomas than in the other groups (PZ0.039), but the basal

Recombinant Growth Hormone added to physical therapy in

PRL levels were not different between the groups. The response to dopamine

GH-deficient adults with complete (ASIA A) Spine Injury

agonist (DA) treatment of iso- and hyperintense prolactinomas is much better than

(EudraCT 2011-005377-23)

the hypointense group (P!0.001). Tumor diameter was larger in hyperintense

Guillem Cuatrecasas¹, Hatice Kumru^2,3, M8Josep Coves¹, Ioana Patrascioiu¹

corticotrophinomas than the other two groups (PZ0.012), but there was no

& Josep Vidal^2,3

difference between the baseline cortisol and ACTH levels of the groups. Sparsely

¹Department of Endocrinology, Hospital Quiron-Teknon, Barcelona, Spain;

granulation pattern was higher in hyperintense corticotrophinomas and densely

²Fundación Institut Guttmann, Badalona, Spain;³Institut Universitari de

granulation patern in hypointense corticotrophinomas

(PZ0.029), whereas

Neurorehabilitació (UAB), Badalona, Spain.

granulation pattern distribution in isointense group was not different from the

other two groups. There was no difference between the groups in terms of

Introduction

remissions and recurrences.

Although in-vitro models suggest GH-induced differentiation, migration and

Conclusion

survival of astrocytes and oligodendrocytes, no studies had been published

Hyperintense somatotrophinomas support literature knowledge with increased

in-vivo. We want to evaluate the efficacy and safety of GH associated with

tumor diameter, sparsely granulation pattern and less responsiveness to SSA

physical therapy compared to placebo in patients with complete spine injury (SI)

treatment. The response to DA treatment of iso- and hyperintense prolactinomas

and associated GH deficiency (GHD).

is much better, but there was no difference between the groups in terms of

Methods

remissions and recurrences in corticortophinomas. Our results in prolactinomas

Eighteen Patients with complete SI were screened for GHD (glucagon test). 12

and corticotrophinomas should be supported by further studies.

severe

(GH!3 ng/ml) or partial (!10 ng/ml) GHD were randomized in a

DOI: 10.1530/endoabs.49.OC12.1

double-blind placebo-controlled study. Motor and sensory ASIA scale, SCIM-III

(spinal cord injury independence measure), Ashworth (spasticity), Neuropathic

Pain Scale and Quantitative Sensory tests were assessed. Patients received

subcutaneous injections of placebo or GH (Nutropinw) 6 days/week IGF1-

adjusted, in addition to intensive physical therapy 2 h/day, for 6 months. Both

groups were similar according to age, sex, BMI, waist circumference.

Results

Significant (PZ0.05) improvement was observed in SCIM-III score at 3 months:

55.6

(14.4 S.D.) vs 74 (2.8 S.D.) and 6 months: 55.4 (14.2 S.D.) vs 73.5 (2.1 S.D.),

OC12.2

comparing GH-treated group with placebo. A significant improvement in the

electrical perception threshold from the 1st up to the 5th metamera below the SI

Use of temozolomide in a large cohort of patients with aggressive

site was observed on both sides after 6 months of treatment in the GH, but not in

pituitary tumours and pituitary carcinomas: Results from a European

the placebo group. These differences were observed intra-individually (PZ0.04

Society of Endocrinology (ESE) survey

Friedman’s test) and between groups (5th left level (PZ0.023) and 5th right level

Ann McCormack, Olaf M Dekkers, Stephan Petersenn, Vera Popovic,

Jacqueline Trouillas, Gerald Raverot & Pia Burman

(PZ0.031), mixed linear model). No correlations with IGF1 were observed. No

¹Garvan Institute, Darlinghurst, Australia;²Leiden University Medical

GH-related adverse events were reported.

Centre, Leiden, The Netherlands;³ENDOC Center for Endocrine Tumors,

Conclusions

Hamburg, Germany;⁴Medical Faculty, University Belgrade, Belgrade,

Not studied so far, GHD seems very prevalent in SI. This is the first trial with

Serbia;⁵Faculté de Médecine Lyon-Est, Lyon, France;⁶Universite de Lyon,

complete SI and concomitant GHD. GH added to intense physical rehabilitation

Lyon, France;⁷Medical Faculty, University of Lund, Malmo, Sweden.

improved functional parameters (SCIM) and changes in sensory quantification

up to 5 levels below SI. Larger studies should be performed to confirm a GH

beneficial effect on sensitive pathways in SI.

Objective

DOI: 10.1530/endoabs.49.OC12.3

To collect clinical and treatment outcome data in a large patient cohort, and

specifically to report experience with temozolomide (TMZ).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

OC12.4

2.79, C.I. 95%1.03-7.61; PZ004). By contrast, no significant differences in

incident VFs were found between patients receiving PegV and those treated with

Subclinical cardiovascular system dysfunction in the patients with

SRLs alone, either when disease was persistently active (58.3% vs 60.0; PZ0.94)

Cushing’s disease

or when disease was controlled by treatment (20.0 vs 27.0%; PZ0.67). In

Przemyslaw Witek¹, Beata Uzieblo-Zyczkowska², Pawel Krzesinski²,

conclusion, this longitudinal study showed that PegV and SRLs had comparable

Agnieszka Jurek², Grzegorz Zielinski³, Andrzej Skrobowski³ &

effects on VF risk in acromegaly. Biochemical control as well as early diagnosis

Grzegorz Gielerak³

of the disease are the main endpoints for fracture prevention in acromegaly.

¹Department of Endocrinology and Isotope Therapy, Military Institute of

Medicine, Warsaw, Poland;²Department of Cardiology and Internal

DOI: 10.1530/endoabs.49.OC12.5

Medicine, Military Institute of Medicine, Warsaw, Poland;³Department of

Neurosurgery, Military Institute of Medicine, Warsaw, Poland.

Background

Hypercortisolism in Cushing’s disease (CD) is associated with high cardiovas-

Reproduction & Endocrine Disruption

cular risk. Hemodynamic disturbances, especially excessive vasoconstriction and

elevated blood pressure

(BP), may contribute to accelerated myocardial

OC13.1

remodeling. Early identification of subclinical left ventricular (LV) dysfunction

may be crucial for optimizing treatment and reducing mortality in patients

with CD.

Abstract withdrawn.

Purpose

The aim of this study was to assess the hemodynamic function of cardiovascular

system in three groups of patients: 1/ with CD (CD), 2/ with essential arterial

hypertension (AH) and healthy volunteers (HV).

Methods

In 171 subjects (CD - 22, AH - 114, HV - 35), without any symptoms of heart

failure, the echocardiographic assessment of LV systolic and diastolic function

and non-invasive hemodynamic assessment by impedance cardiography (ICG)

were performed. Statistical comparison included separate analysis for women and

men.

Results

CD revealed good BP control

(82% below 140/90 mmHg). However, in

OC13.2

comparison to AH and HV they presented: 1) significantly lower LV contractility

Thyroid peroxidase antibodies do not predict outcome in 900 women

expressed by global longitudinal strain (GLS: K17.7% vs K19.2 vs K20.0;

with recurrent pregnancy loss

PZ0.004); 2) higher prevalence of LV diastolic function (45.0% vs 14.2% vs

Sofie Bliddal¹, Henriette Svarre Nielsen², Aase Krogh-Rasmussen¹,

0.0%; P!0.00001); 3) lower impedance indices of LV performance: stroke index

Astrid Marie Kolte², Ole Bjarne Christiansen², Claus Henrik Nielsen³

(SI: 39.8 vs 52.2 vs 49.9 ml/m²; P!0.00001) cardiac index (CI: 2.86 vs 3.54 vs

& Ulla Feldt-Rasmussen¹

3.27 l/min/m²; P!0.0001) and 4) higher afterload: systemic vascular resistance

¹Department of Medical Endocrinology, Copenhagen University Hospital

index (SVRI: 2560 vs 1901 vs 1907 dyn*s*m²/cm⁵; P!0.0001). Men with CD

(Rigshospitalet), Copenhagen, Denmark;²Recurrent Pregnancy Loss Unit,

distinguished with lower CI (P!0.00001) and SVRI (P!0.0001), as though

Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark;

worse LV diastolic function

(e‘: PZ0.0002; GLS: PZ0.052). In women

³Institute of Inflammatory Research, Copenhagen University Hospital

hypercortisolism was more related to impaired LV systolic function

(GLS:

(Rigshospitalet), Copenhagen, Denmark.

PZ0.010; e‘: NS).

Conclusions

Introduction

Cushing’s disease, even with well-controlled BP, is associated with LV systolic

Thyroid autoimmunity has been associated with pregnancy loss. A possible

and diastolic dysfunction and pronounced vasoconstriction which individual

mechanism is an overactive maternal immune system leading to rejection of the

presentation depends on sex. These hemodynamic alterations can be detected by

fetal allograft. In women with recurrent pregnancy losses (RPL), we investigated

modern non-invasive diagnostic tools and became potential therapeutic

the association of thyroid peroxidase antibodies (TPOAbs) with number of losses

objectives.

and outcome of first pregnancy after referral.

DOI: 10.1530/endoabs.49.OC12.4

Methods

Prospective study of women with RPL

(R3) followed at the RPL Unit,

Copenhagen University Hospital, from 2011 to 2016. Upon first visit, all women

were screened for TSH

(Roche Modular E170

electrochemiluminescense

immunoassays) and TPOAbs (automated Kryptor immunoflourescent assay).

OC12.5

TPOAb-positivity O60 kU/l. We performed test for trends by chi-square or

Effects of pegvisomant and somatostatin receptor ligands on risk of

independent t-tests as appropriate, and adjusted regression analyses with

vertebral fractures in patients with Acromegaly

covariates: maternal age, TSH (logtransformed), number of losses, immunother-

Sabrina Chiloiro¹, Gherardo Mazziotti³, Antonella Giampietro¹, Anna

apy, thyroxine replacement therapy. The National Data Protection Agency

Maria Formenti², Antonio Bianchi¹, Marilda Mormando¹,

approved the project.

Alfredo Pontecorvi¹, Andrea Giustina⁴ & Laura De Marinis¹

Results

¹Pituitary Unit, Catholic University of the Sacred Heart, Rome, Italy;

We included 5219 pregnancies (76.6% spontaneous) in 900 women; 119 (13.2%)

²Department of Molecular and Translational Medicine, University of

women were TPOAb-positive. TPOAb-positivity was neither associated with

Brescia, Brescia, Italy;³Department of Internal Medicine, Mantua Hospital,

number of losses (PZ0.87, aOR 0.004 (-0.3-0.3), PZ0.98), nor number of

Mantua, Italy;⁴Chair of Endocrinology, Vita-Salute San Raffaele

pregnancies (PZ0.62, aOR 1.02 (0.92-1-11) PZ0.76). Among TPOAb-positive

University, Milan, Italy.

women, TPOAb-concentration was not associated with number of losses (BZ

0.75

(-0.12-0.27), PZ0.45). In women with a registered first pregnancy after

referral, TPOAb-positivity (72 of 557 (12.9%)) was not associated with live birth

Acromegalic osteopathy is an emerging complication of chronic GH excess

rate (54.4 vs 60.6%, PZ0.35, aOR 0.78 (0.42-1.43) PZ0.38). However, live birth

characterized by increase in bone turnover, deterioration in bone microarchi-

rate was significantly associated with total number of losses (aOR 0.53 (0.45-

tecture and high risk of vertebral fractures (VFs). Medical therapies may exert

0.61) PZ0.000). TSH-levels were positively associated with TPOAb-positivity

direct effects on peripheral targets leading to improvement of clinical outcomes

(PZ0.00), but not with any investigated outcome. Immunoglobulin therapy or

regardless of biochemical control of acromegaly. In this longitudinal study, we

thyroxine replacement did not alter results.

compared the effects pegvisomant (PegV) and somatostatin receptor ligands

Conclusion

(SRLs) on VF risk in 80 acromegaly patients (47 females, 33 males; mean age 53

In a large cohort of women with RPL, we found no association between TPOAbs

years, range 24-86 years) who were prospectively evaluated by quantitative

and pregnancy outcome. TSH-levels were significantly increased in TPOAb-

vertebral x-ray morphometric approach. During the 30 month study period, 39

positive women and screening according to guidelines should be performed.

patients (48.8%) were treated with PegV, 33 (41.2%) with SRLs and 8 (10%)

However, if RPL is caused by an immunological reaction, thyroid autoimmunity

showed a controlled disease after neurosurgery. At follow-up, 23 patients (28.8%)

does not seem to be a sensitive marker hereof.

experienced incident VFs which were significantly correlated with persistently

DOI: 10.1530/endoabs.49.OC13.2

active disease (OR .49, C.I.95% 1.75-17.22; PZ0.003) and preexisting VFs (OR

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

OC13.3

parameters showed worsening MMP in diabetic patients (P!0.05). Patients with

DM2 showed a significant decrease in the degree of sperm vitality and increased

Sertoli cell expressed hydroxysteroid (17beta) dehydrogenase 1 is

spermatozoa in late apoptosis vs Controls and of the DNA fragmentation

required for male fertility

compared to the other two groups (P!0.05). Moreover, patients with DM1 had a

Janne Hakkarainen¹, Heli Jokela¹, Fuping Zhang¹, Noora Kotaja¹,

lower progressive motility when the disease duration was O10 years vs the other

Petra Sipila¹ & Matti Poutanen^1,2

two groups, and lower MMP after 5 years of disease (P!0.05). The degree of PL

¹Department of Physiology and Turku Center for Disease Modeling,

was higher in DM2 patients compared to the other two groups (P!0.05), while

Institute of Biomedicine, University of Turku, Turku, Finland;²Institute of

the concentrations of mitochondrial superoxide were greater in DM2 patients

Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg,

compared to DM1 and control group (P!0.05). The ultrasound data showed that

Sweden.

the diameter of the epididymal head and tail after ejaculation were greater in

patients with DM1 long term than those of short duration compared to controls

(P!0.05). Testosterone levels were lower in DM2 patients vs controls (P!0.05).

Hydroxysteroid (17beta) dehydrogenase 1 (Hsd17b1) is a steroidogenic enzyme

Conclusion

catalyzing the conversion of estrone (E1) to estradiol (E2), and androstenedione

Patients with DM1 have low ejaculate volume for an altered epididymal emptying

(A-dione) to testosterone (T). We have shown that the deletion of Hsd17b1 gene

and a mitochondrial damage that anticipates the later decline of sperm motility.

in mice resulted in the failure of ovarian estrogen production and subfertility. In

DM2 is instead characterized by an inflammatory condition with increased

this study, we clarified the role of Hsd17b1 in male reproduction. The data

leukocyte and oxidative stress and elevated levels of sperm DNA fragmentation

revealed that in mice Hsd17b1 mRNA is highly expressed in the Sertoli cells at

and decreased sperm vitality.

the fetal age. The Sertoli cell function is critical for normal spermatogenesis, and

DOI: 10.1530/endoabs.49.OC13.4

their action is dependent on the pituitary gonadotropins and testosterone. The

breeding tests revealed that the Hsd17b1 knockout male mice (HSD17B1KO)

were infertile. Because the Hsd17b1 is part of the steroid synthesis machinery, we

analyzed the in vivo biomarkers for androgen action, while no changes were

observed in fetal masculinization or in onset of puberty. Furthermore, the weights

of androgen-dependent tissues in HSD17B1KO were neither affected. Also, the

serum gonadotropin levels and the steroid concentrations in the testis, were close

to normal in the HSD17B1KO males, with minor changes in the E1/E2 and

A-dione/T ratios. Interestingly, several steroidogenic genes, Hsd17b3, Star,

Cyp11a1 and Hsd3b1, were significantly upregulated in HSD17B1KO testes,

suggesting a functional compensation due to the lack of Hsd17b1 activity.

Although no marked changes were observed in the hormonal environment,

OC13.5

histological analysis of HSD17B1KO testis revealed defects in the organization of

Urinary cadmium excretion is associated with increased synthesis of

differentiating germ cells in the seminiferous epithelium, and major defects in the

haploid germ cell differentiation, particularly in the head shaping of elongating

cortico- and sex steroids in a family-based Swiss population study

spermatids. Consequently, the epididymal sperm count was dramatically reduced

Murielle Bochud¹, Judith Jenny-Burri², Menno Pruijm³, Belen Ponte⁴,

in the HSD17B1KO males, and the remaining spermatozoa were morphologically

Idris Guessous¹, Georg Ehret⁵, Dusan Petrovic¹, Vincent Dudler²,

abnormal. These results revealed a novel role for Hsd17b1 in the control of

Max Haldimann², Geneviève Escher⁷, Bernhard Dick⁷, Markus Mohaupt⁷,

spermatogenesis and male fertility, and suggest that Hsd17b1 is required for a

Fred Paccaud¹, Michel Burnier³, Antoinette Péchère-Bertschi⁶,

proper function of Sertoli cells.

Pierre-Yves Martin⁴, Bruno Vogt⁷ & Daniel Ackermann⁷

¹Institute of Social and Preventive Medicine (IUMSP), Lausanne, Switzer-

DOI: 10.1530/endoabs.49.OC13.3

land;²Federal Food Safety and Veterinary Office, Bern, Switzerland;

³Service of Nephrology, Lausanne, Switzerland;⁴Service of Nephrology,

Geneva, Switzerland;⁵Cardiology, Department of Specialities of Internal

Medicine, Geneva, Switzerland;⁶Endocrinology, Department of Special-

ities of Internal Medicine, Geneva, Switzerland;⁷University Clinic for

Nephrology and Hypertension, Bern, Switzerland.

Background

Cadmium (Cd) is considered as a human carcinogen. A potential intermediate

OC13.4

mechanism could be hormone-related by disturbing steroidogenesis in gonads and

Diabetes mellitus: a new cause of male infertility

adrenal glands. We tested whether urinary Cd excretion, as a marker of long-term

Rosita Angela Condorelli, Sandro La Vignera, Rossella Cannarella,

exposure, is associated with the urinary steroid profile in the general adult

Laura Maria Mongioì & Aldo Eugenio Calogero

population.

Unit of Andrology and Endocrinology, Department of Clinical and

Methods and Findings

Experimental Medicine, Catania, Sicily, Italy.

The Swiss Kidney Project on Genes in Hypertension (SKIPOGH) is a multicentric

family-based population study with a response rate of 25.6%. We measured 24-h

Introduction

urinary excretions of Cd and steroid hormone metabolites by gas chromatography

Diabetes mellitus (DM) may cause male infertility acting with pre-testicular,

and mass spectrometry in 1000 participants (473 men, 527 women), with separate

testicular and post-testicular mechanism.

day and night collections. Mixed linear models were used to analyse the

Aim

associations of each steroid metabolite with Cd excretion.

To evaluate the presence of male infertility and the mechanisms of sperm damage

Cd and testosterone excretions were positively associated in men (b[SE, P]:

in diabetic patients in childbearing age.

1.378[0.242,

!0.00001] and

1.440[0.333,

0.00002] for day and night,

Patients and methods

respectively), but not in women (0.333[0.257, 0.2] and 0.674[0.361, 0.06]).

Thirty-four patients with DM1, 55 with DM2 and 100 healthy fertile men

There was a strong positive association of the urinary excretion of Cd and cortisol

(controls) were enrolled. Diabetic patients were further divided into three groups

(0.475[0.157,

0.0025] and

0.877[0.194,

0.00001], for day and

0.875[0.253,

based on their glycometabolic status and illness duration. Conventional and

0.00053] and 1.183[0.277, 0.00002] for night, respectively). Cd excretion was not

biofunctional sperm parameters were evaluated by standard semen analysis

associated with the excretion of tetrahydroaldosterone, the major metabolite of

and flow cytometry. This latter included sperm DNA fragmentation, vitality, early

aldosterone, but with other mineralocorticoid metabolites (P!0.01 in men and

and late apoptosis, chromatin condensation, mitochondrial membrane potential

women). Further adjustment revealed an independent effect between the synthesis

(MMP), leukocyte subpopulations, lipid peroxidation (PL) and sperm mito-

of sex hormones and corticosteroids and an interdependent effect of Cd on gluco-

chondrial superoxide. In addition, all patients and controls underwent testicular

and mineralcorticoid synthesis.

ultrasound sca and serum LH and testosterone measurements.

Conclusions

Results

Our findings provide evidence for a global stimulating effect of low-dose Cd

Diabetic patients had lower sperm concentration, progressive motility and

exposure on sex and corticosteroid synthesis in the general adult population.

morphology vs controls (P!0.05). The ejaculate volume is significantly lower in

Further studies are needed to explore the health consequences of chronic low-dose

patients with DM1 vs controls (P!0.05). Leukocyte concentrations were higher

exposure to Cd on selected diseases such as steroid-sensitive cancers or metabolic

in patients with DM2 (P!0.05), showing a statistically significant reduction in

disorders.

the percentage of T helper cells and an increase of the suppressor T lymphocytes

DOI: 10.1530/endoabs.49.OC13.5

compared to controls

(P!0.05). The analysis of the biofunctional sperm

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Thyroid Cancer

with advanced tumor stage in thyroid cancer. Therefore, we hypothesize that

HO-1 may represent a potential target for cancer therapy. HO-1 inhibitors

OC14.1

have been clinically used in patients with hyperbilirubinemia and hereditary

Anti-Mullerian hormone (AMH) in pre-menopausal females after

porphyria. In the present study, thyroid cancer cells were treated with two

ablative radioiodine (RAI) treatment for differentiated thyroid cancer

different classes of HO-1

inhibitors: metalloporphyrin and imidazole-

(DTC): single-center study

dioxolane compound. We found that treatment with HO-1

inhibitors

Miranda Mittica¹, Paola Comite², Claudia Campana¹, Stefano Gay¹,

suppressed cell growth, colony formation, cell migration, and invasion of

Michele Mussap² & Massimo Giusti¹

thyroid cancer cells in a dose-dependent manner. Cell cycle analysis by flow

¹UO Clinica Endocrinologica, Azienda Ospedaliera Universitaria San

cytometry revealed that growth arrest in the G0/G1 phase. However, there

Martino - IST, Genoa, Italy;²UO Laboratorio Analisi, Azienda Ospedaliera

was no synergistic effect of HO-1

inhibitors in combination with

Universitaria San Martino - IST, Genoa, Italy.

doxorubicin or sorafenib. Our results suggest a modest susceptibility of

thyroid cancer cells to HO-1 inhibitors. Nonetheless, HO-1 inhibition may

not act as a sensitizer to chemotherapy in thyroid cancer.

Background

It is generally reported that female fertility is not affected by high-dose RAI

DOI: 10.1530/endoabs.49.OC14.2

treatment. AMH has been considered a reliable and accurate index of ovarian

reserve. There are few data on AMH values in thyroid diseases. Recently, in DTC

women who had undergone RAI ablation treatment, Acibucu et al. (2016)

reported low AMH levels without significant impairment of fertility.

Aim

The aim of this single-center study was to evaluate AMH levels in association

with the characteristics of spontaneous menstrual cycles and the levels of

pituitary-gonadal hormones in our cohort of pre-menopausal women with a

history of low-risk DTC.

OC14.3

Subjects

From a group of 68 women, 39 who were not on oral contraceptive therapy were

TERT, BRAF and NRAS in the molecular profile of metastatic thyroid

enrolled. All hormone evaluations were performed on chemiluminescence assays.

cancer: differences between primary and distant disease

AMH, FSH, 17B-estradiol (E2) were assayed on day 2 and PRL and progesterone

Miguel Melo^1,2, Adriana Gaspar da Rocha^1,3, Rui Batista^1,4, Joao Vinagre¹,

(P) levels on day 21-24 of the same menstrual cycle. Twenty-seven women (aged

Maria Joao Martins⁵, Gracinda Costa⁶, Cristina Ribeiro²,

40G6 years) were studied 7G4 years after primary DTC treatment, which

Francisco Carrilho², Valeriano Leite^7,8, Claudia Lobo⁹, Jose Manuel

included at least one RAI treatment (median activity 80 mCi). As a control group,

Cameselle-Teijeiro¹⁰, Manuel Sobrinho-Simoes^1,11 & Paula Soares^1,12

female DTC patients

(aged

40G8 years) who had undergone only

¹Instituto de Investigac¸ão e Inovação em Saúde (I3S), Porto, Portugal;

thyroidectomy were used.

²Department of Endocrinology - Centro Hospitalar e Universitário de

Results

Coimbra, Coimbra, Portugal,³Unidade de Saude Publica de Cantanhede,

All women were free from DTC. Pregnancy (study group 62%; control group

ACeS do Baixo Mondego, Cantanhede, Portugal;⁴Medical Faculty,

50%) and abortion rates (17 and 33%) were similar. TSH and f-T4 were similar in

University of Porto, Porto, Portugal;⁵Department of Pathology - Centro

both groups. Hyperprolactinemia was found only in one patient, while FSH

Hospitalar e Universitário de Coimbra, Coimbra, Portugal;⁶Department of

O30 mU/l was found in 2 (1 study, 1 control). Regular (28G2 days) menses were

Nuclear Medicine - Centro Hospitalar e Universitário de Coimbra,

reported in 33% of both groups. A high incidence of polymenorrhea was reported

Coimbra, Portugal;⁷Unit for Investigation of Molecular Pathobiology,

in the study group (33%), while a high incidence of oligomenorrhea was noted in

Portuguese Institute of Oncology - Lisbon Center, Lisboa, Portugal;

the control group (50%). Ovulatory cycles (PO4 ng/ml) were noted in 72 and

⁸Department of Endocrinology, Portuguese Institute of Oncology - Lisbon

60% of study and control women, respectively. AMH levels were found to be

Center, Lisboa, Portugal;⁹Department of Pathology, Portuguese Institute of

negatively correlated with age (PZ0.002), but not with E2, FSH, TSH or f-T4

Oncology - Porto Center, Porto, Portugal;¹⁰Department of Pathology,

levels. AMH levels were 2.0G0.4 ng/ml and 2.3G1.5 ng/ml in the study and

Clinical University Hospital, SERGAS, Medical Faculty, University of

control groups, respectively.

Santiago de Compostela, Santiago de Compostela, Spain;¹¹Department of

Limitations

Pathology, Hospital S. João, Porto, Portugal;¹²Department of Pathology and

These data are preliminary, as data collection is still ongoing.

Oncology, Medical Faculty, University of Porto, Porto, Portugal.

Conclusions

AMH should replace FSH in the evaluation of gonadal reserve in pre-menopausal

Context

DTC women. At present, age is the only predictor of AMH levels. About one out

Little is known about the frequency of key mutations in thyroid cancer metastases

of two women with a history of DTC suffers from menstrual dysregulation, but

and its relationship with the primary tumor genotype.

infertility must be considered a low risk.

Objectives

DOI: 10.1530/endoabs.49.OC14.1

To evaluate the frequency of TERT promoter (TERTp), BRAF and NRAS

mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors,

lymph node metastases (LNM) and distant metastases.

Material and Methods

Mutation analysis was performed in 437 tissue samples from 204 patients, mainly

with papillary thyroid carcinomas (PTC) (nZ180), including 196 LNM and 56

distant metastases. All the distant metastases included corresponded to radio-

iodine-refractory metastatic tissue.

Results

We found the following mutation frequency in primary thyroid tumors, LNM and

OC14.2

distant metastases, respectively: TERTp- 15.9, 10.8, and 52.4%; BRAF (PTC-

Suppression of heme oxygenase-1 inhibits growth and invasion of

only)- 44.6, 41.7, and 23.8%; NRAS- 1.7, 1.3, and 11.9%. In the subgroup of

thyroid cancer

patients with PTC, the TERTp mutation frequency in primary tumors, LNM and

Shih-Ping Cheng^1,2, Jie-Jen Lee^1,2, Ming-Jen Chen^1,2, Chien-Liang Liu^1,2,

distant metastases was

12.9,

10.5, and

52.4%, respectively. There was a

Po-Sheng Yang^1,2 & Yi-Chiung Hsu³

significant concordance between the primary tumor genotype and the

¹MacKay Memorial Hospital, Taipei, Taiwan;²Mackay Medical College,

corresponding LNM, in particular for BRAF-mutated PTC. The overall

Taipei, Taiwan;³National Central University, Taoyuan City, Taiwan.

concordance between primary tumors and respective distant metastases was

low. In the group of patients with PTC, we found a high frequency of TERTp

mutations and a low frequency of BRAF mutations in distant metastases, in

comparison to the paired primary tumors.

Oxidative stress generated in the process of iodide metabolism and thyroid

Conclusions

hormone synthesis may play a role in thyroid tumorigenesis and progression

The frequency of BRAF, NRAS and TERTp mutations is similar in primary

of thyroid cancer. The transcription factor Nrf2

is the most important

tumors and matched LNM, whereas distant metastases show an enrichment in

regulator of antioxidant responses. It has been shown that Nrf2 expression is

TERTp mutations and a decrease in BRAF mutations. TERTp mutations seem to

upregulated in papillary thyroid cancer. In response to oxidative stress,

play an important role in distant metastases.

nuclear Nrf2 activates antioxidant-responsive elements and induces the

expression of stress-responsive genes, including heme oxygenase-1 (HO-1).

DOI: 10.1530/endoabs.49.OC14.3

Previously we have demonstrated that HO-1 overexpression was associated

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

OC14.4

OC14.5

Inverse relation between thyroid cancer incidence and threshold for

Dose aggressive variants of papillary thyroid carcinoma have worse

thyroid surgery: a national population-based retrospective study

clinical outcome than classical papillary carcinoma?

Brigitte Decallonne¹, Van den Bruel Annick³, Elaut Nathalie¹ &

Eyun Song¹, Min Ji Jeon¹, Hyemi Kwon¹, Suyeon Park¹, Hye-Seon Oh¹,

De Schutter Harlinde²

Jin-Sook Ryu¹, Dong Eun Song¹, Eui Young Kim², Tae Yong Kim¹,

¹KU Leuven, Leuven, Belgium;²Belgian Cancer Registry, Brussels,

Young Kee Shong¹, Won Bae Kim¹ & Won Gu Kim¹

Belgium;³General Hospital Sint Jan, Bruges, Belgium.

¹Asan Medical Center, Seoul, Republic of Korea;²Dongnam Institute of

Radiological & Medical Sciences Cancer Center, Busan, Republic of Korea.

Background

In Belgium, lower thyroid cancer incidence - most pronounced for microcancers

Unlike excellent prognosis of classical papillary thyroid carcinoma (cPTC),

(T1a) - is present in the North compared to the South. This variation is paralleled

certain pathological subtypes of aggressive variants of PTC

(AV-PTC) are

by differences in clinical practice: in the North less thyroid surgery is performed,

considered to have poor clinical outcome. However, the evidence of unfavorable

more surgery is preceded by fine needle aspiration (FNA), and more patients with

outcome of AV-PTC is not clear because previous studies did not control other

a final cancer diagnosis (2004-2006) underwent a presurgical FNA or a lymph

confounding factors contributed to clinical outcomes.

node dissection (LND) at fist surgery.

Methods

Aim

This retrospective cohort study initially included 4339 patients with cPTC and

To study 1/ the evolution in the use of FNA and LND, and 2/ the weight of T1a

121 patients with AV-PTC including tall cell, columnar, hobnail, solid and diffuse

non-thyrotoxic thyroid glands in a recent thyroid cancer cohort.

sclerosing variants. Dynamic risk stratification

(DRS) and recurrence free

Methodology

survival

(RFS) between the two groups were compared after two-to-one

Population-based retrospective study, using data from the Belgian Cancer

individual risk factor matching by age, sex, tumor size, and initial surgical extent.

Registry

(including case-by-case study of pathology protocols) and Belgian

Outcome

Healthcare Insurance database for differentiated thyroid cancer (DTC) cases

AV-PTC was associated with larger tumor size (P!0.001) and higher rates of

diagnosed between 2009 and 2011 (nZ2659).

cervical lymph node (LN) metastasis (P!0.001) compared to cPTC. A total of

Results

121 patients with AV-PTC and 242 patients with cPTC were evaluated after

Linkage of both databases resulted in 2557 DTC cases (96%). In the North a

individual risk factor matching. There were no significant differences in the tumor

higher proportion of DTC cases underwent FNA before surgery: 62.3%[95%CI

size and cervical LN metastasis between the two groups after mating. When we

58.3;66.3] compared to 33.6%[95%CI 29.3;39.9] in the South (P!0.0001),

compared the proportion of patients according to the DRS, there was no

confirming geographical differences. A positive trend for FNA was observed in

significant difference between patients with cPTC and those with AV-PTC

the period 2004-2012, at national and regional level, especially in the South. The

(PZ0.14). There was also no significant difference in RFS (hazard ratio [HR]

execution of LND during first thyroid surgery was proportionally higher in the

1.93, 95% confidence interval [CI] 0.68-5.47, PZ0.23) between the two groups.

North

(24.3%[95%CI

20.6;28.0]) compared to the South

(15.3%[95%CI

In subgroup analysis including patients with tall cell, columnar, and hobnail

12.0;18.7], P!0.0001), without temporal trend. Finally, in the subgroup of T1a

variants of PTC, there were no significant differences in DRS (PZ0.68) and RFS

DTC cases - considered to be mainly incidental findings - the mean thyroid

(HR 2.04, 95% CI 0.56-7.41, PZ0.29) compared with matched patients with

weight was 57.7G52.1 g in the North, compared to 37.99G29.1 g in the South

cPTC.

(P!0.0001).

Conclusion

The clinical outcome of patients with AV-PTC was not different with those with

In the present cohort, more FNA precedes thyroid cancer diagnosis, according

cPTC when their other clinicopathological risk factors were similar. Therapeutic

to international guidelines. However, geographical differences clearly persist.

and follow-up strategies for PTC might not need to be modified according to

A lower thyroid weight is present in DTC T1a in the South. These findings

presence of AV-PTCs.

support the alignment of a higher thyroid cancer incidence with a lower threshold

DOI: 10.1530/endoabs.49.OC14.5

for thyroid surgery in case of nodular disease, strongly suggesting overdiagnosis.

DOI: 10.1530/endoabs.49.OC14.4

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Adrenal 1

these mutations in regulating aldosterone biosynthesis has been clearly

established, the mechanisms involved in proliferation and APA formation still

GP1

remain to be elucidated. The aim of our study was to identify pathways involved

PRKACA mutations in adrenal Cushing can alter substrate specificity

in adrenal cortex nodulation and APA formation.

Kerstin Bathon^1,2, Isabel Weigand³, Jens T Vanselow⁴, Cristina L Ronchi^3,5,

Transcriptomic analysis from 123 APA and 11 control adrenal and correlations of

Guido Di Dalmazi^6,7, Felix Beuschlein⁶, Silviu Sbiera³, Andreas Schlosser⁴,

gene expression with genetic, morphological and functional characteristics of the

Martin Fassnacht^3,5 & Davide Calebiro^1,2

tumors allowed us to identify retinoic acid receptor (RAR) signalling as a central

¹Institute of Pharmacology and Toxicology, University of Wurzburg,

molecular network involved in APA formation independently of the mutation status.

Wurzburg, Germany;²Bioimaging Center, University of Wurzburg,

Treatment of H295R cells with all-trans retinoic acid and 9-cis retinoic acid

Wurzburg, Germany;³Division of Endocrinology and Diabetes, Department

reduced cell viability in a time and dose dependent manner. This effect was due to

of Internal Medicine I, University Hospital, Wurzburg, Germany;⁴Rudolf

decreased cell proliferation and increased cell apoptosis. In contrast to the effects

Virchow Center, University of Wurzburg, Wurzburg, Germany;⁵Compre-

observed in vitro, 9-cis retinoic acid did not modify tumor progression in a mouse

hensive Cancer Center Mainfranken, University of Wurzburg, Wurzburg,

xenograft model.

Germany;⁶Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians

Investigation of the adrenal phenotype of rara^K/K mice demonstrated that in

University, Munchen, Germany;⁷Division of Endocrinology, Department of

young (12 weeks) and old (52 weeks) rara^K/K mice the characteristic cellular

Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

arrangement of the adrenal cortex was replaced by an enlarged zona glomerulosa

and a disorganized zona fasciculata. This is also associated to dilatation and

disorganisation of vessels and increased capsule thickness. Furthermore, young

Previously, we identified seven mutations in the main catalytic subunit of protein

rara^K/K mice displayed lower plasma aldosterone concentration and decreased

kinase A

(PKA Ca) to be responsible for cortisol-secreting adrenocortical

expression of steroidogenic enzymes. Interestingly, this was associated with the

adenomas

(CPAs): L206R, L199_C200_insW, S213R_L212_K214insIILR,

inhibition of WNT/b-catenin pathway.

C200_GlyinsV, W197R, del244-248CE249Q, E32V. Here we performed a

Our results suggest that RAR signaling contributes to normal adrenal morphology

functional characterization of these mutants. Specifically, we evaluated the

and functional zonation through modulation of WNT/b-catenin pathway and that

association between PKA regulatory and catalytic subunits using co-immuno-

its disruption could contribute to abnormal cell proliferation in the adrenal cortex,

precipitation and PKA activity using a kemptide assay and a western blot analysis.

creating a propitious environment for the emergence of specific driver mutations in

Our results show that four mutations

(L206R, L199_C200_insW, W197R,

APA.

del244-248CE249Q) cause increased basal PKA activity. Interestingly, the

measured activity varied considerably among mutants depending on the assay

DOI: 10.1530/endoabs.49.GP2

used, suggesting changes in substrate specificity. Binding to RIa and RIIb

subunits was lost for three and two mutants respectively. One mutant (E32V)

showed no differences with the wild type. The S213R_L212_K214insIILR

mutant was associated with a loss of PKA activity, but showed a strong

accumulation in the nucleus. The C200_G201insV mutant was associated with a

GP3

loss of activity in the kemptide assay but showed normal behavior in the western

blot and nuclear translocation. For all mutants we performed an in silico analysis

Exosomal hsa-miR-483-5p and hsa-miR-101 are potential minimally

to predict the effect of the mutation on substrate specificity. The analysis

invasive biomarkers of adrenocortical carcinoma

suggested changes in substrate specificity for five mutants. Based on this, we

Pal Perge¹, Henriett Butz², Raffaele Pezzani³, Irina Bancos⁴, Zoltan Nagy¹,

performed phosphoproteomic experiments, which directly compare the phos-

Abel Decmann¹, Michaela Luconi⁵, Massimo Mannelli⁵, Edit Iren Buzas⁶,

phorylation of a large number of PKA substrates. The results directly

Miklos Toth¹, Marco Boscaro³, Attila Patocs^2,7 & Peter Igaz¹

demonstrated altered substrate specificity for three mutants (L206R, del244-

¹2nd Department of Medicine, Semmelweis University, Budapest, Hungary;

248CE249Q, C200_G201insV). Taken together, these findings suggest that the

²Molecular Medicine Research Group, Hungarian Academy of Sciences and

PKA Ca mutations found in CPAs alter substrate specificity and that interference

Semmelweis University, Budapest, Hungary;³Endocrinology Unit,

with the formation of a stable PKA holoenzyme is probably just one of the

Department of Medicine, University of Padua, Padova, Italy;⁴Division of

mechanisms through which these mutations affect PKA signaling, ultimately

Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal

leading to increased cortisol production and cell proliferation. The results of the

Medicine, Mayo Clinic, Rochester, MN, USA;⁵Department of Experi-

phosphoproteomics analysis might lead to the identification of new PKA targets

mental and Clinical Biomedical Sciences, Endocrinology Unit, University

involved in the pathogenesis of CPAs.

of Florence, Florence, Italy;⁶Department of Genetics, Cell- and

Immunobiology, Semmelweis University, Budapest, Hungary;

DOI: 10.1530/endoabs.49.GP1

⁷‘Lendulet-2013’ Research Group, Hungarian Academy of Sciences and

Semmelweis University, Budapest, Hungary.

Background

Extracellular vesicles

(exosomes, microvesicles) shed from tumor cells

GP2

containing microRNAs can be exploited as markers of malignancy. The

Contribution of retinoic acid receptor signalling to adrenal cortex

preoperative diagnosis of adrenocortical malignancy is difficult and microRNAs

morphology and functional zonation through modulation of

have proved useful in the diagnosis of many tumors, including adrenocortical

WNT/b-catenin pathway

cancer (ACC), but there have no studies to date on extracellular vesicle associated

Rami El Zein¹, Amanda J Rickard¹, Golib Dzib Jose Felipe²,

microRNAs in ACC.

Benoit Samson-Couterie¹, Angélique Rocha¹, Marko Poglitsch³, Celso

Aim

E Gomez-Sanchez⁴, Laurence Amar^1,5, Fabio Luiz Fernandes-Rosa^1,6,

To evaluate the diagnostic potential of extracellular vesicle-associated

Norbert B Ghyselinck⁷, Arndt Benecke², Enzo Lalli^8,9,

(exosomal) microRNAs in human adrenocortical tumors.

Maria-Christina Zennaro^1,6 & Sheerazed Boulkroun¹

Methods

¹INSERM, UMRS_970, Paris Cardiovascular Research Center and

The isolation of extracellular vesicles (EV) was performed either by differential

Université Paris Descartes, Sorbonne Paris Cité, Paris, France;²Centre

centrifugation/ultracentrifugation or by applying Total Exosome Isolation Kit.

National de la Recherche Scientifique (CNRS), Institut des Hautes Etudes

EV preparations were also assessed by transmission electron microscopy and flow

Scientifiques, Bures sur Yvette, France;³Attoquant Diagnostics GmbH,

cytometry. 6 adrenocortical adenomas (ACA) and 6 histologically verified ACC

Vienna, Austria;⁴Division of Endocrinology, G.V. (Sonny) Montgomery

samples were profiled by Taqman Human Microarray A-cards in the discovery

VA Medical Center and University of Mississippi Medical Center, Jackson,

cohort. The significantly differentially expressed microRNAs were validated in

MS 39216, USA;⁵Assistance Publique-Hôpitaux de Paris, Hôpital

13 ACAs and 12 ACCs by targeted quantitative real-time PCR.

Européen Georges Pompidou, Unité d’hypertension, Paris, France;

Results

⁶Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges

Significant overexpression of EV-associated hsa-miR-101 and hsa-miR-483-5p

Pompidou, Service de Génétique, Paris, France;⁷Institut de Génétique et de

was measured in ACC vs ACA samples in the microRNA profiling. We could

Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104-INSERM

confirm the overexpression of these microRNAs in the validation cohort, too.

U964, Department of Functional Genomics and Cancer, Illkirch, France;

dCThsa-miR-483-5p normalized to cel-mir-39 showed the highest area under

⁸Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de

curve (AUC) value (0.96), with 91.67 sensitivity and 92.33 specificity.

Recherche 7275, CNRS, Valbonne, France;⁹Université de Nice-Sophia

Conclusions

Antipolis, Valbonne, France.

Extracellular vesicle-associated

(exosomal) hsa-miR-483-5p might be a

promising minimally invasive biomarker in the preoperative diagnosis of ACC.

Recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1 and ATP2B3 have

DOI: 10.1530/endoabs.49.GP3

been identified in aldosterone producing adenoma (APA). Although the role of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP4

NCI-H295R cells co-transfected with RIIb and Ca-WT or different Ca mutants,

only the L206R mutation led to a full degradation of RIIb and this degradation

Androgen receptor signalling is essential for regression

could not be abolished by proteasome and lysosome inhibition but, surprisingly, by

of the adrenal x-zone and regulation of the adrenal cortex

stimulating PKA signaling. Same co-transfections with RIa did not lead to its

in the male mouse

degradation. By performing RIIb co-IP experiments in the presence of Ca-WT or

Anne-Louise Gannon, Laura O’Hara, Rod Mitchell, Ian Mason & Lee Smith

Ca-L206R, followed by nanoLC-MS/MS analysis, we could identify possible

University of Edinburgh, Edinburgh, UK.

novel RIIb interaction partners mediating RIIb stability in NCI-H295R cells. In

conclusion, our data demonstrate that mutations in PKA Ca lead to post-

Introduction

transcriptional downregulation of the main regulatory subunit in CPA. In NCI-

Androgens have long been known to play an important role in health and wellbeing.

H295R cells, transfection with the L206R mutant led to full degradation of RIIb,

A range of clinical disorders in males and females can arise due to disruption to

which could not be rescued by different degradation mechanisms, suggesting

production and action of androgens. Androgen receptor (AR) is widely expressed

another mechanism that can be abrogated by stimulating PKA signaling.

throughout the adrenal cortex, yet the wider role for androgen signalling in the

LC-MS/MS revealed putative RIIb interaction partners affecting its stability in

adrenal remains underexplored due to the lack of suitable animal models.

the presence of Ca L206R only after stimulation of PKA signaling.

Methods

DOI: 10.1530/endoabs.49.GP5

An adrenal-specific androgen receptor knockout mouse model was created by

targeting GFP-Cre-GC to the mouse Cyp11a1 locus to drive Cre Recombinase

expression in steroidogenic cells. Males were then mated to C57BL/6 female

homozygous AR^fl/fl mice. C57BL/6 mice were also used to investigate normal

adrenal function. Tissue was analysed through qRT-PCR and statistical analysis by

one way ANOVA. Immunohistochemistry was used to determine changes in

protein localisation.

Results

Results highlight that androgens signalling through AR is essential for the

regression of the foetal ‘X-zone’ during puberty in male mice. Loss of androgens

(through castration) or AR results in significant morphological differences in the

adrenal cortex and X-Zone cells. However, interestingly, loss of androgens or AR

impact cortex structure, gene expression and protein localisation differently.

Conclusions

We show that androgen signalling through AR is essential for removal of X-zone

GP6

cells during puberty. We also demonstrate that androgens can act independently of

AR to modulate cortex function. Additionally, the loss of androgen signalling

Involvement of ARMC5 in proliferation and cell cycle control

results in a decrease in apoptotic cells, suggesting the adrenal has become more

of human cell cultures from adrenal nodules of primary

resistant to cell death. Improper removal of cortical cells and loss of apoptosis could

macronodular adrenocortical hyperplasia (PMAH)

have serious implications for adrenal function and disease progression. The impacts

Isadora Cavalcante¹, Mirian Nishi², Maria Claudia Zerbini⁴,

of this are undergoing further investigation.

José Luiz Chambo³, Madson Almeida^2,5, Claudimara Lotfi¹ &

2,5

DOI: 10.1530/endoabs.49.GP4

Maria Candida Fragoso

¹Institute of Biomedical Sciences, São Paulo, Brazil;²Laboratory de

Medical Investigation LIM 42, São Paulo, Brazil;³Department of Urology,

São Paulo, Brazil;⁴Department of Pathology, São Paulo, Brazil;

Adrenal Unit, São Paulo, Brazil.

Background

The mechanisms causing hypercortisolism in primary macronodular adrenocor-

tical hyperplasia (PMAH) are not fully clarified. The participation of ectopic

receptors and autocrine/paracrine regulation of intra-adrenal ACTH in

hyperplastic tissue have been considered. Additionally, germline ARMC5

mutations have been described as main cause of PMAH. So far, the functional

study that analyzed the role of ARMC5 used the adrenocortical carcinoma cell

GP5

line, H295R. Therefore, we propose a more suitable model in cell cultures

Protein Kinase A signaling saves regulatory subunit IIb from PRKACA

obtained from nodules of PMAH.

mutation-mediated degradation

Aim

Isabel Weigand¹, Kerstin Bathon², Cristina Ronchi¹, Marthe Rizk-Rabin³,

To investigate the role of ARMC5 related to PMAH.

Guido Di Dalmazi⁴, Vanessa Wild⁵, Beatrice Rubin⁶, Jens T Vanselow⁷,

Methods

Andreas Schlosser⁷, Davide Calebiro², Felix Beuschlein⁴,

Cell cultures obtained from nodules of 13 unrelated patients with PMAH ARMC5

Jérôme Bertherat³, Martin Fassnacht¹ & Silviu Sbiera¹

mutated or not were analyzed for: i) Morphological and functional character-

¹Division of Endocrinology and Diabetes, University Hospital Wuerzburg,

ization; ii) ARMC5 sequencing; iii) ARMC5 silencing through shRNA in non-

Wuerzburg, Germany;²Institute of Pharmacology and Toxicology,

mutated PMAH cells for steroidogenic and proliferative functional studies;

Bioimaging Centre, University of Wuerzburg, Wuerzburg, Germany;

iv) ARMC5 overexpression through transient transfection in mutated PMAH cells

³Institut Cochin, Department of Endocrinology, Hôpital Cochin, Paris,

and viability analyses.

France;⁴Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians

Results

University, Munich, Germany;⁵Institute of Pathology, University of

i) The cell cultures demonstrating presence of steroidogenic cells, ectopic/aber-

Wuerzburg, Wuerzburg, Germany;⁶Department of Medicine, University of

rant receptors and functional intra-adrenal ACTH. ii) ARMC5 mutations were

Padua, Padua, Italy;⁷Rudolf Virchow Center for Experimental Biomedi-

located mostly in exons 1, 2 and 3, responsible for protein-protein interactions of

cine, University of Wuerzburg, Wuerzburg, Germany.

ARM repeat family; ARMC5 germline mutations identified in seven samples were

associated or not to somatic mutations or LOH. In six samples, ARMC5 mutation

Protein Kinase A (PKA) consists of two catalytic and two regulatory subunits with

was not identified; iii) ARMC5 silencing in non-mutated PMAH cell cultures

several isoforms

(Ca,b,g, RIa,IIa,Ib,IIb). In

30-40% of cortisol-producing

decreased StAR, CYP17A1, CYP11A1, NR5A1 and MC2R, increased CCNE1

adrenocortical adenomas (CPA) heterozygous activating somatic mutations in the

mRNA expression and its proliferative capacity, but without interference in cell

catalytic subunit a (Ca) of PKA have been found. Previous reports found strikingly

viability. iv) ARMC5 overexpression induced apoptosis and necrosis after 8h in

reduced levels of RIIb in CPA compared to other adrenocortical tumors. Here, we

PMAH mutated cell cultures, decreasing cell viability.

investigated the correlation between Ca mutational status, RIIb expression levels

Conclusions

and the underlying regulation mechanisms in CPA and the adrenal cell line NCI-

We confirm the role of ARMC5 as a pro-apoptotic protein and its importance in

H295R. RIIb expression was strongly reduced in Ca-mutated CPAs, especially in

the steroidogenesis related to PMAH, as previously described in H295R cells. We

tumors harboring the frequent L206R mutation (34 Ca-WT and 23 Ca-mutated

also report for the first time the involvement of ARMC5 in proliferation control

CPA) by both immunohistochemistry (mean expression: 1.5G0.7 vs 0.4G0.5,

and cell cycle regulation of PMAH cell cultures, which needs to be further

P!0.05) and WB. Similar results were observed for RIa (1.8G0.9 vs 2.6G0.6,

explored.

P!0.05) but not for the other regulatory subunits. Notably, mRNA expression of

DOI: 10.1530/endoabs.49.GP6

all subunits was unchanged in Ca-WT compared to Ca-mutated CPA. In

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP7

cut-off value for miR483-5p (0.221 ng/ml) significantly predicted overall and

recurrence-free survival. miR483-5p was the only variable that significantly

Identification of a new glucocorticoid receptor mutation underscores

predicts recurrence, but not overall survival, in a multivariate Cox analysis (HR

the substantial prevalence of genetic NR3C1 alterations in adrenal

16.2, 95%CV[1.39-188.6, P!0.026]). In addition, miR483 and 483-5p levels

hyperplasia: the French National Research Program MUTA-GR

significantly correlated with the number of circulating tumor cells in the same

Géraldine Vitellius¹, Brigitte Delemer², Philippe Caron³, Antoine Bennet³,

blood samples, independently of the timing of sampling. Analysis of an

Jerome Bouligand^1,4, Anne Guiochon-Mantel¹, Say Viengchareun¹,

independent cohort of metastatic ACC (nZ21) revealed that miR483 negatively

Christian Dani⁶, Severine Trabado^1,4 & Marc Lombes^1,5

correlated with mitotane levels.

¹Inserm UMR S 1185, Kremlin Bicetre, France;²Service d’Endocrinologie,

In conclusion, we demonstrated that miR483 and miR483-5p absolute plasma

Hopital Robert Debré, CHU de Reims, REIMS, France;³Service

levels in ACC patients are powerful molecular markers that may help to follow

d’endocrinologie, maladies métabolique et nutrition,CHU Larrey,

patients after surgery and chemotherapy, and contribute to better classify and

TOULOUSE, France;⁴Service de Génétique moléculaire,

predict tumor evolution.

pharmacogénétique et hormonologie, KREMLIN BICETRE, France;

⁵Service d’Endocrinologie et des Maladies de la Reproduction, KREMLIN

DOI: 10.1530/endoabs.49.GP8

BICETRE, France;⁶Université Côte d’Azur, CNRS, Inserm, iBV, NICE,

France.

Primary generalized glucocorticoid resistance is characterized by glucocorticoid

excess without any Cushing syndrome. Patients exhibit variable clinical

presentation including arterial hypertension, hirsutism or adrenal hyperplasia.

Although glucocorticoid resistance has been associated with glucocorticoid

GP9

receptor (GR) mutations (encoded by NR3C1 gene), only 23 mutations have been

Mortality is increased in patients with Cushing’s disease in long-term

reported so far. We have conducted a French National Research Program, referred

remission: A nation-wide study

to as MUTA-GR that aims at determining the prevalence of NR3C1 genetic

Dimitrios Chantzichristos¹, Eleni Papakokkinou¹, Per Dahlqvist²,

alterations in patients with adrenal masses associating by glucocorticoid

Elin Segerstedt², Tommy Olsson², Katarina Berinder³, Charlotte Hoybye³,

resistance. In this context, we have recently identified a novel GR stop mutation

Sophie Bensing³, Britt Edén Engstrom⁴, Pia Burman⁵, Cecilia Folin⁶,

in a 43-year-old man presenting with glucocorticoid resistance, bilateral adrenal

Eva Marie Erfurth⁶, Jeanette Wahlberg⁷, Bertil Ekman⁷, Erik Schwarcz⁸,

hyperplasia and biological hypercortisolism (1.5 to 3-fold increased in 24 h

Ing-Liss Bryngelsson⁹, Eva Andersson¹⁰, Gudmundur Johannsson¹,

urinary free cortisol, negative response to dexamethasone suppression test and

Daniel S Olsson¹ & Oskar Ragnarsson¹

normal plasma ACTH concentrations). Alteration of GR signaling is currently

¹Institute of Medicine at Sahlgrenska Academy, University of Gothenburg

validated by transient transfection assays, binding studies, subcellular trafficking,

and the Department of Endocrinology, Sahlgrenska University Hospital,

Chromatin Imunoprecipitation experiments, stability investigation, three-dimen-

Gothenburg, Sweden;²Department of Medicine, Umeå University, Umeå,

sional modeling and gene expression studies.

Sweden;³Department of Molecular Medicine and Surgery, Karolinska

More than 120 patients have been enrolled and five original GR heterozygous

Institutet, and Department of Endocrinology, Metabolism and Diabetology,

mutations (two missense and three false sense including R469X, R477S, Y478C,

Karolinska University Hospital, Stockholm, Sweden;⁴Department of

L672P) were discovered. Each original mutation impaired a different step of GR

Medical Sciences; Endocrinology, Diabetes and Metabolism, Uppsala

intracellular signaling. Ex vivo experiments performed on patients’ fibroblasts

University Hospital, Uppsala, Sweden;⁵Department of Endocrinology,

demonstrated that some mutations (R469X, R477S) led to an haploinsufficiency

Skane University Hospital, Malmo, University of Lund, Malmo, Sweden;

phenotype with a decreased response in glucocorticoid-dependent target gene

⁶Department of Endocrinology, Skane University Hospital, Lund, Sweden;

expression (FKBP5, SGK1).

⁷Department of Endocrinology and Department of Medical and Health

Interestingly, all mutated patients present with metabolic disorders (high BMI,

Sciences, Linkoping University, Linkoping, Sweden;⁸Department of

metabolic syndrome, .), supporting the essential role played by glucocorticoid

Internal Medicine, School of Health and Medical Sciences, Orebro

signaling in adipocyte physiology that we are currently exploring. Altogether, GR

University, Orebro, Sweden;⁹Department of Occupational and Environ-

mutations are not such an uncommon event given that 5% of our patients carried

mental Medicine, Orebro University Hospital, Orebro, Sweden;

NR3C1 alterations. Collectively, GR defects are not a rare cause of glucocorticoid

¹⁰Department of Occupational and Environmental Medicine, Institute of

resistance, an incidence initially minimized. We propose that genetic screening of

Medicine, Sahlgrenska Academy, University of Gothenburg and Sahl-

the NR3C1 gene should be conducted in patients with adrenal incidentalomas and

grenska University Hospital, Gothenburg, Sweden.

subclinical hypercorticism.

DOI: 10.1530/endoabs.49.GP7

Background

It is still undetermined whether patients with Cushing’s disease (CD) in remission

have an increased mortality. Most previous studies are limited by small numbers

of patients and/or short follow-up time.

Objective

To study mortality in a nation-wide cohort of patients with CD during long-term

follow-up.

GP8

Methods

Clinical and translational relevance of circulating miR483 in

Patients with ICD codes for Cushing’s syndrome and/or CD, between 1987 and

adrenocortical cancer

2013, were identified in the Swedish National Patient Registry. Medical records

Letizia Canu¹, Francesca Salvianti¹, Giada Poli¹, Roberta Armignacco¹,

of the patients were reviewed (clinical, biochemical, imaging and histopatholo-

Giulia Cantini¹, Alessandra Di Franco¹, Stefania Gelmini¹,

gical data) to verify the diagnosis, and to determine remission status. All other

Tonino Ercolino¹, Massimo Terzolo², Gabriella Nesi¹, Pamela Pinzani¹,

forms of Cushing’s syndrome than CD were excluded from the study.

Massimo Mannelli¹ & Michaela Luconi¹

Standardized mortality ratios

(SMRs) with 95% confidence intervals were

¹University of Florence, Florence, Italy;²University of Turin, San Luigi

calculated using the Swedish general population as reference.

Gonzaga Hospital, Orbassano, Turin, Italy.

Results

Out of 1252 identified patients, 502 (387 women (77%)) had a confirmed CD

Adrenocortical cancer

(ACC) is a rare aggressive malignancy, with poor

diagnosis. Of these, 411 (82%) were in biochemical remission. The meanGS.D. age

prognosis when metastaic at diagnosis. Recent ACC pan-genomics analysis

at diagnosis was 46G16 years. The median (interquartile range) follow-up time was

contributed to redefine the risk groups on molecular bases, including tumor micro

(6-23) years, resulting in 7165 patient-years of follow-up. Of the 502 patients, 364

RNA (miR), which can be detectable not only in the primary lesion but also in the

(73%) had been treated with pituitary surgery, 129 (26%) with radiotherapy and 102

bloodstream.

(20%) with bilateral adrenalectomy. The observed number of deaths was 133 vs 54

We develop a quantitative real-time assay for the measurement of absolute levels

expected, resulting in an overall SMR of 2.46 (95% CI 2.06-2.91). SMR in patients

in plasma samples of miR483 and its mature miR483-5p form. miR483/miR483-5p

not in remission (nZ91) was markedly increased, SMR 8.23 (95% CI 5.42-12.0).

levels were evaluated in plasma samples of 27 patients with ACC before surgery

Mortality in patients in biochemical remission was lower (P!0.0001), but increased

and at follow up, and in an independent validation cohort of 21 metastatic ACC.

compared to the general population, SMR 1.80 (95% CI 1.44-2.23).

Statistically significant difference in miR483-5p and miR483 levels of pre-surgery

Conclusion

and post-surgery samples was found between low (stage 1/2) and high (stage 3/4)

This large nation-wide study demonstrates that patients with CD have an excess mortality,

risk groups. Moreover the mean levels of both miRs were significantly higher in

irrespective of remission status. The findings emphasize the importance of curative

plasma of patients belonging to the high stage risk group compared to subjects with

treatment as well as continued active surveillance after remission has been achieved.

the benign form (ACA) and healthy subjects. ROC curves analysis of miR483-5p

DOI: 10.1530/endoabs.49.GP9

levels resulted in predicting the risk stage (accuracy 0.917G0.084). The best ROC

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP10

higher in patients with SAI than PAI. Most patients were treated with conventional

hydrocortisone, with similar mean doses administered in Germany, the Nether-

Expression of GATA transcription factors and their role in the aetiology

lands, Sweden and the UK (PAI: 24.7G8.4 mg/day, 22.2G5.7 mg/day, 21.5G

of Testicular Adrenal Rest Tumours

10.0 mg/day,

21.0G9.3 mg/day; SAI:

20.0G6.4 mg/day,

20.8G6.1 mg/day,

Manon Engels^1,2, Paul Span³, Monica Marijnissen-van Zanten⁴, Teun van

21.6G9.4 mg/day, 18.9G5.2 mg/day). Cortisone acetate was most commonly

Herwaarden², Christina Hulsbergen-van de Kaa⁴, Rod Mitchell⁶,

used in the Netherlands (PAI, 23%; SAI, 27%). No difference was observed in

Lee Smith⁶, Nike Stikkelbroeck⁵, Fred Sweep² &

fludrocortisone dosing in patients with PAI between countries (0.1G0.07 mg/day,

Hedi Claahsen-van der Grinten¹

0.1G0.04 mg/day,

0.1G0.05 mg/day,

0.1G0.12 mg/day). Patients with PAI

¹Department of Pediatrics, Radboud University Medical Center, Nijmegen,

treated with dual-release hydrocortisone (DRHC) were treated with lower doses

The Netherlands;²Department of Laboratory Medicine, Radboud

in Germany 21.3G2.3 compared with those in Sweden 28.0G6.0 mg/day.

University Medical Center, Nijmegen, The Netherlands;³Department of

Conclusions

Radiation Oncology, Radboud University Medical Center, Nijmegen, The

The maintenance doses of hydrocortisone observed in this study are in line with

Netherlands;⁴Department of Pathology, Radboud University Medical

international guidelines in all four countries. The country difference in maintenance

Center, Nijmegen, The Netherlands;⁵Department of Internal Medicine,

doses in DRHC is consistent with data showing that mean daily doses of

Radboud University Medical Center, Nijmegen, The Netherlands;⁶Medical

hydrocortisone tend to be higher in Sweden than in other countries.

Research Council Centre for Reproductive Health, University of Edinburgh,

Edinburgh, UK.

DOI: 10.1530/endoabs.49.GP11

Background

Recently, GATA transcription factors have been linked to the development of

Testicular Adrenal Rest Tumours (TART), benign adrenal-like testicular tumours

that frequently occur in male patients with congenital adrenal hyperplasia (CAH).

The objective of this study is to determine GATA expression in TART and other

steroidogenic tissues, examining their discriminative potential and their possible

role in the aetiology of TART.

Methods

GATA1-6 expression was determined in TART, Leydig cell tumour (LCT), adult testis,

adult adrenal, foetal testis, and foetal adrenal tissues. In addition, GATA expression was

measured in Hs181.tes cells after induction with dibutyryl cAMP (dbcAMP).

Results

GP12

In TART, testis-like GATA4 gene expression, but higher compared to adult adrenal,

Activation of the cAMP/PKA transduction system triggers

was found. In contrast, GATA3 and GATA6 expression in TART is similar to adrenal,

abnormal expression of the serotonin signaling pathway in human

but higher compared to adult testis or LCT. GATA3 and GATA6 could discriminate

adrenocortical cells

between TART and testis (AUC of 0.982 and 0.920, respectively). ACTH is a

Julie Le Mestre¹, Céline Duparc¹, Zakariae Bram¹, Yves Reznik²,

potential stimulator of TART differentiation in CAH. Stimulation of the Hs181.tes cell

Jérôme Bertherat³, Philippe Touraine⁴, Jacques Young⁵, Olivier Chabre⁶,

line with 0.1 mM dbcAMP for 4 hours increased gene expression of both GATA3 and

Constantine A. Stratakis⁷, Hervé Lefebvre^1,8 & Estelle Louiset¹

GATA6.

Conclusion

¹Normandie University, UNIROUEN, INSERM, U1239, Rouen, France;

Gene expression of GATA transcription factors in TART shows both testicular and

²Department of Endocrinology-Diabetology, Caen University Hospital,

adrenal characteristics. Additionally, GATA3 and GATA6 mRNA levels can help

Caen, France;³Department of Endocrinology and Metabolic Diseases,

discriminate TART from LCT. Furthermore, we found that dbcAMP can induce

Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Paris, France;

GATA3 and GATA6 gene expression, which might indicate that ACTH can stimulate

⁴Department of Endocrinology and Reproductive Medicine, Assistance

testis cells to become more adrenal like and eventually TART cells. To confirm this,

Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Paris, France;

we are pending on the results of stimulation experiments with dbcAMP or ACTH in

⁵Department of Endocrinology, Assistance Publique-Hôpitaux de Paris,

ACTH-responsive H295RA cells.

Hôpital Bicêtre, Kremlin-Bicêtre, France;⁶Department of Endocrinology,

CHU de Grenoble, Grenoble, France;⁷Section of Endocrinology and

DOI: 10.1530/endoabs.49.GP10

Genetics, PDEGEN, NICHD, Bethesda, Maryland, USA;⁸Department of

Endocrinology, Rouen University Hospital, Rouen, France.

In human adrenals, serotonin (5-HT), released by subcapsular mast cells,

increases aldosterone secretion through activation of type

4 serotonin

Adrenal 2

receptors (5-HT₄R) but only exerts a modest control on cortisol production.

Interestingly, illicit synthesis of 5-HT in adrenocortical cells as well as

GP11

overexpression of the 5-HT₄R and ectopic expression of the type 7 receptor

A country comparison of glucocorticoid replacement therapy in

(5-HT₇R) have been observed in bilateral macronodular adrenal hyperplasia

patients with primary and secondary adrenal insufficiency: data from

responsible for hypercortisolism. In this study, we have investigated the

the EU-AIR

expression of the key enzyme of 5-HT synthesis tryptophan hydroxylase

Bertil Ekman¹, Marcus Quinkler², Pinggao Zhang³, Pierre Zelissen⁴ &

(Tph) and 5-HT₄R, 5-HT₆R, 5-HT₇R in the adrenal samples removed from

Robert D. Murray⁵

patients suffering from diseases associated with activation of the

¹Linkoping University, Linkoping, Sweden;²Endocrinology in Charlotten-

cAMP/PKA pathway in adrenocortical cells, such as primary pigmented

burg, Berlin, Germany;³Shire, Lexington, Kentucky, USA;⁴University

nodular adrenocortical disease (PPNAD), Cushing’s disease (CD), ectopic

Medical Center Utrecht, Utrecht, The Netherlands;⁵St James’s University

secretion of ACTH, and

21-hydroxylase deficiency

(21-OHD), in

Hospital, Leeds, UK.

comparison with normal adrenals. In PPNAD cells, we observed

upregulation of Tph together with 5-HT₄R, 5-HT₆R and 5-HT₇R. Over-

Introduction

expression of the 5-HT signaling pathway appeared to be the consequence of

The daily maintenance dose of conventional hydrocortisone currently recommended

the activation of PKA by PRKAR1A gene mutations which cause the disease.

by international guidelines for the management of primary adrenal insufficiency

5-HT strongly stimulated cortisol production and inhibition of Tph reduced

(PAI) or secondary adrenal insufficiency (SAI) is 15K25 mg/day, in 2K3 divided

corticosteroidogenesis in cultured PPNAD cells. High expression of Tph

doses. The aim of this analysis was to investigate inter-country differences in

and 5-HTRs was also detected in adrenal tissues exposed to high plasma

glucocorticoid replacement doses in patients with PAI and SAI.

ACTH levels, including CD, 21-OHD and ectopic Cushing’s syndrome. Our

Design

results indicate that activation of the cAMP/PKA pathway in adrenocortical

EU-AIR (ClinicalTrials.gov identifier: NCT01661387) with 20 contributing centres

cells resulting either from PRKAR1A mutations or activation of the MC2R

across Germany, the Netherlands, Sweden and the UK started enrolling patients

by sustained increase in plasma ACTH levels induces an aberrant

with AI in August 2012. Baseline clinical and biochemical data from patients in the

serotonergic stimulatory loop in zona fasciculata. They also suggest that

four countries were compared. 1798 patients (626 PAI, 1172 SAI) were included in

the intraadrenal 5-HT signaling pathway may participate in the pathophy-

the current analysis of data collated until November 2016. Patients with congenital

siology of PPNAD-associated and ACTH-dependent hypercortisolisms and

adrenal hyperplasia or tertiary AI were excluded.

could represent an adaptive mechanism to increase glucocorticoid synthesis

Results

in 21-hydroxylase deficiency.

No major differences between countries were seen in disease duration, BMI, blood

DOI: 10.1530/endoabs.49.GP12

pressure or blood lipids in patients with PAI and SAI. However, BMI was generally

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP13

(aldosterone). The analytical sensitivity of this particularly novel active

PRKARIA (Carney complex gene) is a major regulator of the tight link

renin assay was 0.1 pg/ml, which was better than that of radioimmunoassay

between cell cycle phases and steroidogenesis in the adrenocortical

(2.0 pg/ml). Using Bland-Altman plots with the mass-spectrometry values,

tumor cells H295R

both bias and limits of agreement with 95% confidence interval of the

Marthe Rizk-Rabin¹, Bruno Ragazzon¹ & Jerôme Bertherat^1,2

automated aldosterone assay were smaller than those of the radioimmuno-

¹INSERM U1016, CNRS UMR8104 Paris Descartes University, Paris,

assay, indicating smaller systemic errors in the novel measurement. The

France;²Center for Rare Adrenal Diseases, Department of Endocrinology,

ratio of aldosterone-over-renin concentrations of 11.2 (ng/dl per pg/ml)

Hôpital Cochin, Paris, France.

provided

80.8% sensitivity and

94.9% specificity as a cut-off for

differentiating primary aldosteronism from essential hypertension. This

novel measurement is expected to be a clinically reliable alternative for

conventional radioimmunoassay and to provide better throughput and cost-

The cyclic AMP/PKA signalling cascade is involved in the pathogenesis of

effectiveness in diagnosis of hyperaldosteronism from larger numbers of

cortisol-secreting adrenocortical tumors

(ACT). Defects in cell cycle

hypertensive patients in clinical settings.

checkpoints play a major role in oncogenesis. The PKA regulatory subunits

DOI: 10.1530/endoabs.49.GP14

PRKARIA and PRKARIIb are involved in cell survival and steroidogenesis

in the adrenocortical carcinoma H295R cell line. We have previously shown

that their inactivation enhances the accumulation of cells in the G2 phase

and activates PKA and MAPkinases pathways.

This study investigates the correlation between the cell cycle phases and the

adrenal steroid secretion, as well as their control by PKA.

Methods

Using pharmacologic drugs, H295R cells were synchronized at specific cell cycle

check point (G1 phase), (S phase) and (G2 phase). The cell cycle distribution

(Cytometry), the expression of cyclins, PKA subunits, cell signalling pathways,

StAR and steroidogenic enzymes were analysed. The effect of PKA activation

GP15

either by the different PKA subunits, or cAMP, PKA inactivation by H89 and PKI

Integrated genomic and phenomic analysis reveals key molecular

along the cell cycle synchronization were studied.

pathways of aldosterone producing adenoma

Results

Fabio Fernandes-Rosa^1,2, Sheerazed Boulkroun¹, Felipe Golib Dzib³,

Cells synchronized at G2 phase increased the expression of the steroidogenic

Georgios Daniil¹, Laurence Amar^1,4, Bastien Rance⁵,

enzymes and steroid secretion. Arresting H295R in G1 phase decreased the

Benoit Samson-Couterie¹, Xavier Jeunemaitre^1,2, Tchao Meatchi^1,6,

steroidogenic enzymes expression and cortisol secretion. PKA subunits

Arndt Benecke^7,8, Tim Strom^9,10 & Maria-Christina Zennaro^1,2

distribution and PKA activity modulation were cell cycle dependent. PKA

¹INSERM, UMRS_970, Paris Cardiovascular Research Center, Université

activation by PRKARIA inactivation counteracted specifically the decrease of

Paris Descartes, Sorbonne Paris Cité, Paris, France;²Assistance Publique-

steroidogenesis in cells arrested in G1 phase: StAR/luc reporter gene activity and

Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de

cell progression in G2

phase were stimulated. PRKARIIb inactivation and

Génétique, Paris, France;³Institut des Hautes Etudes Scientifiques, Bures

PRKACA overexpression or cAMP increased the StAR/luc reporter gene activity,

sur Yvette, France;⁴Assistance Publique-Hôpitaux de Paris, Hôpital

independently of the cell cycle check point arrest. The H89 and PKI differentially

Européen Georges Pompidou, Unité Hypertension artérielle, Paris, France;

reduced StAR/luc reporter gene activity, and both reversed the cell cycle in the G2

⁵Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges

arrested cells.

Pompidou, Département d’Informatique Hospitalière, Paris, France;

Conclusion

⁶Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges

Inactivation of the Carney complex gene stimulates steroidogensis in the low

Pompidou, Service d’Anatomie Pathologique, Paris, France;⁷Université

steroidogenic G1 phase arrested cells. This study shows a link between the cell

Pierre et Marie Curie, Paris, France;⁸CNRS UMR 7224, Paris, France;

cycle check points and the regulation of steroidogenesis, in which the PRKARIA

⁹Institute of Human Genetics, Helmholtz Zentrum Munchen, Neuherberg,

subunit is a key regulator of both cell cycle and steroidogenesis.

Germany;¹⁰Institute of Human Genetics, Technische Universitat Munchen,

DOI: 10.1530/endoabs.49.GP13

Munich, Germany.

Primary aldosteronism is the most common form of secondary hypertension.

Somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D have been

described in 50% of aldosterone producing adenomas (APA). To identify

genetic alterations in new genes, we performed whole exome sequencing in

GP14

23 patients with APA negative for recurrent mutations in known driver

genes. A low number of somatic variations were identified per patient,

Simultaneous assays of aldosterone and renin concentrations in just ten

ranging from 1 to 22. No somatic variations were identified in two patients.

minutes could change the clinical assessment for the diagnosis of

Somatic mutations in KCNJ5 and CACNA1D were identified in 12 APA.

primary aldosteronism

These mutations were not observed or were present at very low levels on

Fumitoshi Satoh^1,2, Morimoto Ryo², Yoshikiyo Ono², Yuta Tezuka^1,2,

previous Sanger sequencing, indicating tumor heterogeneity. Two patients

Kei Omata^1,2, Masahiro Nezu², Yoshitsugu Iwakura², Yoshuhiro Igarashi²,

harbored mutations in genes involved in the Wnt/b-catenin pathway, which

Masataka Kudo² & Sadayoshi Ito²

represents, together with the membrane ion transporter activity, the two

¹Tohoku University Graduate School of Medicine - Division of Clinical

significantly overrepresented pathways in gene ontology analysis. Sequen-

Hypertension, Endocrinology and Metabolism, Sendai, Japan;²Tohoku

cing of CTNNB1 in somatic DNA from 150 subjects with APA identified

University Hospital - Division of Nephrology, Endocrinology and Vascular

additional variants in 13 subjects, including 2 APA harboring also a KCNJ5

Medicine, Sendai, Japan.

mutation. Transcriptome data obtained from 123 APA and 11 control

adrenals did not show differences on the expression levels of Wnt4, an

activator of the Wnt/b-catenin pathway, and LEF1 and Axin2, two b-catenin

Measurement of plasma aldosterone and renin concentration, or activity, is

target genes, as a function of the mutation status. Hierarchical clustering of

useful for selecting antihypertensive agents as well as detecting

transcriptional profiles at a genome-wide scale was not associated to the

hyperaldosteronism in hypertensive patients. However, it takes several

APA mutation status, supporting a model whereby all recurrent mutations

days to get results when measured by radioimmunoassay and development

converge upon activation of calcium signaling and increased aldosterone

of more rapid assays has been long expected. We have developed

production. In addition, b-catenin activation was observed by immunohis-

chemiluminescent enzyme immunoassays enabling the simultaneous

tochemical analysis in two thirds of APA independently of CTNNB1

measurement of both aldosterone and renin concentrations in ten-minutes

mutations, suggesting the involvement of additional mechanisms promoting

by a fully automated assay using antibody-immobilized magnetic particles

cell proliferation. Using transcriptome affinity-propagation-based analysis

with quick aggregation and dispersion. We performed clinical validation of

we identified 15 different clusters of APA. These clusters are not associated

diagnostic ability of this newly developed assay-based screening of 125

with demographic or clinical data, highlighting additional molecular

patients with primary aldosteronism from

patients with essential

pathways underlying APA development and identifying subgroups to be

hypertension. Results of this novel assay significantly correlated with the

targeted for gene discovery.

results of radioimmunoassay (aldosterone, active renin concentration and

DOI: 10.1530/endoabs.49.GP15

renin activity) and liquid chromatography-tandem mass spectrometry

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP16

test (DST). Patients who failed to suppress to %50 nmol/l after the DST were

further examined with 48 h low dose dexamethasone suppression test (LDDST)

Cardiovascular features of autonomous cortisol secretion in patients

and 24-h urinary free cortisol collection (UFC). Patients with elevated cortisol

with adrenal incidentalomas

levels according to LDDST or UFC underwent ACTH measurements and

Emilia Sbardella¹, Marianna Minnetti¹, Laura Rizza¹, Maria Rosaria

imaging.

Di Giorgio¹, Valeria Hasenmajer¹, Denise D’Aluisio², Sergio Morelli²,

Results

Andrea Lenzi¹ & Andrea M Isidori¹

(22%) patients had elevated cortisol after DST of whom 20 (5%) failed to

¹Department of Experimental Medicine, Sapienza University of Rome,

suppress after LDDST and/or had elevated UFC. No significant difference in age,

Rome, Italy;²Department of Internal Medicine and Medical Specialties,

BMI, HbA1c, T-score, Total Body Fat or blood pressure were recorded between

Sapienza University of Rome, Rome, Italy.

the two groups. Among the 20 patients with biochemical CS subsequent imaging

with either pituitary MR or abdominal CT, according to suppressed (nZ10) or

Background

unsuppressed (nZ10) ACTH levels, revealed adrenal adenoma(s) in nine cases

Possible Autonomous Cortisol Secretion (pACS) is a condition found in 1-29% of

and a pituitary macroadenoma in one case.

patients with adrenal incidentalomas. The diagnosis of pACS has been variably

Conclusion

associated with an increased risk of cardiovascular events and mortality.

i) The prevalence of hypercortisolism is high in T2D, also in unselected newly

However, dedicated studies describing the morphologic and functional cardiac

diagnosed patients, ii) Hypercortisolism was not associated with a persuasive

alterations in these patients are lacking.

phenotype, iii) The clinical implications remain uncertain but continued interest is

Aim

justified, preferably in terms of randomized intervention trials.

To compare the cardiovascular features of patients with pACS to those with

DOI: 10.1530/endoabs.49.GP17

nonfunctioning (NF) adrenal masses.

Materials and methods

Fifty-eight patients with adrenal incidentaloma without the classic signs or

symptoms of overt hypercortisolism were prospectively enrolled. Anthropo-

metric, metabolic and hormonal parameters, adrenal magnetic resonance,

echocardiography B-mode ultrasound and arterial stiffness calculated with

oscillatory method were assessed in all patients. We diagnosed patient with

pACS after

1-mg overnight dexamethasone suppression test

(1 mg-DST),

confirmed by traditional 48-h Liddle tests, if post-test serum cortisol felt between

51 and 138 nmol/l.

Results

Overall 30 patients had pACS and 28 NF adrenal masses. No differences in

gender, smoke habits, hypertension, obesity and diabetes prevalence were

observed between pACS and NF patients. Mean left ventricular (LV) mass index

was increased in the pACS compared to the NF group (112.6G29.2 vs 94.8G

31 g/m² PZ0.032). We also detected a significantly higher prevalence of LV

hypertrophy in PACS than NF group (35.7% vs 14.3% PZ0.007). Furthermore,

there was a negative correlation between the post-dexamethasone cortisol levels

GP18

and ejection fraction (rZK0.26; PZ0.041). The assessment of arterial stiffness

Effects of two mineralocorticoid receptor antagonists on the

showed a higher pulse wave velocity in pACS compared with the NF group

morphology of the adrenal cortex

(11.3G1.4 vs 10.2G0.6 m/s; PZ0.048).

Sofia S Pereira^1,2, Madalena M Costa¹, Ângela Moreira¹, Liliana Carvalho³,

Conclusions

Mariana Monteiro¹, Gavin Vinson⁴ & Duarte Pignatelli^2,5

Autonomous Cortisol Secretion (pACS) can lead to early cardiac and vascular

¹Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical

dysfunction even in apparently asymptomatic patients. These results underline the

Research) of ICBAS, University of Porto, Porto, Portugal;²IPATIMUP/I3S,

need for further studies, including second line cardiovascular assessment, to

Porto, Portugal;³Departament of Experimental Biology, Faculdade de

correctly define the management of pACS and allow early recognition of possible

Medicina, University of Porto, Porto, Portugal;⁴The School of Biological

complications.

and Chemical Sciences Queen Mary University of London, London, UK;

DOI: 10.1530/endoabs.49.GP16

⁵Department of Endocrinology, Hospital S.Joa˜o, Porto, Portugal.

Arterial hypertension usually results from the deregulation and hyperactivity

of the renin angiotensin-aldosterone system. One of the available

therapeutic approaches for its treatment is the use of mineralocorticoid

receptor (MR) antagonists, thus blocking aldosterone action.

The aim of this study was to characterize the effects of spironolactone and

eplerenone, on the morphology of the adrenal gland of spontaneously

hypertensive (SHR) and normotensive (Wistar-Kyoto) rats.

SHR (nZ18) and Wistar-Kyoto (nZ18) rats were exposed, for 1 month, to

spironolactone (100 mg/kg per day, nZ6), eplerenone (50 mg/kg per day,

GP17

nZ6) or not exposed to either drug (nZ6) and at the end of this period their

Hypercortisolism is prevalent in newly diagnosed type 2 diabetes: a

adrenal glands were collected and we evaluated the percentage of the stained

prospective study of 384 consecutive patients

area (%SA) of CyP11B1, CyP11B2, the adrenal inner zone antibody (IZAb),

Charlotte Steffensen¹, Olaf M Dekkers^2,3, Johanne Lyhne¹, Per L Poulsen¹,

a proliferation marker

(ki-67), b-catenin and finally the percentage of

Jørgen Rungby⁴, Henrik T Sørensen² & Jens Otto L Jørgensen¹

cellular area occupied by lipid droplets as well as the capsular width.

¹Department of Endocrinology and Internal Medicine, Aarhus University

SHR Hypertensive rats presented higher area of lipid droplets in all layers of

Hospital, Aarhus, Denmark;²Department of Clinical Epidemiology, Aarhus

the adrenal cortex, an effect that was even further increased by the exposure

University Hospital, Aarhus, Denmark;³Department of Epidemiology,

to eplerenone, in the fasciculata and reticularis zones. In the normotensive

Leiden University Hospital, Leiden, The Netherlands;⁴Department of

rats it was only spironolactone that elicited this effect, being significant only

Clinical Pharmacology, Aarhus University, Aarhus, Denmark.

in zona reticularis. Both drugs also increased Ki-67 expression in the

hypertensive rats, but only eplerenone increased it on normotensive rats.

Background

Finally, spironolactone decreased the capsular size but only in the

Cross-sectional studies in small and selected populations indicate a relatively high

normotensive rats. No significant differences were found for the % SA of

prevalence of incipient and/or subclinical Cushing’s syndrome (CS) in patients

CyP11B1, CyP11B2, IZAb or b-catenin.

with type 2 diabetes (T2D), which could have therapeutic implications.

In conclusion, we have found that, morphologically the adrenal glands of

Aim

normotensive and SHR only differed in number of lipid droplets. Exposure

To estimate the prevalence of CS in a large, unselected cohort of recently

to the MR antagonists had significant consequences on the capsular size,

diagnosed T2D patients.

lipidic depots and on the cellular proliferation of both normotensive and

Methods

SHR adrenal glands.

A total of 384 consecutive out - patients with T2D diagnosed after 1 January 2009

DOI: 10.1530/endoabs.49.GP18

were investigated by means of an overnight dexamethasone (1 mg) suppression

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP19

for patients who had died and those alive for each AI subset. Patients with

congenital adrenal hyperplasia or tertiary AI were excluded. 1798 patients were

Plasma cortisol and aldosterone responses to insulin tolerance test and

included (626 PAI, 1172 SAI) in the current analysis.

sodium depletion in women with non classic 21-hydroxylase deficiency

Results

caused by bi-allelic CYP21A2 mutations (NC-CAH)

To November 2016, 21 deaths had occurred (7 PAI, 14 SAI). Causes of death

Peter Kamenicky^1,2, Anne Blanchard³, Antonin Lamaziere⁴,

were cardiovascular (nZ8), infection (nZ3), unclear (nZ3), Addisonian crisis

Bruno Donadille⁴, Lise Duranteau¹, Sylvie Salenave¹, Laurence Pietri⁵,

(nZ1), suicide (nZ2), renal failure, drug-induced hepatitis, cachexia and brain

Marie Laure Raffin-Sanson⁶, Jean-Franc¸ois Gautier7, Philippe Chanson1,2,

tumour (each nZ1). Patients who died were significantly older at enrolment than

Sophie Christin Maitre⁴, Veronique Tardy⁸, Yves Le Bouc⁴, Sylvie

those alive (PAI, 63.4G13.4 vs 50.0G15.8 years, PZ0.0253; SAI, 64.0G16.6 vs

Brailly-Tabard¹ & Jacques Young^1,2

54.3G16.2 years, PZ0.0250). Interestingly, duration of AI was shorter in

¹APHP Hôpital Bicêtre, Paris, France;²University Paris Sud- Reproductive

patients with PAI who died versus alive patients (6.5G5.7 vs 16.3G13.1 years,

Endocrinology, Paris, France;³APHP Hôpital Georges Pompidou, Paris,

PZ0.0035), whereas the reverse was true for SAI (20.4G13.2 vs 13.7G11.1

France;⁴APHP-UPMC Hôpital Saint-Antoine, Paris, France;⁵Hôpital Saint

years, PZ0.0257). There were no significant differences in sex, BMI, blood

Joseph, Paris, France;⁶APHP Hôpital Ambroise Paré, Paris, France;⁷APHP

pressure, triglycerides, LDL-cholesterol, cholesterol or HbA1c between the

Hôpital Lariboisière, Paris, France;⁸Hôpital Nord-Hôpitaux Civils de Lyon,

deceased and alive cohorts. Patients who died were generally more likely to have

Lyon, France.

hypertension

(PAI,

85.7% vs

21.8%, PZ0.0007; SAI,

71.4% vs

33.9%,

PZ0.0076) and diabetes mellitus (PAI, 57.1% vs 14.4%, PZ0.0112; SAI,

28.6% vs 11.5%, ns) at study inclusion.

NC-CAH is diagnosed in pubertal/post-pubertal women because of

Conclusions

androgen excess however, the risk of potential adrenal insufficiency is not

This is the first study providing detailed characteristics of AI patients who died.

known, and indication of systematic glucocorticoid replacement therapy is

Hypertension and diabetes, as well as infectious diseases, appear to play a major

controversial.

role in mortality.

Aim

DOI: 10.1530/endoabs.49.GP20

To evaluate cortisol and aldosterone secretions in response to challenges tests.

Design

Prospective controlled clinical study in a tertiary referral center. 20 women with

NC-CAH (serum stimulated 17-OHP O10 ng/ml/250 mg, Synacthen) compara-

tively to matched healthy women, were included if they had not receive

glucocorticoid treatment O1 year and estrogen-based oral contraception stopped

O3 months. Each participant underwent sequentially two tests separated by a 2 to

7-days: insulin tolerance gold standard test (ITT) and a sodium depletion test (oral

40 mg furosemide under low sodium diet) to stimulate both endogenous active

renin (AR) and aldosterone. Steroid levels measured by LC-MSMS.

Adrenal 3

Results

NC-CAH had lower pic plasma cortisol concentrations during ITT than healthy

GP21

women: 17.2 mg/dl (13.1-22.8) vs 21.2 mg/dl (17.1-33.5), PZ0.0002. A peak

Is diabetes mellitus associated with catecholamine-secreting tumours

plasma cortisol above 17.0 mg/dl was obtained in all controls but only in 60%

always a secondary diabetes?

NC-CAH women. NC-CAH had higher baseline ACTH and AR levels. 24-h after

Mara Baetu¹, Ana Maria Stefanescu¹, Simona Jercalau¹, Victor Tomulescu²,

sodium depletion, mean plasma aldosterone levels were comparable between the

Anna-Maria Tinu³ & Corin Badiu^1,4

two groups, but NC-CAH women had higher (PZ0.003) stimulated AR levels

¹‘C.I. Parhon’ National Institute of Endocrinology, Bucharest, Romania;

than healthy women: 67 mUI/l (15-156) vs 39 mUI/l (6-87).

²‘Fundeni’ Clinical Institute, Bucharest, Romania;³‘N.C. Paulescu’

Conclusions

National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest,

Forty percent women with NC-CAH have subnormal glucocorticoid adrenal

Romania;⁴‘Carol Davila‘ University of Medicine and Pharmacy, Bucharest,

function. Their aldosterone secretion was maintained normal by increased AR

Romania.

levels. Besides androgen excess therapy, clinical management of NC-CAH

women should include assessment of their cortisol and aldosterone secretion;

systematic chronic replacement therapy is still an open question, but transient

Introduction

glucocorticoid supplementation and rehydration during periods of stress should

Hyperglycaemia occurs frequently in catecholamine-secreting tumours due to

be considered.

insulin suppression or induced insulin resistance. These changes can be reversible

DOI: 10.1530/endoabs.49.GP19

postoperatory (postOp).

Objective

Our study aims to establish the impact of surgery in patients with catecholamine-

secreting tumours upon glucose metabolism disorders, as well as the predictive

factors for postOp diabetes-free patients.

Methods

We retrospectively analysed 72 patients (46 women-26 men), mean age 48 years

(9-82), median body mass index 24.5 kg/m² (16-36.19), 66 with pheochromo-

cytoma, 6 with paraganglioma, 3 malignant, 12 known with genetic syndromes.

We evaluated their glycaemic status preoperatory (preOp), and for 64 of them

GP20

postOp, with a median follow-up of 4.17 years. Glucose metabolism disorders

were diagnosed according to World Health Organization criteria.

Which are the factors and causes of death in patients with adrenal

Results

insufficiency? Mortality data from EU-AIR

We found preOp diabetes mellitus (DM) in 32 patients (44.44%). We identified

Marcus Quinkler¹, Bertil Ekman², Pinggao Zhang³, Pierre Zelissen⁴ &

significant glycaemic changes in older patients, with longer hypertensive period,

Robert D Murray⁵

higher frequency of metabolic syndrome, adrenal tumours rather than ectopic, and

¹Endocrinology in Charlottenburg, Berlin, Germany;²Linkoping

a higher level of ChromograninA (P!0.05). PostOp, 66.6% of patients were free

University, Linkoping, Sweden;³Shire, Lexington, Kentucky, USA;

of DM, 30% of them starting from week one postOp. We found significantly more

⁴University Medical Center Utrecht, Utrecht, The Netherlands;

cases of remnant DM in patients with longer duration of preOp DM (PZ0.0004,

⁵St James’s University Hospital, Leeds, UK.

110-vs-10 months) and in those requiring insulin preOp (PZ0.005). Patients with

or without postOp DM did not differ in presence of metabolic syndrome (but all

Introduction

patients with remnant DM had metabolic syndrome), history of familial DM,

If untreated, adrenal insufficiency (AI) leads to premature death. Hospital record

tumour characteristics, clinical or laboratory findings.

data suggest mortality associated with primary (PAI) and secondary AI (SAI) to

Conclusions

be 2-3-fold higher than in the general population. Major causes of death include

Our study found that DM is associated frequently with catecholamine-secreting

cardiovascular disease, Addisonian crises, brain tumours and infections; however,

tumours and

thirds disappear postOp. Remnant DM suggests that DM

there is little further characterization of patients who died.

associated with catecholamine-secreting tumours is not always a secondary DM.

Design

A longer duration of preOp DM and the fact that the glycaemic control is obtained

We analysed real-world data from the European Adrenal Insufficiency Registry

with insulin upon tumour diagnosis are predictive factors for remnant DM.

(EU-AIR; NCT01661387) with centres across Germany, the Netherlands,

DOI: 10.1530/endoabs.49.GP21

Sweden and the UK. Clinical and biochemical data at enrolment were compared

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP22

SDHBZ16,7%; SDHDZ55,6%. Family history of SDHx-related PPGL was

present in 20%. Deletions in SDHB exon-1 were the most frequent genetic defect.

Epithelial to mesenchymal transition in adrenocortical tumours: focus

Complete resection was achieved in

7(33,3%) and pre-surgery vascular

on FGF-FGFR pathway and c-MET

embolization was performed in 10(47,6%) of HNPGL patients. Radiotherapy

Iuliu Sbiera¹, Barbara Altieri^1,2, Annette Feuchtinger³, Kerstin Hofner¹,

was used in 12(40%) patients (mainly unresectable HNPGL) achieving partial

Axel Walch³, Martin Fassnacht^1,4, Cristina L Ronchi¹, Matthias Kroiss^1,5 &

response/stabilization. 177Lu-DOTATOC or 131I-MIBG were used in 4. Overall,

Silviu Sbiera^1,4

remission was observed in 33,3%, stable disease in 53% and progression in 13,3%

¹Division of Endocrinology and Diabetes, University Hospital, University of

of patients. Related morbidity was observed in 66,6% of patients, and one death

Wurzburg, Wuerzburg, Germany;²Division of Endocrinology and

occurred.

Metabolic Diseases, Catholic University of the Sacred Heart, Rome, Italy;

Conclusion

³Research Unit Analytical Pathology, Helmholtz Zentrum Munchen,

SDHC and SDHD patients are prone to develop single and multiple HNPGL,

Oberschleissheim, Germany;⁴Comprehenssive Cancer Center Mainfran-

respectively, and SDHB patients carry increased risk of malignancy, as suggested

ken, University of Wurzburg, Wuerzburg, Germany;⁵Clinical Chemistry

in other studies. SDHB patients and HNPGL had the worse prognosis, the former

and Laboratory Medicine, University Hospital, University of Wurzburg,

related to malignancy, and the last to cranial nerve deficits, unresectable disease

Wuerzburg, Germany.

and multimodality interventions. Radiotherapy represented a good alternative in

unresectable HNPGL.

Ad Adrenocortical carcinoma (ACC) is an aggressive tumour and treatment

DOI: 10.1530/endoabs.49.GP23

remains unsatisfactory in advanced disease. Activation of epithelial to

mesenchymal transition (EMT) is considered causative for metastatic spread in

a variety of human cancers. Accordingly, new drugs were developed specifically

targeting EMT with a focus on hepatocyte growth factor (HGF)/HGF receptor

(c-MET) and fibroblast growth factor (FGF)/FGF receptor (FGFR) signalling.

We here asked whether EMT is relevant to ACC progression to evaluate the

GP24

therapeutic potential of small molecule drugs targeting EMT.

Increased exosomes in endogeneous Cushing syndrome

Expression of FGFR family members and c-MET was analysed in 20 normal

Gloria Aranda¹, Gemma Xifra², Jose Manuel Fernandez-Real²,

adrenal glands (NAG), 23 adrenocortical adenomas(ACA) and 27 ACC at mRNA

Guillermo Garcia-Eguren¹, Gregori Casals³, Adriana Pane¹, Mireia Mora¹,

and protein level. Expression of FGFR1-4 was quantified in FFPE tumour tissue

Irene Halperin¹ & Felicia A Hanzu¹

using RNAscope mRNA in situ hybridization technique. c-MET mRNA was

¹Group of Endocrine Disorders, Department of Endocrinology Hospital

quantified by qRT-PCR. In a subset of 40 samples we quantified expression of 92

Clinic Barcelona, IDIBAPS, CIBERDEM, Barcelona, Spain;²Department

different genes involved in FGF-FGFR pathway signalling.

of Endocrinology, Hospital de Girona ’Dr Josep Trueta’; IdIBGi Girona,

FGFR2 mRNA was lower in ACC compared to ACA (3.1G2.1 vs 6.5G2.3

CIBERobn, Girona, Spain;³Biochemistry and Molecular Genetics, Hospital

mRNA copies/cell, PZ0.0005) whereas FGFR1 (7.5G5.3 vs 4.5G2.9, PZ0.09)

Clinic Barcelona, Barcelona, Spain.

and FGFR4 (5.1G2.3 vs 2.6G1.3, PZ0.002) were higher in ACC. FGFR4

expression was higher in advanced vs localized ACC (6.2G1.6 vs 3.9G2.7,

Exosomes are nano-sized vesicles secreted by the cells in the exatracellular fluids

PZ0.03). Pan-FGF-FGFR pathway qRT-PCR confirmed differential FGFR

representing a novel way of intracellular communication. Exosomes secreted

expression and revealed decreased expression of FGF7, FGF17 and mitogen

from blood cells like monocytes and platetes have been reported to be checkpoints

associated protein kinases in tumours compared with NAG. In advanced ACC

involved in haemostatic and thrombotic response. Glucocorticoids are inducing a

protein kinase c PRKCA was decreased but PRKCQ increased.

profound alteration of blood cells homeostasis with atherothrombotic, bleeding

c-MET mRNA expression was significantly higher in ACC compared to ACA and

and immune response alterations. Hereby we quantified for the first time

NAG (0.03G0.05 vs 0.01G0.03 and 0.01G0.02, respectively, PZ0.02).

circulating exosomes in overt Cushing syndrome (CS) patients.

Considering median expression as a cut-off, high c-MET expression in ACC

Methods

was associated with decreased overall survival (HRZ8.8, PZ0.02).

Cross sectional study in CS patients and controls. Diagnosis of CS was performed

In conclusion, EMT appears to be relevant for adrenocortical tumourigenesis and

following ECE and Endo guidelines. Blood samples from active, drug naive CS

progression. PRKCQ may be involved in EMT signalling in advanced ACC.

patients (nZ20) and age and sex matched controls (nZ20) were obtained after

EMT-related kinases such as c-MET and FGFR4 may be suitable treatment

overnight fast. Peripheral blood cells, biochemical and hormonal parameters were

targets in advanced ACC.

analyzed using standard methods. Circulatory exosomes were quantified in plasma by a

DOI: 10.1530/endoabs.49.GP22

sandwich enzyme-linked-immuno-sorbent assay (ExoTEST) employing a monoclonal

antihuman CD9 antibody. Further exosome phenotyping and analysis is ongoing.

Results

CS patients present as compared to controls a significant increased number of

CD9 positive exosomes (2.35!10¹⁰ vs 7.74!10⁹/100 ml; PZ0.005**). Absolute

monocytes (MN) number and 24 h urinary free cortisol (UFC) level correlates

GP23

with the number of exosomes, respectively PZ0.022* with r:0.391 for MN and

Clinical features and treatment outcomes in a group of SDHx-related

PZ0.005** with an r:0.467 for UFC.

pheochromocytoma/paraganglioma patients

Conclusion

Helder Simoes, Pedro Antunes, Ana Pinto, Sara Donato, Valeriano Leite &

Circulatory exosomes are increased in the hypercortisolemic state of Cushing

Branca Cavaco

syndrome.

Portuguese Oncology Institute, Lisbon Centre, Lisbon, Portugal.

DOI: 10.1530/endoabs.49.GP24

Introduction

Germline mutations in succinate dehydrogenase complex (SDHx) are a risk factor

for developing Pheochromocytoma (Pheo) and/or Paragangliomas (PGL) (named

together PPGL), being responsible for approximately 30% of cases. The precise

GP25

genotype-phenotype correlations and best management strategies are still uncertain.

Tumor microenvironment increases migration/invasion of murine

Objective

pheochromocytoma SDHB silenced spheroids

To characterize the clinical features and genotype-phenotype associations in a

Vanessa D’Antongiovanni¹, Serena Martinelli¹, Susan Richter^3,4,

group of SDHx-mutated PPGL patients.

Letizia Canu¹, Daniele Guasti², Paolo Romagnoli², Karel Pacak⁵,

Methods

Graeme Eisenhofer^3,4, Massimo Mannelli¹ & Elena Rapizzi²

Retrospective analysis of all germline SDHx-mutated PPGL cases followed in a

¹Department of Experimental and Clinical Biomedical Sciences, University

reference centre.

of Florence, Florence, Italy;²Department of Experimental and Clinical

Results

Medicine, University of Florence, Florence, Italy;³Institute of Clinical

Total PPGL patients with SDHx-mutation:

(16

female). SDHB-related:

Chemistry & Laboratory Medicine, Dresden, Germany;⁴Department of

18(60%); SDHD-related: 9(30%); SDHC-related: 3(10%). Mean age at diagnosis:

Medicine III, Technische Universitat Dresden, Dresden, Germany;⁵Eunice

36,8G15,4 years. Median follow-up: 94,8 months. Twenty nine patients had

Kennedy Shriver National Institute of Child Health and Human

symptoms at diagnosis. Cathecholamine secretion was detected in 9(30%). Nine

Development, National Institutes of Health, Bethesda, USA.

cases (30%) were malignant. Anatomical distribution: SDHB: 9 head and neck

PGL (HNPGL), 5 Pheo and 5 thoraco-abdominal PGL (TAPGL) cases; SDHD: 9

HNPGL, 1 Pheo and 1 TAPGL cases. All SDHC were single non-metastatic

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendo-

HNPGL. Malignancy: SDHBZ44,4%; SDHDZ11,1%. Multiple PPGL:

crine tumors. About 30-40% of Pheo/PGLs are due to a germ-line mutation in one

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

of the 13 main susceptibility genes which include the genes encoding the four

Tumours caused by mutations in the SDH enzyme complex have a unique

subunits of the succinate dehydrogenase (SDH - mitochondrial complex II). In

tumour metabolome due to a truncated citric acid cycle. The accumulation

PHEO/PGL due to SDHB mutations up to 80% of affected patients develop

of the onco-metabolite succinate is believed to drive tumourigenesis. The

metastatic disease and no successful cure is at present available. To obtain an

aim was to investigate the role of MRI spectroscopy (H-MRS) to detect

experimental model resembling the in vivo conditions of the SDHB-mutated

in vivo succinate elevations in suspected SDH deficient tumours including

PHEO, we used multicellular tumor spheroids (3D culture) of a murine cell line

GIST, phaeochromocytoma/paraganglioma (PPGL) and pituitary adenomas

cultured alone or in co-culture with mouse primary fibroblasts, evaluating the

(PA). Suitable patients were identified based on SDH germline status,

effects of SDHB silencing and microenvironment on invasion and migration

clinical phenotype and or tumour SDHB immunonegativity. A minimum

processes. The growth of spheroids is linear with clear edges. When the spheroids

tumour size of 1.5 cm was applied. H-MRS was performed on a 3T MRI

are treated with conditioned medium of cancer-associated fibroblasts (CAFs), we

scanner and spectra with and without water suppression, was obtained.

observe an evident detachment of clusters of viable cells in the surrounding space.

Succinate when detected, was visible on the spectra at a frequency of

SDHB silenced cells show a greater migratory capability than negative control

2.4 ppm and a succinate to choline ratio of O0.1 was deemed confirmatory

(NC) cells. In particular, SDHB silenced cells invade the surrounding space

of succinate detection. H-MRS was performed on nine patients to date

moving collectively, unlike the NC spheroids where cells tend to move

including four patients with GIST, 4 with PPGL and 1 with a PA. A

individually. This difference was even more evident when spheroids were

succinate peak was detected in

7/9

patients and correlated with the

co-cultured directly with mouse primary fibroblasts. Using electronic microscopy

immunohistochemistry (IH) and or germline status in all seven cases.

on spheroids, we observed that SDHB silenced cells show swollen mitochondria

H-MRS of a PA in a patient with a germline mutation in SDHB

and, alterations of mitochondrial crests (similarly to mitochondria of patients with

demonstrated no succinate peak and this correlated with the tumour

SDHB mutations) while SDHB mutated spheroids show borders that are more

SDHB immunopositivity. H-MRS successfully detected a succinate peak in

fraying than those of NC spheroids. In conclusion, SDHB silencing strongly

a patient with a metastatic GIST and a somatic mutation in SDHC. This is

increased the invasion/migration capabilities, and these changes are more evident

the first study to investigate the use of in vivo metabolomics in SDH

in SDHB spheroids co-cultured directly with primary fibroblasts. Further studies

deficient GIST and pituitary adenomas and has proven efficacy as a non-

on these mechanisms may suggest new therapeutic targets.

invasive test for the identification of in vivo succinate peaks and detection of

DOI: 10.1530/endoabs.49.GP25

SDH deficient tumours. It may be particularly useful for the detection of

somatic SDH mutations and to clarify the role of SDH mutations in newly

identified phenotypes. Future application includes the use of in vivo

succinate detection as a biomarker for therapeutic response.

DOI: 10.1530/endoabs.49.GP27

GP26

Metformin reduces viability and proliferation of pheochromocytoma

cells in vitro

Cinthia Meireles, Francisco Neves, Luiz Simeoni & Adriana Lofrano-Porto

GP28

University of Brasilia, Brasilia, Brazil.

A PRKACB somatic mutation in a cortisol producing adenoma: a new

example of protein kinase A activation leading to adrenal Cushing

Background

syndrome

Pheochromocytomas (PHEO) are rare neuroendocrine tumors derived from

Stéphanie Espiard^1,4, Matthias Knape², Kerstin Bathon³, Guillaume Assié¹,

chromaffin cells of the adrenal medulla. Catecholamins’ secretion is associated

Daniel Abid², Simon Faillot¹, Davide Calebiro³, Friedrich Herberg²,

with a high risk of cardiovascular complications. Malignancy is rare, but still

Constantine Stratakis⁴ & Jérôme Bertherat¹

demands effective treatment. Metformin has been shown to have antiproliferative

¹Team Endocrine Tumors and Signaling, Cochin Institute, Paris Descartes

properties in several cancer cell lines, possibly related to its ability to inhibit cell

University, Paris, France;²Department of Biochemistry, Kassel University,

proliferation pathways. Accordingly, we aimed to evaluate the effects of

Kassel, Germany;³Institute of Pharmacology and Toxicology and

metformin in the survival and proliferation of PHEO cells.

Bio-Imaging Center/Rudolf Virchow Center, University of Wurzburg,

Methods

Wurzburg, Germany;⁴Program on Developmental Endocrinology and

Cell viability was evaluated by MTT and TRIPAN assays using the PC12-Adh

Genetics, Eunice Kennedy Shriver National Institute of Child Health and

PHEO cell line treated with metformin in increasing concentrations (0-30 mM).

Human Development, National Institutes of Health, Bethesda, France.

A lipid peroxidation assay and determination of O₂

consumption using a

respirometer were performed to evaluate cellular stress. The effects of metformin

Introduction

on cell proliferation markers were analyzed by western blot.

Alterations of the cAMP signaling pathway are described in adrenal tumors

Results and Discussion

causing Cushing syndrome, specifically mutations in the gene coding for the

Metformin at 20 mM induced an inhibition of 60% of cell viability after 48 h

protein kinase A (PKA) catalytic subunit alpha (PRAKCA) in cortisol producing

treatment, as compared to untreated controls, and increased cellular lipid

adenomas (CPA) with overt Cushing syndrome.

peroxidation, while decreased O₂

consumption in PC12-Adh PHEO cells.

Materiel and Methods

Moreover, metformin treatment reduced the activation of proteins of the

Eight CPAs without PRKACA mutations were analyzed by whole exome

AMPK/PTEN/AKT/mTOR pathway, which suggests growth and cell prolifer-

sequencing. Direct sequencing of PRAKCB encoding for the catalytic subunit

ation impairment. We then performed a primary culture of a PHEO from a

beta (Cb) of the PKA was performed in 21 others. Interaction of WT or mutant Cb

10-year-old boy with VHL disease to test wheter metformin exerts its

with the PKA-regulatory subunits was studied by bioluminescence resonance

antiproliferative effects ex vivo. Our results suggest that metformin has a

energy transfer and surface plasmon resonance analysis. To study the PKA

moderate inhibitory effect on the viability of PC12-Adh PHEO cells. This effect is

activity, phosphorylation of the synthetic PKA-substrat Kemptide was analyzed

associated with enhanced lipid peroxidation and decreased O₂ consumption by

in cellulae in HEK293 cells transfected with a combination of RIa and Cb and

those cells, which are both suggestive of increased cellular stress. Moreover,

in vitro with purified proteins.

metformin treatment induced a positive modulation of the AMPK/PTEN/AKT/m-

Results

TOR signaling pathway. Altogether our results corroborate the hypothesis of an

A PRKACB somatic mutation p.S54L was found in one CPA, from a 41-year-old

inhibitory effect of metformin on PHEO cellular proliferation in vitro.

patient presenting with a severe form of Cushing syndrome. Direct sequencing of

DOI: 10.1530/endoabs.49.GP26

PRKACB did not show any other mutations in additional samples. Functional

studies demonstrated loss of interaction between the mutant Cb and the regulatory

subunit type 1 (RIa, RIb). After stimulation by cAMP or forskolin, dissociation of

Cb and RIa was faster and stronger with the mutant than with the WT Cb. In

addition, basal PKA activity was higher for the mutant catalytic than the wild-

type while the maximal activity after stimulation was lower.

GP27

Conclusions

The role of in vivo metabolomics using H-MRS in SDH deficient disease

PRKACB is a new gene responsible for at least one CPA, mutated in the somatic

Ruth Casey^1,3, Mary McLean^1,2, Madhu Bassetti², Ben Challis³,

state. This finding suggests that the Cb subunit of the PKA, too, may have specific

Helen Simpson³, Mark Gurnell^1,3, Ramesh Bulusu³, Alison Marker³,

functions in the adrenal cortex. Particularly, the role of the residue Ser54 (as was

Olivier Giger^1,3, Kieran Allinson³, Krishna Chatterjee^1,3, Eamonn Maher^1,3

previously suggested) may be very important for PKA function in the adrenal

& Ferdia Gallagher^1,3

cortex.

¹Cambridge University, Cambidge, UK;²Cancer Research UK, Cambridge,

UK;³Cambridge University Hospital NHS Foundation Trust, Cambridge,

DOI: 10.1530/endoabs.49.GP28

UK.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP29

GP31

Familial case of SDHB mutation presenting as a macroprolactinoma

Long-term treatment of acute ectopic ACTH syndrome with Etomidate

Edouard Mills, Pratibha Machenahalli, Ali Naqvi & Jeannie Todd

Zydrune Visockiene^1,2, Vilija Guntaite³, Vigantas Dunauskas²,

Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust,

Donatas Vajauskas^1,2, Gintautas Kekstas^1,2 & Giedre Vasyliene⁴

London, UK.

¹Vilnius Univesity Faculty of Medicine, Vilnius, Lithuania;²Vilnius

University Hospital Santariskiu Clinics, Vilnius, Lithuania;³Republican

Siauliai Hospital, Siauliai, Lithuania;⁴Republican Panevezys Hospital,

Panevezys, Lithuania.

Germline mutations in the succinate dehydrogenase subunit-B gene (SDHB)

are well recognised for predisposing to head and neck paraganglioma,

sympathetic paraganglioma, phaeochromocytoma and renal cell carcinoma.

Case description

The co-existence with pituitary adenomas remains uncommon.

A 25-year-old male was admitted to the Intensive Care Unit due to progressive

We report a 31-year-old female who presented at age 29 years old with 9

muscle weakness, difficulty walking, weight loss, headache, chest discomfort,

months of secondary amenorrhoea. Prolactin was 3000 mIU/l and a 1.7-cm

type 1 diabetes for few months. He was confused and irritated, with “moon” face,

macroprolactinoma revealed on MR pituitary. Taking prolactin-lowering

facial plethora, acne, and hyperpigmentation of the skin, few obscure red-bluish

therapy, she achieved normal menses and subsequent MRI imaging

striae and significant wasting of proximal and distal muscles of lower limbs.

demonstrated reduction in the size of this macroprolactinoma. At age 30

Cortisol hypersecretion due to ectopic ACTH production was confirmed by

years, she was found to have a paraganglioma in the aortic-pelvic region. On

plasma ACTH (O1250 ng/l) and cortisol (1120-2145 nmol/l), 24-h urinary free

reflection, she had noticed anxiety, sweating, palpitations and extreme

cortisol (14 726 nmol/24 h), failure to supress cortisol on a high dose intravenous

exercise intolerance for the 2 years preceding diagnosis, which resolved

and 16 mg oral 2 days dexamethasone suppression tests. Severe hypercortisole-

following surgical resection. She was screened for familial paragangliomas,

mia resulted in critical fluid and electrolyte imbalance, deterioration in physical

which revealed she was a carrier of the SDHB mutation. Interval screening

and mental state. Daily Etomidate infusion 20-60 mg for 14 days stabilized

MRI neck to pelvis has since demonstrated no evidence of recurrent or new

condition and later was used for treatment on alternate days in the dose of 20-

disease. Plasma metanephrines have subsequently remained normal.

40 mg for 10 months in day care clinic. Alternative treatment with Ketoconazole

Her father, aged 64 years old, was referred for genetic counselling and

induced hepatic injury, Octreotide was ineffective, Metyrapone was not available.

testing. He too is an SDHB mutation carrier. His plasma metanephrines are

Following Etomidate infusions, plasma cortisol decreased to 280-560 nmol/l,

normal and MRI neck to pelvis has not revealed a paraganglioma or

potasium

- 3.7-4.3 mmol/l with oral supplementation of KCl

3 g/day and

phaeochromocytoma. Both the index case and father will remain under

Spironolactone 50 mg, glucose became normal without insulin. In 10 months

lifelong specialist care in a Neuroendocrine Tumours Clinic. Family

Metyrapone became available and 1 g/day was used to achieve control. Patient

members have been advised to seek genetic counselling.

refused from adrenalectomy.

Although uncommon, increasing incidence of pituitary adenomas in carriers

Pituitary MRI, chest and abdomen CT, somatostatin receptor scintigraphy,

of SDH mutations are being reported. These pituitary adenomas tend to be

bronchoscopy, esophagogastroduodenoscopy, colonoscopy revealed no potential

larger with macroprolactinomas commoner than other pituitary adenomas.

source of ectopic ACTH production. Further assessment by whole body 18F-FDG

Screening programmes vary widely for carriers of SDH mutations and tend

PET-CT and 68Ga-DOTATOTE PET-CT scans, selective sinus petrosus inferior

not to involve pituitary imaging. However, given the association with

sampling and enteroscopy failed to detect the source of ACTH. Thorax CT and

pituitary lesions, screening imaging might need to include the pituitary. At

colonoscopy was performed three times, abdominal CT and pituitary MRI - twice

present, however, it is thought that this is likely to be a low-yield strategy.

during 16 months. Primary tumour was not detected.

DOI: 10.1530/endoabs.49.GP29

Conclusion

Etomidate infusion could be used for long term treatment of ectopic ACTH

syndrome when other options are ineffective or unavailable.

DOI: 10.1530/endoabs.49.GP31

GP30

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with

cyclical ectopic adrenocorticotrophic hormone secretion

Pratibha Machenahalli, E Mills, N Ali & JF Todd

GP32

Imperial College Hospitals NHS Trust, London, UK.

Multiple pathologic fractures as the presenting manifestation of

Cushing’s syndrome in patients with vitamin D receptor FokI gene

polymorphism

Vasiliki Daraki¹, Paraskevi Floroskoufi¹, Theodoros Liarigkovinos¹,

DIPNECH is pre-invasive precursor to carcinoid tumors and tmorlets, most

Maria Chrysoulaki¹, Vasilios Tsamadias², Emmanuel Economou² &

of which present with pulmonary symptoms. We present a case of ectopic

Stathis Papavasiliou¹

cyclical ACTH producing DIPNECH.

¹Department of Endocrinology Diabetes and Metabolic Diseases, University

33-year lady presented with a short history of weight gain, abdominal striae,

Hospital of Crete, Heraklion, Greece;²Laboratory of therapeutic

proximal myopathy and secondary amenorrhoea. She reported a previous

individualization, University of Athens, Aretaieio University Hospital,

episode with similar symptoms one year earlier which resolved spon-

Athens, Greece.

taneously after a few weeks. Random cortisol 4000 nmol/l, ACTH 98 ng/l.

LDDST failure to suppress cortisol levels. IPSS showed no central:per-

ipheral ACTH gradient, representing ectopic ACTH source. CT chest

showed multiple pulmonary nodules, a dominant RLL nodule larger since

Rare cases of Cushing’s syndrome have been diagnosed only based upon

2006. 68-Gallium DOTATATE PET/CT scan was normal. Metyrapone was

bone manifestations. Fracture risk is related to individual susceptibility to

commenced. One week later, Metyrapone was stopped due to low cortisol

glucocorticoids that is genetically determined by several factors, including

levels. Off Metyrapone, cortisol levels remained low with concomitant

VDR gene polymorphism.

reduction of ACTH levels, indicating another spontaneous remission of

We report three patients with VDR FokI gene polymorphism and multiple

Cushing’s syndrome. Histology from an excision biopsy of the RLL nodule

non-traumatic pathologic fractures as the presenting manifestation of

revealed tumourlets with a typical carcinoid appearance and a background

Cushing’s syndrome.

of DIPNECH. Post-operatively, she was treated with hydrocortisone

Case reports

replacement for a couple of weeks. After a few months later symptoms of

The first case is a 55-year-old man who presented with pain in the right hip. CT

Cushing’s recurred and repeat imaging of the chest has not shown any

scan revealed fracture in the right femur. Additionally bone scintigraphy revealed

progression of the lung nodules. Repeat LDDST confirmed the biochemical

non-traumatic micro-fractures in ribs and pelvis.

excess of cortisol. She is currently awaiting bilateral adrenalectomy.

The second case is a 44-year-old woman who presented with pain in the left hip.

As per the literature review, DIPNECH is common in female. There is only

She reported weight gain (25 kg) in the last 6 years, depression, fatigue, and

one case presented with ACTH secretion. It is relatively a stable disease with

muscle weakness. MRI revealed fracture in the left hip, while bone scintigraphy

only

26% of the patients deteriorates clinically and radiologically.

showed multiple non-traumatic micro-fractures in ribs and right femur.

Octreotide has not shown to improve the prognosis.

The third case is a 64-year-old woman presented with recurrent rib and low

DOI: 10.1530/endoabs.49.GP30

extremities fractures the last 10 years. She also suffered from depression and

hypercholesterolemia.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Dual-energy X-ray absorptiometry (DXA) revealed severe osteoporosis in all

GP34

patients. Additionally laboratory tests and imaging techniques confirmed the

Fat mass distribution and resistin are independent predictors of bone

diagnosis of Cushing’s syndrome due to an adrenal mass. Further investigation for

mass in postmenopausal, but not premenopausal women.

FokI and Bsm polymorphism of VDR gene by polymerase chain reaction and

Stefana Catalina Bilha^1,2, Maria-Christina Ungureanu^1,2, Petru Cianga^3,4,

restriction fragment length polymorphism (PCR-RFLP) analysis showed that all

Catalin Buzduga^1,2, Adrian Aancute¹, Valentin Zaharia¹,

patients had the ff genotype of the VDR FokI gene.

Daniela Constantinescu^3,4, Ecaterina Anisie³, Adrian Covic^5,6 &

Discussion

Dumitru Branisteanu^1,2

VDR FokI gene polymorphism correlates significantly with an increased rate of

¹Endocrinology Clinic, “Sf.Spiridon” Hospital, Iasi, Romania;

bone loss in ff postmenopausal women. However data of its functional

²Endocrinology Department, “Gr. T. Popa” University of Medicine and

significance on glucorticoid-induced osteoporotic fractures is lacking so far.

Pharmacy, Iasi, Romania;³Laboratory of Immunology and Genetics, ”Sf.

We report for the first time an association between the ff genotype and multiple

Spiridon” Hospital, Iasi, Romania;⁴Immunology Department, “Gr. T. Popa”

non-traumatic fractures as the predominant manifestation of Cushing’s syndrome.

University of Medicine and Pharmacy, Iasi, Romania;⁵Nephrology Clinic,

Our findings suggest that VDR FokI gene polymorphism may increase fracture

“Dr. C.I. Parhon” University Hospital, Iasi, Romania;⁶Nephrology

risk in ff subjects with endogenous hypercortisolism.

Department, “Gr. T. Popa” University of Medicine and Pharmacy, Iasi,

DOI: 10.1530/endoabs.49.GP32

Romania.

Introduction

Body weight and lean mass (LM) are classic bone mass determinants. However,

the association between total fat mass (FM), regional FM and bone remains

controversial, especially as fat is a source of adipocytokines, with both positive

Bone & Calcium Homeostasis 1

and negative bone consequences.

GP33

Materials and methods

“Hyperparanet”: a multicenter Italian study on Primary

Anthropometric, bone mass (assessed by Dual X-Ray Absorptiometry; DXA) and

Hyperparathyroidism

body composition parameters (assessed by DXA) and also serum adipocytokine

Federica Saponaro¹, Filomena Cetani¹, Valentina Camozzi²,

(leptin, adiponectin, resistin) levels were determined from 93 female volunteers

Antonella D’Angelo³, Salvatore Minisola³, Alfredo Scillitani⁴,

(38 premenopausal and 55 postmenopausal women). Correlation analysis was

Claudia Cipri⁵, Serena Palmieri⁶, Iacopo Chiodini⁶, Francesco Romanelli⁷,

performed in order to assess the association between body mass index (BMI),

Bruno Madeo⁸, Elena Castellano⁹, Laura Gianotti⁹, Antongiulio Faggiano¹⁰,

body composition parameters, adipocytokines and bone mass. Multivariable and

Luisella Cianferotti¹¹, Maria Luisa Brandi¹¹, Sabrina Corbetta¹², Maria

hierarchical regression models were used to determine which of the above factors

Laura De Feo¹³, Andrea Palermo¹⁴ & Claudio Marcocci¹

are independent predictors of bone mass.

¹Endocrine Unit 2, University of Pisa, Pisa, Italy;²Endocrine Unit,

Results

University of Padova, Padova, Italy;³Department of Internal Medicine and

In correlation analysis, BMI, total LM, total FM and regional FM (trunk FM and

Medical Disciplines’Sapienza’ University, Rome, Italy;⁴Casa Sollievo della

lower limbs FM) were positively associated with bone mass in both groups.

Sofferenza,’’ IRCCS, San Giovanni Rotondo, Italy;⁵Endocrinology and

Correlations between adipocytokines and bone were found only in the

Metabolism Unit University-Hospital of Udine, Udine, Italy;⁶Unit of

postmenopausal group. In multivariable regression analysis, only LM remained

Endocrinology and Metabolic DiseasesFondazione IRCCS Cà Granda-

an independent predictor of bone mass in premenopausal women, explaining

Ospedale Maggiore Policlinico, Milan, Italy;⁷Department of Experimental

38.1% (P!0.001) of femoral neck, 24.5% (PZ0.002) of total hip and 20%

Medicine, Sapienza University of Rome, Rome, Italy;⁸Unit of Endo-

(PZ0.005) of whole-body bone mineral density (BMD) variance; in post-

crinology, Modena, Italy;⁹Division of Endocrinology, Diabetes and

menopausal women, LM, trunk-to-lower limbs FM ratio (together explaining

Metabolism, Santa Croce and Carle Hospital, Cuneo, Italy;¹⁰Endo-

30.9% of the variance of total hip BMD, P!0.001) and resistin (adipokine known

crinology, Federico II University of Naples, Naples, Italy;¹¹Department of

to regulate bone cell proliferation and bone turnover) remained independent

Internal Medicine, University of Florence, Florence, Italy;¹²Area di

positive predictors of bone mass. Hierarchical regression showed no additional

Endocrinologia e Malattie Metaboliche, IRCCS Policlinico San Donato,

effect of BMI or of total FM to that of total LM in predicting bone mass in both

Milano, Italy;¹³Endocrinology Unit, Careggi Hospital and University of

groups.

Florence, Florence, Italy;¹⁴Department of Endocrinology and Diabetes,

Conclusions

University Campus Bio-Medico, Rome, Italy.

LM independently predicts bone mass in premenopause, while after menopause

FM distribution becomes an important factor in regulating bone mass together

with total LM and resistin. These parameters may find their place for fine tuning

The aim of the present study was to evaluate the phenotype of PHPT, the

the evaluation of fracture risk.

adherence to International Guidelines and the rate of surgical cure of PHPT in

DOI: 10.1530/endoabs.49.GP34

Italy. From January 2014-January 2016, we conducted a prospective, multicenter

(nZ29 endocrine tertiary referral centers) study on patients with PHPT, recording

clinical and biochemical data, parathyroid imaging and therapy choice at baseline

and at last follow-up. The study group included 604 patients with PHPT, with a

mean age of 61G14 yrs (F:MZ5:1). Most patients had sporadic PHPT (nZ566

(93.7%), mean age 63G13 yrs); the remaining 38 (6.3%, mean age 41G17 yrs)

were familial forms. Follow up data were available in 345 patients: 158 (45.8%)

with symptomatic and 187 (54.2%) with asymptomatic PHPT. Eighty-six patients

GP35

(54.4%) of the former group underwent PTx, mainly for symptomatic

nephrolithiasis (nZ71, 82.6%). One hundred twenty-one asymptomatic patients

Aldosterone and parathyroid hormone - is there a connection?

(64.7%) met at least one criterion for PTx according to the 2008 International

Mara Ventura, Miguel Melo, Diana Oliveira, Diana Martins, Adriana Lages,

guidelines for parathyroidectomy and 65 patients (53.7%) underwent surgery.

Nelson Cunha & Francisco Carrilho

Criteria for PTX were: serum calcium levels 1 mg above the upper normal limit

University and Hospital Center of Coimbra, Coimbra, Portugal.

(nZ37, 56.9%), osteoporosis (nZ35, 53.8%) and age !50 yrs (nZ14, 21.5%).

Surgery was not performed in the remaining patients (nZ56, 46.3%) despite the

Introduction

presence of serum calcium levels 1 mg above the upper normal limit (nZ12,

Recent studies seem to support a bidirectional positive interaction between

21.4%), osteoporosis (nZ44, 78.6%) and age !50 yrs (nZ11, 19.6%). Surgery

aldosterone and parathyroid hormone

(PTH). Understanding the normal

was also performed in 16 of the 66 (25.7%) patients who did not meet the criteria

physiological relationship between renin-angiotensin-aldosterone system

for surgery. A total of 168 patients underwent PTX. The histological diagnosis

(RAAS) and PTH is of clinical interest because their inappropriate activity may

was single adenoma in 89% of cases, hyperplasia in 9%, atypical adenoma in 1%,

negatively impact cardiovascular and skeletal health.

and carcinoma in 1%. The large majority (nZ158, 94%) of patients were cured.

Objective

Persistence of PHPT was observed in the remaining 10 patients, who were

To evaluate the presence of an interaction between aldosterone and PTH in a

apparently sporadic. Patients followed without surgery showed a stable clinical

cohort of patients assessed for suspicious hyperaldosteronism or hyperparathyr-

and biochemical disease, after one year of follow-up. This is the first multicenter

oidism.

Italian study with the specific aim of evaluating PHPT phenotype and therapeutic

Material and Methods

approach. International guidelines recommendations for surgery were observed in

We retrospectively evaluated consecutive patients followed in our Endocrinology

half of cases, either for symptomatic or asymptomatic patients.

Department between January 2014 and December 2016. We collected data about

DOI: 10.1530/endoabs.49.GP33

renin-angiotensin-aldosterone system and calcium metabolism from clinical and

laboratorial records and selected patients whenever both data were available.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

GP37

We identified

patients evaluated for suspicious hyperaldosteronism or

Effects of BCR-ABL targeted tyrosine kinase inhibitors on the whole

hyperparathyroidism. 51 patients were excluded due to insufficient data. From

transcriptome pattern of cultured murine osteoblasts

the 46 patients included, 8(17%) had confirmed primary hyperparathyroidism and

Bernadett Balla¹, Gyongyi Kirschner¹, Péter Horváth¹, Gergely Lakatos²,

one had confirmed primary hyperaldosteronism; 74% (nZ34) were women, mean

János Kósa¹ & Péter Lakatos¹

age of 60.0G13.2 years and mean BMI of 27.8G4.1 Kg/m². This group had a

¹First Department of Internal Medicine, Semmelweis University, Budapest,

mean aldosterone level of 141.9G74.6 pg/ml (reference range: 40-310), PTH

Hungary;²Second Department of Internal Medicine, Semmelweis

level of 87.3G48.0 pg/ml (reference range: 9-72), 25(OH) vitamin D level of

University, Budapest, Hungary.

26.5G10.2 ng/ml and plasma calcium level of 9.6G1.1 mg/dl (reference range:

8.8-10.6). PTH and aldosterone levels presented a moderate correlation in our

cohort (rhoZ0.474, P ! 0.01). After exclusion of the patients with confirmed

Breakpoint cluster region abelson fusion oncoprotein

(BCR-ABL) targeted

disease, PTH and aldosterone levels presented a week correlation, though still

tyrosine kinase inhibitors (TKIs) are widely used in long-term medications of

statistically significant (rhoZ0.377, PZ0.021).

hematological malignancies. Numerous clinical observations confirmed that these

Conclusion

drugs significantly modify the physiology of bone tissue as a side effect.

Aldosterone levels were positively correlated to PTH levels in our sample. This

Currently, there are numerous contradictory results regarding the complex effects

interaction may be one of the mechanisms responsible for hypertension and

of TKIs on bone metabolism, as well as there is no clear evidence to explain them,

increased cardiovascular risk in patients with hyperparathyroidism. On the other

either in the level of basic or clinical research.

hand, hyperaldosteronism may indirectly impair calcium metabolism and bone

The aim of the present study was to analyze the whole transcriptome differences

health.

of cultured murine osteoblasts (MC3T3E1) after imatinib or nilotinib treatment

DOI: 10.1530/endoabs.49.GP35

using SOLiD next generation RNA sequencing technique. Based on the cell

viability test,

1 mM drug concentration and 6-day incubation period had the

greatest effects on the expression profile of osteoblastic cells.

The results showed only three common up-regulated genes in the TKI-treated

groups with almost the same expression activity compared to the control one.

Ingenuity Pathway Analysis was applied to reveal the cellular response for the

two drugs. Six and five top canonical pathways were identified from the whole

transcriptome sequencing data in case of imatinib and nilotinib, respectively.

GABA receptor cascade was found among the markedly upregulated signaling

GP36

pathways in both of the treated groups. During the bone remodeling process, this

Relationship between circulating microRNAs and bone mineral density

signal transduction network is deeply involved in bone cell proliferation,

in patients with active acromegaly

differentiation and development.

Elena Valassi¹, Natalia García-Giralt², Jorge Malouf³, Iris Crespo¹ &

In conclusion, this was the first study to observe the complete mRNA pattern of

Susan M. Webb¹

osteoblasts after selective TKI administration. These preliminary transcriptional

¹Endocrinology/Medicine Department, Hospital Sant Pau, Centro de

results indicate various mechanisms of action of the examined TKIs on osteoblast

Investigación Biomédica en Red de Enfermedades Raras (CIBERER 747),

function that might be due to their different chemical profiles and non-kinase

target spectrum. Therefore, further investigation is required to verify the detected

II-B Sant Pau, ISCIII, Universitat Autònoma de Barcelona (UAB),

expression changes of the reported genes as well as to validate the biologically

Barcelona, Spain;²URFOA, IMIM (Institut Hospital del Mar d’Investiga-

significant targets.

cions Mèdiques), Universitat Autònoma de Barcelona, Barcelona, Spain;

³Mineral Metabolism Unit, Medicine Department, Hospital Sant Pau,

DOI: 10.1530/endoabs.49.GP37

Barcelona, Spain.

Objective

Acromegaly (ACRO) is associated with abnormal bone remodeling and reduced

volumetric bone mineral density (vBMD) at the lumbar spine and proximal

femur. Circulating microRNAs (miRNAs) modulate the activity of osteoblasts

and osteoclasts, and are currently being investigated as potential biomarkers of

osteoporosis. The aims of our study were: 1) To identify differentially expressed

miRNAs in the serum of five patients with active ACRO vs. healthy controls, and

GP38

2) To correlate selected miRNAs concentrations with altered bone parameters in

Decreased trabecular bone score but not bone mineral density

11 ACRO patients.

in patients with acromegaly and concurrent hypogonadism:

Patients and methods

cross-sectional study with healthy controls

Eleven patients with active ACRO (six females; mean age, 47.5G6.7 years; BMI,

Martin Kuzˇma1, Dušan Pavai2, Ivana Ságová3, Zdenko Killinger1,

27.2G3.8 kg/m²) and

age-, gender-, and BMI-matched controls were

Peter Jackuliak¹, Anton Va

ˇ uga², Peter Vanˇ uga2 & Juraj Payer1

recruited. Analysis of differential expression of miRs was performed in 5 of

¹Comenius University Faculty of Medicine, Fifth Department of Internal

them (5 males; mean age, 44.3G4.3; BMI, 26.2G2.8). Areal BMD (aBMD) at

Medicine, University Hospital Bratislava, Bratislava, Slovakia;²National

lumbar spine and femur was assessed through dual energy X-ray- absorptiometry

Institute of Endocrinology and Diabetology, Lubochna, Slovakia;

(DXA); vBMD was measured by quantitative computed tomography (QCT).

³Comenius University Jessenius Faculty of Medicine, First Department of

Serum miRNA levels were assessed by qPCR. Osteocalcin (OC), type 1 amino-

Internal Medicine, University Hospital, Martin, Slovakia.

terminal propeptide (P1NP) and carboxy-terminal collagen crosslinks (CTx) were

measured using electrochemiluminescent immunoassay.

Results

Introduction

Expression of miR-885-5p, miR-99a-5p, and miR-29a-3p was significantly

Acromegaly is associated with higher prevalence of vertebral fractures (VFx) and

higher, while that of miR-7-1-3p and miR-335-3p was significantly lower in the

bone microarchitecture potentially play a role in fracture development.

ACRO patients. Both miR-885-5p and miR-7-1-3p were inversely associated with

Trabecular bone score (TBS), a novel indicator of bone microstructure could

femoral aBMD (rZK0.64, PZ0.034 and rZK0.73, PZ0.009, respectively),

provide additional information.

and trocantheric vBMD (rZK0.66; rZ0.038 and rZ0.67; PZ0.023) in ACRO

Objectives

but not in the controls. They were also positively associated with P1NP (rZ0.82,

Assessment of BMD, TBS and bone turnover markers (BTM) in acromegaly

PZ0.002 and rZ0.79, PZ0.004, respectively) and CTx (rZ0.73, PZ0.010 and

patients in comparison to healthy controls with regard to gender, hypogonadism

rZ0.68, PZ0.019) in ACRO. MiR-99a-5p was inversely associated with femoral

and disease activity.

aBMD (rZK0.66, PZ0.26) and positively associated with P1NP (rZ0.83;

Patients and methods

PZ0.001) and CTx (rZ0.88, P!0.001) in ACRO only. The relationship

A cross-sectional study of acromegaly patients with age-, gender- and BMI-

between femoral aBMD and miR-99a-5p remained significant after adjusting for

matched healthy controls was conducted. Study group consisted from all

age and IGF-SDS (bZK0.52, PZ0.012).

acromegaly patients (regardless age, gender, disease duration or activity) which

Conclusions

came for follow-up visit during period 6/2016 - 12/2016 and the control group

Circulating miRNAs may be one of the mechanisms whereby BMD is impaired,

consisted of healthy subjects. In all subjects a single measurements of all pituitary

mainly at the femoral level. Further larger studies are needed to confirm these

axis hormones levels, BTM, BMD of total hip (TH) and lumbar spine (LS) and

preliminary data.

TBS was performed. N-terminal type 1 procollagen (P1NP) - marker of bone

DOI: 10.1530/endoabs.49.GP36

formation and C-terminal telopeptide (CTx) -marker of bone resorption were

analyzed.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

management of nine cases of synchronous PH and NMTC.

Thirty Seven acromegaly patients (12 males/25 females with mean age 56.7 years,

Cases

mean BMI 29.8 kg/m²) and 27 of control group subjects (seven males/20 females

Eight women and one man were included (mean age at diagnosis: 64G6.6 years).

with mean age 59.5 years, mean BMI 30.9 kg/m²) were included. TBS was

In all cases, PH was the initial diagnosis, whereas NMTC was detected

significantly lower in patients in comparison to controls (1.16 vs 1.22; P!0.05),

incidentally, after ultrasound assessment for PH. The histological diagnosis of

but no BMD and BTM difference was observed. Hypogonadal patients had lower

NMTC was classical papillary thyroid carcinoma (PTC) in all cases, with

TBS in comparison to patients without hypogonadism (TBS 1.13 vs 1.20;

follicular subtype in four cases. In one patient, medullary carcinoma was also

P!0.05) and no BMD difference. BTM were increased in hypogonadal patients

detected and a diagnosis of multiple-endocrine neoplasia type 2B syndrome was

(CTx 0.67 vs 0.38 ng/ml; P1NP 75.5 vs 47.5 ng/ml; both P!0.05). No difference

set. In three cases (33.3%), NMTC was multifocal. Extrathyroidal extension was

in TBS, LS BMD and BTM with regard to gender was observed.

detected in one case, but without metastatic disease. In seven cases (78%),

Conclusion

maximum NMTC diameter was !10 mm (mean diameter: 7.6G4.4 mm).

This study indicates that patients with acromegaly, especially those with

Thyroid autoimmunity was positive in two cases.

hypogonadism, despite unchanged BMD, may have impaired trabecular bone

The histological diagnosis of PHPT was single parathyroid adenoma (mean

microstructure, which can lead to increased prevalence of fractures.

diameter: 15.4G19.3 mm, in six cases on the right side) in all cases. In one case,

DOI: 10.1530/endoabs.49.GP38

the adenoma was intrathyroidal. Nephrolithiasis was diagnosed in one case,

hypercalciuria in two, whereas low bone mass in eight patients. Preoperative

mean parathyroid hormone (PTH) and total calcium concentrations were 133.5G

43.9 and 11.3G0.8 mg/dl (corrected calcium: 11G0.78 mg/dl), respectively.

Cardiovascular risk factors, such as arterial hypertension, dyslipidemia and/or

hyperglycemia were diagnosed in six cases (66.7%).

PH and NMTC were successfully managed with parathyroidectomy and total

thyroidectomy (mean post-operative PTH concentrations: 33.3G24.7 pg/ml). No

GP39

case developed post-operative hypocalcemia. Prophylactic central lymph node

resection was performed in one patient. No recurrence of either PH or NMTC has

Association of changes in serum urate level and bone mineral density

been reported (mean follow-up time: 3.8G5.1 years).

during treatment with teriparatide: a retrospective observational study

Conclusions

Tomaz Kocjan¹, Gaj Vidmar², Antonela Sabati Rajic¹, Mojca Jensterle

NMTC may rarely be incidentally detected in patients with PH. It is usually

Sever¹, Marija Pfeifer¹, Janja Marc³, Nina Orehek³ & Barbara Ostanek³

unifocal microcarcinoma of classical PTC subtype, without extrathyroidal

¹University Medical Centre Ljubljana, Ljubljana, Slovenia;²University

extension. The pathogenetic mechanisms linking these two endocrine entities

Rehabilitation Institute, Ljubljana, Slovenia;³Faculty of Pharmacy,

are currently unknown.

University of Ljubljana, Ljubljana, Slovenia.

DOI: 10.1530/endoabs.49.GP40

Serum urate level has recently been associated with increased bone mineral

density (BMD). Teriparatide, an osteoanabolic medication for osteoporosis, is

associated with increased incidence of hyperuricemia. Hence, we hypothesized

that changes in serum urate are associated with changes in BMD and procollagen

type 1 N-terminal propeptide (P1NP) during treatment with teriparatide.

We collected data from 151 women (mean age 72 years, mean BMI 26.6 kg/m²)

with severe postmenopausal osteoporosis who had been treated with teriparatide

for

2 years at our outpatient clinic. They were prescribed with vitamin D3

1000 IU daily and were instructed to ingest 1200 mg of calcium daily. BMD was

measured at the three standard sites by DXA at baseline, after 12 and 24 months

of treatment. Routine laboratory parameters (including serum urate), 25-hydro-

xyvitamin D and P1NP were measured at the same time-points. Estimated

glomerular filtration rate (eGFR) was calculated. The associations were assessed

GP41

using univariate correlations and multiple linear regression models (each fitted

Follow-up of patients with surgical hypoparathyroidism: unknown

using casewise deletion of records with missing data as well as missing data

cause of renal function decline?

imputation). Repeated-measures analysis of variance was used to verify the

Tess van de Meerhaeghe, Sergei Bukowski, Elien Coudenys, David Unuane,

increase in serum urate level and stability of eGFR.

Brigitte Velkeniers & Bert Bravenboer

During the 2-year treatment with teriparatide, we observed no notable univariate

UZ Brussels, Brussels, Belgium.

association between change of serum urate level and change of BMD. When

adjusting for basal eGFR, vitamin D sufficiency, previous bisphosphonate

Background

treatment, change of serum and of urinary calcium during the same period, we

Hypoparathyroidism is a rare endocrine disease with low calcium and insufficient

observed a weak positive association of serum urate level change with change of

parathyroid hormone levels. In most cases it is caused by thyroid surgery. The

BMD at lumbar spine. Conversely, change of serum urate level tended to be

objective of this retrospective cohort study was to evaluate if the typical therapy

weakly positively univariately associated with change of P1NP, but the

regimens of postsurgical hypoparathyroidism with calcitriol have a negative

association vanished when adjusting for the confounders listed above.

effect on renal function.

Our results may indicate that the effect of teriparatide on bone might be partly

Methods

mediated by changes in serum urate level.

We performed a chart analysis of patients that were seen in a tertiary care hospital

DOI: 10.1530/endoabs.49.GP39

in Brussels, Belgium. A total of 101 patients were identified as patients with

permanent post-surgical hypoparathyroidism, based on the hospital records of

patients who underwent a total thyroidectomy between 1996 and 2016, while still

being treated with calcitriol. Patients with pre-existing renal insufficiency and/or

active malignancy were excluded. The cohort was predominantly female of

Caucasian origin. Kidney function was evaluated before and after surgery (with a

maximum follow-up of 12 years), using the CKD-EPI equation.

Results

GP40

A multivariate linear regression model was used to correlate kidney function

Coexistence of primary hyperparathyroidism with papillary thyroid

decline with the duration of calcitriol therapy, while accounting for the mean

carcinoma: a case series

calcium-phosphate product and age. We found a statistically significant

Panagiotis Anagnostis¹, Athanasios Panagiotou¹, Fotini Adamidou¹,

(PZ0.027) relation between the duration of calcitriol treatment and renal

Savvas Rafailidis² & Marina Kita¹

function decline at a rate of 1.06 ml/min/1.73 m² per year of calcitriol therapy.

¹Department of Endocrinology and Diabetes, Hippokration Hospital of

Conclusions

Thessaloniki, Thessaloniki, Greece;²Euromedica Kyanous Stavros,

Renal abnormalities are frequent finding in patients with hypoparathyroidism.

Thessaloniki, Greece.

Our study, although being retrospective, is the first one to demonstrate a

relationship between the duration of calcitriol therapy and progressive renal

insufficiency.

Introduction

Primary hyperparathyroidism (PHPT) may rarely coexist with non-medullary

DOI: 10.1530/endoabs.49.GP41

thyroid carcinoma

(NMTC). We report the clinical manifestation and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP42

Med Genet). These preliminary results prompt us to confirm the causative role of

found genetic variants, and to clarify their role in the pathogenesis of specific and

Expression of hypoxia-inducible factor-1a in Calbindin-D_9k Knockout

unexpected clinical manifestations.

mice

Song Ai Kang, Seon Young Park, Jin Yong An & Eui-Bae Jeung

DOI: 10.1530/endoabs.49.GP43

Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

Introduction

Hypoxia-inducible factors (HIF) are the key transcription factor induced by

hypoxic condition, which regulate expression of specific target genes including

GP44

angiogenic factors, erythropoietin, glucose transporters, and glycolytic enzymes.

Investigation of total and free 25OHD vitamin levels in patients with

Recently, many studies connected to intracellular calcium levels and regulation of

chronic renal failure on different dose of cholecalciferol

HIF-1a protein level. Calbindin-D_9k is a cytosolic calcium-binding protein and

Erzsébet Toldy^1,2, László Kovács^3,4, Réka Németh², Gyuláné Szakács⁴,

compensate with other calcium transporter protein for maintenance of cellular

Imre Kulcsár^3,4 & Zoltán Locsei³

calcium level. It is expressed in primarily duodenum for absorption of calcium

¹Institute of Diagnostics Faculty of Health Science, University of Pécs, Pécs,

and in kidney for resorption of calcium. The objective of this study is to

Hungary;²Central Laboratory, Markusovszky University Teaching Hospi-

investigate interaction between HIF-1a and calbindin-D_9k.

tal, Szombathely, Hungary;³Department of General Internal Medicine of

Materials and methods

Markusovszky University Teaching Hospital, Szombathely, Hungary;

8-10 weeks old C57BL/6 mice and calbindin-D_9K knockout mice were exposed to

⁴B. Braun Avitum 6th Dialysis Centre, Szombathely, Hungary.

hypoxia (12G2% O2) for 3 weeks in closed polycarbonate chamber with nitrogen

supply to remove the oxygen vs the normoxic groups. Calbindin-D_9k-transfected

The total 25-hydroxy-vitamin-D (t-25OHD) level reflects the vitamin-D supply,

ACHN cells were cultured in normobaric hypoxia (1% O2), with match control in

but it is also influenced by the levels of vitamin-D-binding-proteins (DBP) and

normoxic conditions. Expression of HIF-1a and glucose transporter 1 (GLUT1, a

albumin. The type of dialysis influences the levels of serum proteins. The ‘free-

downstream gene of HIF-1a) were analyzed in mRNA or protein level.

hormone hypothesis’ states that only the free molecules (f25OHD) can diffuse

Results

intracellular. Our aim was to evaluate the total, calculated (c-f25OHD) and direct

Protein level of HIF-1a was increased in calbindin-D_9K knockout mice compared

measured (dm-f25OHD) 25OHD levels in patients with chronic renal disease on

with that of control in normoxic condition. However, increased protein level of

cholecalciferol.

HIF-1a of calbindin-D_9k knockout mice was reduced in hypoxic condition.

Methods

mRNA levels of GLUT1 showed similar pattern with HIF-1a expression. In

100 patients [45 men; 55 women; 69G14 years: 40 on haemodialysis (HD), 26

comparison to in vivo experiment, expression of HIF-1a and GLUT1 in mRNA

chronic renal failure (CRF) both on 1000 IUD₃/day; 34 on peritoneal dialysis

and protein levels corresponded to that of Calbindin-D_9k knockout mice.

(PD) on 3000 IUD₃/day] were investigated. Their sera were analysed for DBP

Conclusions

(Dako), albumin, Ca, PTHi, t-25OHD (Roche), dm-f25OHD (DIAsource).

These results suggest that calbindin-D_9k can regulate expression of HIF-1a in

Results

protein level.

Albumin levels were significantly lower (PD:38G5 HD:40G5; CRF:43G3 g/l;

DOI: 10.1530/endoabs.49.GP42

P!0,001) and DBP concentrations higher (390G55 CRF:352G42; HD:323G

61 mg/l; P!0,001) were in PD group. The t-25OHD and c-f25OHD were the

lowest in PD (t-25OHD: 65G30; CRF:78G38; HD:79G45 nmol/l, c-f25OHD:

14G7; CRF:18G9; HD:20G11 pmol/l, P!0.05). There were no significant

differences among dm-f25OHD levels

(PD:16G5; CRF:16G6; HD:15G

Bone & Calcium Homeostasis 2

6 pmol/l). The highest incidence of suboptimal vitamin D supply was found in

PD patients on the bases of t-25OHD (PD:65%; CRF:42%; HD:43%) and also in

GP43

c-f25OHD levels. These incidences decreased significantly into 15%-23%, when

Chromosome 2q37 microdeletions in two cases of sporadic PHP-1B with

dm-f25OHD was taken into consideration. Out of the three 25OHD fractions only

broad GNAS imprinting defects

dm-f25OHD levels gave the opportunity to prove significant relationship between

Arianna Pirelli¹, Francesca Marta Elli¹, Paolo Bordogna², Luisa de Sanctis³,

PTHi/Ca and 25OHD level (ORZ3.8_{CI:1.024-14.4}; PZ0.036).

Daniele Terraris³, Maura Arosio^1,2 & Giovanna Mantovani^1,2

Conclusions

¹Department of Clinical Sciences and Community Health, Endocrinology

t-25OHD and c-f25OHD values underestimate the vitamin D supply particularly

and Metabolic Sciences, University of Milan, Milan, Italy;²Endocrinology

in PD patients. Patients on PD need much higher doses of cholecalciferol, without

and Metabolic Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale

any differences from other two groups in dm-f25OHD levels either. Patients, who

Maggiore Policlinico, Milan, Italy;³Department of Public Health and

have higher dm-f25OHD level have 3.8 times higher chance for normal Ca/PTHi

Pediatrics, University of Turin, Regina Margherita Children’s Hospital,

levels. In case of dm-f25OHD there was a significant relationship proven between

Turin, Italy.

25OHD level and related biomarkers. The dm-f25OHD seems to be a reliable

marker for estimation of vitaminD supply in patients with chronic renal disease.

DOI: 10.1530/endoabs.49.GP44

Pseudohypoparathyroidism type 1B (PHP-1B) is a rare, familial or sporadic,

imprinting disorder due to the epigenetic dysregulation of the GNAS locus, whose

main product is the a subunit of the stimulatory G protein (Gsa). Sporadic PHP-

1B cases (spor-PHP-1B) display broad methylation abnormalities at multiple

GNAS DMRs, but the underlying molecular mechanism is still unknown.

Classically, PHP-1B patients show PTH and TSH resistance, but, in the past

GP45

years, also physical features of Albright hereditary osteodystrophy (AHO) were

Methylation patterns at the novel DMR of GNAS (GNAS-AS2) in

described, suggesting the existence of an overlap among PHP subtypes.

pseudohypoparathyroidism 1B (PHP1B or iPPSD3) subtypes

Moreover, mutations in PRKAR1A and PDE4D genes, and deletions of 2q37

Patrick Hanna¹, Anne Rochtus², Harald Jueppner³, Deborah Mackay⁴,

were reported in small subsets of clinically diagnosed PHP patients with no

Bruno Francou⁵, Jérôme Bouligand⁵, Anne Mantel⁵, Elli Anagnostou⁶,

detectable GNAS defects, highlighting the clinical overlap with diseases in

Dominique Gaillard⁷ & Agnès Linglart^1,8

differential diagnosis. Brachydactyly-mental retardation syndrome

(BDMR),

¹INSERM U1169, Bicetre Paris Sud, France;²University of Leuven,

associated with 2q37 deletions, may present a spectrum of clinical features,

Leuven, Belgium;³Massachusetts General Hospital and Harvard Medical

including intellectual disabilities, developmental delays, behavioural abnormal-

School, Boston, USA;⁴University of Southampton, Southampton, UK;

ities and skeletal abnormalities, among which brachydactyly type E.

⁵APHP, Pharmacogenetics and Hormonology, Bicetre Paris Sud, France;

In the present study, we screened our series of spor-PHP-1B pts with (nZ21) or

⁶Obstetrics and Gynecology, Alexandra Hospital, Athens, Greece;

without AHO (nZ33) for BDMR-associated deletions to find modifier genes

⁷Génétique et Biologie de la Reproduction, Centre Hospitalier Universitaire,

possibly involved in the phenotypic heterogeneity observed in PHP-1B, and we

Reims, France;⁸APHP, CMR Calcium-Phosphore, Bicêtre Paris Sud,

detected 2 different deletions (ranging from w2.83-Mb up to w4.5-Mb) in 2

France.

unrelated pts with AHO. Additional analysis confirmed rearrangements and

allowed to roughly delineate the genetic defects extension.

Deletions overlapped with previously described rearrangements and included

PHP1B -iPPSD3 per the new proposed classification- is a rare disorder

several genes already proposed as causative for BDMR. Interestingly, our

characterized in most patients by proximal tubular resistance to PTH resulting

mutated patients displayed molecular (GNAS loss of imprinting) and endocrine

in hypocalcemia, hyperphosphatemia and elevated PTH. Loss-of-methylation

characteristics (overt PTH resistance) usually absent in BDMR, although so far

(LOM) at the Differentially Methylated Region (DMR) at GNAS exon A/B occurs

only one BDMR patient with raised PTH levels was described (Power et al. 1997 J

in all PHP1B patients, but methylation changes at other DMRs within GNAS

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

occur in some familial and most sporadic PHP1B cases. All patients with

GP47

autosomal dominant PHP1B (AD-PHP1B) due to a maternal deletion that

Recombinant human parathyroid hormone (rhPTH[1-84], parathyroid

comprises the STX16 region (delSTX16C) present with LOM restricted to the

hormone rDNA) improves hypercalciuria in patients with

GNAS-A/B DMR, while sporadic cases (sporPHP1B) present with broad GNAS

hypoparathyroidism: 3-year analysis from RACE study

methylation defects, including LOM at a novel, recently identified DMR within

Bart L Clarke¹, Tamara J Vokes², John P Bilezikian³, Henry G Bone⁴,

the GNAS locus referred to as antisense DMR2 (GNAS-AS2).

Douglas S Denham⁵, Hak-Myung Lee⁶, Michael A Levine⁷,

Objectives and patients

Michael Mannstadt⁸, Munro Peacock⁹, Jeffrey G Rothman¹⁰, Dolores

Characterize the methylation pattern at the GNAS-AS2 DMR in AD-PHP1B

M Shoback¹¹, Mark L Warren¹², Nelson B Watts¹³ & Alan Krasner⁶

delSTX16C (nZ9) and delSTX16- (nZ5) patients; furthermore, sporPHP1B

¹Mayo Clinic, Rochester, Minnesota, USA;²University of Chicago

(nZ10) and healthy controls (nZ10) were investigated. STX16 and GNAS

Medicine, Chicago, Illinois, USA;³College of Physicians and Surgeons,

deletions were excluded in the delSTX16- patients by MLPA, genomic multiplex

Columbia University, New York, New York, USA;⁴Michigan Bone and

and quantitative PCR of the GNAS and STX16 regions.

Mineral Clinic, PC, Detroit, Michigan, USA;⁵Clinical Trials of Texas, Inc.,

Results

San Antonio, Texas, USA;⁶Shire Human Genetic Therapies, Inc.,

Lexington, Massachusetts, USA;⁷Children’s Hospital of Philadelphia,

1. The mean methylation index at the GNAS-AS2-DMR was significantly higher

Philadelphia, Pennsylvania, USA;⁸Massachusetts General Hospital and

in delSTX16- patients (32G14%) than in controls (24G6%), delSTX16C

Harvard Medical School, Boston, Massachusetts, USA;⁹Indiana University

(5G2%) and sporPHP1B patients (3C1%) (P!0.0001).

School of Medicine, Indianapolis, Indiana, USA;¹⁰Staten Island University

2. Bisulfite-treated DNA of PHP1B patients with delSTX16- was PCR amplified

Hospital, Staten Island, New York, USA;¹¹Endocrine Research Unit,

across the GNAS-AS2-DMR and products were cloned into pcDNA3.1. First,

Department of Veterans Affairs Medical Center, Department of Medicine,

we identified 2 CG-rich subdomains (SD1 and SD2) within the GNAS-AS2

University of California, San Francisco, California, USA;¹²Physicians East,

DMR that are separated by 184 bp. Second, in delSTX16- patients we observed

PA, Greenville, North Carolina, USA;¹³Mercy Health, Cincinnati, Ohio,

a unique pattern of methylation including an gain of methylation at SD1 and a

USA.

methylation pattern at SD2

similar to that of controls, whereas both

delSTX16C and sporPHP1B patients displayed full LOM at SD1 and SD2.

Conclusion

We have further refined the GNAS-AS2-DMR and identified a subgroup of

Hypoparathyroidism (HPT) is characterised by hypocalcaemia and impaired

PHP1B patients with a specific pattern of methylation at the GNAS-AS2-DMR.

renal phosphate excretion and calcium conservation. Oral calcium

Our findings reinforce the hypothesis that delSTX16- patients carry a defect in an

supplements and calcitriol can improve serum calcium levels but lack the

element that controls the methylation both at the GNAS-A/B DMR and at the

physiologic effects of PTH on renal reabsorption of calcium. RACE is an

GNAS-AS2 DMR.

ongoing open-label study evaluating the long-term safety of recombinant

human parathyroid hormone

1-84

(rhPTH[1-84], parathyroid hormone

DOI: 10.1530/endoabs.49.GP45

rDNA) in adults with HPT (NCT01297309). In this interim analysis, we

report the 3-year treatment effect with 25-100 mg/day rhPTH(1-84) on 24-h

urinary calcium levels, with or without thiazide diuretics. All data are

presented as mean (SD). The study cohort comprised 49 patients enrolled at

12 USA centres; 38 (78%) completed 36 months of rhPTH(1-84) treatment.

Baseline demographics were as follows: 82% women, age 48 (9.8) years,

HPT duration of

(12.5) years,

100% taking prescribed calcium

GP46

supplements and calcitriol. In response to rhPTH(1-84), albumin-corrected

Vitamin D correction elevates apolipoprotein levels in a sex-specific

serum calcium remained within the target range over the 3 years; 2.1 (0.17)

manner

mmol/l at baseline (i.e., start of rhPTH[1-84], nZ49) and Month 36 (nZ36).

Nasser Al-Daghri¹, Spiros Garbis², George Chrousos³, Shaun Sabico¹,

Treatment with rhPTH(1-84) also led to a reduction in urinary calcium, from

Naji Aljohani⁴ & Yousef Al-Saleh⁵

baseline 8.9 (5.0) mmol/24 h to 6.5 (2.8) mmol/24 h (nZ35; P!0.05).

¹King Saud University, Riyadh, Saudi Arabia;²University of Southampton,

Urinary calcium excretion at Month 36 was similar for men compared with

Southampton, UK;³University of Athens, Athens, Greece;⁴King Fahad

women, and in patients taking or not taking thiazide diuretics. Overall, 71%

Medical City, Riyadh, Saudi Arabia;⁵King Saud bin Abdulaziz University

of rhPTH(1-84)Ktreated patients with baseline hypercalciuria had normal

for Health Sciences, Riyadh, Saudi Arabia.

24-h urinary calcium excretion at Month 36 (nZ12/17). Treatment with

rhPTH(1-84) improved calcium-phosphate product from baseline 3.4 (0.5)

mmol²/l² (nZ49) to 2.9 (0.5) mmol²/l² (nZ36) (P!0.0001). eGFR was

Numerous studies have identified several extra-skeletal health outcomes to

baseline 108.2 (36.4) ml/min (nZ41) and 115.7 (47.3) ml/min (nZ36) at

be associated with vitamin D deficiency, yet a definitive causal link is yet to

Month 36 (P!0.0772). Over 3 years, rhPTH(1-84) maintained target levels

be discovered. Our recent 3D LC-nESI-FTMS proteomic analysis among

of serum calcium and reduced urinary calcium to normal levels in HPT

normal and overweight but apparently healthy adult Saudis identified

patients. More information is needed to understand the timing of the

apolipoproteins, a known independent cardiovascular risk factor, as one of

beneficial effect on urinary calcium excretion.

the serological molecular signatures that modulate vitamin D levels. The

DOI: 10.1530/endoabs.49.GP47

present interventional study aims to compare and validate the identified

apolipoproteins among vitamin D deficient subjects that have achieved full

vitamin D status correction. 199 Saudi adults [89 males, mean age 42.0G

10.4; BMI 28.6G4.4 kg/m²; 110 females, mean age 39.1G12.0; BMI

30.7G5.3]

(with vitamin D deficiency

[25(OH)D

!50 nmol/l] were

GP48

recruited and given 50 000 IU cholecalciferol (VitaD50000w) weekly for

2 months, then twice a month for 2 months, followed by daily 1000 IU

Vitamin D levels after 4 weeks of very low calorie diet (VLCD)

(VitaD1000w) until month 6. Blood samples were taken at baseline and

M^aÁngeles Bennasar Remolar, Ignacio Pérez Catalán & María Guinot Soler

after 6 months. Serum 25(OH)D was measured using electrochemilumines-

Hospital General Universitario, Castellón, Spain.

cence and apolipoproteins

(AI, AII, B, CI, CII, CIII and E) using

commercially available kits. In all subjects, serum

25(OH)D increased

significantly from baseline and after

6 months (32.6G11.1 vs 63.4G

Introduction

16.4 nmol/l; P!0.001). In parallel, a significant increase in apolipoproteins

Vitamin D is a liposoluble molecule which takes part in calcium-phosphorous

B, CI, CII, CIII and E (P-values!0.05) after 6 months compared to baseline

homeostasis of the human body. Its optimum levels according to SEIOMM range

was observed. After stratification according to sex, only apolipoproteins CII

between 30 and 75 ng/ml. Being liposoluble substances they require the presence

and CIII were significantly increased in males (P-values!0.001), and only

of biliar salts for their absorption; 80% is absorbed in the yeyune and in a lesser

apolipoprotein CI was significantly increased in females

(P!0.001),

extent in the duodene. The correct concentration of vitamin D is of key

showing sexual dimorphism in the effects of vitamin D with regards to

significance in obesity, particularly its visceral type. An excessive body weight is

apolipoprotein levels. The rest of the apolipoproteins were not significantly

thought to represent a significant determinant of a reduced vitamin D

different pre- and post-vitamin D correction. The present study partially

concentration in serum. Due to its high metabolic activity, visceral adipose

explains the effects of vitamin D correction in the reduction of

tissue promotes sequestration and alterations in turnover of the vitamin-

cardiovascular risk through significant modification of apolipoproteins,

resembling hormone. Care for elimination of the factors which promote

particularly the apolipoprotein C class. These effects differ according to sex.

deficiencies is particularly essential in obese persons in whom degree of adiposity

DOI: 10.1530/endoabs.49.GP46

correlates with reduced concentrations of this vitamin in blood. Given the

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

importance of this vitamin in the body we have analysed its levels in obese

PHPT should be questioned for UGI symptoms and evaluated with UGI

patients which were going to follow a VLCD (600 kcal) before undergoing

endoscopy when needed.

bariatric surgery. The patients followed a VLCD during 4 weeks before the

DOI: 10.1530/endoabs.49.GP49

surgery. The values of vitamin D were analysed at two different moments: before

beginning the diet and after the diet, 4 weeks later.

Method

We have designed a prospective observational study; 18 patients were analysed

with IMC O35 kg/m² with associated comorbility or IMC O40 kg/m², between

18 and 60 years old, candidate for bariatric surgery with laparoscopic gastric

GP50

by-pass. Vitamin D concentrations were monitored at two different moments: 1

Localisation of parathyroid adenomas using¹¹C-methionine-PET/CT

month before surgery and at the moment of surgery, 4 weeks after the VLCD.

when conventional imaging methods are negative

Objective

Lassi Nelimarkka^1,7, Aapo Ounaslehto⁷, Eija Eloranta⁴, Leena Moilanen⁵,

To establish whether there are statistically significant variations in the values of

Saija Hurme³, Marko Seppänen^2,6 & Pirjo Nuutila^1,2

vitamin D before and after following a VLCD.

¹Turku University Hospital, Department of Medicine, Division of

Results

Endocrinology, Turku, Finland;²Turku PET Centre, Turku University

We obtain an average level of vitamin 25 (OH) D of 16,31 ng/ml in the analytical

Hospital, Turku, Finland;³Department of Biostatistics, University of Turku,

evaluation 1 month before surgery and 21,32 ng/ml at the time of the surgery,

Turku, Finland;⁴Department of Medicine, Division of Medicine and

which takes place at the end of the VLCD. Statistically significant differences are

Pulmonary Diseases, Oulu University Hospital, Oulu, Finland;⁵Division of

observed between the levels of vitamin 25 (OH) D 1 month before surgery and at

Endocrinology, Department of Medicine, Kuopio University Hospital,

the time of the chirurgical act.

Kuopio, Finland;⁶Department of Nuclear Medicine, Turku University

Conclusions

Hospital, Turku, Finland;⁷Department of Medicine, University of Turku,

According to the results, patients that follow a 4-week VLCD significantly improve

Turku, Finland.

the levels of vitamin 25 (OH)D in blood. Those levels do not reach a normal level

after the diet, however it is evident the benefit of the recommended process, and it

would be interesting to evaluate in the long term if such a tendency remains.

In primary hyperparathyroidism

(pHPT) an exact localization of the

DOI: 10.1530/endoabs.49.GP48

pathological parathyroid gland(s) is essential before minimally invasive

parathyroidectomy. We have previously shown in a small group of pHPT

patients, that¹¹C-methionine-PET/CT provides additional information if

123

I/^99m Tc-sestamibi (MIBI) scan remains negative. The aim of the present

study was to evaluate the clinical value of¹¹C-Met-PET/CT in a larger

GP49

pHPT patient cohort.

Upper gastrointestinal symptoms, endoscopic and pathological features,

Methods

and serum gastrin and chromogranin A levels in patients with primary

Totally 89 patients with pHPT (66 females, 23 males, age 18-81 years) and

hyperparathyroidism

negative or inconclusive localisation findings with¹²³I/^99mTc- MIBI-SPECT/CT

Osman Ersoy¹, Berna Evranos Ogmen², Sefika Burcak Polat³,

(78,7%) or^99mTc-MIBI-SPECT/CT (21.3%) were studied with¹¹C-Met-PET/CT.

Levent Ozturk⁵, Berrak Gumuskaya Ocal⁴, Bekir Cakir³ & Reyhan Ersoy³

Most of the patients (87.6%) were surgical treatment naive and the rest of them

¹Yildirim Beyazit University, Faculty of Medicine, Ataturk Education and

(12.4%) were previously operated 1-2 times.

Research Hospital, Department of Gastroenterology, Ankara, Turkey;

Results

²Ataturk Education and Research Hospital, Department of Endocrinology

¹¹C-Met-PET/CT revealed the pathologic parathyroid gland in 48 (60.8%) of the

and Metabolism, Ankara, Turkey;³Yildirim Beyazit University, Faculty of

79 surgically treated patients. Totally 26 patients (32.9%) had a negative¹¹C-

Medicine, Ataturk Education and Research Hospital, Department of

Met-PET/CT finding and 16 of them had further explorative surgery, whereas 10

Endocrinology and Metabolism, Ankara, Turkey;⁴Yildirim Beyazit

of these Met-PET negative patients were not operated, but treated conservatively

University, Faculty of Medicine, Ataturk Education and Research Hospital,

instead. In five cases (6.3%) Met-PET detected a false-positive finding, i.e. the

Department of Pathology, Ankara, Turkey;⁵Yildirim Beyazit University,

pathological parathyroid gland was found in another location. On a per-lesion

Faculty of Medicine, Ataturk Education and Research Hospital, Department

level PET results were 48 true positive (60.8%) and 21 false negative (26.6%).

of Anesthesiology, Ankara, Turkey.

The lesion-based sensitivity was 75.4% (positive predictive value 94.6%) and

specificity 40.0% (negative predictive value 10.5%). The diagnostic accuracy of

C-Met-PET/CT in this study was 73%. Based on the histological examinations

Introduction

67 adenomas (84.8%) and six hyperplastic (7.6%) parathyroid glands were found.

In five cases the finding was normal parathyroid tissue or unspecified. Ten

Upper gastrointestinal (UGI) symptoms are frequently encountered in patients

patients (12.7%) had more than one pathological parathyroid glands. There were

with primary hyperparathyroidism

(PHPT). Some of these symptoms may

no parathyroid carcinomas detected in this study. Totally

79 patients had

improve after PHPT treatment, while hypercalcemic state may also cause

parathyroid surgery and 55 (69.6%) of them were biochemically cured, but in 16

permanent effects. We aimed to evaluate UGI symptoms, UGI endoscopic and

patients (20.3%) pHPT persisted and in eight patients (10.1%) the postoperative

pathologic features and determine the relationship between these features with

status remained unknown.

serum chromogranin A (CgA) and gastrin in PHPT patients.

Conclusion

Methods

¹¹C-methionine-PET/CT offers an additional noninvasive imaging method to

Seventy-one patients diagnosed with PHPT were included in the study after

localize hyperfunctiong parathyroid glands in a situation when conventional

exclusion of patients who refused UGI endoscopy, had an UGI surgery or used

imaging methods^99mTc or¹²³I/^99mTc-sestamibi SPECT/CT fail or are equivocal.

drugs that affect serum chromogranin A or gastrin. Patients were questioned

regarding UGI symptoms. Serum CgA and gastrin were measured. Endoscopy

DOI: 10.1530/endoabs.49.GP50

was performed and gastric biopsy specimens were taken to evaluate atrophic

gastritis.

Results

There were 60 females and 11 males, and median age was 52 years. Mean serum

CgA and gastrin levels were

134.10G19.43 ng/ml

(28-620) and

219.39G

GP51

48.6 pg/ml (14-2255), respectively. Dyspepsia, epigastric pain and weight loss

Calcium to phosphorous ratio (Ca/P) as helpful index to recognize

were the most common symptoms and presented in 61, 51.7 and 46.6% of

primary hyperparathyroidism, but not primary hypoparathyroidism: a

patients, respectively. Endoscopy was normal in 25(35.2%) patients. Erosive

big-data approach

antral gastritis, atrophic gastritis, gastric ulcers, duedonal ulcers, reflux gastritis

Sara De Vincentis^1,2, Daniele Santi^1,2, Vincenzo Rochira^1,2, Monica Setti³,

and nodular gastritis were present in 14 (19.7%), 12 (16.9%), 6 (8.5%), 5 (7%), 4

Simonetta Tagliavini⁴, Manuela Varani⁴, Tommaso Trenti⁴,

(5.6%) and 4 (5.6%) patients, respectively. Intestinal metaplasia, gastric atrophy,

Manuela Simoni^1,2 & Bruno Madeo^1,2

gastric neuroendocrine tumor and Helicobacter pylori infection were detected in

¹Unit of Endocrinology, Department of Biomedical, Metabolic and Neural

29.2,

20,

1.4

and 66.2% of patients, respectively. Serum CgA was similar

Sciences, University of Modena and Reggio Emilia, Modena, Italy;²Unit of

in patients with and without atrophic gastritis, while serum gastrin was higher in

Endocrinology, Department of Medicine, Endocrinology, Metabolism and

patients with atrophic gastritis (PZ0.024). Presence of intestinal metaplasia and

Geriatrics, Azienda OU of Modena, Modena, Italy;³Service of Clinical

Helicobacter pylori infection did not affect serum CgA and gastrin levels.

Engineering, Azienda USL of Modena, Modena, Italy;⁴Department of

Conclusion

Laboratory Medicine and Pathological Anatomy, Azienda USL of Modena,

Dyspeptic symptoms are common in patients with PHPT. The frequencies of

Modena, Italy.

atrophic gastritis and peptic ulcers are increased. We think that patients with

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

in the lung, especially ACE2. The precocious LIR treatment in the inflammatory

Primary hyperparathyroidism

(HyperPT) and primary hypoparathyroidism

phase prevented all these pathogenic alterations.

(HypoPT) are often underdiagnosed. Several strategies have been investigated in

DOI: 10.1530/endoabs.49.GP52

the past in order to identify diagnostic parameters, although the diagnosis of both

HyperPT and HypoPT remains challenging so far, especially in asymptomatic

patients. Calcium (Ca) and phosphorus (P) are inversely related together, thus the

Ca/P ratio could be an useful tool to define these conditions. Recently, we proposed

for the first time a cut-off of 3.5 for Ca/P ratio for the diagnosis of HyperPT.

Aim

To evaluate the diagnostic value of the Ca/P ratio for HyperPT and HypoPT

GP53

through a big-data approach.

Clinical, laboratory and cardiac parameters in overt primary

Methodology

hypothyroidism versus overt central hypothyroidism

A retrospective, observational, case-control study on big-data was carried out. All

Melania Balas¹, Florina Parv², Mihaela Vlad¹, Ioana Golu¹, Daniela Amzar¹

examinations of parathyroid hormone (PTH), Ca and P performed at the laboratory

& Ioana Zosin¹

of Modena Hospital from

2010 to

2016 were consecutively included. We

¹Department of Endocrinology, Victor Babes University of Medicine and

considered only patients between 18 and 90 years of age. Laboratory ranges of

Pharmacy, Timisoara, Romania;²Department of Cardiology, Victor Babes

normality for both PTH and Ca were used to divide records in HyperPT, HypoPT

University of Medicine and Pharmacy, Timisoara, Romania.

and controls.

Statistical analysis

Background

The diagnostic accuracy of Ca/P ratio was investigated using receiver operator

Hypothyroidism affects cardiac function, leading to cardiomyopathy, pericarditis,

characteristics (ROC) curves in order to define cut-off points, which show higher

lower left ventricular performance, etc. The present study investigates different

sensitivity and specificity for the identification of affected patients.

parameters (clinical, hormonal, biochemical, echocardiographic) in overt primary

Results

hypothyroidism (OPHypo) and overt central hypothyroidism (OCHypo).

46 597 records were considered. 576 HyperPT (1.2%), 323 HypoPT (0.7%) and

Material and methods

45 698 controls (98.1%) were found. Ca/P ratio was significantly different among

The study included 33 untreated patients with OCHypo (5 with empty sella, 3

groups (P!0.001). In particular, Ca/P ratio was significantly higher in HyperPT

with idiopathic hypopituitarism, 7 with Sheehan’s syndrome, 18 with different

than controls (P!0.001). For the diagnosis of HyperPT, the threshold of 3.17 for

types of pituitary macroadenomas, before or after surgery) and 67 cases with

Ca/P ratio was obtained by means of the ROC curve analysis, with 85% of both

OPHypo, respectively with chronic autoimmune thyroiditis. Among the patients

sensitivity and specificity. HypoPT showed lower Ca/P ratio compared to controls

with OCHypo,

presented partial pituitary insufficiency

cases on

(P!0.001), although no useful threshold for the diagnosis was found at ROC curve

gonadotropins and TSH secretion and 2 cases on growth hormone and TSH

because of the low sensitivity.

secretion), the rest of the cases showing global pituitary insufficiency. Patients

Conclusions

with acromegaly and Cushing’s disease were excluded.

We confirm the high sensitivity and specificity of Ca/P ratio for the diagnosis of

Results

HyperPT using the largest cohort of patients available so far in the literature. On the

The clinical picture was more severe in OPHypo as in OCHypo (dominated by

contrary, Ca/P ratio does not contribute to identify patients with HypoPT and

fatigue, edema, dry skin, neurological alterations). The values of serum thyroxin

further researches are needed to better describe this condition. In conclusion, Ca/P

were significantly lower in OPHypo (P!0.0001). 40% of OPHypo patients

ratio is a simple and inexpensive diagnostic tool to recognize HyperPT.

presented pericarditis, as compared to OCHypo

cases, PZ0.0003). No

DOI: 10.1530/endoabs.49.GP51

statistical differences were noted between the two groups, regarding heart rate,

systolic and diastolic blood pressure values, isovolumic contraction time.

Nonetheless, the isovolumic relaxation time was significantly higher in OPHypo

group (91.8G8.5 ms), as in OCHypo (80.2G9.9 ms, P!0.0001). Coronary

artery disease was more common in OPHypo group (21 cases, 31.3%), as

compared to OCHypo (5 cases, 15.1%, PZ0.095). Hyponatremia was recorded in

4 patients with OPHypo and in 3 cases with OCHypo (PZ0.68). The values of

serum total cholesterol, LDL-cholesterol, glycemia, creatin-kinase, transamin-

Cardiovascular & Lipid Endocrinology

ases, creatinine were significantly higher in OPHypo group, correlated to lower

GP52

values of serum thyroxin. The incidence of anemia was similar in both groups (18

Liraglutide prevents right ventricle hypertrophy by avoiding ACE1 &

cases in OPHypo group, 6 cases in OCHypo group, PZ0.456).

ACE2 reduction in an experimental model of idiopathic pulmonary

Conclusion

fibrosis

The metabolic and cardiac parameters were more profound altered in primary

Juan Fandin˜ o, Laura Toba, Hugo Ogando, Yolanda Diz, Lucas González &

hypothyroidism, as compared to central hypothyroidism.

Federico Mallo

DOI: 10.1530/endoabs.49.GP53

Biomedical Research Centre (CINBIO, Vigo, Galicia, Spain.

The Glucagon-like peptide-1 (GLP-1) receptor is expressed in the lung having a

very important role in the modulation of the Angiotensin Converting Enzymes

(ACEs). ACE1 cleaves angiotensin-I into angiotensin-II, which is converted by

ACE2 to Ang(1-7). Ang(1-7) has vasodilating effects. The Idiopathic Pulmonary

Fibrosis

(IPF) is characterized by excessive extracellular matrix deposition

GP54

disrupting the alveolar architecture and physiology. IPF develops by a sequence

of inflammation multifocal process that leads to a fibrotic response. IPF presents

Correlation between triglyceride glucose index (TyG) and coronary

pulmonary hypertension and right ventricle hypertrophy.

artery calcification in Korean adults

The aim of this study is to elucidate the effect of precocious treatment with LIR

Jihong You, Kahui Park, Jung Hye Kim, Sang Bae Lee, Yusik Kim,

during the inflammatory phase of IPF in ACE1 & ACE2 in the late fibrotic phase

Ji sun Nam, Jong Suk Park & Chul Woo Ahn

in an experimental model of IPF.

Gangnam Severance Hospital, Seoul, Republic of Korea.

IPF was induced in rats by a single intra-tracheal instillation of Bleomycin (BLM,

2.5 mg/kg) on day 0 (D0). From day K1 to day 6, animals were treated with

Objective

Liraglutide (LIR, 100 mg/kg/12h subcutaneous). On D21 rats were sacrificed.

Triglyceride glucose (TyG) index is considered a surrogate marker of insulin

Heart ventricles and lungs were isolated, weighted and frozen. Histology of lungs

resistance, and insulin resistance is known risk factor of cardiovascular disease.

confirmed interstitial lung fibrosis in all BLM-treated rats.

Until now, few studies have investigated the relationship between TyG index and

The real time-PCR levels of ACE-1 & ACE-2 were lower in lungs of BLM-IPF

coronary artery calcification (CAC), thus we investigated the correlation between

than in controls (40% and 48% reduction, respectively). Right ventricle weight

TyG index and CAC in healthy Korean Adults.

was markedly increased in BLM-IPF rats (C66%). The treatment with LIR at the

Methods

beginning of the inflammatory phase completely restored the levels ACEs at the

A total of 4,463 participants underwent cardiac computed tomography in health

fibrotic phase (21D), and prevented the right ventricle hypertrophy.

promotion center were enrolled. TyG index was calculates as ln[fasting

In conclusion BLM instillation causes local injury with inflammation and

triglycerides(mg/dl) X fasting glucose(mg/dl)/2]. Multi-detector CT was used

alteration of lung vasculature with pulmonary hypertension reflected by right

to measure coronary artery calcium score (CACS) and CACSO0 was defined as

ventricle hypertrophy and related to a reduction in the expression levels of ACEs

the presence of CAC.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

to determine whether circulating PCSK9 concentration is linked to coronary

There were significant differences in cardiovascular parameters among the groups

damage severity in patients with acute coronary syndrome (ACS). We studied 137

and the prevalence of CAC significantly increased with TyG index levels. In the

patients with ACS who underwent coronary angiography. The study population

logistic regression analysis after adjusted for multiple risk factors, the odds ratios

was divided into two groups depending on the presence of coronary artery lesion

(95% CI) for the prevalence of CAC were 1.0, 1.03 (0.72-1.45), 1.23 (0.85-1.74),

(lesion (C): nZ112, lesion (K): nZ25). Baseline characteristics and PCSK9

1.68

(1.15-2.44) for increasing TyG index level (P!0.05).

levels were measured and coronary lesions were evaluated using the SYNTAX

Conclusion

scoring system. After adjustment for established CVD risk factors including age,

There was a significant association between TyG index and prevalence of CAC.

body mass index (BMI), total cholesterol and low-density lipoprotein-cholesterol

TyG index, a simple measure reflecting insulin resistance, might be useful to the

(LDL), ACS patients with coronary artery lesion have significantly higher PCSK9

indicator of atherosclerosis. TyG index is even simple to calculate and seems a

levels than patients without lesion (178.26G63.9 ng/ml vs. 223.0G76.1 ng/ml,

useful marker of atherosclerosis, and reflect cardiovascular risk.

PZ0.026). Spearman’s correlations revealed that PCSK9

was positively

DOI: 10.1530/endoabs.49.GP54

associated with the number of involved coronary artery (Pearson coefficient,

0.034; PZ0.01) and the global registry of acute coronary events (GRACE) risk

score which is a risk prediction tool applicable for ACS patients

(Pearson

coefficient, 0.209; PZ0.015). Furthermore, we found that plasma PCSK9 level

was positively correlated with SYNTAX score

(Spearman’s RZ0.115,

PZ0.048). In the present study, we show that Serum PCSK9 concentration is

GP55

associated with angiographic severity of ACS and GRACE score after

adjustments for established CVD risk factors. Further studies are needed to

Both oral and vaginal combined hormonal contraceptives induce

confirm this observation.

unbeneficial metabolic effects in women with PCOS: a randomized

study

DOI: 10.1530/endoabs.49.GP56

Maria-Elina Mosorin^1,2, Terhi Piltonen^1,2, Juha Tapanainen^3,4 &

Laure Morin-Papunen^1,2

¹Department of Obstetrics and GynecologyOulu University Hospital, Oulu,

Finland;²Department of Obstetrics and Gynecology, PEDEGO, MRC,

University of Oulu, Oulu, Finland;³Department of Obstetrics and

Gynecology, University of Helsinki, Helsinki, Finland;⁴Department of

Obstetrics and Gynecology, Helsnki University, Helsinki, Finland.

GP57

Oral combined hormonal contraceptives (CHCs) have been suggested to induce

Clinical significance and hormonal relationships of visceral adiposity

more unbeneficial metabolic effects than vaginal CHCs. CHCs are used routinely

index (VAI) in independently living old subjects

to treat the clinical symptoms of polycystic ovary syndrome (PCOS), but there are

Mireia Mora^1,2, Elisabet Palomera³, Mateu Serra-Prat³ &

no studies investigating whether the vaginal route is safer in women with known

Manel Puig-Domingo⁴

metabolic risks.

¹Department of Endocrinology and Nutrition1, Hospital Clínic i Universitari

Twenty-five women with PCOS defined according to the Rotterdam criteria were

of Barcelona, Barcelona/, Spain;²Group of Endocrine Disorders, IDIBAPS,

randomized to use either oral contraceptive pills (desogestrel-ethinylestradiol)

Barcelona, Spain;³Research Unit and Ciberhep, Hospital de Mataró,

(nZ14) or contraceptive vaginal rings (etonogestrel-ethinylestradiol) (nZ11)

Mataró, Spain;⁴Department of Endocrinology and Nutrition,

continuously for 9 weeks. Blood samples were drawn and OGTT performed at

Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

baseline and at 9 weeks.

Serum levels of SHBG increased and consequently the free androgen index (FAI)

decreased in both study groups from baseline to 9 weeks of treatment [oral: 3.2

Introduction

(95% confidence interval, CI: 2.2; 4.3) to 0.7 (0.5; 1.0); vaginal: 3.8 (1.8; 5.8) to

The Visceral Adiposity Index (VAI) has been proven to be an indicator of adipose

0.6

(0.5; 0.8), P%0.003 in both groups]. Insulin sensitivity was reduced at 9

distribution and function that indirectly expresses cardiometabolic risk, in

weeks according to the Matsuda index [oral: 2.5 (0.1; 4.8) to 0.2 (0.2; 0.3),

particular in specific populations such as women with polycystic ovary syndrome,

PZ0.035]; vaginal: 3.0 (0.4; 4.4) to 0.2 (0.1; 0.2), PZ0.366]. Serum levels of

acromegaly or type 2 diabetes. Little information is known about its usefulness in

triglycerides [oral 0.9 (0.7; 1.2) to 1.3 (0.8; 1.8) mmol/l, PZ0.132; vaginal 0.8

the definition of cardiometabolic risk in ageing population.

(0.6;

1.0) to

1.3

(0.9;

1.7) mmol/l, PZ0.003] hs-CRP (PZ0.034) and the

Objective

AUCglucose during the OGTT (PZ0.017) rose significantly only in the vaginal

To study VAI in relation to metabolic and hormonal data, frailty and mortality in

group. The AUCinsulin

(oral: PZ0.36, vaginal: PZ0.16) increased non-

non-institutionalized people more than 70 years old of the Mataró Ageing Study.

significantly from baseline to 9 weeks in both treatment groups. There were no

Methods/Design

differences in serum levels of glucose, insulin, hs-CRP, lipids or testosterone

289

participants

(142

men/147

women) were included. Individuals were

between the treatment groups at baseline or after 9 weeks.

characterized by anthropometric variables, metabolic syndrome (MS) parameters

Against our hypothesis, vaginal CHCs were not metabolically safer than oral

by IDF and ATP-III as well as hormonal factors (TSH, free-T4, growth hormone,

CHCs. These results emphasize the importance of monitoring glucose

IGF-I, ghrelin, cortisol, dehidroepiandrosterone -DHEA-, DHEAs, testosterone,

metabolism during CHC use regardless of the route of administration, especially

SHBG, estradiol, estrone, cortisol/DHEA and cortisol/DHEAs), grip strength,

in PCOS women displaying typically risks of type 2 diabetes or cardiovascular

Barthel and assessment of cognitive impairment (MiniCognoscitive Examination

diseases.

-MCE- Spanish version) and frailty by Fried criteria. VAI was calculated

DOI: 10.1530/endoabs.49.GP55

according to Amato et al.

Results

The whole cohort showed a statistically significant association of the individual

components the MS with VAI. In women but not in men, a lineal trend association

was observed between the prevalence of diabetes and VAI categorized in

quartiles. However, VAI showed no association in our sample population with the

presence of cardio or cerebrovascular disease. The multiple regression analysis

showed that ghrelin (BZK0.240, PZ0.005) and SHBG (BZK0.199, PZ0.034)

GP56

were the only hormonal variables independently associated to VAI in women,

PCSK9 in relation to coronary damage severity in patients with

while no associations were found in men. After a prospective follow-up of two

cardiovascular disease

years, those individuals with higher VAI at basal time point were associated to

Nan Hee Cho, Kwi Hyun Bae, Gwon Soo Jung, Mi Jin Kim,

frailty condition at two years (media (SD): 2.47 (2.19) in frail vs 1.71 (0.97) in

Yeon Kyung Choi, Jung Beom Seo & Keun Gyu Park

non-frail, PZ0.064). No significant association was found between VAI and

Kyungpook National University Hospital, Dae Gu City, Republic of Korea.

mortality 2 and 8 years follow-up.

Conclusions

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a circulating protein that

VAI does not provide additional information to MS criteria in ageing individuals

promotes degradation of the low density lipoprotein (LDL) receptor, has been

in relation to cardiovascular risk or mortality in our population. However, VAI

emerged as a novel therapeutic target for the dyslipidemia. It is well known that

was associated to frailty in the whole cohort, and in women, with diabetes and

the pathogenesis of cardiovascular disease (CVD) involves lipid metabolism

ghrelin.

alteration, but the predictive value of circulating PCSK9

level concerning

DOI: 10.1530/endoabs.49.GP57

coronary disease severity is largely unknown. The main objective of this study is

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP58

Results

Descriptive data of the subjects were BMI 24.4 kg/m² (22.4-26.6), waist 88 cm

Circulating levels of miR24-1 cluster microRNAs are increased in

(82-94), percentage lean body mass 79.1% (75.6-82.5), percentage fat mass

primary aldosteronism

17.2% (18.8-21.1), total testosterone 20.7 nmol/l (17.0-25.4), SHBG 27 nmol/l

Josie van Kralingen¹, Cali Anderson¹, E. Marie Freel¹, John M. Connell²,

(21-34) and VO2max 160.3 ml/min/kg 0.73 (143.3-177.6) (median (interquartile

Scott M. MacKenzie¹ & Eleanor Davies¹

range). In bivariate analysis, lean body mass (%) (rZ0.62), SHBG (rZ0.26),

¹University of Glasgow, Glasgow, UK;²University of Dundee, Dundee,

total testosterone

(rZ0.24), and free testosterone

(rZ0.13) were positively

UK.

associated with VO2max, whereas fat mass

(%)

(rZK0.63) and waist

(rZK0.47) were negatively associated with VO2max (all P!0.001). Fat mass

Introduction

(%) and lean body mass (%) were closely associated (rZK0.998, P!0.001). In

Measurement of microRNA (miRNA) in aldosterone-producing adenoma (APA)

multivariate regression analysis, models with VO2max as the dependent variable

tissue from primary aldosteronism (PA) patients show levels of the miR24-1

and lean body mass (%) or fat mass (%) as independent variables were the best

cluster miRNAs (i.e. miRNAs 24-1, 27b and 23b) are significantly reduced

predictors of VO2max (both models R2Z0.47), whereas the models including

relative to normal adrenal tissue. Our previous studies also show that miRNA-24

testosterone (total, free or bioavailable testosterone) or SHBG as independent

directly targets CYP11B2 (aldosterone synthase) gene expression. Circulating

variables had lower R2 values (R2Z0.09-0.13). All models were adjusted for age

miRNAs released into the bloodstream may be diagnostic biomarkers or

and smoking.

signalling molecules. Here, we assessed whether circulating levels of miR24-1

Conclusion

cluster miRNAs differ significantly between PA patients and essential

Body composition measures were the best predictors of VO2max in young men.

hypertensives, and whether they correlate with relevant phenotypic traits.

VO2max was more closely associated with waist than testosterone or SHBG.

Methods

DOI: 10.1530/endoabs.49.GP59

Patients with essential hypertension patients (nZ18) were drawn from the British

Genetics of Hypertension (BRIGHT) study and matched with 18 confirmed PA

patients for age, gender and systolic blood pressure. Circulating miRNA was

isolated from 200 mL EDTA plasma and analysed using quantitative realtime

assays for miRNAs 24, 27b and 23b.

Results

PA patients had significantly increased circulating levels of miRNAs

(P!0.05) and 23b (P!0.0001) relative to primary hypertensive patients; there

were also trends towards higher miRNA-27b but this was not significant.

MiRNA-23b negatively correlated with diastolic pressure

(P!0.05), left

ventricular mass (P!0.01) and age (P!0.05). MiRNAs 27b and 23b positively

correlated with BMI (P!0.05).

Conclusions

We have identified and validated increased circulating miR24-1 cluster miRNA

GP60

levels in PA patients. These contrast with the significantly reduced levels of these

miRNAs observed in APA tissue. Interestingly, miR-24 has been proposed to act

Probiotics and nutraceuticals as a new frontier in obesity prevention

as a feedback signal, repressing CYP11B2 expression when aldosterone levels are

and management

high. Therefore, increased secretion of these miRNAs into the circulation may be

Nazarii Kobyliak¹, Tetyana Falalyeyeva², Petro Bodnar¹ &

the result of high aldosterone levels and be intended to suppress its release. Future

Tetyana Beregova²

studies will examine the role of these miRNAs in the aetiology and pathology

¹Bogomolets National Medical University, Kyiv, Ukraine;²Taras

of PA.

Shevchenko National University of Kyiv, Kyiv, Ukraine.

DOI: 10.1530/endoabs.49.GP58

Introduction

The beneficial interaction between the microbiota and humans is the way how

bacteria contained within the gut ‘talk’ to the immune system. Into this landscape

probiotics and nutraceuticals play a major role. The study aims to determine

whether probiotics plus nutraceuticals such as smectite or omega-3 are superior to

probiotic alone on the monosodium glutamate (MSG) induced obesity model in

rats.

Methods

Totally 75 rats divided into five groups were included (nZ15, in each). Rats of

group I were intact. Newborns rats of groups II-V were injected with MSG. The

III (Symbiter) group received 2.5 ml/kg of multiprobiotic “Symbiter” containing

concentrated biomass of 14 probiotic bacteria genera. The IV (Symbiter-Omega)

and V (SymbiterCSmectite) groups received combination of probiotic biomass

GP59

supplemented with flax and wheat germ oil (250 mg of each, concentration of

omega-3 fatty acids 1-5%) or smectite gel (250 mg) respectively. Anthropo-

Body composition and testosterone determined VO2max in 780 young

metric, biochemical parameters of lipid and carbohydrate metabolism, and level

men - results from the Odense Androgen Study

of proinflammatory cytokines (IL)-1b, IL-12Bp40, INF-g) and anti-inflammatory

Louise Lehmann Christensen, Torben Leo Nielsen, Pernille Hermann,

cytokines (IL-4, IL-10, TGF-b) were measured.

Dorte Glintborg & Marianne Andersen

Results

Odense University Hospital, Odense C, Denmark.

In all interventional groups significant reduction of total body and VAT weight as

compared to MSG-obesity were observed. However, the lowest prevalence of

Background

obesity was noted for Symbiter-Omega (20% vs 33.3% as compared to other

Cardiorespiratory fitness is a measure for physical activity and a prognostic health

interventional groups). Moreover, supplementation of probiotics with omega-3

indicator. However, measurement of maximal oxygen consumption (VO2max) is

lead to more pronounced decreasing of HOMA-IR (2.31G0.13 vs 4.02G0.33,

not possible in clinical practice.

P!0.001) and elevation of adiponectin level

(5.67G0.39

2.61G0.27,

Aim

P!0.001) as compared to obesity group. Both nutraceuticals combination with

We hypothesized that body composition and testosterone levels could be used as

probiotic and probiotic alone equally attenuated inflammation that was confirmed

possible determinants of VO2max in young men.

by the decrease of the pro-inflammatory and the activation of anti-inflammatory

Participants and design

system.

The Odense Androgen Study, a population-based, observational study including

Conclusion

780 men aged 20-30 years. VO2max (ml/min/kg 0.73) was indirectly measured

Probiotics and nutraceuticals led to a significantly lower prevalence of obesity,

by a mechanically braked cycle ergometer. Fat mass (%) and lean body mass (%)

reduction of insulin resistance, total and VAT weight. Our study demonstrated

were assessed by whole-body DXA scans. Total testosterone levels (nmol/l) were

that supplementation of probiotics with omega-3 may have most beneficial

measured (RIA using extraction and chromatography). SHBG levels (nmol/l)

antiobesity properties.

were determined by immunoluminometric assay. Bioavailable and free

DOI: 10.1530/endoabs.49.GP60

testosterone were calculated.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP61

Overexposure to dexamethasone during fetal development intensifies the process

of degeneration of germ cells in the ovary, contributing thus the reduction of

Constructing a long-acting leptin analogue

reproductive potential for the individual.

Suleyman Nahit Sendur¹, Ian R Wilkinson² & Richard J Ross²

¹Hacettepe University Department of Endocrinology and Metabolism,

DOI: 10.1530/endoabs.49.GP62

Ankara, Turkey;²University of Sheffield Department of Oncology and

Metabolism, Sheffield, UK.

Introduction

Leptin is a 16-kDa peptide hormone secreted by adipose tissue and acts as a

GP63

sensor for energy stores. It feedsback at the hypothalamic arcuate nucleus to

Does the loss of RAD52 in PC contribute to resistance to antiandrogen

suppress appetite. Leptin treatment has been highly effective in suppressing

therapy?

appetite in the rare cases of leptin-deficient obesity and improving the metabolic

Mahmoud A. Alfaqih^1,2, Ching yi Chang², John Norris² &

profile in congenital generalised lipodystrophy. These patients require 2.5-10 mg

Donald P. McDonnell²

once daily recombinant leptin treatment. We hypothesised that prolonged

¹Jordan University of Science and Technology, Irbid, Jordan;²Duke

constant exposure to leptin with a long acting leptin may have a more potent

University Medical Center, Durham, NC, USA.

metabolic action and appetite supression and therefore we designed a long acting

leptin molecule.

Recent statistics indicate that prostate cancer (PC) is the most frequent cancer in

Aim

men worldwide and is the leading cause of cancer death in men above 50 years of

To construct, express, purify and test for bioactivity a long acting leptin.

age. The Androgen receptor (AR), a member of the superfamily of nuclear

Methods

hormone receptors, plays a well-established role in the development and

We have previously demonstrated that a fusion of growth hormone to growth

progression of the disease. PC localized to the prostate is commonly treated

hormone binding protein (GHBP) generated a long acting GH. In this project we

with surgical removal of the gland and is often associated with a favorable

utilise GHBP as a fusion partner with leptin the concept being that linking a fusion

outcome. However, metastatic PC requires more aggressive treatment modalities

protein to the C-terminus will decrease clearance through reduced proteolysis and

often consisting of gonadotropin releasing hormone (GnRH) agonists and/or an

renal clearance. We further modified this molecule by introducing a W104A

AR antagonist (ex: bicalutamide). Although initially successful in alleviating

(Tryptophan-Alanine amino acid substitution) in the GHBP to prevent GHBP

symptoms, the disease progresses to a castrate resistant state, where drugs

binding to GH in the circulation.

targeting the AR axis have limited clinical utility. Several mechanisms were

Results

suggested to explain resistance to antiandrogen treatment including AR

GHBP(W104A)-leptin fusion was cloned in to a modified invitrogen pSecTag

mutations, AR amplification and/or local production of androgens. Additionally,

plasmid with the secretion sequence for leptin. This plasmid was transfected into

some studies also suggest that deregulation of AR cofactor expression may permit

CHO Flp-In cells by reagent-mediated transfection. Protein was expressed in

weak androgens or even antiandrogens to function as full AR agonists and fuel

CHO cells grown in roller bottles in the presence of valproic acid at a set

tumor growth, a mechanism that contributes to the castrate resistance phenotype.

temperature of 31 8C and purified by antibody affinity chromatography. In vitro

This puts into context our observation that RAD52, a protein involved in DNA

bioactivity was assessed by luciferase expression induced by leptin. Approxi-

repair machinery also functions as an AR cofactor whose deregulation affects

mately two times fold induction was achieved.

PC response to antiandrogens. Herein, using PC cell models, we found that

Conclusion

knockdown of RAD52

increases AR protein levels and enhances AR

We have demonstrated it is possible to generate a fusion of leptin to GHBP and

transcriptional activity in the presence of low levels of androgens. More

that this fusion retains bioactivity. Future studies will assess pharmacodynamic

importantly, we found that RAD52 knockdown converts the AR antagonist

and pharmacokinetic properties of this molecule.

bicalutamide into a full agonist in cell reporter assays and on AR target genes; an

DOI: 10.1530/endoabs.49.GP61

activity associated with enhanced recruitment of AR to target gene promoters.

Taken together, our results suggest that deregulation of RAD52 expression may

mediate PC resistance to antiandrogen therapy.

DOI: 10.1530/endoabs.49.GP63

Developmental & Protein Endocrinology

GP62

GP64

Effects of prenatal dexamethasone on fetal rat ovary

Thyroid hormone protects hepatocytes from HBx-induced

Natasa Ristic¹, Lazo Pendovski², Milica Manojlovic-Stojanoski¹,

carcinogenesis by enhancing mitochondrial turnover

Dragana Miljic³, Marko Miler¹, Vladimir Ajdzanovic¹,

Hsiang-Cheng Chi & Kwang-Huei Lin

Svetlana Trifunovic¹, Natasa Nestorovic¹ & Verica Milosevic¹

Chang-Gung University, Taoyuan, Taiwan.

¹Institute for Biological Research “Sinisa Stankovic”, University of

Belgrade, Belgrade, Serbia;²Faculty of Veterinary Medicine, Ss. Cyril and

Infection by hepatitis B virus (HBV) accounts for 50w80% of hepatocellular

Methodius University in Skopje, Skopje, Macedonia;³Department of

carcinoma (HCC) development worldwide, in which the HBV encoded X protein

Neuroendocrinology, Clinic for Endocrinology, Diabetes and Metabolic

(HBx) plays critical role in the induction of carcinogenesis. Several studies have

Diseases, Clinical Center of Serbia, Belgrade, Serbia.

shown that thyroid hormone (TH) suppresses HCC development and protects

hepatocytes from HBx induced damage, thus it is of interest to examine whether

Glucocorticoids affect the growth and maturation of fetal organ systems, but

TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx-

overexposure to exogenous glucocorticoids retard fetal growth and may alter

transgenic mice with or without TH, we confirmed the protective effects of TH on

developmental process in sensitive tissues. On the other hand, fetal ovary is not

HBx-induced hepatocarcinogenesis, which was achieved via reduction of ROS

characterized by definitive follicular structure, but the clusters of germinative cells are

inflicted DNA damage. We further found that TH induced biogenesis of

predominant. Germ cells may be in meiotic prophase or with sign of degeneration.

mitochondria

(MITO) and autophagy of HBx-targeted mitochondria simul-

The aim of this study was to determine whether prenatal exposure to

taneously, consequently leading to suppression of HBx-promoted ROS and

dexamethasone (Dx) altered normal structure and development of ovary in

carcinogenesis. Using microarray data analysis, this protective effect of TH was

19 day old rat fetuses. Pregnant females in the experimental group received

found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in

subcutaneous injections of 1.0, 0.5 and 0.5 mg Dx /kg body weight on days 16-18

hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to

of pregnancy. Control mothers were injected with the same amount of saline. On

ubiquitinate MITO-associated HBx protein and trigger selective mitophagy. The

day 19 of pregnancy, the dams and their fetuses were sacrificed under ether

pathological significance of the TH/PINK1 pathway in liver protection was

anesthesia and the fetuses were referred to as 19-day-old fetuses. Fetal ovaries

confirmed by the concomitant decrease in expression of both TR and PINK1 in

were prepared for further stereological examination.

matched HCC tumor tissues and negatively correlated with aggressive

The volume of the fetal ovary estimated using Cavalieri’s principle was

progression of cancer and poor prognosis. Our data indicates that TH/PINK1/-

significantly reduced after exposure to Dx by 22% (P!0.05) in comparison

Parkin pathway plays a critical role in protecting hepatocytes from HBx-induced

with control ovary. Using a fractionator-physical disector method, a reduction in

carcinogenesis. Notably, several liver-targeting therapeutic derivatives of thyroid

total number of germ cells in meiotic prophase by 43% (P!0.05) was observed,

hormone facilitating prevention or therapy of steatosis have been identified.

while total number of germ cells with sign of degeneration increased by 54%

Furthermore, our proof-of-concept experiments suggest that application of T3

(P!0.05), when compared with control values.

constitutes an effective novel therapeutic or preventive option for HCC. Thus, the

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

utilization of the agonists of TRs could be the meaningful strategy in liver relative

severity. To achieve a valid basis of comparison of efficacy outcomes across trials

diseases, ranging from simple hepatic steatosis to HCC.

(VELOCITY, VERTICAL, VISTA (long-term safety)), distribution of clinical

DOI: 10.1530/endoabs.49.GP64

characteristics known to affect HV should be similar between treatment arms

(somavaratan vs daily rhGH) and between trials. The same primary efficacy

endpoint (HV) and similar eligibility criteria were used across trials. Stratification

for Phase 3 randomization (somavaratan vs daily rhGH) was based on region,

expected age, and expected baseline IGF-I SDS. In VELOCITY

(nZ104

somavaratan; nZ32 daily rhGH), meanGS.D. baseline ages were 7.07G2.0 vs

GP65

7.03G2.4 years, respectively, mean GHmax 5.77G2.6 vs 5.87G2.5 ng/ml, mean

3-year safety and efficacy Update of the VERTICAL & VISTA trials of

height-SDS K2.76G0.7

vs K2.64G0.7, mean IGF-I SDS

-1.72G0.7

somavaratan (VRS-317), a long-acting rhGH, in children with Growth

K1.87G0.9, and mean bone ages 5.28G1.9 vs 5.29G2.2 years. In VERTICAL

Hormone Deficiency (GHD)

(NZ64), mean age was 7.8G2.4 years, mean height-SDS K2.6G0.6, mean IGF-

Bradley S. Miller¹, Wayne V. Moore^2,3, Patricia Y. Fechner^4,5, Quentin

I SDS K1.7G0.8, and mean bone age 6.4G2.4 years. No clinically meaningful

L. Van Meter⁶, John S. Fuqua⁷, David Ng⁸, Eric Humphriss⁹,

differences in baseline characteristics were noted between trials, or between

R. William Charlton⁹ & George M. Bright⁹

VELOCITY treatment arms. Collectively, similar populations were achieved

¹University of Minnesota Masonic Children’s Hospital, Minneapolis, MN,

between trials by use of consistent eligibility and stratification procedures. This

USA;²Children’s Mercy Hospital, Kansas City, MO, USA;³University of

allowed balanced treatment arms for clinical characteristics that may influence

Missouri-Kansas City, Kansas City, MO, USA;⁴Seattle Children’s Hospital,

the primary efficacy outcome, thereby achieving a valid basis of comparison

Seattle, WA, USA;⁵University of Washington, Seattle, Seattle, WA, USA;

between trial populations.

⁶Van Meter Pediatric Endocrinology, P.C., Atlanta, GA, USA;⁷Indiana

DOI: 10.1530/endoabs.49.GP66

University School of Medicine, Indianapolis, IN, USA;⁸ResearchPoint

Global, Inc., Austin, TX, USA;⁹Versartis, Inc., Menlo Park, CA, USA.

Requirement for daily rhGH injections is a treatment burden that can compromise

adherence and efficacy in patients with GHD. Somavaratan is a novel long-acting

GP67

rhGH fusion protein in clinical development for pediatric and adult GHD. In a

Karyotype and mid-childhood gonadotropin concentrations in

multicenter, randomized Phase 1b/2a study, somavaratan significantly improved

prediction of spontaneous puberty in Turner syndrome patients

height velocity (HV) and IGF-I in pre-pubertal children with GHD. Preliminary

Aneta Gawlik¹, Magdalena Hankus², Kamil Soltysik³, Kamila Szeliga² &

efficacy and safety in subjects who have completed 3 years of somavaratan

Ewa Malecka-Tendera¹

treatment are presented. Of 64 subjects randomized in the Phase 2a VERTICAL

¹Department of Pediatrics and Pediatric Endocrinology, School of Medicine

study to receive 5.0 mg/kg/month (weekly/twice-monthly/monthly dosing) for

in Katowice, Medical University of Silesia, Katowice, Poland;²Department

6 months, 60 elected to continue treatment in the long-term safety study, VISTA.

of Pediatrics and Pediatric Endocrinology, Upper-Silesian Pediatric Health

Initial IGF-I response supported a dose increase, and all subjects transitioned to

Center, Katowice, Poland;³Department of Anatomy and Molecular Cell

somavaratan 3.5 mg/kg twice-monthly by the 2^nd treatment year. Data cutoff was

Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

December 8, 2016. Of 48 subjects (24 males, 24 females), the meanGSD age was

7.6G2.4 years, and mean IGF-I SDS was K1.6G0.8 at baseline. In Year 3, IGF-I

SDS increased to 1.2G1.7 at peak (3-5 days post-injection) and K0.3G1.0 at

Gonadotropin levels in all Turner syndrome (TS) patients present a diphasic

trough (end of dosing cycle). Mean HV remained consistent during Years 1, 2,

pattern: highest in early childhood, declining at 6-10 years of age, and then

and 3, at

8.4G2.0, 8.3G1.6, and 7.8G1.6 cm/year, and height

(HT)-SDS

increasing again. Here, we have investigated whether karyotype or FSH&LH can

continued to increase from K2.6G0.6 at baseline to K2.1G0.6, K1.6G0.7, and

be used as indicators of spontaneous puberty in TS. From a consecutive group of

K1.2G0.8; delay in bone age (years) was K1.48G0.81 at baseline, K1.34G

139 TS girls treated at one clinical center (1996-2015) the clinical & biochemical

0.89

(Year 1, nZ48), K1.09G1.02 (Year 2, nZ47), and K0.66G0.82 (Year 3,

data were finally analyzed in 110 TS patients (1268 visits). The study population

nZ25). Treatment-related AEs were generally transient and mild. Overall, IGF-I,

was divided into two subsets based on karyotype (type A- 45X, 54%; type B-

HV, HT-SDS, and bone age showed continued improvement through 3 years of

others excluding 45X/46XY). The mean diagnosis age and duration of follow-up

somavaratan treatment in pre-pubertal children with GHD. Dose increase to

were 10.7G4.0 and 5.9 years, resp. The average number of visits was 10.4.

somavaratan 3.5 mg/kg twice-monthly resulted in consistent growth rates through

Spontaneous puberty was confirmed in 48.2% and menarche in 20%, both less

3 years of treatment, and overall Year 3 growth was consistent with daily rhGH

common in group A than B (31.1% and 9.8.% vs 69.4% and 32.6%, resp.,

from US registries. A Phase 3 study of somavaratan 3.5 mg/kg twice-monthly in

P!0.05). The mean age of Tanner B2 and menarche in all girls were 13.7G2.4

treatment-naïve GHD children is ongoing.

and 14.2 years, no difference between the groups (13.5G2.5 and 13.2G1.0 years

DOI: 10.1530/endoabs.49.GP65

(A) vs 13.8G2.3 and 14.6G1.7 years (B), PO0.05). The median FSH and LH

values in all patients at the age of 6-10 were 8.16 and 0.35 IU/l resp., significantly

lower comparing to younger (44.6 and 0.76 IU/l) and older (93.0 and 16.1 IU/l)

age (P!0.0001). LH were similar in both groups, whereas in group B FSH values

were significantly higher only in the older age. At the age of 6-10 FSH and LH

levels Rthan 6.7 and 0.2 resp. decrease the chance of spontaneous menarche

GP66

(33.3% vs 13.9% and 28.6% vs 11.8%). Conclusion: Nearly half of our TS

Achievement of a suitable basis of comparison in phase 2 and 3 clinical

patients showed spontaneous puberty symptoms and every fifth had spontaneous

trials (VERTICAL/VISTA, and VELOCITY) comparing somavaratan

menarche with higher frequency in non-45,X girls. The diphasic pattern of

vs daily rhGH for pediatric GH deficiency

FSH&LH was confirmed, however using their cut-off values one can predict the

Philippe Backeljauw¹, Bradley S Miller², Nancy Wright³,

chance for spontaneous menarche.

Aristides Maniatis⁴, Michael Stalvey⁵, Eric Humphriss⁶,

DOI: 10.1530/endoabs.49.GP67

R William Charlton⁶ & George M Bright⁶

¹Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;

²University of Minnesota Masonic Children’s Hospital, Minneapolis, MN,

USA;³Nancy Wright MD p.a., Tallahassee, FL, USA;⁴Rocky Mountain

Pediatric Endocrinology, Centennial, CO, USA;⁵University of Alabama at

Birmingham, Birmingham, AL, USA;⁶Versartis, Inc., Menlo Park, CA,

GP68

USA.

Assessment of reports of behaviour by patients and their parents in

paediatric Cushing disease

Margaret Keil, Elena Belyavskaya, Charalampos Lyssikatos, Maya Lodish

Efficacy of rhGH for treatment of pediatric GH deficiency (PGHD) may depend

& Constantine Stratakis

on several variables at treatment initiation (age, body weight, height velocity

NIH, NICHD, Bethesda, MD, USA.

(HV), IGF-I SDS, skeletal maturation, GHmax), but may be compromised by

poor adherence to required daily injections. Somavaratan is a novel, long-acting

rhGH fusion protein that demonstrated clinically meaningful improvements in

Context

HV and IGF-I concentration in PGHD patients. Over 200 pre-pubertal GHD

Prior studies of children with endogenous Cushing syndrome (CS) have identified

subjects have enrolled in somavaratan trials to date, including 137 in the Phase 3

cognitive decline despite reversal of brain atrophy after remission as well as

noninferiority VELOCITY trial comparing somavaratan vs daily rhGH. In the

residual impairment of quality of life measures. Although parental observations

randomized Phase 1b/2a VERTICAL study in pre-pubertal children with GHD,

support personality changes with CS, significant psychopathology has not been

primary determinants of Year 1 HV included age at treatment initiation and GHD

described. We investigated the feasibility of using paediatric Patient-reported

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

outcomes (PROMIS) using a computer interface to assess patient perception of

GP70

burden of illness and correlation with parent proxy report using Child Health

The adverse effects of prescribed glucocorticoids are worsened by

Questionnaire (CHQ).

co-administration of 5a-reductase inhibitors

Setting

Tom Marjot, Nantia Othonos, Conor Woods, Jonathan Hazlehurst,

Subjects were enrolled in a clinical protocol at the National Institutes of Health

Ahmad Moola, Leanne Hodson & Jeremy Tomlinson

Clinical Center in Bethesda, MD, USA.

Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR

Method

Biomedical Research Centre, Churchill hospital, University of Oxford,

We report 9 children (6F, 12G3.5 years) diagnosed with Cushing disease (CD).

Oxford, UK.

Prior to surgical treatment, subjects completed paediatric PROMIS measures and

parents completed CHQ using an online secure website.

Results

Introduction

PROMIS measures scores (meanGS.D.): anxiety (54G9), depression (55G11)

Glucocorticoids (GC) are prescribed to 2-3% of the population of the UK and

anger (50G9), and emotional support (52G10) (higher scores indicate more of

USA. Their use is associated with a significant side effect profile that includes

the concept being measured); CHQ total Psychosocial score (meanGS.D.) (43G

the development of central obesity, insulin resistance and type

2 diabetes.

10)

(lower values are associated with a greater deficit in functioning). A

5a-reductase (5aR) inhibitors (Finasteride and Dutasteride) are also commonly

significant correlation was found between Psychosocial summary score of CHQ

prescribed in the context of prostate disease, where they inhibit the conversion of

and paediatric PROMIS measures of anxiety

(rZK70.5; P!0.03) and

testosterone to dihydrotestosterone. Additionally, they have a role to inactivate

depression (rZK0.9; P!0.002). No correlation was found between urinary

and clear GC. We have therefore hypothesised that 5aR inhibitors have the

free cortisol level or midnight serum cortisol and PROMIS measures.

potential to exacerbate the adverse metabolic effects of GC.

Conclusion

Methods

Prior to treatment for CS, a significant correlation was found between children’s

We conducted a prospective, randomised, study in 19 healthy male volunteers

endorsement of anxiety and depression symptoms and parental proxy report of

(age; 45G8.5 years, BMI; 27.1G3.1 kg/m²). Participants underwent detailed

psychosocial function. Our findings support that paediatric PROMIS measures

metabolic assessments including a 2-step hyperinsulinaemic euglycaemic clamp

represent feasible and potentially valuable instruments for future studies to assess

incorporating stable isotopes, adipose tissue microdialysis and biopsy. They were

behavioural symptoms in children diagnosed with CS prior to and after treatment.

then randomised to receive either prednisolone (10 mg OD) or prednisolone

DOI: 10.1530/endoabs.49.GP68

(10 mg OD) and a 5aR inhibitor (finasteride 5 mg OD or dutasteride 0.5 mg OD)

for 7 days, metabolic assessments were then repeated.

Results

We have previously shown that high dose parenteral GC administration decreases

glucose utilization (M value; 3.1G0.4 vs 1.6G0.1 mg/kg per min, PZ0.001) and

5aR inhibitors alone are without effect (M value; 3.5G0.4 vs 3.3G0.4 mg/kg per

min, PZ0.42). In this study, prednisolone only did not alter glucose utilization

(M-value; 3.2G1.3 vs 2.8G1.6 mg/kg per min, PZ0.37), however, co-adminis-

GP69

tration of prednisolone and 5aR inhibitors significantly decreased it (M-value;

5b-reductase (AKR1D1) is a potent regulator of carbohydrate and lipid

4.0G2.0 vs 2.6G1.3 mg/kg per min, PZ0.02). Similarly, high dose GC, but not

5aR inhibitors alone, impair insulin-mediated suppression of circulating non-

metabolism and inflammation in human liver

esterified fatty acids

(NEFA). Prednisolone 10mg OD did not alter insulin-

Nikolaos Nikolaou¹, Laura Gathercole³, Charlotte Green¹,

mediated suppression of NEFA (0.15G0.27 vs 0.13G0.13, PZ0.88), however,

Catriona McNeil¹, Wiebke Arlt², Leanne Hodson¹ & Jeremy Tomlinson¹

co-administration with 5aR inhibitors impaired the ability of insulin to suppress

¹University of Oxford, Oxford, UK;²University of Birmingham,

NEFA (0.15G0.1 vs 0.29G0.18, PZ0.01).

Birmingham, UK;³Oxford Brookes University, Oxford, UK.

Conclusion

5aR inhibitors exacerbate the adverse metabolic effects of prescribed GCs. This

Non-alcoholic fatty liver disease

(NAFLD) is the hepatic manifestation of

has significant translational implications, not only with regards to the need to

metabolic disease. 5b-reductase (AKR1D1) is highly expressed in human liver

consider steroid dose reductions, but also the necessity for increased vigilance for

where it inactivates steroid hormones and catalyzes a fundamental step in bile

the development of adverse effects.

acid synthesis. Steroid hormones, including glucocorticoids, as well as bile acids

DOI: 10.1530/endoabs.49.GP70

are established regulators of metabolic phenotype. We hypothesized that

AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis.

Genetic manipulation of AKR1D1 (over-expression, siRNA knockdown) was

performed in human liver HepG2 and Huh7 cells. Gene expression changes were

confirmed by qPCR. Functional activity, assessed using gas chromatography mass

spectrometry to measure cortisone clearance and tetrahydrocortisone generation

was paralleled by the anticipated changes in glucocorticoid receptor activation

measured by luciferase reporter assays. AKR1D1 knockdown in HepG2 cells

increased glucose transporter mRNA expression and extracellular glucose

Diabetes & Complications 1

concentrations in the cell media decreased (15.3G1.5 vs 12.1G0.9 mmol/mg,

GP71

P!0.05) while intracellular glycogen levels were increased (18.9G0.3 vs 22.7G

Carbohydrates metabolism and H. pylori: case-control study

0.3 mg/ml, P!0.05). AKR1D1 knockdown increased Fatty Acid Synthase and

Isabel Ma Cornejo-Pareja¹, M Mar Roca-Rodríguez², Leticia

Acetyl CoA Carboxylase

expression, the rate-limiting step in de novo

Coín-Araguez³, Araceli Mun˜ oz-Garach1, María Molina-Vega1,

lipogenesis, DNL)

(0.52G0.06

0.89G0.04, P!0.01), and increased

Cristina Díaz-Perdigones¹, Carmen Hernández-García¹, Juan

intracellular triglyceride (54.3G12.7 vs 73.3G11.0 nmol/mg, P!0.01). Further-

Alcaide-Torres³, Carlos Clu-Fernández¹, Laura Vin˜ uela-González4,

more, 3-hydroxybutyrate levels in the cell media were reduced, indicative of

Laura Mora-Navas⁴, Isabel Mancha-Doblas¹ &

impaired fatty acid oxidation (18.7G2.3 vs 11.4G2.7 nmol/mg, P!0.01). Mass

Francisco J Tinahones-Madue

˜o¹

spectrometry analysis of lipid composition demonstrated increased palmitic and

¹Endocrinology and Nutrition Department. Virgen de la Victoria Hospital,

palmitoleic acid production consistent with increased DNL and fatty acid

Málaga, Spain;²Endocrinology and Nutrition Department Puerta del Mar

saturation. In addition, bile acid composition was altered with a significant

Hospital, Cádiz, Spain;³Research Laboratory IBIMA, Málaga, Spain;

increase in chenodeoxycholic acid levels. Conversely, pharmacological manipu-

⁴Microbiology Department, Virgen de la Victoria Hospital, Málaga, Spain.

lation of the bile acid receptors FXR and LXR using the FXR agonist GW4064

and LXR antagonist

22-S-Hydroxycholesterol rescued HepG2

cells from

metabolic dysfunction by reducing the expression of lipogenic genes.

Introduction

Furthermore, AKR1D1 knockdown increased proinflammatory cytokine IL-1,

H. pylori infection has been related with extragastric diseases such as type 2

IL-6 and IL-8 mRNA expression; changes were confirmed by elevated cell media

diabetes.

IL-8

levels

(4.68G0.70

13.39G2.28 ng/ml, P!0.05), increased IkBa

Aim

degradation and induced IRE-1a protein expression, indicative of inflammation

to evaluate changes in carbohydrate metabolism induced by 75g oral glucose

and cellular ER stress. In conclusion, AKR1D1 activity regulates steroid hormone

tolerance test (OGTT), before and after antibiotic eradication treatment in patients

and bile availability, potently modulating hepatic carbohydrate and lipid

colonized by H. pylori compared to healthy controls.

metabolism in addition to an inflammatory phenotype suggesting a crucial role

Materials and methods

in the pathophysiology of NAFLD.

A prospective case-control study. Biochemical parameters, carbohydrate profile,

DOI: 10.1530/endoabs.49.GP69

ghrelin and GLP1 levels before and after antibiotic eradication treatment were

analyzed.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

GP73

We studied 40 cases and 21 controls (60% and 57.1% women, respectively).

Permanent neonatal diabetes in a 24 year old Spanish patient

Mean age: 46,95G2,02 vs 44,52G2,73 years, family history of digestive

Milagros Sierra, Elena Garcia, David Males, Juan Carlos Romero,

disorders: 70% vs 57.1% and clinical history of gastrointestinal disease: 57,5% vs

Carlos Silva, Gonzalo Allo & Guillermo Martinez

42.9%, respectively. After antibiotic treatment, significant improvements in

12 De Octubre University Hospital Endocrinology and Nutrition

HbA1c (PZ0,014), glucose levels post OGTT at 60⁰ and 120⁰ (PZ0,018 and

Department, Madrid, Spain.

PZ0,019, respectively) and HDL Cholesterol

(PZ0,021) were observed.

Significant changes in basal ghrelin levels (PZ0,05) were found, but C peptide

levels did not change. We observed differences between infected population by

Introduction

H. pylori and healthy people: lower post OGTT insulin levels at 30⁰ and 60⁰

Neonatal diabetes mellitus is a rare form of diabetes, diagnosed within the first six

(PZ0.042 and PZ0.03, respectively) in infected patients. Those differences

months of life. We report a case of a 24-year-old patient with permanent neonatal

disappeared after treating the infection. In cases and controls, we found significant

diabetes.

positive correlations in carbohydrate metabolism, and significant negative

Case Report

correlations in controls between ghrelin with basal insulin and C peptide. No

The patient had no relevant family history. Her mother had no gestational

significant correlations respect to GLP1 were found. 90% of patients completed

diabetes. Personal history included: Normal birth weight, polycystic ovarian

correctly the treatment, 31,6% needed ranitidine and 97,5% eradicated H. pylori

syndrome and ovarian teratomas. She was diagnosed of diabetes at 3 months of

after conventional antibiotic treatment.

age, starting immediately with insulin treatment. Glucose control had always been

Conclusion

optimal (HbA1c l !6.7%). Acute diabetic complications included: symptomatic

1) H. pylori eradication improved carbohydrate metabolism.

2) Significant

hypoglycemias every 3 days, usually after dinner and, less frequently nighttime

positive correlations in carbohydrate metabolism in cases and controls were

hypoglycemias. No hyperglycemias that required in hospital management. No

found. 3) Negative correlations between ghrelin and pancreatic reserve were

chronic metabolic complications. The patient came to our clinic to continue

observed in cases. 4) Carbohydrate metabolism differences between healthy and

follow up. We completed her work up doing islet antibodies detection (anti

infected people disappeared after eradication treatment. 5) More than 95% of

GAD65, anti tyrosine phosphatase IA2, anti insulin and anti zinc transporter), and

patients achieved H. pylori eradication with conventional antibiotic treatment.

as expected the results were negative. Considering the age of the diagnosis,

DOI: 10.1530/endoabs.49.GP71

genetic testing for monogenic forms of diabetes was performed, discovering a

heterozygous mutation c.323Ag (pY108C) in INS gene. Family genetic mutation

are still pending.

Discussion

Neonatal diabetes mellitus have an incidence of 1 in 500000 live births. Most

common genes are KLF 11, ABCC8 and less frequently INS gene (30%, 19% and

14% respectively). Depending on the severity of the mutations insulin bioactivity

will be affected, ranging from a decreased biosynthesis to altered transcription.

Clinical implications include transient requirement of insulin, later switching to

sulfonylureas or even completely stopping hypoglycemic treatment; and

permanent insulin treatment. In the latter, the risk of ketoacidosis also depends

GP72

and the recessive or dominant inheritance.

Specific plasma amino acids alternations associated with metabolic

Conclusions

syndrome

Monogenic forms of diabetes are uncommon, however it is important to consider

Marta Siomkajło¹, Jacek Rybka³, Andrzej Gamian^2,3, Joanna

them in the differential diagnosis of particular cases. Genetic mutation study is

Stankiewicz-Olczyk¹, Marek Bolanowski¹ & Jacek Daroszewski¹

important to assess future treatment options and the risk of ketoacidosis.

¹Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw

DOI: 10.1530/endoabs.49.GP73

Medical University, Wroclaw, Poland;²Department of Medical Biochem-

istry, Wroclaw Medical University, Wroclaw, Poland;³Ludwik Hirszfeld

Institute of Immunology and Experimental Therapy, Polish Academy of

Sciences, Wroclaw, Poland.

GP74

Objectives

Rescue study of trapped AVPR2 mutants with chemicals

Amino acids (AA) plasma profile is associated with cardiometabolic diseases

(CMD), predicts diabetes mellitus type 2 (DM2) and cardiovascular diseases

Beril Erdem, Emel Saglar, Tugce Karaduman, Merve Ozcan, Dilara Sahin

(CVD) many years in advance. Metabolic syndrome (MS) defines the area of

& Hatice Mergen

metabolic disturbances that precede DM2 and CVD development. The primary

Department of Biology, Faculty of Science, Hacettepe University, Ankara,

Turkey.

objective of the study was to examine the association between BCAA (branched

chain amino acids), AAA (aromatic amino acids) profile and MS’s phenotype and

to evaluate its clinical utility for MS diagnosis.

Diabetes insipidus (DI) is a disorder that characterized by producing large volume

Methods

of urine for daily due to the problems at the arginine vasopressin (AVP-NPII),

263 healthy, professionally active men, with and without MS (MSC, nZ165;

aquaporin 2 (AQP2) and arginine vasopressin receptor 2 (AVPR2) genes. These

MSK, nZ98) were included into the study. Anthropometrical, biochemical and

problems can be inherited or acquired. Among these genes, AVPR2 is a G protein

AA measurements were performed. AA were tested for the ability to discriminate

coupled receptor and most of the inherited type of DI are caused by mutations in

subjects with MS and insulin resistance irrespectively. Based on logistic

AVPR2 gene. Mutations can cause improper folding of the receptor protein and

discrimination multivariate early MS diagnostic model was built and its

this situation causes to retention of the protein in cellular compartments such as

discrimination properties were evaluated.

endoplasmic reticulum

(ER) or Golgi apparatus. For treatment strategies,

Results

researchers try to use chemicals to rescue of mutant proteins from the control

2 functionally independent AA clusters were identified. BCAA and phenylalanine

mechanisms to make them at least functional. In this study, we aimed to do pre-

differed strongly between MSC and MS- participants (pZ0.003), appeared as

research for the rescuing mutant receptors

(R68W, V162A, T273M,

significant indicator of MSC individuals (AUC 0.66; 95%CI: 0.5757-0.7469)

R67_G69del/G107W, V88M, R106C, G12E). We performed functional

and correlated with cardiometabolic factors. No statistical significant differences

characterization of these mutant receptors in our previous study and they were

in AAs concentrations between IRC and IRK groups were noted and none of the

observed as trapped in the ER or Golgi apparatus. In the present study, COS-7

AA group appeared as meaningful IRC indicator. Proposed MS multivariate

cells were transfected with mutant and wild type AVPR2s. 48 hours after the

diagnostic model consisted of phenylalanine, insulin, leptin, adiponectin and had

transfection, different concentrations of DMSO and glycerol were performed to

good discrimination properties - AUC 0,79; (95% CI: 0.7239-0.8646).

the cells. 16-18 hours after the treatment of DMSO and glycerol, cell surface

Conclusions

ELISA were performed to understand cell surface expression of the mutant

MS is associated with selective hiperaminoacydemia that could be a part of CMD

proteins when they were treated with different concentrations of DMSO and

pathogenesis. Present study suggests that AA disturbances do not derive directly

glycerol. According to the ELISA results, mutant receptors showed different

from insulin sensitivity impairment nor obesity or muscle mass. AA utility for MS

rescue profile compared to the wild type receptor. As a result, we can say that

diagnosis needs further evaluation. The original outcome of the study became MS

rescuing trapped mutant receptors from ER or Golgi apparatus control

diagnostic model creation - MS screen test, with good discrimination properties

mechanisms using with chemicals could be a forward step for the treatment of

and that could be validated in the next coming studies.

DI. Receptors that have mutations which cause retention in ER or Golgi apparatus

DOI: 10.1530/endoabs.49.GP72

may be functional if they are rescued by chemicals. For further studies, instead of

chemicals, pharmacochaperons could be use. We can conclude that, rescue

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

studies of mutated proteins by using chemicals or pharmacochaperons shed light

were calculated from the glucose and insulin response during OGTT.

to the treatment strategies of DI. This work was supported by The Scientific and

Results

Technological Research Council of Turkey (Project Numbers: 216S304 and

After controlling for confounding factors, the group treated with statins during the

112S513).

entire follow-up had a, nominally significant, 79% (95% CI 1.16, 2.76 PZ0.008)

DOI: 10.1530/endoabs.49.GP74

increased risk of developing incident diabetes, compared to the group without statins,

and statin use was significantly associated with higher levels of fasting plasma

glucose (FPG) and 2 hour plasma glucose (2hPG). Statin therapy was associated with

a reduced CIR30, but not IGI30. Beta blocker therapy was associated with a

nominally significant 63% increased risk of developing incident diabetes.

Conclusion

Statin treatment is associated with an increased risk of incident diabetes, higher

GP75

levels of FPG and 2hPG, and reduced insulin secretion. Beta blocker therapy is

GLP-1 acutely regulates carbohydrate and lipid metabolic routes in

associated with an increased risk of incident diabetes.

the liver

DOI: 10.1530/endoabs.49.GP76

Laura Toba, Yolanda Diz-Chaves, Juan Fandin˜ o, Hugo Ogando,

Lucas González-Matías & Federico Mallo

University of Vigo, Vigo, Spain.

The Glucagon-like peptide-1 receptor is widely expressed in diverse tissues

GP77

including the liver. GLP-1

contributes itself to the regulation of glucose

Susceptibility to type 2 diabetes may be modulated by haplotypes in

homeostasis and has important effects in lipid metabolism even preventing liver

G6PC2, a target of positive selection

steatosis induced by high fat diets.

Mario Clerici¹, Nasser Al-Daghri², C Pontremolli¹, R Cagliani¹,

The aim of this study was to analyse the short-term effects of liraglutide on key

Diego Forni¹, Majed Alokail², Omar Al-Attas², Shaun Sabico²,

enzymes of the hepatic energy metabolism.

S Riva¹ & M Sironi¹

Thirty-six Sprague-Dawley young adult male rats were studied (weight range

¹University of Milano, Milan, Italy;²King Saud University, Riyadh,

350-400 g). Control rats were fed ad libitum, while the fast group (F) were

Saudi Arabia.

deprived of food for 48 hours, and treated with liraglutide (100 mg/Kg/12 h;

CT/LIR; F/LIR) or vehicle (CT/VEH; F/VEH) for 48 hours. Rat body weight was

measured at 0, 24 and 48 hours. At 48 h, rats were sacrificed and liver samples

Introduction

were collected and stored at K80 8C until analysis. mRNA expression of G6P,

The endoplasmic reticulum enzyme glucose-6-phosphatase catalyzes the

PCK-1, DGAT-1, GPAT4, CPT1A and ACACA in the liver were assessed by real

common terminal reaction in the gluconeogenic and glycogenolytic pathways

time PCR.

and plays a central role in glucose homeostasis. In most mammals, different G6PC

CT/LIR rats gained less body weight (K6.4 g/100 g, P!0.0001) than CT/VEH at

subunits are encoded by three paralogous genes (G6PC, G6PC2, and G6PC3).

24 h and still less at 48 h (K2.9 g/100 g, P!0.0001). The expression levels of

Mutations in G6PC and G6PC3 are responsible for human Mendelian diseases,

G6P and PCK-1, key enzymes in gluconeogenesis, decreases in rats treated with

whereas variants in G6PC2 are associated with fasting glucose (FG) levels.

liraglutide by a 58% (P!0.05) and 75% (P!0.01) respectively. On the other

Methods

hand, DGAT-1 and GPAT4 levels, involved in synthesis of triacylglycerol, were

We analyzed the evolutionary history of G6Pase genes in mammals. Results

not modified by LIR. In addition, CPT1a and ACACA, enzymes implicated in the

indicated that negative selection was the major force shaping diversity at these

synthesis & metabolism of fatty acids, yielded no significant differences. Fasting

genes. Nonetheless, site-wise estimation of evolutionary rates at corresponding

just increased CPT1 levels

(271% F/VEH vs CT/VEH, P!0.01), and LIR

sites revealed weak correlations, suggesting that G6Pases have evolved different

treatment reduced them (92% F/LIR, P!0.01 vs F/VEH).

structural features over time. We also detected pervasive positive selection at

In conclusion, Liraglutide modifies the metabolism of energy substrates in the

mammalian G6PC2 genes. Most selected residues are located in the C-terminal

liver reducing glucose production in normal feeding and CPT1a specially in

protein region, where several human variants associated with FG levels also map.

fasting, limiting lipid access to mitochondria. These metabolic changes may

This region was thus re-sequenced in a cohort of w560 subjects from Saudi

underlie the prevention of liver steatosis attributed to GLP-1 analogues.

Arabia, 185 of whom suffering from type 2 diabetes (T2D).

DOI: 10.1530/endoabs.49.GP75

Results

The frequency of rare missense and nonsense variants was not significantly

different in T2D and controls. Association analysis with two common missense

variants (V219L and S342C) revealed a weak but significant association for both

SNPs when analyses where conditioned on rs560887, previously identified in a

GWAS for FG. Two haplotypes were significantly associated with T2D with an

GP76

opposite effect direction.

Increased risk of diabetes and hyperglycaemia associated with

Conclusion

treatment with statins, beta-blockers and diuretics: the PPP-Botnia

These results, although preliminary, suggest that distinct haplotypes at the G6PC2

study

locus modulate susceptibility to T2D.

Liisa Hakaste^1,2, Teo Helkkula², Bo Isomaa², Marja-Riitta Taskinen^3,4,

DOI: 10.1530/endoabs.49.GP77

Leif Groop^5,6 & Tiinamaija Tuomi^1,2

¹Endocrinology, Helsinki University Hospital, Helsinki, Finland;

²Folkhalsan Research Center; Diabetes and Obesity Research Program,

University of Helsinki, Helsinki, Finland;³Research programs Unit,

Diabetes and Obesity, University of Helsinki, Helsinki, Finland;⁴Heart and

Lung Center, Helsinki University Hospital, Helsinki, Finland;⁵Lund

University Diabetes Center, Malmo, Sweden;⁶Finnish Institute for

Molecular Medicine, University of Helsinki, Helsinki, Finland.

GP78

Background

Contribution of genetic predisposition and lifestyle to gestational

Statin medication is commonly used in prevention of cardiovascular diseases.

diabetes risk

Pooled evidence shows that statin therapy is associated with increased risk of

Polina Popova^1,2, Alexandra Tkachuk¹, Yana Bolotko¹,

incident diabetes, but studies vary in results and there is no consensus of the

Andrey Gerasimov¹, Alexandra Klyushina¹, Anna Kostareva¹ &

diabetogenic mechanism of statins. Beta blockers and diuretics are commonly

Elena Grineva^1,2

used antihypertensive agents that also have been shown to increase the risk of

¹Almazov Federal North-West Medical Research Centre, Saint-Petersburg,

incident diabetes. Our objective was to examine the effects of statins, beta

Russia;²St Petersburg Pavlov State Medical University, Saint-Petersburg,

blockers and diuretics on glucose metabolism and the risk of incident diabetes.

Russia.

Methods

5208 subjects from western Finland identified through the Population registry

participated in the baseline PPP-Botnia Study, and 3,614 subjects participated in

Aim

the follow-up study after a mean time of 6.7 years. Participants underwent oral

The aim of our study was to assess the contribution of genetic variation in some

glucose tolerance tests

(OGTT) and gave information about their use of

previously reported gestational diabetes mellitus (GDM) susceptibility loci and

medication. Insulinogenic index

(IGI) and corrected insulin response

(CIR)

lifestyle parameters to GDM risk.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

T1DM high-risk HLA- DR/DQ haplotypes. In conclusion, our data confirms the

We performed a case-control study of 278 GDM cases and 179 controls who had

association between the ERBB3 rs2292239 and risk for T1DM in a population

filled up special questionnaires concerning their lifestyle habits during the oral

from Southern-Brazil.

glucose tolerance test (OGTT) on the 24-32 week of gestation. The questionnaire

DOI: 10.1530/endoabs.49.GP79

consisted of the following sections, stratified in a semi-quantitative manner: the

consumption of major food groups and drinks, the amount of physical activity and

smoking before and during pregnancy. GDM was diagnosed according to the

IADPSG criteria. Maternal blood was sampled for further genotyping of single

nuclear polymorphisms (SNPs) in MTNR1B (rs10830963 and rs1387153), GCK

(rs1799884), KCNJ11 (rs5219), IGF2BP2 (rs4402960), TCF7L2 (rs7903146),

CDKAL1 (rs7754840) and IRS1 (rs1801278). Binary logistic regression (forward

conditional) was accomplished to identify the contribution of «classical» risk

factors for GDM (advanced maternal age, higher body mass index (BMI), history

of GDM, impaired glucose tolerance, arterial hypertension, family history of

diabetes), lifestyle parameters and the above mentioned SNPs to the assessment

GP80

of GDM risk.

Trace elements as an oxidative stress marker in women with gestational

Results

diabetes and their neonates

After automatic lineal modeling the following factors proved to be associated

Georgios Boutzios¹, Eleni Koukoulioti¹, Ioannis Papoutsis²,

with the increased GDM risk: age (ORZ1.11, 95% CIZ1.06-1.16, P!0.001),

Sotirios Athanaselis², Gerasimos Tsourouflis¹ & Evangelia Zapanti³

BMI (ORZ1.09, 95% CIZ1.05-1.14, P!0.001), the presence of G allele of

¹Endocrine Unit, Department of Pathophysiology, Laiko University

rs10830963

(ORZ2.1, 95%CIZ1.4-3.1, PZ0.001), T allele of rs1799884

Hospital, Medical School, University of Athens, Athens, Greece;

(ORZ2.1, 95%CIZ1.3-3.4, PZ0.003) and consumption of sausage O 3 times a

²Department of Toxicology, Medical School, University of Athens, Athens,

week (ORZ2.55, 95%CIZ1.36-4.78, PZ0.004) compared to less consumption.

Greece;³Endocrine Unit, Alexandra Maternity Hospital, Athens, Greece.

Legumes consumption 1-2 times a week was associated with the decreased risk of

GDM, when compared to less consumption (ORZ0.59, 95%CIZ0.36-0.97,

PZ0.036).

Background and aims

Conclusion

Gestational diabetes (GD) is closely related to unbalanced zinc (Zn) and cooper

MTNR1B and GCK variants, some eating habits along with an increment in

(Cu) serum levels. The aim of this study was to investigate serum zinc and cooper

maternal age and BMI were associated with the increased risk of GDM.

levels in relation to the metabolic profile, and the impact on fetal development in a

DOI: 10.1530/endoabs.49.GP78

cohort of gestational diabetes GD(N) neonates and their mothers GD(M)

compared to normal pregnancies.

Material and Methods

Prospective controlled study in a tertiary Academic medical center. The study

population included 101 mother/neonate pairs; 50 control group (C) and 51 GD

group. Intervention: Diet and/or insulin administration in GD(M). Anthropo-

metric, metabolic parameters, and trace elements serum levels were assessed.

Results

Age and body weight change during pregnancy (DBW) were similar in both

groups. HbA1c was comparable between C and GD group (5.37G0.34 and

5.39G0.48%, for C and GD respectively, PZ0.844). Mean serum Cu levels were

(150.1G45.85, 32.16G43.37)mg/dl in C and (203.53G65.63, 23.62G13.42)

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mg/dl in GD, mean Zn levels (87.8G17.48, 120.47G37.16)mg/dl in C and (88.1G

27.1,

113.76G36.77)mg/dl in GD, for mothers and neonates, respectively.

The rs2292239 polymorphism in the ERBB3 gene is associated with risk

Neonates had statistically significantly lower serum Cu levels but higher Zn levels

for type 1 diabetes mellitus

compared to their mothers (P!0.0001, P!0.0001). Serum cooper levels in

Daisy Crispim^1,2, Cristine Dieter^1,2, Natalia Lemos^1,2, Tais Assmann^1,2,

mothers (Cu(M) levels were statistically significantly higher in GD(M) compared

Guilherme Duarte^1,2, Luiza Dorfman³ & Andrea Bauer^1,2

to C(M) (P!0.0001). There was a negative correlation between Zn(M) and

¹Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre,

Rio Grande do Sul, Brazil;²Post-graduation Program in Medical Sciences:

insulin levels(M) in C (rZK0.284, PZ0.045), between Zn(M) and insulin(N) in

GD (rZK0.372, PZ0.012), and between Zn(N) and head circumference in C

Endocrinology, Faculdade de Medicina, Universidade Federal do Rio

group (rZK0.423, PZ0.013). There was a positive correlation between Cu(N)

Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil;³Universidade do

and insulin(N) in GD (rZ0.365, PZ0.019), and between Cu (M) and birth weight

Vale do Rio dos Sinos - UNISINOS, Sao Leopoldo, Rio Grande do Sul,

in C (rZ0.304, PZ0.042).

Brazil.

Conclusions

Serum cooper levels are higher in women with gestational diabetes and

Background and Aim

independently of diabetes control. Both serum trace element levels in neonates

Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from the

seem to correlate with neonatal head circumference and birth weight only in

complex interaction among multiple genes, environmental factors and the

control group.

immune system. Genome-wide association studies identified ERBB3 (Erb-b2

DOI: 10.1530/endoabs.49.GP80

receptor tyrosine kinase 3) gene as a main susceptibility locus for T1DM. This

gene encodes a member of the family of intracellular receptors of protein tyrosine

kinases, which activates multiple signaling pathways including PI3K-Akt and

MAPK; thus, regulating cell survival and proliferation. Moreover, ERBB3 seems

to contribute to T1DM pathogenesis by modulating antigen-presenting cell

function and autoimmunity as well as beta-cell apoptosis and insulin production.

Therefore, the aim of this study was to investigate the association of the

rs2292239 (C/A) polymorphism in the ERBB3 gene with susceptibility to T1DM

in a Brazilian population from Southern-Brazil.

Methods

Frequencies of the rs2292239

polymorphism were analyzed in 461 T1DM

patients

(cases) and

570

non-diabetic subjects

(controls). Genotyping was

performed using Real-Time PCR and TaqMan MGB probes (Thermo Scientific).

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Results

Genotype distributions of the ERBB3

rs2292239

polymorphism were in

agreement with those predicted by the Hardy-Weinberg Equilibrium in the

Abstract withdrawn.

control group (P R0.05), with the A/A genotype being more frequent in T1DM

patients compared with non-diabetic subjects (PZ0.007). The A allele frequency

was 39.7% in the T1DM group and 32.8% in the control group (PZ0.008).

Moreover, the A allele was significantly associated with T1DM risk when taking

into account additive (ORZ1.67, 95% CI 1.07 - 2.61; PZ0.023) and recessive

(ORZ1.58, 95% CI 1.04 - 2.40; PZ0.031) inheritance models, adjusting for

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

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PZ9!10^K6) and 1,25(OH)₂D₃ (median 59.05 vs

41.15 pg/ml PZ0.006)

compared to HC with the same genotype.

Reduced level of soluble TLR2 in type 2 diabetes despite increased

Conclusion

TLR2 monocyte expression

We describe an association of the IL1b with T2D in German patients.

Emanuela Zaharieva¹, Tsvetelina Velikova², Elena Vikentieva³,

Significantly lower 25(OH)D₃ and 1,25(OH)₂D₃ levels were observed in T2D

Dora Popova³, Adelina Tsakova⁴ & Zdravko Kamenov¹

patients with the GG genotype. Whereas the major allele A appears to be

¹Medical University Sofia, Alexandrovska University Hospital, Clinic of

protective, the minor allele G is may predispose to T2D in combination with a

Endocrinology, Sofia, Bulgaria;²Medical University Sofia, St Ivan Rilski

vitamin D deficiency. Our results suggest that VD deficiency enhances the genetic

University Hospital, Laboratory of Clinical Immunology, Sofia, Bulgaria;

risk for T2D conferred by the genotype GG of IL1b SNP rs16944. Whether and

³Military Medical Academy, Department of Clinical Laboratory and

how vitamin D interacts with IL1b through this polymorphism is subject to further

Immunology, Sofia, Bulgaria;⁴Medical University Sofia, Alexandrovska

studies.

University Hospital, Central Clinical Laboratory, Sofia, Bulgaria.

DOI: 10.1530/endoabs.49.GP83

Background

Chronic low-grade inflammation is a major factor in the pathogenesis of type 2

diabetes. One way for promoting inflammatory cytokines secretion is through

activation of toll-like receptors (TLR). Their overexpression on monocytes has

been demonstrated in insulin resistance and type 2 diabetes. Soluble forms of toll-

like receptors (sTLR) are considered a regulatory mechanisms of their activation.

Their role has been described in modulation of bacteria-induced infective diseases

but has not been analysed in diabetes. The aim of the study was to evaluate the

place of sTLR2 in type 2 diabetes and compare it with monocyte expression.

Subjects and methods

We performed a cross-sectional study that included 63 patients with type 2

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diabetes and 25 controls. All were assayed for soluble forms of TLR2 through

Antidiabetic medication use and the risk of fracture in type 2 diabetic

Enzyme-Linked Immunosorbent Assay. We evaluated monocyte expression of

patients: a nested case-control study

TLR2 in

diabetic patients and

control subjects through direct

Eladio Losada¹, Berta Soldevila^2,3, M. Sanni Ali⁴, Daniel Martinez-

immunofluorescence with conjugated monoclonal antibodies. All participants

Laguna⁵, Xavier Nogués^6,7, Adolfo Diez-Perez^6,7, Manel Puig-Domingo^2,3,

were assayed for Interleukin

(IL-6) through Electro-Chemiluminescence

Dídac Mauricio^2,3 & Daniel Prieto-Alhambra^4,5

Immunoassay and high sensitivity C-reactive protein (hs-CRP) through Particle

¹Section of Endocrinology, Hospital Can Misses, Ibiza, Spain;²Department

Enhanced Immunoturbidimetric Assay.

of Endocrinology and Nutrition. University Hospital & Health Sciences

Results

Research Institute “Germans Trias i Pujol”, Badalona, Spain;³CIBER of

TLR2 expression in patients with type 2 diabetes was higher compared to controls

Diabetes and Associated Metabolic Diseases (CIBERDEM). Carlos III

(89.85G9.66% vs. 50.20G36.91% for CD14CCCD16C monocytes, PZ0.003

Institute of Health, Madrid, Spain;⁴Oxford NIHR Musculoskeletal

and

34.54G12.38% vs.

17.12G15.39%, PZ0.011

for CD14CCD16CC

Biomedical Research Unit. Nuffield Department of Orthopaedics. Rheu-

monocytes) but sTLR2 was significantly lower in diabetic subjects (1.15G

matology and Musculoskeletal Sciences. University of Oxford., Oxford,

0.65 ng/ml vs 1.44G0.60 ng/ml, PZ0.019). Inflammatory status between groups

UK;⁵GREMPAL Research Group. IDIAP Jordi Gol Primary Care Research

was confirmed significantly different concerning hs-CRP (2.79G2.89 mg/l vs.

Institute. Autonomous University of Barcelona, Barcelona, Spain;⁶Internal

0.70G0.89 mg/l, PZ0.000) and IL6 (2.65G2.46 ng/ml vs 1.44G0.22 ng/ml,

Medicine Department. IMIM (Hospital del Mar Research Institute).

PZ0.005) with higher values in diabetic group, although correlations with TLR2

Autonomous University of Barcelona, Barcelona, Spain;⁷Cooperative

expression were not established (PO0.05).

Research Network on Aging and Fragility (Spanish acronym: RETICEF).

Conclusion

Carlos III Institute of Health, Madrid, Spain.

Type 2 diabetes-associated chronic inflammatory state is characterised by

elevated monocyte expression of TLR2 but decreased serum sTLR2 level. This

poses the question about presence of an impaired immunomodulation of TLRs’

Background

activation in diabetes.

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility

DOI: 10.1530/endoabs.49.GP82

fractures. Anti-diabetic oral agents and insulin may also impact on fracture risk.

There is however scarce data available on the effect of such therapies combined as

usually prescribed in real-life practice conditions.

Objectives

The objective of this study was to compare the risk of fracture among T2DM

patients who are users of different antidiabetic treatments.

Methods

A nested case-control study was conducted using incident T2DM patients

registered in computerised primary care records in the Sistema d’Informació per

Diabetes & complications 2

al Desenvolupament de la Investigació en Atenció Primària (SIDIAP) between

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2006-2012, with follow-up available until end/2013. Each case

(incident

fractures of the hip, spine, wrist, or proximal humerus in 2006-2013) was risk-

Vitamin D metabolites and IL1b RS16944 polymorphism in type 2

set matched with five controls of the same gender, calendar year of T2DM

diabetes patients: evidence for functional interaction

diagnosis and age at index date (G10 years). Study exposure included metformin

Nojan Nejatian, Marissa Penna-Martinez & Klaus Badenhoop

mono-therapy (reference category) and other antidiabetic medications (alone or in

Division of Endocrinology, Diabetes and Metabolism, University Hospital

combination as prescribed in actual practice) in the 180 days before the index

Frankfurt, Frankfurt am Main, Hessen, Germany.

date. Conditional logistic regression analysis was used to estimate odds ratios and

95% confidence interval adjusting for the following confounders: age, gender,

We investigated the SNP rs16944 in German type 2 diabetes (T2D) patients and

HbA1c level, body mass index, history of fracture, co-morbidities, and

healthy controls (HC) and correlated the findings with concentrations of VD

concomitant medication use.

metabolites.

Results

Methods

Data on 12,277 T2DM patients (2,049 cases and 10,2280 controls) was analysed.

504 T2D patients and 447 HC were genotyped by a Taqman assay. Additionally

Insulin use was associated with increased fracture risk (adj OR 1.63 [95%CI 1.30-

25(OH)D3 and 1,25(OH)2D3 plasma levels of 76 T2D patients and 267 HC were

2.04]), as was the combination of metformin C sulphonylureas (adj OR 1.29

measured by radioimmunoassay.

[1.07-1.56]). No significant association was found with other antidiabetic

Results

medications and/or combinations.

The AA genotype was significantly less frequent in T2D compared to HC whereas

Discussion

GG and AG genotypes were more frequent in T2D (AA: 48.5 vs 37.95%; AG

Insulin and sulphonylureas use appear to be associated with an increased fracture

40vs 49.7%; GG: 11.4 vs 12.4%; PZ0.003). Furthermore the allele A was less

risk when compared to metformin amongst recently diagnosed T2DM patients.

(68.6 vs 62.7% ORZ0.77; 95% CI: 0.64-0.93) and allele G was more frequent

Residual confounding cannot be ruled out, and more studies are needed to confirm

(31.4

37.3% ORZ1.3 95% CI: 1.07-1.57, PZ0.008) in T2D patients

these findings. Given their impact, risk of fracture should be taken into account in

compared to HC. Both T2D patients and HC with IL1b genotypes AA and AG did

the management of T2DM patients.

not differ for the VD metabolites. However T2D patients with the GG genotype

DOI: 10.1530/endoabs.49.GP84

showed significantly lower levels of 25(OH)D₃ (median 34.95 vs 13.7 ng/ml

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

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glucose, AUC-insulin, and etc.) were monitored; in addition, ex vivo glucose-

stimulated insulin secretion (GSIS) and glucagon secretion (GSGS) with isolated

islets were performed.

Results

Abstract withdrawn.

Insulin secretion in response to high glucose stimulation

(16.7 mM) was

significantly higher in islets isolated from the groups administered 50, 100,

150 mg/kg baicalin compared to HF control; glucagon secretion was significantly

suppressed by high glucose stimulation in islets from the same groups.

Conclusion

This study showed that baicalin had positive effects on glycemic control by

regulating secretion of insulin and glucagon, possibly through GABA_AR

mediation.

DOI: 10.1530/endoabs.49.GP87

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Increased incidence of diabetes mellitus 30 years after the radiation

impact in persons exposed to ionizing radiation during the Chernobyl

NPP accident

Oleksii Kaminskyi, Dmitrii Afanasyev, Olga Kopilova, Irina Chikalova,

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Irina Muravyova, Olena Tepla, Oleksii Pronin, Irina Kiselova,

Effect of insulin on neurotrophins’ levels in the muscular wall of mice

Natalia Dombrovska & Dimitrii Bazyka

intestine and colon

National Research Center for Radiation Medicine of NAMS of Ukraine,

Mohammad Alqudah, Ayman Mustafa, Mohammad Allouh,

Kiev, Ukraine.

Othman Alshboul & Ahmad AlDwairi

Jordan University of Science and Technology, Irbid, Jordan.

Several million people in Ukraine and other countries had been exposed to

ionizing radiation during the Chernobyl nuclear power plant accident (ChNPPA)

Background

on April 26, 1986. The ChNPPA clean-up personnel involved in emergency and

Neurotrophins are implicated in the physiology and pathophysiology of the

recovery works in the 30-kilometer exclusion zone of power plant in the nearest

mature gastrointestinal tract (GIT) such as motility and inflammatory bowel

days or months and/or for a long time had received the highest radiation doses due

disease. Moreover, GIT disturbances has been attributed to hyperinsuliemia.

to external gamma-exposure and from incorporated radioactive isotopes with high

Insulin-neurotrophins interactions in the (GIT) have not been investigated yet.

affinity to endocrine organs, including the thyroid, pancreas, and cerebral

Aim

endocrine structures. Consequently a dramatic elevation in non-cancer endocrine

To test the effect of Insulin on the expression of neurotrophins in the muscular

morbidity emerged due to thyroid disease, pre-diabetes, diabetes mellitus, and

wall of mice intestine and colon.

obesity. Despite pancreas was previously considered resistant to ionizing

Methods

radiation the recent research however suggests high sensitivity of endocrine

Total protein extracts from intestinal and colonic muscular wall treated for

cells, particularly pancreatic beta cells to radiation exposure. It just explains a

24 hours with insulin were subjected to ELISA assays specific for different

high prevalence of diabetes mellitus (up to 23%) in the ChNPPA survivors, whilst

neurotrophins and data were analyzed using suitable statistical test with graph

the respective value for population of Ukraine is much lower, i.e. from 3 to 7%

pad.

depending on data source. According to retrospective review of endocrine system

Results

data from the ChNPPA clean-up workers (nZ13,158) the prevalence of pre-

Insulin treatment resulted in significant reduction of neurotrophin-3

(NT-3)

diabetes and diabetes mellitus had increased dramatically 10 years upon the

protein levels in the muscular wall of both mice intestine and colon. Moreover,

accident and continues to increase 30 years later. Now it is in average w16% and

neurotrophin-4 (NT-4) levels were significantly reduced in response to insulin

w12% respectively. At that not only a radiation dose but also the duration of

treatment in muscular tissue from both intestine and clone as well. Interestingly

moderately intensive gamma-exposure, namely 0.082G0.01 Gy, is critical for the

the effect of insulin was more profound in the colon on NT-3 and NT-4.

onset of type 2 diabetes mellitus. Persons involved in recovery operations for

Conclusion

more than 4-6 months are of concern here. Survey results in the ChNPPA

These results indicate that changes in GIT structure and function seen in

emergency workers demonstrate an increased incidence of latent autoimmune

hyperinsulinemia might be due to the effect of insulin on neurotrophins

diabetes in adults (LADA).

expression levels. However, functional studies are needed to elucidate the exact

interactions between insulin and neurotrophins in the GIT.

DOI: 10.1530/endoabs.49.GP86

DOI: 10.1530/endoabs.49.GP88

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Baicalin lowers glucose intolerance by controlling pancreatic hormone

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in high fat-induced obese diabetic rats

Clinical assessment of trabecular bone microstructure in type 2 diabetes

Kahui Park, Jung Hye Kim, Sang Bae Lee, Ji Hong You, Yusik Kim,

mellitus with Trabecular Bone Score (TBS)

Ji sun Nam, Jong Suk Park & Chul Woo Ahn

María Dolores Avilés Pérez, Antonia García Martín, Cristina

Gangnam Severance Hospital, Seoul, Republic of Korea.

Novo Rodríguez, Rafael Nieto Serrano, Elena Torres Vela &

Manuel Mun˜ oz Torres

Hospital Campus de la Salud, Granada, Spain.

Objective

Bacalin was known as an allosteric modulator of the benzodiazepine sites of the

g-aminobutyric acid A receptor (GABA_AR), which produce anxiolytic effects in

Introduction

mice without myorelaxant or sedative effects. Baicalin occur flavonoid found in

Type 2 diabetes mellitus (T2DM) is a risk factor for osteoporotic fractures

naturally in the genus Scutellaria. It has been recently shown to exert metabolic

although bone mineral density is increased. As such, there is a need for improved

effects by attenuating hyperglycemia-induced mitochondrial damage in b-cells in

approaches to estimate fracture risk in such individuals. The Trabecular Bone

diabetic rats, high-fat diet- (HFD-) induced body weight gain, and lipid deposits

Score

(TBS) is a new technique to determine the trabecular bone micro-

in the liver and systemic inflammation in mice. This study investigated the effects

architecture.

of baicalin on islet functions and diabetic status in HFD-induced obese diabetic

Objective

mice.

Our aim was to evaluate evaluate the usefulness of TBS in T2DM patients.

Methods

C57BL/6 mice were grouped into normal control, HF control, HF sham, and 4

We compared TBS values in T2DM group (n: 31) and control group (n: 25) and

different baicalin dose-administered groups (25, 50, 100, and 150 mg/kg). HFD

we analized its relationship with bone mineral density (BMD), history of prior

containing 60% fat and water were fed ad libitum for 24 weeks. Designated doses

fractures and glycemic control. BMD was evaluated by conventional bone

of baicalin or

0.9% saline were administered intraperitoneally 5d/wk. Body

densitometry (DXA) and 3D (3D-DXA).TBS values were determined using TBS

weight (BW) and conventional glucose homeostasis parameters (FPG, FPI, AUC-

InSightw software.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

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T2DM patients had lower TBS than controls

(1.14G0,17

1.25G0,16,

Dipeptidyl peptidase-4 inhibitor therapy and risk of diabetic

PZ0.013). However, there were no differences in the densitometric or volumetric

retinopathy: a population based study

parameters measured by conventional DXA and 3D-DXA. In T2DM group, TBS

Nam Hoon Kim¹, Hye Suk Kim², Hye Jin Yoo¹, Ji A Seo¹, Nan Hee Kim¹,

at the lumbar spine showed degraded microarchitecture (TBS % 1.2) in 16

Kyung Mook Choi¹, Sei Hyun Baik¹, Juneyoung Lee¹, Jung Hyun Noh³ &

patients (51.6%); 13 patients (41.9%) had partially degraded structure (TBS O

Sin Gon Kim¹

1.20 & ! 1.35); and only 2 patients (6.5%) had normal TBS values (TBS R1.35).

¹Korea University College of Meidicine, Seoul, Republic of Korea;

TBS results differed between groups close to statistical significance (Default 1).

²Anyang SAM Hospital, Anyang, Republic of Korea;³Inje University

We did not find diferences in TBS values according densitometric diagnosis of

College of Medicien, Ilsan, Republic of Korea.

osteoporosis (Tscore % 2.5 S.D.) or history of prior fracture in either group. We

found a significant correlation of TBS with age, body mass index and lumbar

spine BMN both in diabetic patients and controls (P ! 0.05). Finally, we did not

Background

observe relationship with glycemic control or duration of diabetes in T2DM

Given the possible association between dipeptidyl peptidase-4 (DPP-4) inhibitor

group.

and risk of diabetic retinopathy (DR), we examined whether DPP-4 inhibitors are

Conclusion

beneficial or harmful for DR compared with other glucose-lowering agents.

TBS is shown as a promising method in the clinical assessment of trabecular bone

Methods

microstructure in T2DM.

From a Korean population-based cohort, we identified 67,743 adults with type 2

DOI: 10.1530/endoabs.49.GP89

diabetes treated with oral glucose-lowering agents between 2008 and 2013.

Matching (1:1) was done for comparative groups: ever-used (case) and never-

used (control) DPP-4 inhibitors (nZ14,522 each group). Cox regression analyses

assessed the risk of DR events: vitreous hemorrhage, vitrectomy or photo-

coagulation, intravitreal agent use, and blindness.

Results

During a median follow-up of 28$4

(14.0-45.2) months, there were 305 (control

group) and 342 (case group) composite DR events, respectively. Use of DPP-4

inhibitors was not associated with overall risk of composite DR events (adjusted

hazard ratio [HR] 1.08, 95% CI 0.93-1.26). Each DR events including vitreous

hemorrhage, vitrectomy or photocoagulation, use of intravitreal agents, and

blindness were also not increased with DPP-4 inhibitor therapy. The results were

consistent according to baseline retinopathy. However, in the analyses by

duration of treatment, a DPP-4 inhibitor treatment duration of !12 months was

associated with increased risk of composite DR events (adjusted HR 1.95, 95% CI

1.61-2.36).

Conclusion

DPP-4 inhibitor treatment did not increase the overall risk of DR compared with

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other oral glucose-lowering agents. Given that short-term DPP-4 inhibitor use

The G allele of the BDKRB1 rs12050217 polymorphism is associated

was associated with increased risk of DR, the need to assess the aggravation of

with protection for diabetic retinopathy

retinopathy in the early phase of DPP-4 inhibitor use is warranted.

Leticia A. Brondani^1,2, Julia Pisco¹, Jorge A. Guimarães^1,2, Daisy Crispim^1,2

DOI: 10.1530/endoabs.49.GP91

& Markus Berger¹

¹Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil;²Universidade

Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Background

Diabetic retinopathy (DR) is a chronic diabetic complication occurring in most

diabetic patients after

20 years of disease. Progression of DR to its sight

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threatening stages is usually associated with worsening of underlying retinal

vascular dysfunction and disease. The plasma kallikrein kinin system is activated

Non-genetic rat model of nephropathy in type 2 diabetes with

during vascular injury, mediating important functions in inflammation, blood

attenuated streptozotocin-induced tubular alteration

flow, and coagulation. Bradykinin B1 receptor (B1R) is expressed in human

Valentina Bayrasheva^1,2, Alina Babenko^1,2, Ivan Pchelin³, Anna Arefjeva²,

retina, and retinal B1R levels are increased in murine models of diabetes.

Svetlana Chefu^1,2, Ivan Shatalov⁴, Yurii Dmitriev¹, Alexandra Ivanova^3,5,

Furthermore, experimental studies reveal that B1R antagonists ameliorate retinal

Pavel Andoskin¹, Parvis Aliev² & Elena Grineva^1,2

functional abnormalities caused by diabetes in rodents. Thus, B1R gene

¹Federal Almazov North-West Medical Research Centre, Saint Petersburg,

(BDKRB1) is a candidate gene for DR.

Russia;²Pavlov First Saint Petersburg State Medical University, Saint

Objective

Petersburg, Russia;³Saint Petersburg State University, Saint Petersburg,

To investigate the association between rs12050217A/G polymorphism in the

Russia;⁴Saint Petersburg National Research University of Information,

BDKRB1 gene and DR in patients with type 2 diabetes mellitus (T2DM).

Technologies, Mechanics and Optics, Saint Petersburg, Russia;⁵Komarov

Methods

Botanical Institute of the Russian Academy of Sciences, Saint Petersburg,

We analyzed 1129 T2DM patients and 416 non-diabetic subjects. T2DM patients

Russia.

were categorized by the presence of non-proliferative DR (NPDR, nZ476),

proliferative DR (PDR, nZ275) and absence of DR (nZ200). The local ethic

Non-genetic animal models of diabetic nephropathy (DN) are most commonly

committee approved the study, and all subjects signed a consent form. The

reproduced by using streptozotocin (STZ) which preferentially gets into b-cells

BDKRB1 rs12050217A/G polymorphism was genotyped by Real-Time PCR

via GLUT2 transporters. However, STZ administration results in nephrotoxic

using TaqMan MGB probes.

effects as well, due to expression of GLUT2 by renal tubular epithelial cells. We

Results

hypothesized that nicotinamide

(NA), which is considered to attenuate the

The genotype frequencies of the BDKRB1 rs12050217A/G polymorphism are in

severity of STZ-induced b-cell damage, could also prevent tubular alteration.

Hardy-Weinberg equilibrium, and did not differ between T2DM patients and

Starting at 3 weeks after unilateral nephrectomy, thirty adult male Wistar rats

normoglycemic subjects (PO0.05). The presence of the minor G allele of the

were fed the high-fat diet for 5 weeks and then successively received either NA

rs12050217 polymorphism was less frequent mainly in patients with PDR when

(230 mg/kg) and STZ

(65 mg/kg, NA-STZ-group) or STZ in a low dose

compared to patients with NPDR and without DR (31.5, 41.8 and 41.2%,

(40 mg/kg, LD-STZ-group) intraperitoneally in

15-min interval. Control

PZ0.034; respectively). Interestingly, we observed that the presence of the G

nondiabetic uninephrectomized rats received vehicle and were fed normal

allele was associated with protection for PDR, which was confirmed after

chow (C-group). At weeks 10, 20, and 30 (the end of the study), metabolic

correction for the presence of hypertension, ethnicity, diabetes duration and age

parameters, creatinine clearance, albuminuria, and urinary tubular injury markers

((95% CI) Z0.580 (0.398-0.843); PZ0.004).

(NGAL, KIM-1) were evaluated as well as renal ultrastructural and light

Conclusions

microscopic changes at weeks

and

30. NA-STZ-group showed higher

The BDKRB1 rs12050217 G allele is associated with protection for the advanced

reproducibility and stability of metabolic parameters. By week 10, NA-STZ-

stage of DR in T2DM patients.

injected rats showed overweight (328.9G22.7 g (NA-STZ) vs 285.4G20.5 g

DOI: 10.1530/endoabs.49.GP90

(C)), mild hyperglycemia (HbA1c 5.39G0.24% vs 3.6G0.29%), significant

increase in insulin resistance

(HOMA-IR 3.2G0.39 vs 1.93G0.29),and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

dyslipidemia (total cholesterol 2.89G0.25 mmol/l vs 1.55G0.35; triglycerides

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1.05G0.18 mmol/l vs 0.57G0.1), P!0.05 each, that were observed until the end

The A allele of the -866G/A polymorphism in UCP2 gene decreases high

of the study. At 20 weeks, development of early stage of DN was confirmed by

glucose-induced UCP2 expression in HUVECs

glomerular basement membrane thickness, gradual decline in creatinine

Tais Assmann^1,2, Daisy Crispim^1,2, Michelle Rodrigues², Liana Silva²,

clearance, and mild albuminuric status

(478.4G63.3 m/24 h vs

35.8G

Ana Paula Bouças^1,2, Rodrigo Carlessi², Leticia Brondani^1,2, Luis

3.6 m/24 h), with progression by week 30, when light microscopic features of

Henrique Canani^1,2 & Bianca Souza^1,2

DN were observed. Morphofunctional renal changes in NA-STZ appeared to be

¹Postgraduate Program in Medical Sciences: Endocrinology, Universidade

more pronounced than those in LD-STZ despite lower levels of KIM-1 and

Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil;

NGAL (2535.8G303.9 ng/24 h (LD-STZ) at week 30) vs 1704.4G444.7 ng/24 h

²Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre,

in NA-STZ, PZ0.037. We have described a model of type 2 diabetes and DN

Rio Grande do Sul, Brazil.

with attenuated STZ-induced tubular alteration in rats that is characterized by

stable metabolic disorders and renal morphofunctional changes similar to

relatively early stages of human DN.

Uncoupling protein

(UCP2) is a mitochondrial protein located in the

DOI: 10.1530/endoabs.49.GP92

mitochondrial inner membrane, and it uncouples substrate oxidation from ATP

synthesis, thereby dissipating the membrane potential energy and consequently

decreasing reactive oxygen species (ROS) formation by mitochondrial respiratory

chain. ROS overproduction is related to diabetic retinopathy (DR), a chronic

complication of diabetes mellitus (DM). Recently, our group reported that the

-866A/55Val/Ins haplotype (-866G/A, Ala55Val and Ins/Del polymorphisms) of

the UCP2 was associated with risk for proliferative DR in both type 1 and type 2

diabetic patients. Additionally, this haplotype influenced UCP2 expression in

human retina samples. Indeed, some studies suggest that the

-866G/A

polymorphism directly affect UCP2 expression; however, its effect on endothelial

cells under different glucose concentrations is not well defined.

Objective

To investigate the effect of -866G/A polymorphism on UCP2 expression in an

endothelial cell line under different glucose concentrations.

Methods

HUVECs cells were transfected with pGL3 plasmids containing the promoter

Diabetes therapy & complications 1

region of UCP2 gene and the coding sequence of firefly luciferase, using LTX

GP93

Lipofectamine (Life Technologies). The test conditions were: 1) transfection with

microRNA expression profile in plasma from patients with diabetic

the wild-type allele-containing plasmid (pGL3-UCP2-G); and 2) transfection with

kidney disease

the mutated allele (pGL3-UCP2-A), under conditions of normoglycemia (4 mM)

or hyperglycemia (25 mM) after 24 h and 48 h. Plasmid pCMV encoding renin

Tais Silveira Assmann^1,2, Marcia Punales³, Balduino Tschiedel³, Luis

luciferase and pEGFP were co-transfected as internal control and transfection

Henrique Canani^1,2, Andrea Carla Bauer^1,2 & Daisy Crispim^1,2

control, respectively. Luciferase levels were measured with Luminescent Dual-

¹Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul,

luciferase Assay (Promega).

Brazil;²Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;

Results

³Instituto da Criança com Diabetes, Porto Alegre, Brazil.

HUVECs cells transfected for 24 h and 48 h with the plasmid containing the

-866A allele under normal glucose conditions had 47% and 37% decrease in

Introduction

UCP2 expression than cells transfected with the plasmid containing the G allele

Diabetic kidney disease (DKD) is the major cause of end-stage renal disease;

(PZ0.011 and PZ0.0001; nZ3). Interestingly, under high glucose conditions,

however, the pathogenesis of this disease is not fully understood. Currently

cells containing the A allele had a more drastic decrease in UCP2 expression

available therapies are not totally efficacious in the treatment and prognosis of

(70% and 54%) compared to cells with the G allele (PZ0.0001 and PZ0.028;

DKD, suggesting that further understanding of the molecular mechanisms

nZ3) after 24 and 48 h.

underlying the pathogenesis of this disease is necessary to improve its

Conclusion

management. Recently, research on microRNAs (miRNAs) has become a hotspot

Our preliminary results demonstrate that the UCP2 -866A allele decreases UCP2

because of their critical role in regulating posttranscriptional levels of protein-

expression in HUVEC cells, which is exacerbated under high glucose conditions.

coding genes. Several miRNAs were found to participate in DKD pathogenesis;

The -866G/A polymorphism of the UCP2 gene is associated with increased UCP2

nevertheless, results are still inconclusive. Therefore, the identification of

protein concentrations in human retina, which may explain the previous reported

miRNAs involved in DKD may help in the diagnosis and treatment of this

association between the -866A/55Val/Ins haplotype and risk for DR.

disease.

DOI: 10.1530/endoabs.49.GP94

Objective

To identify a miRNA expression profile associated with DKD in plasma from

patients with type 1 diabetes mellitus (T1DM) with different degrees of this

diabetic complication.

Design

Expressions of 48 miRNAs were investigated in the plasma from 46 T1DM

patients: 24 patients in group 1 [patients with T1DM for more than 10 years, with

GP95

urinary excretion of albumin (UEA) !30mg/g and estimated glomerular filtration

The relation between PON-1 activity and 25-OH hydroxyvitamin D3

rate (eGFR) R60 ml/min/1.73 m²)], 11 in group 2 (patients with T1DM with

levels and other biochemical parameters in diabetic patients with

UEA 30-300mg/g or eGFR 45-59 ml/min/1.73 m²) and 11 in group 3 (patients

respect to obesity and diabetic complications

with T1DM with UEAO 300 mg/g or eGFR 15-29 ml/min/1.73 m²), using Stem-

Pinar Karakaya¹, Meral Mert¹, Hamide Karagoz¹ & Bahar Ozdemir²

loop RT-PreAmp Real-time PCR and TaqMan Low Density Array cards (Thermo

¹Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul,

Scientific Inc).

Turkey;²Department of Internal Medicine, Bakirkoy Dr. Sadi Konuk

Results

Training and Research Hospital, Istanbul, Turkey.

Eighteen miRNAs were differently expressed between T1DM patients without

DKD (controls) and T1DM patients with different levels of DKD (cases).

Seventeen miRNAs were downregulated (miR-126, miR-146a, miR-155, miR-

Objective

192, miR-200a, miR-200b, miR-204, miR-216a, let-7b, miR-29c, miR-200a,

To evaluate the relation of mean platelet volume (MPV) levels with serum

miR-20b, miR-216a, miR-25, miR-320, miR-92a and miR-638) and one miRNA

paraoxonase-1 activity in diabetic patients with respect to obesity and diabetic

was upregulated (miR-124) in cases compared to controls. In addition, miRNAs

complications.

let-7b, miR-155, miR-200a, miR-20b, miR-216a, miR-25, miR-29c, miR-320 and

Methods

miR-92a were downregulated in T1DM patients with severe DKD (group 3)

A total of 201 diabetic patients grouped with respect to obesity obese (nZ89) and

compared to controls.

non-obese (nZ112) and diabetic complications with (nZ50) or without (nZ150)

Conclusion

microvascular complications and with

(nZ91) or without (nZ108) macro-

Our preliminary results show that some circulating miRNAs are differentially

vascular complications groups were included. Data on demographic and lifestyle

expressed between T1DM patients with and without DKD.

characteristics of patients, anthropometric measurements, diabetes related

DOI: 10.1530/endoabs.49.GP93

microvascular and macrovascular complications, Correlation of MPV values to

paraoxonase and arylesterase activities.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

GP97

Mean(SD) paraoxonase and arylesterase values were

119.8G37.5 U/l and

Comparison of current perception threshold measured by Neurometer

149.0G39.9 U/l, respectively in the overall population, with no significant

in patients with type 2 diabetes mellitus to a group of normal individuals

difference with respect to obesity and macrovascular diabetic complications,

Chin-Hsiao Tseng^1,2

whereas significantly lower values for paraoxonase 107.5G30.7 vs. 123.9G

¹National Taiwan University College of Medicine, Taipei, Taiwan;

38.8 U/l, (PZ0.007) and arylesterase 132.1G30.2 vs. 154.G41.2 U/l (PZ0.001)

²National Taiwan University Hospital, Taipei, Taiwan.

were noted in patients with than without diabetic microvascular complications.

Mean(SD) MPV values were 9.10G0.87 fL in the overall population, with no

significant difference with respect to obesity and diabetic complications. No

Purpose

significant correlation of MPV values to paraoxonase and arylesterase activities.

To determine the proportion of abnormal current perception threshold (CPT) in

A significant positive correlation was determined with plasma

25-(OH)

patients with type 2 diabetes mellitus.

hydroxyvitamin D3

levels

(rZ0.398, PZ0.001 and rZ0.484, respectively

Methods

PZ0.001). HOMA-IR exhibited a significant negative correlation with PON and

A total of

1360

patients with type

diabetes mellitus involved in an

arylesterase in the groups.

epidemiological study received an examination of CPT measured by Neurome-

Conclusion

terw CPT/C (Neurotron, Inc., Baltimore, Maryland, USA) on a supine position.

In conclusion, our findings revealed a significant decrease I PON-1 activity in

The measurement was taken for three frequencies, i.e., 5, 250 and 2000 Hz at

diabetic patients with microvascular rather than macrovascular complications,

three sites: the preauricular area (trigeminal nerve), the index finger (median

whereas regardless of obesity and diabetic complications, no increase in

nerve) and the great toe (superficial peroneal nerve) on both sides. The three

thrombogenic activity and no relation of thrombogenic activity with PON-1

frequencies measure small unmyelinated C fiber (5 Hz), small myelinated Ad

activity. PON-1 activity exhibited a significant negative correlation, independent

fiber

(250 Hz), and large myelinated Ab fiber (2000 Hz), respectively. The

of obesity, sex and age, with plasma glucose, HbA1c and HOMA-IR values in all

normative data from 75 normal individuals were used as control and an “abnormal

patients and a significant positive correlation with 25-OH vitamin D3 values. Low

CPT” was defined as a value greater than the normal mean plus 3 standard

PON-1 activity and 25 OH vitamin D3 levels may be a marker of inadequate

deviations derived from the normal individuals. Age, sex, body height and body

glycemic control independent of obesity in diabetic patients They may play an

weight were treated as potential confounders. Student’s t test, Chi-square test,

important role for early atherosclerosis who had only in obese diabetic especially

correlation coefficient and stepwise regression were used for statistical analyses

microvascular diabetic complications well glysemic control of the most factor

and a P value !0.05 was considered as statistically significant.

that it prevents diabetic complications and also well glysemic control and

Results

apropiate vitamin D levels have good affect on diabetic complications.

Accept for a significantly older age in the diabetes group, the distribution of sex, body

DOI: 10.1530/endoabs.49.GP95

height and body weight were not different significantly. CPT measurements on the

right and left sides correlated significantly with correlation coefficients mostly O0.7

(P!0.0001) in the diabetes patients. The trigeminal nerve had the most commonly

reported “abnormal CPT” that involved approximately 60% of the diabetes patients,

followed by the superficial peroneal nerve (50%) and the median nerve. The median

nerve showed frequency-dependent abnormality with higher proportion of “abnormal

CPT” involving lower frequency. For the frequency of 2000, 250 and 5 Hz,

“abnormal CPT” was observed in 15-20, 30-33 and 56-59%, respectively. In

stepwise regression analyses, diabetes and age were consistently predictive for CPT.

Conclusions

GP96

Patient with type 2 diabetes mellitus have higher CPT values than normal individuals

in all anatomical sites. The application of Neurometerw for screening of diabetes

High prevalence of lower extremity peripheral artery disease in type 2

neuropathy awaits further confirmation.

diabetes patients with diabetic nephropathy and the role of netrin-1

levels

DOI: 10.1530/endoabs.49.GP97

Ahmet Kor, Suleyman Baldane, Suleyman Hilmi Ipekci,

Kamile Marakoglu, Ali Altinok, Ali Unlu, Fatih Colkesen, Bahadir Ozturk,

Cem Onur Kirac & Levent Kebapcilar

Selcuk University, konya, Turkey.

Background

Netrin-1 is an early biomarker of acute kidney injury. Besides, recent studies have

GP98

showed that netrin-1 promotes angiogenesis; but its usefulness for peripheral

Gestacional diabetes mellitus: the new screening criteria and its

artery disease (PAD) in type 2 diabetes patients is unknown.This study aimed at

outcomes

investigating whether netrin-1 levelsare increased in peripheral artery disease

Pedro Gouveia, Maritza Sá, Eduarda Resende, Margarida Ferreira &

among patients with type 2 diabetes and also investigating possible associa-

Silvestre Abreu

tionsbetween diabetic nephropathy (DN) and PAD.

Centro Hospitalar do Funchal, Funchal, Portugal.

Material and Methods

This was a cross-sectional observational clinical study. This study involved a total

of 84 adults with type 2 DM, who underwent ABI (low ankle-brachial index)

Background

measurement in an outpatient clinic. PAD was defined as ABI !0.9 in either leg.

Gestational Diabetes Mellitus (GDM) is one of the most common illness of

ABI of 42 patients with PAD were compared with 42non-PADpatients. Diabetic

pregnancy. Despite its frequency, there’s no worldwide accepted screening

nephropathy was evaluated by estimated glomerular filtration rate and urinary

criteria for GDM. In 2011, Carpenter and Coustan (CC) screening (50-g glucose

albumin-creatinine ratio (ACR).

challenge test (GCT) followed by 100-g glucose tolerance test (OGTT) if GCT

Results

screen was positive) was abandoned and began the implementation of the

Compared with control group, the levels of Netrin-1

levels and diabetic

screening of the International Association of Diabetes and Pregnancy Study

nephropathy subjects were significantly increased in the PAD group. As regards

Group (IADPSG) 2010 (75-g OGTT).

similar GFR values, patients with higher urinary albumin-creatinine ratio (ACR)

Aims

values had significantly lower ABI parameters than the patients without

Asses and compare perinatal outcomes of these two screening criteria.

albuminuria.(Right:

0.96G0.1 vs 1.05G0.01, Left:

0.94G0.1 1.04G0.01vs

Materials and methods

P!0.01).Binary logisticregression analysis revealed that diabetic nephropathy

We undertook a retrospective study, of gestacional diabetes followed on

(vs non-DN) was associated with PAD (OR Z2.94, 95%CI: 1.2-7.1; PZ0.017)

Endocrinology department. Two groups were constituted: CC

(followed in

.In multivariate models, adjusted additionally for the mean duration of diabetes,

2009 and 2010) and IADPSG (followed in 2014 and 2015). All patients were

gender, BMI, HbA1c, hyperlipidemia and hypertension, theassociations with

treated with nutrition and exercise. When target glucose levels were not met,

netrin-1and PAD persisted (beta: 0.238, PZ0.042).

insulin was initiated, no oral antidiabetic agents were used. Analysed data

Conclusion

included birthweight, premature delivery, macrosomia, mode of delivery,

Our study in patients with type 2 DM demonstrated that PAD was associated with

maternal parity, body mass index (BMI) and insulin treatment.

diabetic nephropathy and netrin-1 levels. In conclusion, changes in netrin-1 levels

Results

are likely to be used as a biomarker for monitoring the risk of PAD in patients

In 2009 and 2010, of 4705 childbirths in the hospital, 259 (5.5%) women met the

with Type 2 diabetes.

CC criteria, of which 134 were included in this study. In 2014 and 2015, of 3496

DOI: 10.1530/endoabs.49.GP96

childbirths in the hospital, 348 (9.9%) women met the IADPSG criteria, of which

221 were included in this study. Those with GDM per IADPSG criteria had more

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

insulin treatment (46.6 vs 23.1%; P!0.0001), fewer large for gestacional age

Results

fetus

(3.6

9.0%, PZ0.038) and less premature delivery

(1.4

5.2%,

Fifteen articles fulfilled the inclusion criteria and passed the quality control

PZ0.033).

evaluation. In most studies, hearing loss (HL) was defined as pure tone greater

Conclusions

than 25 dB in the worse ear of at least one frequency. The incidence of HL ranged

Although the application of the IADPSG criteria increased the number of women

between 0 and 48% for diabetics, which was higher than in controls (ORZ12.43

diagnosed with GDM, there was an increase in insulin treatment, and an overall

95% CI 3.09-49.95). The tendency of mean PTA (pure tone audiometry)

better newborn outcomes. This could mean that the IADPSG criteria identified a

thresholds were greater in diabetics than in controls for higher frequencies,

group of women with a increased risk of perinatal outcomes that were not

however the results were not significant. Auditory brainstem response (ABR)

recognized by the CC screening.

latencies were longer in diabetic patients compared to controls. Statistical

DOI: 10.1530/endoabs.49.GP98

significance was obtained in wave III and V (ZZ3.18, PZ0.001 I²Z82%;

Z89% respectively).

ZZ2.55, PZ0.01, I²

Conclusions

Patients with type

1 diabetes have a significantly greater incidence of HL

compared to the control group. However, hearing thresholds seems to be not

significantly different from control subjects. Mean PTA thresholds were greater at

6000 and 8000 Hz. Despite a trend of higher threshold difference at higher

GP99

frequencies tested, the mean differences between groups at any frequency were

Higher levels of adiponectin might contribute to lower bone mass

not statistically significant. A significant prolonged ABR of waves III and V

observed in patients with type 1 diabetes, through alterations in

latencies in the diabetic group suggest a retro-cochlear involvement in hearing

osteocalcin energy circuit signaling of bone cells.

damage in type 1 diabetes.

Charalampos Tsentidis¹, Dimitrios Gourgiotis², Lydia Kossiva¹,

DOI: 10.1530/endoabs.49.GP100

Artemis Doulgeraki³, Antonios Marmarinos² & Kyriaki Karavanaki¹

¹Diabetes Clinic, Second Pediatric Department, University of Athens, “P&A

Kyriakou” Children’s Hospital, Athens, Greece;²Biochemistry Laboratory,

Second Pediatric Department, University of Athens, “P&A Kyriakou”

Children’s Hospital, Athens, Greece;³Department of Bone and Mineral

Metabolism, Institute of Child Health, “Aghia Sophia” Children’s Hospital,

Athens, Greece.

GP101

Introduction

Abstract withdrawn.

Recent advances in energy homeostasis revealed a significant interconnection

between bone and adipose tissue through osteocalcin. Reduced bone mass

documented in type 1 diabetes mellitus (T1D) could be related to disregulation of

adipokine signaling on bone.

Materials and Methods

We evaluated 40 children and adolescents with T1D (meanGS.D. age 13.04G

3.53 years, meanGS.D. T1D duration 5.15G3.33years) and 40 healthy age- and

gender-matched controls (meanGS.D. age 12.99G3.3years). Adiponectin, leptin

and bone metabolism markers were measured, while lumbar spine (LS) and total

body (TB) Bone Mineral Density (BMD) were evaluated with dual energy X-ray

absorptiometry (DXA).

GP102

Results

Comparison of the effects of combinations of different antihypertensive

Lower BMD values have already been documented in patients, as well as lower

therapies on microalbuminuria and renal functions in type 2 diabetic

osteocalcin (log(osteocalcin) 3.44G0.5 vs 3.6G0.51). Patients had higher levels

patients

of adiponectin (18078G8645 vs 13536G6703 ng/ml, PZ0.007) while leptin

Muge Erek¹, Alparslan Ersoy¹ & Canan Ersoy²

levels were comparable between groups

(8.85G8.73 vs 10.03G8.75 pg/ml,

¹Uludag University Medical Faculty, Department of Nephrology, Bursa,

PZ0.13). Both adipokines were associated with Body Mass Index (BMI) in both

Turkey;²Uludag University Medical Faculty, Department of Endocrinology

groups. Adiponectin was positively associated with osteocalcin only in controls

and Metabolism, Bursa, Turkey.

(RhoZ0.31, PZ0.05) possibly indicating altered energy signaling in bone of

T1DM patients, whereas in patients it was negatively associated with IGF1

(RhoZK0.30, PZ0.05) and positively associated with HbA1c (RhoZ0.38,

Renin angiotensin system blockers are currently used in the treatment of diabetic

PZ0.01) and i-phosphorus (RhoZ0.39, PZ0.01). No associations of leptin with

nephropathy. Carvedilol, 3. generation beta-blockers, may provide additional

bone markers were observed.

benefits in diabetic patients. Its antiproteinuric activity is not investigated in

Conclusion

patients with diabetic nephropathy. We aimed to compare short-term additive

Increased adiponectin might contribute to lower bone mass observed in young

effects of losartan with cilazapril or carvedilol combination on blood pressure,

T1D patients with altered interconnection of energy signaling in bone cells,

proteinuria and renal functions in microalbuminuric patients with type 2 diabetes

through osteocalcin circuit.

mellitus and hypertension.

Methods

DOI: 10.1530/endoabs.49.GP99

Thirty patients with type 2 diabetes, stage 1 hypertension and albuminuria of 30-

300 mg/day, were enrolled in the study. After the 2 week follow-up period, all

patients were started on losartan

50 mg/day for 6 weeks. Then, they were

randomized to three groups for 6 weeks: 1st group (n:10) on losartan 100 mg/day,

2nd group (n:10) on carvedilol 25 mg/day C losartan 50 mg/day and 3rd group

(n:10) on cilazapril 5 mg/day C losartan 50 mg/day treatment.

GP100

Results

Type 1 diabetes and hearing loss: a meta-analysis

Characteristics of groups were similar. In all groups, systolic and diastolic

Mario Mujica-Mota & Neel Patel

blood pressures (BP) were significantly decreased. Greatest decrease in systolic

Montreal, Québec, Canada.

(16.5G7.4 mmHg) and diastolic (10.5G2.8 mmHg) BPs were seen in group 3

and smallest decreases were seen in group 1 (systolic BP: 9G6.1 mmHg, diastolic

BP: 3G4.8 mmHg). Microalbuminuria levels in all groups decreased signi-

Objective

ficantly when compared to the period of 50 mg losartan alone (P!0.05). Renal

Evidence shows type 1 diabetes leads to vascular damage and neuropathy. The

functions of the groups did not change significantly. But creatinine clearances

purpose of this study was to perform a systematic review and a meta-analysis to

significantly increased in all groups after the randomization, although there was

asses the evidence of the effects of type 1 diabetes on hearing function.

no significant difference between groups.

Methods

Conclusion

Three different electronic databases were used to identify eligible studies

We observed that the combination of carvedilol in hypertensive type 2 diabetics

including a manual searching of references. The articles obtained were

patients with microalbuminuria safely controlled blood pressure more effectively

independently reviewed by two authors using predefined inclusion criteria to

without additional benefit in reducing microalbuminuria

identify eligible studies. Meta-analysis was performed on pooled data of hearing

DOI: 10.1530/endoabs.49.GP102

loss incidence, PTA thresholds and ABR wave latencies.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Diabetes therapy & complications 2

Excess consumption of saturated fatty acids may lead to an increased production

of ceramides that contribute to development of insulin resistance and type 2

GP103

diabetes. Substantial research demonstrated that inhibition of ceramide

biosynthesis ameliorates atherosclerosis, hepatic steatosis, insulin resistance

and obesity. However, as ceramides and their sphingolipid products are involved

Abstract withdrawn.

in multiple fundamental cellular processes, concerns exist about possible risks or

adverse effects resulting from overall inhibition of sphingolipid synthesis for

treatment of chronic diseases. Therefore, the inhibition of specific ceramide

species represents a new strategy for pharmaceutical intervention. Recent

research demonstrated that specifically CerS6 mediated C16 ceramide synthesis

plays a key role in the development of obesity mediated insulin resistance.

In the current study, we investigated the effects of specifically knocking-down

CerS6 in ob/ob mice using CerS6 anti-sense oligonucleotides (ASO). In this

animal model, CerS6 expression is significantly higher vs. lean control mice (w2

fold in the liver and BAT) which correlates with a 4-fold increase of C16

GP104

ceramide in the plasma and a 2-fold increase in the liver. CerS6 ASO treatment

led to selective and significant w80% knockdown of the CerS6 expression in the

Non-stimulated c-peptide is independently associated with requirement

liver and correlated with a significant 50% reduction of C16 ceramide in the liver

at 1 year for insulin therapy in patients with diabetes: a retrospective

and plasma compared to control ASO-treated ob/ob mice. CerS6 knockdown

cohort study of 872 patients

protected against body weight gain and was associated with a significant

Emma Leighton¹, Karen Smith², Christopher Sainsbury¹ & Gregory Jones

reduction in fat mass and blood glucose levels. Moreover, insulin resistance was

¹Gartnavel General Hospital, Glasgow, UK;²Glasgow Royal Infirmary,

significantly improved by ASO treatment as evidenced by oral glucose tolerance

Glasgow, UK.

and insulin tolerance tests (w50% reduction in AUC during oGTT).

In conclusion, CerS6 dependent C16 ceramide synthesis represents a distinct

Introduction

sphingolipid species, which contributes to the development of obesity and insulin

C-peptide is frequently used in clinical practice to estimate insulin secretion, and

resistance and therefore may represent a unique and attractive novel target to treat

guide need for future insulin treatment. Present practice is based on studies with

obesity and type 2 diabetes.

small patient numbers.

DOI: 10.1530/endoabs.49.GP105

Aim

To explore the association between non-stimulated c-peptide and progression to

insulin therapy in patients with diabetes.

Patients and Methods

1971 patients with c-peptide measurements were identified (February 2007-

December 2016) within a single health board. 940 individuals also appeared on

national diabetes database. 872 individuals within this dataset have a defined

diabetes diagnosis and were analysed. The date of first encashed insulin

prescription for each individual was extracted from the national diabetes dataset.

Insulin-free survival (time to first insulin prescription or end of follow-up) in

individuals who were insulin-naive at the time of c-peptide measurement was

GP106

investigated using survival analysis. Individuals with c-peptide values below

Outcomes of integrating personal continuous glucose monitors with

median were compared with those above median value. Time to insulin

insulin pumps in a University Diabetes Unit

prescription was analysed using cox proportional hazard model with age and

Ali Rizvi & Kyoka Smith

BMI as covariables. The positive predictive value

(PPV) of c-peptide for

University of South Carolina School of Medicine, Columbia, SC, USA.

predicting insulin use at 1 year was calculated in 0.2 nmol/l increments.

Results

Objective

458 individuals had BMI data available, and were insulin-naive at the time of

Personal continuous glucose monitoring (pCGM) with interstitial fluid glucose

c-peptide measurement. In this cohort a c-peptide in the lower half of the range of

sensing is rapidly becoming the standard of care for real-time, intensive insulin

observed values (!0.76 nmol/l) is associated with a significantly decreased

therapy of diabetes. We report our experience of glycemic control in patients in an

insulin-free survival time (P!0.001, HR 3.0). PPV for initial c-peptide(nmol/l)

academic setting using minimally invasive pCGM with continuous s.c. insulin

increments were: c-peptide 0.01-0.2 PPVZ0.95, 0.2-0.4 PPVZ0.67, 0.4-0.6

infusion (CSII, or insulin pump) vs CSII alone.

PPVZ0.6, 0.6-0.8 PPVZ0.43, 0.8-1.0 PPVZ0.3.

Methods

Conclusion

Over a two-year period, we reviewed all patients treated with insulin pumps at the

Unstimulated c-peptide is independently associated with increased probability of

Diabetes Unit of the Palmetto Health-University of South Carolina Medical

requiring insulin at 1 year. This is a simple test which offers potentially useful

Group. Group A (CSII alone) used only meters to self-monitor blood glucose, and

information allowing patients to plan for future treatment.

while Group B additionally used pCGM integrated with CSII to adjust pump

DOI: 10.1530/endoabs.49.GP104

settings, including basal rate and/or short-acting bolus insulin doses, and change

insulin-to-carbohydrate ratio and supplemental factor. The data was analyzed

with respect to age, gender, glucose control as assessed by glycosylated

hemoglobin (HbA1c), and severe hypoglycemia.

Results

There were 54 patients in group A and 59 in group B. They were comparable in

mean age and gender breakdown (47.3 vs 45.2 years, and 66.8% vs 62.7%

females, respectively). The average glycosylated hemoglobin (HbA1c) changed

from 8.8% to 8.2% and from 8.2% to 7.3% from baseline to the end of one year in

the two groups respectively. The number of severe hypoglycemic episodes per

patient during the one year was 0.2 and 0.07 respectively.

Discussion

CSII patients who used pCGM were similar in demographics to those who used

GP105

insulin pumps alone, but had a lower baseline A1c, exhibited a larger decrease in

Ceramide synthase 6 inhibition as a novel therapeutic approach for

A1c at one year (0.9% vs 0.6%), and had fewer severe hypoglycemic events.

obesity and type 2 diabetes

Conclusions

Maximilian Bielohuby¹, Surya Prakash¹, Bodo Brunner¹, Anja Pfenninger¹,

The better outcomes with pCGM-integrated pump therapy may be explained by a

Ulrich Werner¹, Sarah Turpin-Nolan², Jens Bruning² & Norbert Tennagels¹

higher motivation ability for self-monitoring and care, and by the pCGM being a

¹Sanofi-Aventis Deutschland GmbH, R&D Diabetes Division, Industriepark

valuable informational tool in assessing glucose trends when used in properly

Hochst, Frankfurt am Main, Germany;²Max Planck Institute for Metabolic

chosen insulin pump patients who are managed by qualified experts.

Research, Cologne, Germany.

DOI: 10.1530/endoabs.49.GP106

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP107

and treated with liraglutide as add-on to metformin, 0.6 mg/day for two weeks,

followed by a dose of 1.2 mg/day. At baseline and every 6 months fasting samples

Specific Oct1 gene variants are associated with changes in the risk of

were taken for laboratory analyses and carotid-intima media thickness (cIMT)

cardiovascular death in metformin users

was assessed by B-mode ultrasound. Statistical analysis was performed by

Natascha Schweighofer^1,7, Bernd Genser^2,3, Winfried März^4,5, Marcus

ANOVA and the Spearman correlation method.

E Kleber⁶, Thomas R Pieber^1,7 & Barbara Obermayer-Pietsch^1,7

Results

¹Division of Endocrinology and Diabetology, Department of Internal

After18 months of liraglutide therapy HbA1creduced significantly in both groups

Medicine, Medical University Graz, Graz, Austria;²BG Statistical

(from

9.02G1.06

6.93G1.25

and from

8.50G0.71

6.74G0.90%,

Consulting, Vienna, Austria;³Institute of Public Health, Social and

respectively) as well as fasting glycemia

(from

9.57G3.33

7.16G

Preventive Medicine, Medical Faculty of Mannheim, University of

2.83 mmol/l; and from 9.14G3.71 to 7.28G2.29 mmol/l, P!0.0001 for all.

Heidelberg, Mannheim, Germany;⁴Clinical Institute of Medical and

Anthropometric parameters changed although not significantly. Lipids, with the

Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria;

exception of HDL-cholesterol, reduced significantly only in pre-elderly subjects

⁵Synlab Center of Laboratory Diagnostics, Heidelberg, Germany;⁶Vth

(triglycerides from 1.94G1.48 to 1.57G0.80 mmol/l, PZ0.0458; total choles-

Department of Medicine (Nephrology, Hypertensiology, Endocrinology,

terol from 4.90G1.57 to 4.27G1.04 mmol/l, PZ0.0025; LDL-cholesterol from

Diabetology, Rheumatology), Medical Faculty Mannheim, Heidelberg

2.92G1.44 to 2.34G0.91 mmol/l, PZ0.0054. cIMT significantly decreased in

University and Competence Cluster of Nutrition and Cardiovascul,

both groups (from 0.96G0.18 to 0.78G0.20 mm; and from 0.98G0.17 to 0.79G

Heidelberg/Halle-Jena-Leipzig, Germany;⁷CBmed GmbH, Center for

0.20 mm, respectively; P!0.0001 for both). Changes in cIMT were positively

Biomarker Research in Medicine, Graz, Austria.

associated only with changes in triglycerides in both pre-elderly

(rZ0.245,

PZ0.0398) and elderly (rZ0.566, P!0.0001) groups.

Aim

Conclusion

Increased cardiovascular incidents and a high risk for microvascular compli-

Liraglutide significantly reduced cIMT in both pre-elderly and elderly subjects

cations are associated with type 2 diabetes. Worldwide, metformin is the most

with T2DM, beyond glycemic control.

commonly prescribed antidiabetic drug. Polymorphisms in the Oct1 gene can

DOI: 10.1530/endoabs.49.GP108

alter the function or activity of organic cation transporter 1 (Oct1), thus changing

metformin efficacy (Oct1 acting as its main transporter) as well as influencing the

actions of Oct1 physiological substrates. In the past, polymorphisms in Oct1 were

associated with cardiovascular risk factors, thus they might contribute to

cardiovascular risk development.

We investigated, whether the Oct1 polymorphism rs3777392 is associated with

increased risk for cardiovascular death in a cohort of patients with and without

type 2 diabetes (T2DM) on various therapies.

Methods

Data from the LURIC study (nZ3316), a prospective cohort study of Caucasians

scheduled for coronary angiography were analysed. We identified 1820 non-

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diabetics,

1220 T2DM patients, including

73 metformin users

(Met),

154

Treatment of diabetic ketoacidosis at type 1 diabetes mellitus

sulfonylurea users

(SF) and

967

T2DM individuals without medication.

presentation: 13 year experience from a tertiary centre (2004-2016)

Cardiovascular mortality was assessed in all groups according to Oct1

Joana Serra-Caetano¹, Lia Gata¹, Alexandra Dinis¹, Rita Cardoso¹,

rs3777392 genotypes using Cox proportional hazard models and associations

Isabel Dinis¹, Miguel Patrício² & Alice Mirante¹

with cardiovascular biomarkers were investigated.

¹Pediatric Hospital, Coimbra Universitary Hospital Centre (CHUC),

Results

Coimbra, Portugal;²Laboratory of Biostatistics and Medical Informatics

Cardiovascular mortality risk for each minor allele copy was HR 2.08 (95% CI:

and IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

1.01, 4.28) only in metformin users. Variants of rs3777392 were associated with

BMI, baseline insulin values and triglyceride levels in all T2DM patients

(PZ0.016, PZ0.048 and PZ0.007, respectively), patients without medication

Introduction

(PZ0.006, PZ0.041, PZ0.008, respectively) and non-diabetics (PZ0.021,

Diabetic ketoacidosis (DKA) is an endocrine emergency and the leading cause of

PZ0.074, PZ0.125, respectively) but not in the Met and SF groups.

morbi-mortality in children with type 1 diabetes mellitus (1DM). DKA treatment

Conclusion

is still controverse, mainly regarding hydroelectrolytic replacement and insulin

In our study, the minor allele of rs3777392 in the Oct1 gene was associated with

dose.

an increased cardiovascular mortality risk in T2DM patients on metformin

Aims

therapy, which might be due to loss of association with cardiovascular

To evaluate efectiveness and safety of our tertiary centre protocol in DKA

parameters. Besides very positive effects in the majority of metformin users,

treatment, which included initial volume expansion with isotonic saline in the first

some individuals may profit from a pre-treatment genotyping and careful

two hours followed by 0.45% sodium chloride with 5% glucose and insulin

monitoring.

infusion (0.1 U/kg per h). Potassium replacement with potassium phosphate in the

first 12 h.

DOI: 10.1530/endoabs.49.GP107

Methods

Retrospective study of all children with moderate and severe DKA

1DM

presented from 2004 to 2016. Data collected: insulin infusion dose, glycemia, pH.

Osmolarity, corrected sodium, potassium and phosphate along the first 12 h of

treatment. Statistic analysis with SPSS21 (P!0,05).

Results

179 new cases of 1DM were admitted and 45 (25%) had DKA at presentation (15

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severe, 12 moderate and 18 mild DKA). Within moderate and severe DKA

Liraglutide improves carotid intima-media thickness in pre-elderly and

(NZ27), 18(67%) were female and mean age at diagnosis was 8.5G3.8 years.

elderly patients with type-2 diabetes: an 18-month prospective, real life

Means at admission were:

528G138 mg/dl glycemia,

310G12 mosm/kg

study

osmolarity, 146G5 mmol/l corrected sodium, 4.5G0.73 mmol/l potassium and

Ali Rizvi¹, Angelo Maria Patti², Giuseppa Castellino², Carlo Mannina²,

1.5G0.5 mmol/l phosphate. Mean insulin infusion dose at treatment start was

Dragana Nikolic², Rosaria Vincenza Giglio², Roberta Chianetta²,

0.08G0.03 U/kg per h. Along the first 12 h mean replacement doses were 4.3G

Giuseppe Montalto² & Manfredi Rizzo^1,2

1.3 gr/U per h of glucose, 0.13G0.04 mmol/kg per h of potassium, 0.33G

¹University of South Carolina School of Medicine, Columbia, SC, USA;

0.1 mmol/kg per h of sodium and 0.06G0.02 mmol/kg per h of phosphate. There

²University of Palermo, Palermo, Sicily, Italy.

were 12(45%) cases of hypokalemia and 10(37%) of hypophosphatemia. There

was no hypocalcemia nor cerebral edema. There was statistical significance in

Introduction

variation regarding glucose, pH, corrected sodium and osmolarity along the 12 h

Liraglutide exerts cardio-protective effects beyond of those on glucose

(P!0.0001). Sodium decreased in the first 8 h. Potassium decreased along the

metabolism, affecting several cardio-metabolic parameters, such as subclinical

first 4 h and rose from 8 h forwards.

atherosclerosis. However, it is not known if those effects differ in the long-term

Conclusions

between pre-elderly and elderly subjects with type-2 diabetes (T2DM).

Our protocol allowed a safe treatment of DKA at 1DM presentation, with gradual

Methods

correction of dehydration and acidosis. However, sodium and potassium

We included 135 subjects with T2DM divided in 2 groups: i) 71 pre-elderly

replacement should be adjusted, leading to our actual protocol.

subjects (46 men and 25 women, 55G7 years), and ii) 64 elderly subjects (33 men

DOI: 10.1530/endoabs.49.GP109

and 31 women, 70G5 years). All subjects were naïve to incretin-based therapies

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

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Conclusion

In our study, six- month therapy with Liraglutide improves, not only risk factors

The method of reporting hypoglycemia in Randomized Control Trials

for cardiovascular disease, but also hepatic steatosis as shown by a decrease in

(RCTs): a systematic review on RCTs conducted for SGLT-2 inhibitors

HSI index and ALT.

Noor Kassir¹, Sarah Medeiros² & Pendar Farahani³

¹National University of Ireland, Galway, Ireland;²University of Western

DOI: 10.1530/endoabs.49.GP111

Ontario, London, Ontario, Canada;³McMaster University, Hamilton,

Ontario, Canada.

Background

Hypoglycemia is an important side effect in pharmacotherapy of patients with

GP112

diabetes mellitus. Medical organizations have tried to define hypoglycemia in

Exenatide treatment causes suppression of serum fasting ghrelin levels

clinical practice and RCTs with scientific statements and guidelines.

in patients with type 2 diabetes Mellitus

Objective

Metin Guclu¹, Sinem Kiyici¹, Zulfiye Gul² & Sinan Cavun²

To explore the method of reporting hypoglycemia conducted on SGLT-2 inhibitor

¹Department of Endocrinology and Metabolism, Health Sciences

RCTs.

University, Bursa Yuksek Ihtisas Education and Training Hospital, Bursa,

Methods

Turkey;²Uludag University Medical Faculty, Department of Pharmacology,

A systematic review using PubMed to find data on RCTs conducted for SGLT-2

Bursa, Turkey.

inhibitors, limited to English language.

Results

Aim

Of 155 RCTs, 95(61.3)

(n(%)) were found to have defined and reported

Ghrelin plays an important role in the stimulation of food intake and long-term

hypoglycemia. The results showed that 8(5.2) RCTs were reported as event/arm,

regulation of body weight. In present study we investigate the long term effect of

15(9.7) as event/combined all arms, 69(44.5) as event/patient/arm and 3(1.9)

exenatide treatment on serum fasting ghrelin levels in patients with type 2

RCTs reported as both event/arm and event/combined all arms. Additionally,

diabetes mellitus.

3(1.9) RCTs defined hypoglycemia but did not report it. Hypoglycemia was

Methods

neither defined nor reported in 57(36.8) of the RCTs. In addition, 41(26.5) RCTs

Type 2 diabetic patients who were using metformin with and without the other

had hypoglycemic episodes that were confirmed, by glucose threshold, whereas

oral antihiperglycemic drugs on a stable dose for at least 3 months were enrolled

only 24(15.5) RCTs had episodes that were reported as symptoms from patients.

in the study. Body mass index (BMI) O 35 kg/m² and hemoglobin A1c (HbA1c)

Hypoglycemic episodes were reported and confirmed in 5(3.2) of the RCTs and

O 7.0% were the additional inclusion criteria. Oral antihyperglycemic drugs

27(17.4) showed that the episodes were reported or confirmed.

other than metformin were stopped and metformin treatment was continued at

Conclusion

2000 mg per day. Exenatide treatment was initiated at 5 mcg per dose sc twice

This study illustrates that around 40% of RCTs on SGLT-2 inhibitors did not

daily and after one month the dose of exenatide was increased to 10 mcg twice

define and report hypoglycemia. The method of reporting hypoglycemia was

daily. Changes in anthropometric variables, glycemic control, lipid parameters,

variable among the RCTs. Almost half the RCTs reported as event/patient/ arm.

and total ghrelin levels were evaluated at baseline and following 12 weeks of

Additionally, a quarter of RCTs only reported hypoglycemic episodes with

treatment.

confirmation of glucose threshold. Future RCTs should unify the reporting of

Results

hypoglycemia for safety assessment of diabetic medication.

Thirty-eight patients (male/femaleZ7/31) with type 2 diabetes mellitus entered to

DOI: 10.1530/endoabs.49.GP110

the study. Mean age of patients was 50.5G8.8 years with mean diabetes duration

of 8.5G4.9 years. Mean BMI was 41.6G6.3 kg/m² and mean HbA1c of patients

was 8.9G1.4%. Percentage change in weight of patients was K5.2G3.7%

following 12 weeks of treatment. BMI and HbA1c levels of patients were

decreased significantly (P!0.001 and P!0.001; respectively) while there was no

GP111

change in lipid parameters. Serum fasting ghrelin levels were suppressed

Hepatic effects of GLP-1 receptor agonist Liraglutide in patients with

significantly after 12 weeks of exenatide treatment compared with baseline values

type 2 diabetes

(328.4G166.8 vs 245.3G164.8 pg/ml) (PZ0.024).

Maria Hayon¹, Marta Fernandez¹, Silvia Maraver², Teresa Muros¹,

Conclusion

Daniel Cepero³, Martin Lopez¹, Miguel Quesada¹, Joaquin Pechuan⁴ &

These results suggest that the effect of exenatide on weight loss may be related

Gonzalo Piedrola¹

with the suppression of serum fasting ghrelin levels, which is an orexigenic

¹Complejo Hospitalario Universitario de Granada, Granada, Spain;²Clínico

peptide.

Virgen de la Victoria Hospital, Malaga, Spain;³Torrecardenas Hospital,

DOI: 10.1530/endoabs.49.GP112

Almeria, Spain;⁴Endocrinology Private Office, Granada, Spain.

Introduction

The aim of this study was to analyze the effects of Liraglutide in hepatic steatosis

as well as clinical and biochemical data before and after 6 months.

Endocrine Nursing

Methods

We have retrospectively analysed epidemiological, anthropometric and labora-

GP113

tory data of 83 type 2 diabetic patients treated with Liraglutide and followed at

Impact of the socio-economic level on the management in type 2

different endocrinology units across east Andalusia. We have evaluated

diabetes

nonalcoholic fatty liver disease using liver enzymes and hepatic steatosis index

Boulbaba Kolsi¹, Mouna Elleuch¹, Rihab Ben Abdallah²,

(HSI). HSIO36 reflects fatty liver, !30 absence, and intermediate values are

Feten Haj Kacem¹, Fatma Mnif¹ & Mohamed Abid¹

considered indeterminated.

¹Hedi Chaker Hospital, Sfax, Tunisia;²Faculty of Sciences of sfax, Sfax,

Results

Tunisia.

Of the 83 cases evaluated, 54.2% were male, mean age 56.76G9.87 years, time

from diagnosis 9.46G5.46 years. Prior to treatment, patients had BMI 37.68G

6.82 kg/m², blood pressure

138.80/82.87 mmHg, fasting glucose

187.33G

Diabetes is a chronic disease whose associated comorbidities are largely

55.11 mg/dl, glycated hemoglobin

(HbA1C) 8.62G1.3%, total cholesterol

influenced not only by pathology but also by socio-economic conditions. The

178.1G35.74 mg/dl (c-LDL 97.66G32.16 mg/dl, c-HDL 44.54G13.78 mg/dl),

aim of this study is to investigate the influence of social conditions on the

triglycerides 197.64G24.19 mg/dl, AST 29G20.311 U/l, ALT 39.88G31.69 U/l

evolution of diabetes. A retrospective, comparative study of 111 patients with

and HSI 46.44G6.48.

type

2 diabetes Follow-up in the Endocrinology-Diabetology department in

Clinical and biochemical figures at 6 months were: BMI 36.08G6.32 kg/m²,

hospital Hedi Chaker of Sfax. Patients were divided into two groups with

blood pressure 132.76/77.41 mmHg, fasting glucose 165.16G56 mg/dl, HbA1C

unfavorable (G1) and good (G2) socio-economic conditions, both groups had 58

7.73G1.33%, total cholesterol 170.6G39.19 mg/dl (c-HDL 46.25G15.03 mg/dl,

and 53 patients, respectively. The average age of our patients was 54 in G1 and 49

c-LDL 87.74G30.5 mg/dl), triglycerides 198.29G22.29 mg/dl, AST 24.97G

in G2 (PZ0.7). A female predominance was noted in the G 1/64% while the male

12.49 U/l, ALT 32.76G18.24 U/l, and HSI 43.98G6.38.

sex was predominant in the G 2: 80%. The age of diabetes was comparable

Statistically significant differences were found regarding several variables, such

between the two groups (12.5 years vs 11 years, PZ0.09). Fasting glucose was

as BMI, HbA1C, fasting glucose, blood pressure and c- LDL, as well as in ALT

significantly higher in G 1 (15 mmol / l) versus 9 mmol / l in G2 (P!0.0001). The

and HSI, showing an amelioration in hepatic steatosis. No differences were found

number of hospitalizations was higher in G1: 2.8 versus 1.3 in G2 (PZ0.005).

in total cholesterol, c-HDL, triglycerides and AST.

The food investigation showed a higher caloric intake in G2

estimated at

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

2615 Kcal/d versus

2184 Kcal/d for the G1. Infectious complications and

Endocrine teams and in particular the specialist nurses role involves teaching

amputation were significantly more frequent in G 1 compared to G2. Similarly,

patients with new diagnosis as well as building on information they have gained

microangiopathic complications were more frequent in G1

patients. This

from their consultations etc. We wanted to see how many patients with

imbalance was related to management difficulties, so no patient of G1 group

pituitary/adrenal failure have gaps in the understanding of their condition,

was placed under insulin analogs versus 23% of G2 patients. Socioeconomic

particularly in relation to their sick day rules.

status seems to play a crucial role in the glycemic balance and the occurrence of

We surveyed 18 patients on hydrocortisone replacement who completed a

chronic complications of diabetes. This is mainly due to the restriction of access

questionnaire assessing their knowledge and understanding of their condition.

to health care structures and therapeutic, sometimes expensive, and the level of

When asked what action they would take if they had flu and a high temperature,

instruction of these disadvantaged classes.

nine would double their steroid dose, three would triple it. This leaves six patients

DOI: 10.1530/endoabs.49.GP113

at potential risk of admission. When asked about vomiting and/or diarrhoea, six

said they would double their dose, one would triple it and one would take their

emergency hydrocortisone injection, potentially leaving ten patients at risk of an

Addisonian crisis. Within this group of patients seven had been given intra

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muscular hydrocortisone, but only four had been shown how to use it.

The national annual admission rate for patients with Addison’s disease/syndrome

Outcomes of a nurse-led thyroid clinic at a tertiary-care endocrine

is 8%. Within this sample group the admission rate was 27.7%.

centre

We need more resources to build on our initial and ongoing education/teaching

Violet Fazal-Sanderson¹, Niki Karavitaki², Ashley Grossman³ &

programme to work on patient awareness of their condition as a whole, including

Atul Kalhan⁴

sick day rules.

¹Royal Berkshire Hospital, Reading, UK;²Queen Elizabeth Hospital,

Birmingham, UK;³Oxford University Hospitals NHS Foundation Trust,

DOI: 10.1530/endoabs.49.GP115

Oxford, UK;⁴Royal Glamorgan Hospital, Wales, UK.

Introduction

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A Nurse-led Thyroid Clinic (NLTC) in a tertiary-care Endocrinology centre (EC)

Recovery of the hypothalamus-pituitary-adrenal axis after

in Oxford was set up in 2005. The patients were managed by an Endocrine

transsphenoidal surgery for pituitary adenomas

Advanced Nurse Practitioner.

J P van Eck, S J C M M Neggers, J A M J L Janssen, Y B de Rijke,

Aims

A H G Dallenga, A P Nagtegaal, A J van der Lely & R A Feelders

To evaluate standard of clinical care (SOCC) quality of service provision (QOSP)

Erasmus Medical Center, Rotterdam, The Netherlands.

and cost effectiveness (CE) of the NLTC.

Methods

Three aspects of service were assessed:

Purpose

Hypopituitarism is frequently associated with lifelong replacement therapy.

a) SOCC: Data were collected for patients managed over 12 months between

However, it has been suggested that recovery from hypopituitarism after

1/2014 and 1/2015. Diagnosis, investigations and management plans for

transsphenoidal surgery (TSS) for pituitary adenomas may occur during follow

individual patients were compared against accepted regional and national

up. The aim of this study was to assess the frequency of hypothalamus-pituitary-

guidelines.

adrenal (HPA) axis recovery after TSS in patients with non-functioning pituitary

b) QOSP was evaluated from standardised patient feedback questionnaires (PFQ)

adenomas and acromegaly.

that were anonymised for confidentially

Methods

c) CE was analysed through collection of retrospective data of filed patients clinic

Over the 3-year observational study-period, 146 patients underwent transsphe-

lists between 1/2014 and 1/2015. A new patient (NP) tariffed at £120, follow-

noidal pituitary surgery. The metyrapone test was used to assess the HPA-

up, at £90 per visit according to finance department protocol. Annual data

integrity after 1 week and after 3-12 months after TSS. The pituitary-thyroid,

recorded of non-face-to-face-telecommunication (NFTFT) costed at £30 per

-gonadal and growth hormone axis were measured one week after TSS.

call.

Results

Patients with Cushing’s disease and panhypopituitarism were excluded from the

study. 44 subjects had a sufficient HPA-axis one week after surgery. 14 subjects

a) SOCC: 214 patient appointments for 134 patients were reviewed; 112 patients

with an insufficient HPA-axis were excluded, as the

11-deoxycortisol after

had Graves’ disease, 10 subacute thyroiditis,10 toxic nodular diseases and

metyrapone was !100 nmol/l. Eighteen patients were eligible to re-assess the

two subclinical thyrotoxicosis. Patients were managed with a departmental

HPA-integrity. In 10 out of 18 patients, insufficiency of the HPA-axis appeared to

protocol based on British Thyroid Association guidelines 2006.

be reversible. Eight patients had persistent secondary adrenal insufficiency. The

b) QOSP: 50 out of 60 PFQ were returned (34 women/16 men, median age 52.3

number of other pituitary hormone insufficiencies one week after TSS was

years, range 21-85). Majority of the patients expressed high satisfaction with

associated with recovery of the HPA-axis after TSS.

the quality of services provided, with 86% “Extremely Likely” to recommend

Conclusion

the TNLC to friends and family.

After TSS, recovery of the HPA-axis over time does occur in a proportion of

c) CE: New and follow-up patients generated an annual income of £20,490.

subjects. Therefore it is recommended to re-assess the HPA-integrity during

NFTFT calls (908 patients) generated an income of £27,240. 41 empty NP

follow up to prevent unnecessary glucocorticoid replacement therapy. Pituitary

clinic slots, 22 follow up cancellations and 19 patients who failed to attend the

adenoma, reversible hypopituitarism, recovery HPA-axis, pituitary surgery,

clinic, amounted to a loss of £8610.

adrenal insufficiency.

Conclusions

Key words

The audit supports the value of NLTCs in EC’s with a significant thyroid-

Pituitary adenoma, reversible hypopituitarism, recovery HPA-axis, pituitary

dysfunction workload. These clinics can provide high quality of clinical care and

surgery, adrenal insufficiency.

potentially be cost-effective.

DOI: 10.1530/endoabs.49.GP116

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The Swedish Pituitary Register Nursing Group (SPRNG) Projects and

GP115

Experiences

Education, patient empowerment and admission avoidance

Maria Forsgren¹, Caroline Alkebro², Margareta Lindgren³, Helena Wik⁴,

Anna Hawkins, Edel Casey & Khash Nikookam

Maria Warn⁵ & Christina Dahlgren⁶

Barking, Havering & Redbridge University NHS Trust, ESSEX, UK.

¹Uppsala University Hospital, Uppsala, Sweden;²Orebro University

Hospital, Orebro, Sweden;³Norrland University Hospital, Umeå, Sweden;

Sahlgrenska University Hospital, Gothenburg, Sweden;⁵Karolinska

It is paramount to educate our patients, thereby empowering them to manage their

University Hospital, Stockholm, Sweden;⁶Linkoping University Hospital,

chronic conditions. This is an evidence based fact. As healthcare professionals our

Linkoping, Sweden.

challenge is to provide and ensure patients have been well informed in order to

understand and manage their condition successfully on a daily basis.

In today’s healthcare service patient education has become a casualty of the

Background

reduced resources; there are ever increasing restrictions on both the length and

The Swedish Pituitary Register (SPR) is a national quality register founded in

frequency of consultations.

1991 by the Swedish Pituitary Group and it provides important data in the

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

continuous quality assessment and improvement work within the Swedish health

GATA4 downstream targets in the adrenocortical tumors in both, inha/Tag and

care system.

human could be of importance to find potential therapeutic targets for human

The Swedish Pituitary Register Nursing Group (SPRNG) was formed by nurses at

adrenocortical tumors.

the University Hospitals, working with the register, in 2011.

DOI: 10.1530/endoabs.49.GP118

Purpose

To increase the coverage rate and improve the data quality in the register.

To strengthen the endocrine nurse role and encourage and promote the nurses to

own register projects.

Methods

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The SPRNG, consisting of endocrine nurses, one responsible for the register at

each University Hospital. Meetings are performed 1-2 times /year. The SPRNG is

Targeted molecular analysis in adrenocortical carcinomas: a way

working for the same routines considering the register and is actively working

towards personalized medicine

with projects in the SPR.

Cristina L Ronchi¹, Juliane Lippert², Silke Appenzeller³, Silviu Sbiera¹,

Results

Sonja Steinhauer¹, Raimunde Liang¹, Andrea Gehrig², Matthias Kroiss¹,

Since the SPRNG was started the coverage rate and the reporting speed in the SPR

Simone Rost², Andreas Rosenwald⁴, Clemens Muller-Reible² &

Martin Fassnacht¹

have increased. Several nurse projects during

2016. Implement PREM and

¹Division of Endocrinology and Diabetes, University Hospital of

disease-specific PROM variables. User Survey in the register. Register data

Wuerzburg, Wuerzburg, Germany;²Institute of Human Genetic, University

template for the hospitals operations managers and for the public to increase the

of Wuerzburg, Wuerzburg, Germany;³Core Unit Bioinformatics, Compre-

knowledge of this patient group.

hensive Cancer Center Mainfranken, University Hospital of Wuerzburg,

A study ‘Time from first symptoms to diagnosis’, where approximately 600

Wuerzburg, Germany;⁴Department of Pathology, University of Wuerzburg,

patients with pituitary tumours

(Acromegaly, Mb Cushing, NFPA and

Wuerzburg, Germany.

Prolactinomas) are included, will be compiled 2017. The purpose of this study

is to find these patients earlier and to identify how we can do that.

The SPRNG have been active at international conferences with several abstracts.

Adrenocortical carcinoma (ACC) is a rare tumor with heterogeneous outcome and

Meeting and sharing experiences of the register with finish endocrine nurses.

no available targeted therapy. The aim of the study is to identify prognostic

Conclusion

molecular markers and novel potential drug targets.

The SPRNG has contributed to increase the data quality and coverage rates in the

A total of 43 FFPE tumor samples were retrospectively investigated for somatic

SPR.

mutations and copy number variations (CNV) by next-generation sequencing

The SPRNG is a good example of how nurses can be supported by each other and

(160

cancer-related genes, Qiagen). Gene expression was evaluated by

share experiences, skills and knowledge but also operate their own project.

quantitative RT-PCR in a subgroup of 25 ACC samples (84 cancer drug targets,

DOI: 10.1530/endoabs.49.GP117

Qiagen). The major clinical endpoint was progression free survival (PFS).

We observed 123 protein-altering mutations in 47 genes (median 2 per sample),

with the most frequent known to be ACC-related: TP53 (28% of samples),

CTNNB1 (26%), ZNRF3 (19%), NF1 (16%) and GNAS (14%). Notably, we also

detected recurrent mutations in genes previously not clearly associated with ACC

Endocrine Tumours

(i.e. ABL1, KDM6A, TSC1, FBXW7, DNMT3A, BRCA1, BRCA2). Some focal

GP118

CNV were found in O30% samples (i.e. gains of CDK4, MDM2, IL7R, and losses

Luteinizing hormone receptor mediated GATA4 induction promotes

of TNFRSF14). A noisy pattern was associated to a shorter median PFS than

adrenocortical tumorigenesis in gonadectomized mice

chromosomal or quiet pattern (4.5 vs 7 vs 14 months, respectively, PZ0.07).

Milena Doroszko¹, Marcin Chrusciel¹, Joanna Stelmaszewska²,

Most affected genes were involved in p53/Rb or Wnt/b-catenin pathway or

Tomasz Slezak³, Adolfo Rivero-Muller^4,5, Artur Padzik⁴,

chromatin remodeling, but also in immune response or DNA repair mechanisms.

Slawomir Anisimowicz⁶, Slawomir Wolczynski², Ilpo Huhtaniemi^1,7,

Patients with alterations in DNA repair genes had longer PFS than others

Jorma Toppari^1,8 & Nafis Rahman^1,2

(PZ0.067, HRZ1.78). At mRNA level, most frequently overexpressed genes (O

¹Department of Physiology, Institute of Biomedicine, Turku, Finland;

2.5 fold change) were IGF2 (92%), TOP2A (92%), CDK1 (72%) and PLK1

²Department of Reproduction and Gynecological Endocrinology, Medical

(60%). Tumors with increased BUB1B-PINK1 (O5.9) were associated with a

University of Bialystok, Bialystok, Poland;³Department of Biochemistry

trend to worst PFS (PZ0.16, HRZ1.98).

and Molecular Biology, University of Chicago, Chicago, Illinois, USA;

This pilot study demonstrates the feasibility of molecular analysis in FFPE

⁴Turku Center for Biotechnology,

˚boAkademi and University of Turku,

samples. We identified some genetic variants previously not associated with ACC

Turku, Finland;⁵Department of Biochemistry and Molecular Biology,

and new potential drug target genes. These results will be validated in a larger

Medical University of Lublin, Lublin, Poland;⁶Center of Gynecology and

series in order to path the way to a personalized medicine in ACC.

Reproductive Endocrinology Artemida, Bialystok, Poland;⁷Institute of

DOI: 10.1530/endoabs.49.GP119

Reproductive and Developmental Biology, Imperial College London,

London, UK;⁸Department of Pediatrics, Turku University Hospital, Turku,

Finland.

The role of luteinizing hormone (LH) and its receptor (LHCGR) signaling in the

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adrenal gland remains unknown. Gonadectomy-induced chronically elevated LH

Evaluation of the occurrence of the manifestations of Carney complex

levels trigger neoplastic transformation in genetically susceptible mouse strains

in a french cohort of 70 patients during a three years standardized

(DBA/2J) or transgenic mice expressing the Simian Virus

T antigen

follow-up

(SV40Tag) oncogene under inhibin-a promoter (inha/Tag). In order to study

Stéphanie Espiard^1,2, Catherine Cardot-Bauters², Gerald Raverot³,

the functional role of LHR and GATA4

in the onset and progression of

Marie-Laure Nunes⁴, Françoise Brucker-Davis⁵, Muriel Houang⁶,

adrenocortical tumors in ovariectomized (OVX) inha/Tag females in vivo and

Françoise Archambeaud-Mouveroux⁷, Anne Lienhardt⁸, Hervé Lefebvre⁹,

in vitro, we crossbred the inha/Tag with LHR knockout

(LuRKO) mice.

Olivier Chabre¹⁰, Antoine Tabarin⁴, Marie-Christine Vantyghem² &

Additionally we knocked out Lhr (Lgr-ko) and Gata4 (Gata4-ko) in the Ca1 cell

Jérôme Bertherat¹

line derived from an adrenal tumor of inha/Tag mice. In inha/Tag mice, we

¹Department of Endocrinology, Paris Public University Hospitals, Cochin

identified two distinct types of SV40Tag expressing neoplastic cells. The first

Hospital, Paris, France;²Department of Endocrinology, Diabetology and

type, subcapsular non-steroidogenic spindle-shaped A-like cells, which never

Metabolism, Lille University Hospital, Huriez Hospital, Lille, France;

developed to tumors, were found in both intact and OVX inha/Tag females. The

³Department of Endocrinology, Lyon Public University Hospitals, Lyon,

second type, parenchymal tumor cells in the topmost layer of zona fasciculata,

France;⁴Department of Endocrinology, Diabetology and Metabolism,

later forming tumor foci, were found only in OVX inha/Tag mice. Lack of LHR

Bordeaux University Hospital, Haut-Lévêque Hospital, Pessac, France;

in OVX inha/Tag/LuRKO mice adrenals prevented tumor formation. Histological

⁵Department of Endocrinology, Diabetology and Reproductive Medicine,

and immunohistochemical analyses revealed the presence of hyperplastic cells

Nice University Hospital, Nice, France;⁶Department of Pediatric

expressing SV40Tag in parenchyma. These cells were devoid of GATA4 and

Endocrinology, Paris Public University Hospital, Armand-Trousseau

showed signs of apoptosis. In vitro, a complete inactivation of Gata4 significantly

Hospital, Paris, France;⁷Department of Endocrinology, Limoges University

decreased cell proliferation, expression of tumor markers (Inha, SV40Tag, Lhcgr

Hospital, Le Cluzeau Hospital, Limoges, France;⁸Department of Pediatry,

and Esr1) and gonadal-like steroidogenic phenotype of Ca1 cells. Our results

Limoges University Hospital, Limoges, France;⁹Department of Endo-

suggest that at first, the tumor formation was LH-dependent, but later on became

crinology, Diabetology and Metabolism, Rouen University Hospital, Rouen,

LH-independent. GATA4

is responsible for the Inha/SV40Tag expression,

France;¹⁰Department of Endocrinology, Grenoble University Hospital,

gonadal steroidogenic phenotype and possibly pro-survival pathways. Identifying

Albert Michallon Hospital, Grenoble, France.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction

In conclusion, ACC patients are characterized by increased circulating immune

The Carney Complex is a multiple endocrine and non endocrine neoplasia mostly

inhibitory Tregs and tumour infiltrating CD4CT-helper cells have a positive

due to PRKAR1A mutations. Spectrum of manifestations and genotype-

influence on patient survival.

phenotype correlations have been previously described by retrospective studies.

DOI: 10.1530/endoabs.49.GP121

A prospective study evaluating the occurrence of the different manifestations was

needed to precise the optimum follow-up.

Methods

Multi-center national prospective study (Clinical Trials NCT00668291) including

70 patients mutated or wild-type for PRKAR1A followed prospectively during

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3years with screening of the different manifestations by annual clinical, biological

The natural history of adrenal incidentaloma - results from the

and radiological evaluation.

international prospective multi-centre EURINE-ACT study

Results

Irina Bancos^1,2, Vasileios Chortis², Katharina Lang², Alessandro Prete²,

The cohort was compound of 50 females and 20 males with a mean age at

Massimo Terzolo³, Martin Fassnacht⁵, Marcus Quinkler⁸, Darko Kastelan⁹,

35.4years C/K16.7. Prevalence of cardiac myxomas at the end of the follow-up

Dimitra Vassiliadi⁷, Felix Beuschlein⁵, Urszula Ambroziak⁴, Alice Sitch¹⁰,

was 22.9% with newly diagnosis during the study period for 3 patients. Forty-

Jonathan Deeks¹⁰ & Wiebke Arlt²

four% of patients with myxomas had related stroke attack and

56% had

¹Mayo Clinic, Rochester, MN, USA;²Institute of Metabolism and Systems

recurrences. Median delay between recurrences was

3.8years

(minimum-

Research, University of Birmingham, Birmingham, UK;³University of

maximum: 0.8-24). Primary pigmented adrenal nodular disease was diagnosed

Turin, Turin, Italy;⁴Warszawski Uniwersytet Medyczny, Warszawa,

in 57.1%. Skin manifestations, abnormal somatotroph hormonal tests and thyroid

Poland;⁵Universitatsklinikum Wurzburg, Wurzburg, Germany;⁶Klinikum

tumors were observed respectively in 58.6, 21.4 and 12.9%. Four% had melanotic

der Ludwig-Maximilian-Universitat Munchen, Munchen, Germany;⁷Attiko

shwannomas confirmed by histology. Spinal magnetic resonance imagery

University Hospital, Athens, Greece;⁸Charité Universitatsmedizin Berlin,

revealed lesions for 8.6%. Characteristic multiples calcified tumors on testicular

Berlin, Germany;⁹University Hospital Zagreb, Zagreb, Croatia;¹⁰Institute

ultrasonography were present in 35% of male patients. Ten% of female patients

of Applied Health Research, University of Birmingham, Birmingham, UK.

had surgery for breast myxoma or adenofibroma. Forty% had lesions classified

ACR2-3 at mammography. Interestingly, four patients

(8%) had breast

Background

adenocarcinomas

(11.1% of female older than

30years). Eighty-three% of

Adrenal masses are discovered in 5% of abdominal imaging scans. Work-up aims at

patients had PRKAR1A mutations. Patients carrying the mutation c.709-7del6

exclusion of malignancy and hormone excess. However, estimates of these risks derive

(34% of the cohort) had no manifestation or phenotype restricted to adrenal,

from retrospective studies only, mostly small and with significant selection bias.

lentigines and abnormal somatotroph test.

Methods

Conclusion

Prospective multi-centre study (2011-2016) in 14 centres (11 countries) of the

The penetrance of the disease is high after screening except for patient carrying

European Network for the Study of Adrenal Tumours (ENSAT) with prospective

the c.709-7del6 mutation. This study highlights the importance of an annual

consecutive enrolment of patients with newly diagnosed adrenal mass. Extra-adrenal

follow-up, with especially annual cardiac imaging for patients with history of

malignancy and phaeochromocytoma were exclusion criteria. Diagnosis was

cardiac myxomas and earlier and regular senologic evaluation.

confirmed by histology or imaging follow-up.

DOI: 10.1530/endoabs.49.GP120

Results

We enrolled 1994 patients, 1746 (87.6%) with a benign adrenocortical adenoma

(ACA), 83 (4%) with other benign masses (e.g. adrenomyelolipoma, cyst), 106 (5.3%)

with adrenocortical carcinoma (ACC) and 59 (3%) with other malignant masses (e.g.

metastases, sarcoma). Risk of ACC was highest in young patients (!40yrs:13%; 40-

60yrs:6%;O60yrs:3%, P!0.0001) and in large masses (O4 cm:21%, !4 cm:0.4%,

GP121

P!0.0001). Of 1746 patients with ACA, imaging for exclusion of malignancy

Immunity in adrenocortical carcinoma patients - interplay between

included unenhanced CT in 1301 patients, with tumour density !10HU indicative of a

anti-cancer immunity and steroid hormones

benign tumour in 69%, with 16% borderline (10-20HU) and 15% suspicious

Silviu Sbiera^1,2, Thomas Dexneit^1,3, Iuliu Sbiera¹, Jochen Schreiner¹,

(O20HU) results. MRI with chemical shift results in 271 ACA patients were indicative

Cristina L. Ronchi¹, Matthias Kroiss^1,2 & Martin Fassnacht^1,4

of a benign lesion in 79%. In 829/1746 (47%) ACA patients, two or more imaging

¹Division of Endocrinology and Diabetes, University Hospital, University of

studies were performed; 19% underwent three or more. Upon re-imaging after R6

Wurzburg, Wuerzburg, Germany;²Comprehenssive Cancer Center Main-

months, the adrenal mass appeared stable in size 601 of 629 ACA patients (96%). Mild

franken, University of Wurzburg, Wuerzburg, Germany;³Department of

autonomous cortisol excess (MACE) was detected in 547/1316 (42%) patients with

Neurosurgery, University Hospital, University of Wurzburg, Wuerzburg,

ACA. Adrenalectomy was performed in 21% (370/1746) of ACA patients. Of those,

Germany;⁴Clinical Chemistry and Laboratory Medicine, University

222

(60%) had overt hormone excess and 64 (17%) had MACE (70; 18%); the

Hospital, University of Wurzburg, Wuerzburg, Germany.

remaining 84 patients (23%) had non-functioning ACA.

Conclusions

Adrenocortical carcinoma

(ACC) is one of the most aggressive endocrine

Overall risk of ACC is 5.3% and is highest in young patients with adrenal mass size

malignancies. By applying a ‘multiple omics’ approach, we recently identified

O4 cm. ACAs are frequently misclassified as malignant by routine imaging,

two distinct subgroups of ACC patients, a good prognosis “immune” and bad

resulting in a high rate of interval imaging and unnecessary adrenalectomies.

prognosis “steroid” phenotype.

DOI: 10.1530/endoabs.49.GP122

We hypothesized that the steroid phenotype is associated with glucocorticoid-

induced suppression that can be ‘rescued’ by reactivating the immune system

using immune checkpoint inhibitors and inhibitors of steroidogenesis.

To assess changes induced by ACC on circulating immune cells we isolated

PBMCs from blood of 19 healthy controlsZHC and 163 ACC patients (41:

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tumour freeZTF, 82: tumour present without cortisol excessZTP and 40: tumour

Outcome of patients with adrenocortical cancer after discontinuation of

present and cortisol excessZCE) and performed FACS analyses to quantify

adjuvant mitotane therapy

T-cells (CD3CCD4C and CD3CCD8C), B-cells (CD19), monocytes (CD14)

Massimo Terzolo¹, Vittoria Basile¹, Felix Megerle², Wiebke Hermann²,

and regulatory T-cells

(T-reg) as a sign of immune suppression

(CD4C

Federica Cicciarella¹, Rossella Libè³, Eric Baudin⁴, Harm Haak⁵,

CD25^highFOXP3C). Using immunofluorescence, we analysed the presence of

Massimo Mannelli⁶, Marco Boscaro⁷, Marcus Quinkler⁸,

tumour infiltrating T-cells, Tregs, B-cells, dendritic cells (CD209C) in full FFPE

Isabelle Bourdeau⁹, Paola Perotti¹, Stefanie Hahner², Felix Beuschlein¹⁰ &

from 58 primary ACC tumours. Furthermore, expression of immune checkpoint-

Martin Fassnacht²

markers programmed death 1 (PD1) and its ligand PDL1 was analysed by IHC.

¹Department of Clinical and Biological Sciences, University of Turin, Turin,

From the peripheral cells the percentage of Treg in the circulating T-cell

Italy;²Department of Internal Medicine 1, University of Wurzburg,

population correlated significantly with tumoural and steroid secretion status

Wurzburg, Germany;³Cochin Hospital, Endocrinology Unit, Paris, France;

(4.4G1.2 in HC, 7.9G6.1 in TF, 9.0G7.9 in TP and 11.0G7.8 in CE, P!0.01).

⁴Department of Nuclear Medicine and Endocrine Tumors, Institut Gustave

Using median as cut-off, patients with increased percentage of peripheral Treg

Roussy, Villejuif, France;⁵Maxima Medisch Centrum, Internal Medicine,

had a lower survival rate (HRZ1.8, 95%CI 1.0-3.1, PZ0.02). Most tumours

Eindhoven, The Netherlands;⁶Department of Experimental and Clinical

presented a tumour infiltrate (T-cells: 80%, 37G65 cells/HPF, cytotoxic T-cells:

Biomedical Sciences, University of Florence, Florence, Italy;⁷Department

72%, 24.9G53.0, T-helper: 57%, 19.3G16.9 cells/HPF, Treg: 48%, 3.8G3.8,

of Medicine, University of Padua, Padua, Italy;⁸Endokrinologie in

dendritic cells: 73%, 5.8G3.7, B-cells: 0%, PD1: 36%, 14.7G30.1, PDL-1: 83%,

Charlottenburg, Berlin, Germany;⁹Department of Medicine and Research

34.6G81.6). The only tumour infiltrating cells associated overall survival were

Centre, University of Montreal, Montreal, Canada;¹⁰University of Munich,

the CD4CT-helper cells (HR for death: 0.34, 95%CI 0.12-0.95, PZ0.005).

Medizinische Klinik und Poliklinik IV, Munich, Germany.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

requiring intervention both in univariate (PZ0.03) and multivariate analysis

Adjuvant mitotane therapy is frequently used in Europe following surgery for

(Hazard ratio 2.9, 95% confidence interval 1.2-7.2, PZ0.02).

adrenocortical carcinoma (ACC). Management of adjuvant mitotane is mainly

Conclusion

empirical and a major open question is the optimal duration of therapy, because

Lesion diameter should be the pivot factor in directing PNETs management in

no study has ever addressed this issue.

vHLd. Among patients with a largest PNET diameter O1.2 and !3 cm, VHL

Objective

genotyping may be useful for risk stratification.

We aimed to assess the outcome of ACC patients who were treated with adjuvant

DOI: 10.1530/endoabs.49.GP124

mitotane for at least one year following surgery and then discontinued therapy for

other reasons than ACC recurrence.

Design

We did a retrospective analysis of 132 patients (91 F, 41 M; median age 44 years)

with histologically confirmed ACC who were treated at 9 European centres and 1

centre in Canada since 1999.

Results

Tumour stage was ENSAT I, 11%; ENSAT II, 79%; ENSAT III, 20%; hormone

secretion was present in 44% and resection status was R0, 83% and Rx, 17%.

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Median Ki-67 was 10% and Weiss 6. Duration of adjuvant mitotane therapy was

GPER-stimulation increases proliferation in colorectal cancer via the

34 months (12-141). Median duration of follow-up was 79 months (31-280),

Hippo signalling pathway

including 34 months after discontinuation (1-263). Seventeen patients (13%)

Anastasia Arvaniti, Karthik Basker, Ali Gondal, Habibur Rahman,

recurred after treatment discontinuation with a recurrence-free survival from

Lorna Gilligan & Paul Foster

surgery of

months

(31-277) and tumour-free survival after mitotane

University of Birmingham, Birmingham, West Midlands, UK.

discontinuation of

months

(1-263). The only difference in prognostic

characteristics between patients with recurrent ACC and the remainders was a

higher number of secreting tumours. Interestingly, no recurrence was observed

Colorectal cancer (CRC) is the 2nd most commonly diagnosed cancer in Europe.

among the 41 patients (31%) treated for O48 months; such patients had similar

Previously, we have shown steroid sulphatase (STS), the enzyme that converts

prognostic characteristics and follow-up duration after mitotane discontinuation

conjugated oestrogens to their active forms, is significantly upregulated in human

than the remainders.

CRC tissue. Furthermore, increased STS activity substantiates greater CRC

Conclusions

tumour burden in mouse models. Here we demonstrate that this oestrogen-

These first results suggest that a prolonged duration of adjuvant mitotane therapy

induced increase of CRC proliferation is mediated by G-protein coupled

may be associated with better recurrence-free survival.

oestrogen receptor

(GPER) via Hippo pathway signalling through the yes-

DOI: 10.1530/endoabs.49.GP123

associated protein 1 (YAP1), transcriptional coactivator with PDZ-binding motif

(TAZ), and connective tissue growth factor (CTGF).

To examine how GPER effects CRC proliferation we employed in vitro BrdU

proliferation assays and in vivo mouse models of CRC treated with G1, a GPER

agonist, oestrogens and G15, a GPER antagonist. To investigate whether YAP1,

its target gene CTGF, and its transcriptional co-activator TAZ, were altered by

oestrogen-induced GPER signalling, we used immunoblotting and immunohis-

tochemistry. YAP1 knockdown cells were also examined by treating them with

G1, oestrogens and verteporfin, a YAP1 inhibitor, to assess the role of YAP1 on

proliferation.

GPER-stimulation by G1 and oestrogen increased CRC proliferation in a dose-

GP124

dependent manner, with this effect inhibited by G15 in vitro and in vivo CRC

VHL Genotype and risk stratification of pancreatic neuroendocrine

xenografts. YAP1 mediated this pro-proliferative response in CRC cells in

tumors in patients with von hippel-lindau disease

contrast to colon adenoma cells. These findings were underpinned by increased

Amit Tirosh^1,2, Jasmine Shell³, Patience Green³, Xavier M. Keutgen⁴,

phosphorylation of YAP1 and increased protein expression of TAZ and CTGF

Samira M. Sadowski⁵, Mustapha el Lakis³, Pavel Nockel³, Dhaval Patel³,

after oestrogen and G1 treatment. Intriguingly, CTGF up-regulation correlated

Naris Nilubol³ & Electron Kebebew³

with elevated GPER in human CRC tissue. In line with the above results,

¹National Institutes of Health, Bethesda, MD, USA;²Sackler Faculty of

pharmacological inhibition of YAP1 and YAP1 knockdown blocked G1-induced

Medicine, Tel Aviv University, Tel Aviv, Israel;³Endocrine Oncology

cellular proliferation supporting the functional pro-proliferative role of YAP1

Branch, National Cancer Institute, Bethesda, MD, USA;⁴Department of

in CRC.

Surgery, Rush University Medical Center, Chicago, IL, USA;⁵Endocrine

Taken together, our results propose a new oestrogen-driven pro-proliferative

and Thoracic Surgery, University Hospitals of Geneva, Geneva,

GPER-stimulated pathway through Hippo signalling in CRC. Further studies are

Switzerland.

required to establish whether this early metabolic response translates into

increased cellular viability and cancer development.

Background

DOI: 10.1530/endoabs.49.GP125

About 8-20% of patients with von Hippel-Lindau disease (vHLd) develop

pancreatic neuroendocrine tumors (PNETs). However, prognostic markers for

these tumors are lacking. The VHL gene mutation type is associated with the

clinical phenotype of vHLd. Hence, we aimed to determine whether VHL

mutation characteristics may be associated with PNETs phenotype in patients

with vHLd.

Methods

A prospective study of patients with vHLd and PNETs with follow-up imaging.

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VHL mutation type and position were defined using Sanger sequencing of

germline DNA.

Inhibition of hRAS and CDK4/6 leads to an antiproliferative activity,

blocks cell cycle and induces cell death in anaplastic thyroid cancer

Results

cell lines

182 patients (476 PNETs) were followed for a median of 52 months (range 3-84).

Marta Pojo¹, Sara Lopes-Ventura¹, Ana Matias¹, Valeriano Leite^1,2 &

The VHL gene was sequenced in 154 patients: 75 patients (48.7%) had a missense

Branca Cavaco¹

mutation [MisM], 51 (33.1%) - deletion, 12 (7.8%) - nonsense, one (0.6%) -

¹Unidade de Investiga

¸a˜o em Patobiologia Molecular (UIPM), Instituto

rearrangement, and 15 (9.7%) had frameshift mutations. Patients with a largest

Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal;

lesion diameter

!1.2 cm had a lower risk for metastases (Log-Rank test,

²Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa

PZ0.006) compared with larger diameters, whereas those with diameter O3 cm

Francisco Gentil E.P.E., Lisbon, Portugal;³Faculdade de Ciências Médicas,

had higher risk for metastases compared with other patients (Log Rank test,

Universidade Nova de Lisboa, Lisbon, Portugal.

PZ0.007). Patients with MisM had a higher risk of requiring an intervention

(Log-Rank test PZ0.01) and for developing metastases during follow-up

(PZ0.007) compared to those with other mutation types. Among patients with

The unresponsiveness of anaplastic thyroid carcinomas (ATCs) to multimodal

a largest lesion diameter between 1.2 and 3 cm, those with MisM had higher risk

therapy represents the major challenge in thyroid cancer treatment. Our group

for metastases (Log-Rank test, PZ0.048) compared to other mutation types, and

previously showed that genes involved in cell cycle are differentially expressed in

patients with mutation positioned in exon 3 of the VHL gene had higher risk for

ATCs compared to normal thyroid, and that the most common mutations found in

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

these tumours are related with proliferation and cell cycle genes, namely TP53,

GP128

RAS, CDKN2A and CDKN2B. Therefore, these genes are promising new targets in

Peptides derived from the sst5TMD4 extracellular domain increase

ATCs.

malignancy of endocrine-related cancer cells

Here, we investigated if the inhibition of HRAS by Tipifarnib (TIP) and CDK4/6

Manuel D Gahete, Mercedes del Rio-Moreno, Emilia Alors-Perez,

by Palbociclib (PD) could be an option in ATC treatment. Different ATCs cell

Patricia Borges de Souza, Maria E Prados-Gonzalez, Justo P Casta

˜o&

lines with distinct mutational patterns for RAS, CDKN2A and CDKN2B were used

Raul M Luque

to evaluate the cytotoxic effects of these drugs. The IC50 for TIP and PD were

Maimonides Institute of Biomedical Research of Cordoba; Reina Sofía

determined, and the effects of these compounds in cell cycle, cell death and cell

University Hospital; Department of Cell Biology, Physiology and

proliferation were analysed.

Immunology, University of Cordoba; CIBER Physiopathology of Obesity,

Cell culture studies demonstrated that low doses of TIP, at 48 h, induced cell

Cordoba, Spain.

cycle arrest in G2/M phase (50%, P!0.01), cell death (20%), and inhibition of

cell viability

(P!0.001), only in the HRAS mutated cell line. PD at low

concentration increased significantly cell cycle arrest on G0/G1 phase (80%,

A growing number of studies suggest that extracellular fragments derived from

P!0.05), only in cell lines with deletion/mutation in CDKN2A or CDKN2B

plasma membrane receptors can play relevant functional roles in the development

genes, however only higher doses induced more than 50% of cell death. The

and progression of certain tumoral pathologies which might, therefore, serve as

inhibition of cell viability was more pronounced in cell lines with deletion/muta-

novel tools in the diagnostic and prognostic of such pathologies. In this scenario,

tion in CDKN2A or CDKN2B genes than in wild type thyroid cancer cell lines or

the truncated somatostatin receptor sst5TMD4, which is overexpressed in various

in normal thyroid cells (P!0.05).

endocrine-related cancers

(i.e. breast, prostate, neuroendocrine, liver and

In conclusion, this study suggests that TIP and PD, which are currently in clinical

pituitary), is an aberrant splicing variant with only 4 transmembrane domains,

trials for other types of cancer, could play a relevant role in inhibiting the

wherein its C-terminal tail is exposed towards the extracellular matrix and could,

progression of ATC, depending on the specific molecular profile of the tumour.

therefore, be the substrate for proteolytic enzymes. Thus, to explore the plausible

DOI: 10.1530/endoabs.49.GP126

generation of soluble peptides derived from the sst5TMD4 extracellular domain

and their potential patho-physiological implications, in silico and in vitro

approaches were implemented using several cancer-derived cell lines (i.e. breast,

prostate, neuroendocrine and liver). Firstly, in silico analysis predicted the

existence of two cleavage sites for metalloproteases (MMP) 2, 9, 14 and/or 16,

which could generate the release of three possibly soluble peptides. We, then,

chemically synthetized these sst5TMD4-derived peptides and demonstrated that

they were able to enhance malignancy features (proliferation, migration and

dedifferentiation processes) in all the tumoral cell lines tested, probably acting

through PI3K/Akt and/or MEK/ERK signalling pathways. Moreover, treatment

with sst5TMD4-derived peptides altered the expression pattern of several genes

involved in cancer development and progression (e.g. certain MMPs, Ki67,

ARP2/3 or CD24/44). Therefore, based on these results, it is possible that

sst5TMD4-derived peptides could be linked to the pathological role of sst5TMD4

previously observed in these tumoral pathologies. Altogether, these studies

provide new information about the patho-physiological role of this truncated

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variant of sst5 and suggest that sst5TMD4-derived peptides could be potential

Benign prostatic hyperplasia is associatied with liver inflammation: it’s

candidates for future studies aimed to identify novel diagnostic, prognostic and/or

time for prevention?

therapeutic targets in certain endocrine-related cancers.

Giorgio Ivan Russo², Aldo E. Calogero¹, Giuseppe Morgia²,

DOI: 10.1530/endoabs.49.GP128

Rosita Angela Condorelli¹ & Sandro La Vignera²

¹Andrology Center of Catania University, Catania, Italy;²Urology Center of

Catania University, Catania, Italy.

Metabolic Syndrome (MetS) has been frequently associated with an overall

GP129

inflammation status, called “metaflammation”, including atherosclerosis and non-

Androgen receptor activation inhibits endothelial cell proliferation

alcholic steatohepatitis

(NASH), In this study we aimed to evaluate the

through an extra-nuclear signaling pathway

relationship between intra-prostatic inflammation and NASH in a cohort of

Yen-Nien Huo¹, Shauh-Der Yeh², Chih-Ming Chou³ & Wen-Sen Lee⁴

patients affected by BPH. Between January

2012 and January

2016,

132

¹Graduate Institute of Medical Sciences, Medical College, Taipei Medical

consecutive patients with BPH-related lower urinary tract symptoms (LUTS) who

University, Taipei 110, Taiwan;²Departments of Urology, Taipei 110,

underwent transurethral resection of the prostate were prospectively enrolled. The

Taiwan;³Departments of Biochemistry and Molecular Cell Biology,

presence of NASH was evaluated using the NASH score: 1.18*MetS (yesZ1)C

Taipei 110, Taiwan;⁴Departments of Physiology, School of Medicine,

0.45*Diabetes

(yesZ2)C0.15*fasting serum insulin C0.04*serum AST

Medical College, Taipei Medical University, Taipei 110, Taiwan.

0.94*(AST/ALT) - 2.89. A cut-off of 1.05 was set to predict NASH (AUC:

0.82). Prostate samples were anlaysized for the evaluation of inflammation and

this was classified accordindg to Irani score (score from 0 to 6). Patients with viral

The effect of androgen on angiogenesis has been documented. However, its

hepatitis or alcohol steatohepatitis were excluded. A final cohort of 132 patients

molecular mechanisms underlying has not been well illustrated. Here, we show

were included. The median age was 70.8 (interquartile range (IQR) 64.65-73.97),

that treatment with an androgen receptor (AR) agonist, metribolone (R1881) at

the median IPSS was 24.0 (IQR; 20.0-25.75) and the median prostate volume was

a range of concentrations (0.05-5 nM) or dihydrotestosterone (DHT) at a range

50.5

(IQR: 40.0-72.25). The prevalence of patients affected by MetS alone was

of concentrations

(0.4-40 nM) caused concentration-dependent inhibition of

56.8% (76/132), by NASH in 56.8% (76/132) and by severe intraprostatic

proliferation in human umbilical venous endothelial cells (HUVEC). The R1881-

inflammation (Irani R4) in while by the both disease in 27.3% (36/132). When

induced proliferation inhibition was also observed in human dermal micro-

considering patients with Irani score R4, we observed significant increase of

vascular endothelial cells

(HDMVE). Blockade of the AR activity by pre-

NASH score (K0.45 vs K1.01; P!0.01). The age-adjusted linear regression

treatment with HF (5 nM), an AR antagonist, or knockdown of AR expression

analysis demonstrated that waist circumference

(rZ0.35; P!0.01), fasting

using the shRNA technique abolished the R1881-induced proliferation inhibition

glucose (rZ0.32; P!0.01), LDL (rZ0.15; P!0.05), tryglycerides (rZ0.42;

in HUVEC, suggesting that AR receptor activation can inhibit endothelial cell

P!0.01) and Irani score (rZ0.12; P!0.05) were associated with increase in

proliferation. To further delineate the signaling pathway involved in the AR

NASH score. The age adjuested logistic regression analysis revealed that Irani

activation-induced proliferation inhibition, our data indicate that R1881 inhibited

score R4 (OR: 3.06; P!0.05) was an independent risk factor of NASH. Further,

proliferation in vascular endothelial cells through activating the AR/cSrc/AKT/-

the combination between MetS and NASH was significantly associated with

p38/ERK/NFkB signaling pathway, which in turn up-regulated the expression of

severe intra-prostatic inflammation (OR: 10.8; P!0.01) while vs MetS as single

p53, p21 and p27 protein, and finally reduced endothelial cell proliferation. Using

alteration. Patients with BPH are more frequently associated with a parallel liver

the zebrafish model, we also demonstrate that R1881 inhibited angiogenesis

inflammation. These findings can be explained by the metaflammation condition,

through the AR-mediated pathway in vivo. The findings of the present study

associated with metabolic aberration. Further studies should be conducted with

highlight the molecular mechanisms underlying AR activation-induced prolifer-

the scope to revert or prevent prostate related inflammation.

ation inhibition in vascular endothelial cells.

DOI: 10.1530/endoabs.49.GP127

DOI: 10.1530/endoabs.49.GP129

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP130

an important mediator of hot flushes in rodents and elevated hypothalamic

expression occurs in menopausal women. Neurokinin B acts via the neurokinin 3

Long non-coding RNA expression profiles in human parathyroid

receptor. We therefore hypothesised that neurokinin 3 receptor antagonism could

tumors

be a novel treatment for menopausal hot flushes.

Annamaria Morotti¹, Irene Forno¹, Valentina Andrè², Andrea Terrasi¹,

Methods

Chiara Verdelli², Vito Guarnieri³, Alfredo Scillitani⁴, Leonardo Vicentini⁵,

This phase

2, randomised, double-blind, placebo-controlled, crossover trial

Edoardo Beretta⁶, Valentina Vaira^1,7 & Sabrina Corbetta⁸

assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901)

¹Division of Pathology, Department of Pathophysiology and Trans-

on menopausal hot flushes in an ambulatory setting

(Clinicaltrials.gov

plantation, University of Milan, Fondazione IRCCS Ca’ Granda Ospedale

NCT02668185). Sixty-eight women were screened between February and

Maggiore Policlinico, Milan, Italy;²Laboratory of Experimental Endo-

October 2016 in a single-centre, of which 37 were randomised and included in

crinology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy;³Genetic

an ITT analysis. Twenty-eight participants (aged 49-62yrs, experiencing O7 hot

Medicine, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo

flushes/24 h some of which were reported as bothersome or severe), completed

(FG), Italy;⁴Endocrinology Unit, IRCCS Casa Sollievo della Sofferenza,

the trial, and were included in a Per-Protocol analysis. They received 4 weeks of

San Giovanni Rotondo (FG), Italy;⁵Endocrine Surgery, IRCCS Fondazione

MLE4901 and placebo in random order separated by a washout period.

Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;⁶Endocrine

Randomisation was completed by a central computer, and participants were

Surgery, IRCCS Ospedale San Raffaele, Milan, Italy;⁷Istituto Nazionale

allocated to treatment number in numerical order. Primary outcome was total

Genetica Molecolare “Romeo ed Enrica Invernizzi” (INGM), Milan, Italy;

number of hot flushes during the final week of both treatment periods.

⁸Endocrinology Unit, Department of Biomedical Sciences for Health,

Findings

University of Milan, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.

MLE4901 significantly reduced the total weekly number of hot flushes by 45%

compared to placebo

(adjusted means: placebo

49.01

(CI:

40.81-58.56),

Aberrant epigenetic signatures have been preliminary detected in parathyroid

MLE4901 19$35

(CI:

15.99-23.42), P!0.0001)

(ITT). MLE4901

also

tumors, in terms of microRNAs (miRNAs) and methylome deregulation. In this

significantly reduced weekly hot flush severity, bother, and interference compared

study, we profiled the expression of 90 long non-coding (Lnc) RNAs in 4

to placebo by

41% (P!0.0001), 45% (P!0.0001), and 58% (P!0.0001)

parathyroid carcinomas

(PCas),

parathyroid adenomas

(PAds) and

respectively. Treatment was well tolerated.

parathyroid glands from normocalcemic patients

(PaNs). Matched miRNA

Interpretation

profiles were available for a subset of cases. Unsupervised clustering distributes

Treatment with a neurokinin 3 receptor antagonist (MLE4901) could be practice

samples in two groups clearly distinguishing PCas from PaNs. Further analyses

changing as it safely and effectively relieves hot flush symptoms without the need

identified

9 LncRNAs significantly deregulated between PCas and PaNs, 12

for oestrogen exposure. Larger scale studies of longer duration are now indicated.

LncRNAs between PAds and PaNs, and 23 LncRNAs between PAds and PCas.

Funding

Five LncRNAs with a fold change O

2.0, namely MEG3, SGNH6

and

MRC (UK) (MR/M024954/1)

KCNQ1OT1 downregulated in PCas, NEAT1 and HAR1B upregulated in PAds,

DOI: 10.1530/endoabs.49.GP131

were validated by qPCR in an independent series of 3 PCas, 4 atypical PAds, 22

PAds and 2 PaNs. PCas and atypical PAds showed similar expression levels of the

5 LncRNAs, whereas PAds were distinguished in two clusters with 10 PAds

similar to PaNs. Clinically, PAds with the LncRNA profile similar to normal

glands had lower mean serum calcium and ionized calcium than PAds with the

LncRNA profile similar to PCas and PAds with intermediate profile (10.2G0.5 vs

12.1G0.2 vs 11.5G0.8 mg/dl; PZ0.006 and 1.36G0.06 vs 1.81G0.11 vs 1.51G

0.08 mmol/l; PZ0.0001). Correlating LncRNA and miRNA profiles, we detected

an association between the 5 deregulated LncRNAs and a set of miRNAs,

GP132

including miR-296-5p, previously identified signifcantly downregulated in PCas.

Testosterone administration decreases insulin sensitivity (IS) in adult

Finally, 10 PAds were characterized for the MEN1 gene expression level: PAds

female sheep born to testosterone treated mothers

with lower nuclear menin expression had decreased expression of two LncRNAs

Albert Carrasco¹, Monica P Recabarren¹, Daniel Sandoval¹,

mapping on chromosome 11: KCNQ1OT1 on 11p15.5 and NEAT1 on 11q13.1. In

Teresa Sir-Petermann² & Sergio E Recabarren¹

conclusion, LncRNAs are deregulated in parathyroid tumors and identify 3

¹Laboratory of Animal Physiology and Endocrinology, Faculty of

clusters of parathyroid tumors with different clinical activity. Moreover,

Veterinary Sciences, Universidad de Concepcion, Faculty of Veterinary

LncRNAs deregulation in PAds may be modulated by the genetic background,

Medicine, Chillan, Region del BioBio, Chile;²Laboratory of Endocrinology

while they may be involved in miRNAs deregulation.

and Metabolism, Western School of Medicine, Universidad de Chile

DOI: 10.1530/endoabs.49.GP130

Western School of Medicine, Santiago, Chile.

Different animal models have been used to study the postnatal effect of a prenatal

exposure to an androgen excess on the female offspring. We have established a

sheep model to test the hypothesis that the intrauterine environment of the PCOS

mother may play a role in the etiology of the PCOS. In this regard, our sheep

Female Reproduction

model for the study of PCOS has the advantage that provides mainly an

androgenized milieu to the fetus in comparison to pregnant PCOS women who

GP131

offers a hyperandrogenic and hyperinsulinemic intrauterine environment to the

Neurokinin 3 receptor antagonism as a novel treatment for menopausal

fetus. Previous results from our laboratory have demonstrated that female sheep

hot flushes: a phase 2, randomised, double-blind, placebo-controlled

born to mothers receiving testosterone (T) during part of their pregnancy exhibit

trial

features from early postnatal life until adulthood resembling those of PCOS

Julia Prague¹, Rachel Roberts¹, Alexander Comninos¹, Sophie Clarke¹,

women. In the present work the programming effect of prenatal T on the IS was

Channa Jayasena¹, Zachary Nash¹, Chedie Doyle¹, Deborah Papadopoulou¹,

explored in adult females born to T treated mothers (T-females), and born to

Stephen Bloom¹, Pharis Mohideen², Nicholas Panay^3,4, Myra Hunter⁵,

untreated mothers (C-females). Our aim was to establish if exogenous T may

Johannes Veldhuis⁶, Lorraine Webber⁷, Les Huson⁸ & Waljit Dhillo¹

exacerbate the insulin resistance due to programming effect of prenatal exposure

¹Department of Investigative Medicine, Imperial College, London, UK;

to T. Both groups were injected with T, twice weekly (40 mg per dose), for 8

²Millendo Therapeutics, Inc., Michigan, USA;³Department of

weeks, beginning at 30 weeks of age. Females were estrous synchronized with

Gynaecology, Queen Charlotte’s & Chelsea Hospital and Chelsea &

prostaglandin and 48 hours after the last T dose, an IVGTT was carried out. On

Westminster Hospital, London, UK;⁴Institute of Reproductive and

the day of the IVGTT, there was no difference in plasma concentration of

Developmental Biology, Imperial College London, London, UK;⁵Institute

estradiol, progesterone and T between groups. IS indexes were calculated with the

of Psychiatry, Psychology and Neuroscience, King’s College, London, UK;

plasma insulin and glucose concentrations during the IVGTT. Plasma levels of

⁶Mayo Clinic, Minnesota, USA;⁷Scientific Partnering & Alliances,

glucose were not different during the IVGTT but T-females secreted more insulin

Innovative Medicines & Early Developmental Biotech Unit, Astrazeneca,

(P!0.05) than C-females. The ratio insulin/glucose before the IVGTT tended to

Melbourn, UK;⁸Division of Experimental Medicine, Imperial College,

be higher in T-females (PZ0.054) and the IS Index-C tended to be lower in

London, UK.

T-females compared to C-females (PZ0.054). Results show that T administration

to T-females amplifies the effect of a glucose challenge on the insulin secretion

Background

compared to C-females, suggesting an exacerbation of the insulin resistance

Hot flushes affect 70% of menopausal women, can be long-lasting, and often

induced by fetal programming.

severely impact on physical, psychosocial, sexual, and overall wellbeing.

DOI: 10.1530/endoabs.49.GP132

Hormone replacement therapy is effective but not without risk. Neurokinin B is

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP133

Results

Among the randomized patients in the preceding study (NZ487), 397 were

Influence of BMI on AMH levels in non-PCOS women

enrolled in this extension study; 77 to placebo, 78 to 89 to relugolix groups, and

Joana Simo˜ es-Pereira1, Joaquim Nunes2, Ana Aguiar2, Sandra Sousa2,

69 to leuprorelin. Baseline characteristics were similar between randomized

Cátia Rodrigues², J Sampaio Matias³ & Carlos Calhaz-Jorge²

patients and all patients who entered the extension study. The incidences of

¹Endocrinology Department, Instituto Português de Oncologia de Lisboa,

adverse events including metrorrhagia, menorrhagia, and hot flush in the relugolix

Francisco Gentil, Lisbon, Portugal;²Reproductive Medicine Unit, CHLN-

40 mg group were similar to those in the leuprorelin group. Dose-dependent bone

Hospital de Santa Maria, Lisbon, Portugal;³Clinic Pathology, CHLN-

density loss was observed with relugolix treatment, with the relugolix 40 mg

Hospital de Santa Maria, Lisbon, Portugal.

result consistent with the leuprorelin result. The change from baseline in mean

visual analogue scale score for pelvic pain (in mm) during the last 4 weeks of

Introduction

treatment period was K3.222 in the placebo group, K6.849, K9.032, and

Anti-Mullerian Hormone (AMH) is a useful marker of ovarian reserve (OR),

K11.924 in relugolix

10 mg, 20 mg and 40 mg groups, respectively, and

since it remains stable inter/intra-cycles and presents a good correlation with

K12.552 in the leuprorelin group. Estradiol levels decreased with increasing dose

ultrasonographic antral follicular count. Obesity/overweight are increasing and

of relugolix and were maintained below the postmenopausal levels throughout the

may affect the reproductive health. However, previous studies regarding the effect

24-week relugolix 40 mg treatment period.

of body mass index (BMI) on AMH levels are discordant. Our main goal was to

Conclusion

evaluate the influence of BMI in AMH levels in women with infertility.

Treatment with relugolix for

weeks was generally well tolerated and

Methods

demonstrated similar pelvic pain reduction as leuprorelin in women with EM.

Revision of medical records of 995 women who performed AMH determinations

Relugolix, a once-daily oral nonpeptide GnRH receptor antagonist, demonstrated

as part of their fertility workup, between 2011-2016. Women diagnosed with

similar benefit to injectable leuprorelin in this Phase 2 study.

polycystic ovarian syndrome (Rotterdam criteria) were excluded. We analysed

DOI: 10.1530/endoabs.49.GP134

the influence of BMI, age, ethnicity, smoking and previous ovarian surgery on

AMH levels.

Results

Median AMH concentration was 1.75(0-26)ng/dL and median age at AMH

determination was 35(19-40)years. These women evidenced a median BMI of

23(15-39) kg/m2 and had been struggling with infertility for 60(7-432) months.

The majority [700(70.4%)] presented primary infertility. Caucasian women were

more represented [889(89.3%)]. Smoking habits (present/past) were present in

359(36.1%), and

147(14.8%) harboured a history of ovarian surgery. On

univariable analysis AMH was not correlated with BMI (rZ0.52/PZ0.10); the

only factors influencing AMH were age (P!0.001), ethnicity (PZ0.005) and

GP135

previous surgery (P!0.001). On multivariable analysis, age was the only variable

Brown adipose tissue thermogenesis in women with polycystic ovary

significantly associated with AMH, evidencing a reduction of 6.2% for each

syndrome

additional year (P!0.0001). Furthermore, we verified a trend suggesting an

Soulmaz Shorakae^1,2, Eveline Jona¹, Barbora de Courten^1,2,

AMH reduction of 22% (PZ0.08) in melanodermic patients comparing with the

Gavin Lambert^3,4, Elisabeth Lambert³, Sarah Phillips³, Iain Clarke⁵,

caucasian ones, when controlling for the other variables.

Helena Teede^1,2 & Belinda Henry⁶

Conclusion

¹Monash Centre for Health Research and Implementation, Monash

We report one of the largest series evaluating the influence of BMI on AMH

University, Melbourne, Australia;²Diabetes and Vascular Medicine Unit,

levels and, consequently, on OR. BMI does not seem to affect AMH levels. The

Monash Health, Melbourne, Australia;³Human Neurotransmitters

reported concerns on infertility in overweight/obese women may be related to

Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Australia;

follicular development/endometrial disorders, rather than decreased OR.

⁴Department of Physiology, Monash University, Melbourne, Australia;

DOI: 10.1530/endoabs.49.GP133

⁵Neuroscience Program, Monash Biomedicine Discovery Institute,

Department of Physiology, Melbourne, Australia;⁶Metabolic Disease and

Obesity Program, Monash Biomedicine Discovery Institute, Department of

Physiology, Melbourne, Australia.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of

reproductive age women and is characterized by reproductive, metabolic and

psychological features exacerbated by weight gain. Weight management in PCOS

is challenged by propensity to weight gain and lack of sustainable dietary

interventions. Body weight is regulated by calorie intake and the rate of energy

expenditure. Metabolically active brown adipose tissue (BAT), contributing to

energy dissipation, has been described in humans. The thermogenic activity of

GP134

BAT is controlled by the sympathetic nervous system (SNS). Sex hormones also

Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor

play role in modulating BAT. Human studies confirm association of

antagonist, in women with endometriosis (EM)-associated pain: Phase 2

supraclavicular skin temperature, where most human BAT is located, with

safety and efficacy 24-week results

BAT activity. This observational study aimed to explore BAT thermogenesis and

Yutaka Osuga¹, Yoshifumi Seki², Masataka Tanimoto², Takeru Kusumoto²,

its associations, for the first time, in PCOS. Cutaneous wireless temperature

Kentarou Kudou² & Naoki Terakawa³

probes (2 cm diameter, 0.5 depths) were taped to supraclavicular (BAT) and

¹The University of Tokyo, Tokyo, Japan;²Takeda Pharmaceutical Company

upper arm (muscle) regions of 49 premenopausal women with PCOS, over

Limited, Osaka, Japan;³Tottori University Faculty of Medicine, Yonago,

96 hours, (mean age: 29.85G5.93, mean BMI: 29.02G5.43), recruited from

Japan.

community. Multiunit muscle SNS activity (by microneurography) and plasma

noradrenaline levels were measured as markers of SNS activity. Fasting lipids,

Objective

serum androgens, markers of insulin resistance and inflammation were measured.

The objective of this Phase 2 study was to evaluate the safety of relugolix when

Recorded temperature data from both regions were available in 41 participants.

administered for 24 weeks in women with EM-associated pain. Efficacy was

Supraclavicular temperature was significantly higher than arm temperature

exploratory assessed using leuprorelin as a reference.

(33.87G0.65

32.23G0.85, P

! 0.0001). Supraclavicular temperature

Design

correlated with testosterone

(rZK0.410, PZ0.011), noradrenaline

(rZK

This was an open-label extension study evaluating safety of 3 doses (10 mg,

0.488, PZ0.005) and triglycerides (rZK0.393, PZ0.015) which remained

20 mg, and 40 mg) of relugolix administered orally once daily for a total of 24

significant after adjustment for BMI. Arm temperature did not correlate with

weeks in women with EM-associated pain, who had participated in a preceding

testosterone, noradrenaline and triglycerides. This is the first study of BAT

12-week study.

thermogenesis in PCOS using cutaneous temperature probes. The negative

Materials and methods

correlation of BAT temperature with noradrenaline levels could implicate a

Premenopausal women with EM-associated pain who completed a preceding

maladaptive thermogenic response to chronic SNS activation in PCOS. Chronic

12-week study and were eligible to continue for an additional 12-week treatment

sympathoexcitation and hyperandrogenism play potential roles in modulation of

were enrolled. The primary endpoint was the safety including assessment of

BAT thermogenesis in PCOS.

change in bone mineral density using dual energy x-ray absorptiometry. Analysis

DOI: 10.1530/endoabs.49.GP135

sets were defined as all patients who were administered the study drug.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP136

Results

Despite no difference in total-testosterone levels, in PCOS with AH (nZ58,

Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin improved beta cell

18.9%) the SHBG (27.6G3.6 vs 44.5G3.3 nmol/L, P! 0.0002) was lower and

function and prevented a conversion rate to MTG and DM2 in

FAI (14.0G2.2 vs 8.7G0.7, P! 0.002), 2-h insulin in OGTT (111.2G26.0 vs

metformin intolerant PCOS with high metabolic risk

77.3G6.9 mUI/L, P!0.044) and systolic BP

(123.7G4.26

114.4G

Andrej Janez, Simona Ferjan & Mojca Jensterle

1.8 mmHg, P!0.045) were higher than in PCOS without AH. SNPs

University Medical Center Ljubljana, Ljubljana, Slovenia.

corresponding to at least 15 genes were positive in CT test with DHEAS levels.

Among them, INSR and CDH13 were the most significant with numerous SNPs

Objective

having a P value ! 1.0!10-5 after Bonferroni correction. In genetic association

Metformin is the first-line therapy for PCOS with high metabolic risk, yet a large

by logistic regression between two groups, other genes were also confirmed, the

proportion of patients cannot tolerate it due to associated gastrointestinal adverse

most influential being IL2RA, PTER, SORCS1, LGR4 and KSR2. For instance,

events. The alternative pharmacological strategy when metformin cannot be

LGR4 (Chr 11) was associated with P! 0.005, OR 5.6, 95%CI [1.6-19].

tolerated is not well established in this population. Our aim was to evaluate

Conclusion

whether sitagliptin

(SITA) preserves metabolic profile in metformin (MET)

These data indicated that, in PCOS patients, AH may be in part explained by

intolerant PCOS with high metabolic risk.

genetic susceptibility. Despite a full array of genes involved, the insulin-

Design and methods

resistance appears as potential actor of AH in PCOS.

A 12-week prospective randomized open-label study was conducted with 30

DOI: 10.1530/endoabs.49.GP137

obese MET intolerant women with PCOS (aged 35.0G7,2 years, BMI 36,9G

5.5 kg/m²). They were randomized to lifestyle intervention and SITA 100mg QD

or lifestyle intervention alone as controls (CON). All participants underwent

standard anthropometric, endocrine measurements and OGTT. Model derived

indexes of insulin resistance (IR) and b-cell function were calculated.

Results

SITA improved beta cell function as assessed by HOMA beta for 45,9G35,8

(PZ0,001), modified beta cell function index (MBCIZI0XG0/(G120CG60-7))

for 7,9G7 (PZ0,002) and QUICKI for K0,03G0,03 (PZ0,002) and increased

IR as assessed by HOMA-IR and insulin action index (IAIZ1/G0XI0) for 1,8G

1,7 (PZ0,002) and K0,01G0,01(PZ0,003). By contrast, beta cell function

decreased in CON arm. The between group differences were significant for

HOMA-beta (PZ0,000), MBCI (PZ0,010) and QUICKI (PZ0,025). The

conversion rate from normal glucose tolerance to impaired glucose tolerance

(IGT) or T2DM was prevented in SITA (3/15 of subjects with MTG before and

after the study). In CON 4 women had IGT at the beginning. After 12 weeks IGT

GP138

was observed in 2 and T2DM in 3 subjects.

Turner’s syndrome and abnormal liver chemistry: relationship with

Conclusion

karyotype in a large dedicated clinic

SITA improved beta cell function and prevented a conversion rate to IGT and

Matilde Calanchini^1,3, Ahmad Moolla¹, Jeremy W Tomlinson¹,

T2DM in metformin intolerant PCOS with high metabolic risk when compared to

Jeremy Cobbold², Andrea Fabbri³, Ashley Grossman¹ & Helen Turner¹

lifestyle alone.

¹Oxford Centre for Diabetes, Endocrinology and Metabolism - Churchill

DOI: 10.1530/endoabs.49.GP136

Hospital, University of Oxford, Oxford, UK;²Department of Hepatology,

John Radcliffe Hospital, Oxford, UK;³Department of Endocrinology, CTO

Alesini & S. Eugenio, University of Rome Tor Vergata, Rome, Italy.

Introduction

Abnormal liver function tests

([LFTs) are frequently observed in Turner’s

syndrome (TS), although the aetiology is unclear. Obesity is reported as one of the

causes; recently an increased prevalence of elevated GGT was found in TS

patients with a ring X karyotype.

Aim

To analyse the association between abnormal LFTs and TS-related conditions,

and in particular their relationship with the different TS-karyotypes.

Methods

Data on adult TS-patients were collected.

[LFTs was defined as elevated

GP137

aminotransferases G GGT and ALP, for more than 6 months. TS-karyotypes

Genetic susceptibility for adrenal hyperandrogenism in polycystic

were classified in eight groups.

ovary syndrome

Results

Nicoleta Baculescu^1,2, Sarah Haydar³, Monica Livia Gheorghiu^1,2,

109 TS women were studied: mean age 36(G13.1)y, BMI 28.3(G6.9)Kg/m².

Serban Radian^1,2, Corinne Lautier³, Catalina Poiana^1,2, Michel Pugeat⁴ &

45,X was found in 47 patients (46.1%), mosaicism 45,X/46,XX or 45,X/47,XXX

Florin Grigorescu³

in 15 (15.7%), 4 (3.9%) del(X)(p), 1 (1%) del(X)(q), 10 (9.8%) isochromo-

¹Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;

some(X)(q), 10 (9.8%) ring X, presence of Y in 4 (3.9%) and 10 (9.8%) other

²C.I. Parhon Institute of Endocrinology, Bucharest, Romania;³IURC,

TS-karyotypes.

UMR-204 NUTRIPASS, University of Montpellier, Montpellier, France;

38/109 (35%) presented with [LFTs, most frequently a [GGT. Differences

⁴Fédération d’Endocrinologie, Hopital Neuro-Cardio, University of Lyon,

between the normal-LFTs-group versus the [LFTs-group were found for age

Lyon, France.

(33.8 vs 41y, PZ0.008), Tot-Chol (4.9 vs 5.5 mmol/L, PZ0.005), LDL-Chol (2.7

vs 3.2 mmol/L, PZ0.006), and triglycerides (1.1 vs 1.5 mmol/L, PZ0.02). No

Background

differences were noted analysing anthropometric values, HbA1c, history of

Hyperandrogenism is a main feature of the polycystic ovary syndrome (PCOS).

diabetes, hypertension or autoimmunity.

Although its ovarian origin is well recognized, laboratory investigation suggested

The prevalence of [LFTs was significantly higher in the isochromosome(X)(q)-

the contribution of adrenal gland, albeit of unknown mechanism.

group (PZ0.0003); the mosaicism-group had a decreased prevalence of [LFTs

Aim

(PZ0.0092). Using the stringent ALT cut-off of 19UI/L, this was commoner only

To understand the contribution of genetic factors in adrenal hyperandrogenism

in the i(X)(q)-group (PZ0.0134). The i(X)(q)-group showed a similar clinical

(AH) we investigated genome wide SNPs in subgroups of PCOS patients stratified

phenotype compared to 45,X and no increased prevalence of autoimmune disease.

as function of DHEAS levels in two ethnic populations (Romanians and French).

Conclusions

Subjects and methods

This study shows 1) [LFTs are common in TS; 2) the prevalence of [LFTs

Patients recruited during European MEDIGENE program (FP7-279171) with

increases with age and is associated with increased cholesterol and triglycerides;

PCOS (nZ307) of 18-42 years old were stratified in two groups as function of

3) for the first time, a relationship between [LFTs and karyotype was found,

DHEAS level greater than 95th percentiles in age-matched controls. Genotyping

suggesting that liver biochemical abnormalities could be triggered by over-

was performed with customized MEDISCOPE microarray chip with 759 000

expression of Xq genes escaping inactivation.

SNP. Influential SNPs were determined by correlation trend (CT) test and then by

DOI: 10.1530/endoabs.49.GP138

genetic association in two subgroups of patients.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

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(ANOV,PCOM). NAFLD was assessed using NAFLD liver fat score (NAFLD-

LFS) cutoff O K0.640. Differences between groups were age adjusted.

Sensitivity of hypothalamo-pituitary-adrenal axis in women with PCOS

Results

Djuro Macut¹, Ivana Bozic-Antic¹, Jelica Bjekic-Macut², Dusan Ilic¹,

NAFLD was more prevalent in PCOS in comparison to controls (59.7 vs 44.4%,

Danijela Vojnovic-Milutinovic³, Olivera Stanojlovic⁴, Tamara Bogavac¹,

PZ0.009). Our PCOS group consisted of 268 women with phenotype A, 129 with

Bojana Popovic¹, Tatjana Isailovic¹, Valentina Elezovic¹ &

phenotype B, 47 with phenotype C and 35 with phenotype D. Prevalence of

Sanja Ognjanovic¹

NAFLD in phenotypes were: A: 59%, B:61%, C:53% and D:66%. There were

¹Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of

significant differences in the prevalence of NAFLD between controls and

Medicine, University of Belgrade, Belgrade, Serbia;²CHC Bezanijska kosa,

phenotype A (PZ0.015), phenotype B (PZ0.015) and phenotype D (PZ0.028).

Faculty of Medicine, University of Belgrade, Belgrade, Serbia;³IBISS,

There were no significant differences between phenotypes.

University of Belgrade, Belgrade, Serbia;⁴Institute of Physiology, Faculty

Conclusions

of Medicine, University of Belgrade, Belgrade, Serbia.

NAFLD is more prevalent in obese PCOS women than in obese BMI-matched

controls. All four phenotypes have the same risk for NAFLD which confirms

Introduction

susceptibility of PCOS as a whole to develop metabolic derangements.

Increased adrenal androgen production is present in 20-60% of women with

DOI: 10.1530/endoabs.49.GP140

polycistic ovary syndrome (PCOS). Possible mechanism is not clarified yet and

could be related to altered hypothalamic-pituitary-adrenal-axis (HPA) activity or a

consequence of adrencortical steroidogenic abnormalities. The aim of the study was

to assess HPA sensitivity in PCOS women using different doses of dexamethasone.

Methods

We analyzed 359 women with PCOS diagnosed using ESHRE/ASRM criteria (age:

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25.6G5.3 years, BMI: 25.1G6.4 kg/m²), and 58 BMI-matched healthy controls

Effects of central sympathoinhibition with moxonidine on the elevated

(age 28.79G6.1 years, BMI 23.7G6.1 kg/m²). In all subjects serum ACTH,

sympathetic nervous activity and downstream metabolic abnormalities

morning serum cortisol (SC), and DHEAS were measured, and SC and DHEAS

observed in polycystic ovary syndrome

determined after overnight dexamethasone test with 0.5 mg (Dex_0.5mg) and 1 mg

Soulmaz Shorakae^1,2, Elisabeth Lambert^3,4, Eveline Jona¹, Carolina

(Dex_1mg), and marked as SC_dex0.5, SC_dex1, DHEAS_dex0.5

and DHEAS_dex1,

Ika Sari³, Barbora de Courten^1,2, Gavin Lambert^3,4 & Helena Teede^1,2

respectively. Differences between groups were age adjusted and data are presented

¹Monash Centre for Health Research and Implementation, Monash

as ANCOVA-mean (95%CI).

University, Melbourne, Australia;²Diabetes and Vascular Medicine Unit,

Results

Monash Health, Melbourne, Australia;³Human Neurotransmitters

SC was borderline higher [437.9(421.6-454.3) vs. 395.7(356.7-437.8)nmol/l, PZ0.052]

Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Australia;

and DHEAS significantly higher [7.7(7.3-8.2) vs. 5.6(4.6-6.7)nmol/l, P!0.001] in PCOS

⁴Department of Physiology, Monash University, Melbourne, Australia.

than in controls. There was no difference in ACTH among groups. After dexamethasone

tests, both groups significantly lowered SC and DHEAS in comparison to basal analyses. In

The role of the sympathetic nervous system (SNS) in the pathophysiology of

comparison to controls, PCOS had borderline higher SC_dex0.5 [49.9 (22.9-76.9) vs.

PCOS and associated cardiometabolic risks is emerging. Previous studies support

78.5(67.8-89.1)nmol/l, PZ0.055] but similar percentage of SC suppression [86.5 (80.6-

increased SNS activity in PCOS, potentially contributing to metabolic features via

92.3) vs. 82.8(80.4-85.3)%, PZ0.26]. PCOS had lower SC_dex1 [26.8 (23.5-30.2) vs.

multiple mechanisms including insulin resistance. Moxonidine is a second-

22.9(21.6-24.2)nmol/l, PZ0.055] and suppressed SC more than controls [92.5(91.6-93.5)

generation imidazoline I₁ agonist, acting centrally, inhibiting sympathetic outflow

vs.

94.5(94.1-94.9)%, P!0.001]. There were no differences in DHEASdex0.5 and

at the level of rostral ventrolateral medulla with known beneficial effects on

DHEAS_dex1 between groups. Suppression of DHEAS was similar after Dex_0.5mg

hypertension, insulin sensitivity, dyslipidemia and inflammation. This study

(PZ0.92), but PCOS suppressed DHEAS after Dex_1mg less than controls [32.1 (25.9-

aimed to explore pharmacological modification of SNS activity, for the first time,

38.3) vs. 47.7(34.0-61.4)%, PZ0.04].

in women with PCOS, using moxonidine. 51 premenopausal women (mean age:

Conclusions

29.8G5.9 years, mean BMI: 29.0G5.4 kg/m²) with PCOS were recruited, from a

Our women with PCOS, in comparison to BMI-matched controls have increased age-

community setting, in a double blind placebo controlled clinical trial. 48 women

adjusted HPA axis sensitivity to 1 mg but not to 0.5 mg of dexamethasone. DHEAS

were weaned off any interacting medication for 3 months then randomized to

production in PCOS seems to be more independent of ACTH than in controls.

moxonidine (0.2mg daily initially, up titrated to 0.4mg daily in 2 weeks) (nZ23)

DOI: 10.1530/endoabs.49.GP139

or placebo (nZ25) for 3 months. Multiunit muscle SNS activity (MSNA by

microneurography), heart rate variability

(HRV) and endothelial function

(ischaemic reactive hyperaemia index (RHI)) were examined. Fasting lipids,

serum androgens, markers of insulin resistance and inflammatory markers were

measured prior to and following intervention. 45 women completed the trial (19

moxonidine and 23 placebo). Change in MSNA (K3.23G6.71 vs K2.81G8.2

bursts per minute, PZNS), HRV

(5.26G13.56

2.95G15.37 nu in low

frequency component, PZNS) and endothelial function (0.10G0.70 vs 0.06G

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0.67 in RHI, PZNS) did not differ significantly with moxonidine compared to the

Nonalcoholic fatty liver disease liver fat score (NAFLD-LFS) could be

placebo. Mean changes in BP, fasting lipids, HOMA-IR, hs-CRP and androgens

used for the assessment of NAFLD in women with PCOS

were similar in both groups. In women on moxonidine, change in BMI correlated

Jelica Bjekic-Macut¹, Ivana Bozic-Antic², Konstantinos Tziomalos³,

positively with change in MSNA (r²Z0.593, PZ0.03). Central sympathoinhibi-

Dusan Ilic², Danijela Vojnovic-Milutinovic⁴, Olivera Stanojlovic⁵ &

tion with moxonidine does not modify higher SNS activity and downstream

Djuro Macut²

metabolic abnormalities in PCOS. Sympathoexcitation in PCOS may be driven

¹CHC Bezanijska kosa, Faculty of Medicine, University of Belgrade,

peripherally or from other brain regions with further research needed.

Belgrade, Serbia;²Clinic of Endocrinology, Diabetes and Metabolic

DOI: 10.1530/endoabs.49.GP141

Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia;

³Department of Medicine, University of Thessaloniki, Thessaloniki, Greece;

⁴IBISS, University of Belgrade, Belgrade, Serbia;⁵Institute of Physiology,

Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

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Introduction

Steroid receptors involvement in enamel hypomineralization resulting

A relation between polycystic ovary syndrome (PCOS) and nonalcoholic fatty

from exposure to low-dose DEHP and bisphenol A

liver disease (NAFLD) was demonstrated recently. Both NAFLD and PCOS are

Bui Ai Thu^1,2, Sophia Houari^1,2, Sophia Loiodice^1,2, Katia Jedeon^1,2,

associated with increased risk for type 2 diabetes and cardiovascular disease.

Ariane Berdal^1,2 & Sylvie Babajko^1,2

NAFLD liver fat score (NAFLD-LFS) has been implicated as a non-invasive

¹University Paris Diderot, Paris, France;²INSERM, Paris, France.

surrogate marker for NAFLD. The aim of this study was to identify the prevalence

of NAFLD in different PCOS phenotypes using NAFLD-LFS.

Methods

The environment has become increasingly contaminated by various pollutants

We evaluated 489 obese PCOS women (PCOS: 33.2G5.7 kg/m²; 25.6G6.2

including endocrine disrupting chemicals (EDCs). This has led to an increase in

years) diagnosed using ESHRE/ASRM criteria and 97 BMI-matched obese

the incidence and gravity of known pathologies and the emergence of new ones,

healthy women (controls: 32.5G5.5 kg/m²; 31.7G5.1 years). PCOS group was

including dental pathologies as the Molar Incisor Hypomineralization (MIH).

divided into 4 phenotypes: A [anovulation (ANOV), hyperandrogenism (HA),

Among the thousands of EDCs, bisphenol A (BPA) and phthalates (DEHP) are

polycystic ovary morphology (PCOM)], B (ANOV,HA), C (HA,PCOM) and D

widely used by the plastic industry and responsible to frequent contaminations.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

We previously showed a link between experimental exposures to low-dose BPA

GP144

and enamel defects similar to MIH (1). The characterization of enamel defects

Altered protein expression of cell cycle- and EMT-associated genes by

may be helpful to propose them as early markers of exposure to EDCs thanks to

bisphenol compounds in MCF-7 CV human breast cancer cells via

enamel unique properties.

estrogen receptor dependent pathway

The aims of the present work are 1) to compare mouse enamel defects resulting

Ana Patricia Ayala-Cuellar, Kyung-A Hwang & Kyung-Chul Choi

from exposure to low-dose BPA and/or DEHP and,

2) to approach the

Laboratory of Biochemistry and Immunology, College of Veterinary

mechanism, of action of both EDCs during amelogenesis.

Medicine, Chungbuk National University, Cheongju, Chungbuk,

The study was carried out on mice exposed to 5 and 50 mg/kg per day DEHP with

Republic of Korea.

or without 5 mg/kg per day BPA. Exposed animals present enamel defects on their

incisors with similar characteristics than those of MIH affected teeth. In addition,

11% of DEHP mice presented enamel breakdown suggesting a weak enamel

Bisphenol-A (BPA) has been considered as an endocrine disrupting chemical

structure. As both EDCs act through steroid receptors, their presence and

(EDC) because it can exert estrogenic properties. For bisphenol-S (BPS) and

expression levels were investigated in ameloblasts by immunofluorescent assays

bisphenol-F (BPF) that are BPA analogs and substitutes, their risk to estrogen-

and RT-qPCR respectively. We found that dental epithelium express a specific

dependent cancer has been reported rarely compared with the numerous cases of

combinatory of steroid receptors (AR, ERs, ERRs, RARa/RXRa, VDR, GR, MR

BPA. In this study, we examined whether BPA, BPS, and BPF can lead to the

and PGR) depending on their stage of differentiation. These data suggest that

proliferation, migration, and epithelial mesenchymal transition (EMT) of MCF-7

depending on their nature and the time of exposure, phthalates and BPA could

clonal variant (MCF-7 CV) breast cancer cells expressing estrogen receptors

affect enamel quality (through AR) and/or quantity (through ERRg and ERa).

(ERs). In a cell viability assay, BPA, BPS, and BPF significantly increased

Studies are currently driven to decipher the functional role of AR in the

proliferation of MCF-7 CV cells compared to control (DMSO) as did 17b-

mechanism of action of both EDCs in ameloblasts.

estradiol (E2). In Western blot assay, BPA, BPS, and BPF enhanced the protein

References

expression of cell cycle progression genes such as cyclin D1 and E1. In addition,

(1) Jedeon et al., Am J Pathol, 2013, 183(1):108-18.

MCF-7 CV cells lost cell to cell contacts and acquired fibroblast-like morphology

DOI: 10.1530/endoabs.49.GP142

by the treatment of BPA, BPS, or BPF for 24 h. In cell migration assay, BPA,

BPS, and BPF accelerated the migration capability of MCF-7 CV cells as did E2.

In relation with the EMT process, BPA, BPS, and BPF increased the protein

expression of N-cadherin, while they decreased the protein expression of

E-cadherin. When BPA, BPS, and BPF were co-treated with ICI 182,780, an ER

antagonist, proliferation effects were reversed, the expression of cyclin D1 and

cyclin E1 was down-regulated, and the altered cell migration and expression of

N-cadherin and E-cadherin by BPA, BPS, and BPF were restored to the control

level. Thus, these results imply that BPS and BPF also have the risk of breast

cancer progression as much as BPA in the induction of proliferation and

migration of MCF-7 CV cells by regulating the protein expression of cell cycle-

related genes and EMT markers via ER-dependent pathway. (This work was

supported by a grant from the Next-Generation BioGreen 21 Program (no.

PJ011355-2015), Rural Development Administration, Republic of Korea.)

Keywords: Human breast cancer cells, endocrine disrupting chemicals, bisphenol-A,

bisphenol-S, bisphenol-F, epithelial-mesenchymal transition, migration

DOI: 10.1530/endoabs.49.GP144

Male Reproduction and Endocrine Disruptors

GP143

In vitro effects of Bisphenol A on two metabolic receptors signaling:

MC4R and FFAR1

Mathilde Munier^1,4, Mathilde Louvigné⁵, Hélène Rudelle⁴,

Louis Gourdin^1,3, Claire Briet^4,3, Daniel Henrion^1,2, Marie Chabbert^1,2,

Régis Coutant^3,5 & Patrice Rodien^3,4

¹UMR CNRS6015-INSERM1083, Angers, France;²MITOVASC Institute,

GP145

Angers, France;³Reference Center for Rare Diseases of Hormonal

Reproductive toxicity of low dose nonylphenol in mice: a

Receptivity, Angers, France;⁴Department of Endocrinology, Angers,

two-generation study

France;⁵Department of Pediatric Endocrinology, Angers, France.

Sung-Ho Lee, Yong Bin Kim & Hee Su Kim

Sangmyung University, Seoul, Republic of Korea.

Metabolic diseases (type 2 diabetes (T2D) and obesity) prevalence is increasing in

the world. This is partly related to a change in lifestyle with an increase of caloric

Nonylphenol (NP), a member of alkylphenol family, has been widely used in both

intake and a decrease of physical activity. Environmental causes are also involved

industry and household. NP is classified as an endocrine-disrupting chemical and

among them exposure to bisphenol A (BPA). The mode of action of the latter is

is known to act as an agonist of the GPER (GPR30). The aim of this study was to

unknown. Beyond a suggesting effect relayed by nuclear receptors, we propose

address the two-generational effects of para-nonylphenol

(NP) on the body

that BPA can act by modulating the functionality of G protein-coupled receptors

weights, reproductive organ weights and histopathologies of ICR mice. We also

involved in the pathophysiology of metabolic disorders. In order to test this

test the potential reproductive toxicity of octylglucuronide (OG), a substitute

hypothesis, we analyzed the effect of BPA on the activity of MC4R and fatty acid

candidate for NP. The testing drugs were administered as drinking water (50 and

receptor FFAR1 (GPR40). MC4R is involved in obesity by regulating dietary

500 ug/l) throughout the pre-mating period of P0 animals and lactation of F2

intake and energy balance. There are two ligands of MC4R: aMSH (agonist) and

animals. Significant decreases were found in the weights of testis, prostate and

AgRP (inverse agonist). FFAR1

increases the glucose-dependent insulin

seminal vesicle in the F1 NP500 group, in the weights of testis and epididymis in

secretion. It is a new therapeutic target in T2D.

F2 NP50 and NP500 groups. There was no weight change in the OG-treated

Each receptor is transiently expressed in HEK293, and its activity is assessed by

groups. In female, significant decreases in the weights of ovary and uterus in F1

measuring cyclic AMP (cAMP) for MC4R, using a biosensor kit, or calcium for

NP50 group, uterus of F1 NP500 group, and F2 NP500 group were found. The

FFAR1, using a fluorimetric calcium sensor.

weights of ovary in F1 OG50 and OG500 were also significantly decreased.

At a concentration of 10 nM, BPA increased by up to 30% the cAMP production

Histopathological studies revealed that the numbers of Leydig cells were reduced

induced by aMSH and reduced by half the inhibition induced by AgRP, without

in the testes of F1 and F2 NP50 groups. There were no changes in the Leydig cell

modifying the basal activity. These effects are specific for MC4R as BPA did not

numbers of OG groups. In F1 NP500 mice, the increased numbers of primary and

change the activity of the downstream effectors of cAMP pathway (adenylate

secondary follicles and decreased number of corpora lutea were observed. There

cyclase, G protein or phosphodiesterases) or one of endogenous adenosine

was no change in OG-treated group gonad. Finally, vaginal opening was delayed

receptor (negative control).

in F1 NP50 and NP500, and F2 NP50 animals. Present study demonstrated that

In addition,

10 pM BPA decreased by one-third the calcium mobilization

the potential reproductive toxicity in animals long-term exposed to low dose NP

stimulated by GW9508 (a synthetic agonist of FFAR1).

(approximately 15-150 ng of daily intake). Our study also show that OG seems to

We show here new effects of BPA with a disruption of G protein-coupled

be a promising alternative to NP, and further studies are warranted. This work was

receptors activity, which may be worth to take into account when addressing the

supported by the National Research Foundation of Korea Grant funded by the

question of the link between endocrine disruptor and metabolic diseases.

Korean Government (NRF-2016904200).

DOI: 10.1530/endoabs.49.GP143

DOI: 10.1530/endoabs.49.GP145

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP146

MetS rabbits, was significantly ameliorated by MET and completely normalized

by PhyEx. HFD determined a net reduction of electrical field (EF)-vasorelaxation

Psychological rather than organic and/or relational components are

in CC. The relaxant response to sildenafil, abolished in HFD rabbit CC, was

involved in sexual dysfunction in Young/Middle aged human

restored by PhyEx. PhyEx normalized sodium nitroprusside

(SNP)-induced

immunodeficiency virus (HIV)-Infected Men

relaxation, that was enhanced in MetS rabbits. Genes related to NO signaling

Maria Chiara Decaroli¹, Sara De Vincentis¹, Chiara Diazzi¹, Stefano Zona²,

were up-regulated by PhyEx, but not by MET. Similar results were obtained for

Giovanni Guaraldi², Daniele Santi¹ & Vincenzo Rochira¹

smooth muscle-related genes. PDE5 expression was decreased in MetS rabbits

¹Unit of Endocrinology, University of Modena and Reggio Emilia, Modena,

and completely restored by PhyEx. Accordingly, sildenafil-induced increase in

Italy;²Unit of Infectious Diseases, University of Modena and Reggio

SNP relaxation was completely normalized by PhyEx.

Emilia, Modena, Italy.

In conclusion, PhyEx more than metformin, completely restored T levels and

responsiveness to Ach and sildenafil in experimental MetS, even though it was

Background

less effective than metformin in reducing metabolic abnormalities. The effect of

HIV-infection is associated to an increased prevalence of erectile dysfunction

exercise training is most probably related to an improved NO signaling, including

(ED). In HIV-infected men ED seems to be less related to serum Testosterone (T),

PDE5. Hence, PhyEx can be considered a new strategy to treat hypogonadism and

depending from other factors.

ED related to MetS.

Aim

DOI: 10.1530/endoabs.49.GP147

To investigate the role of different components (organic, relational, psycho-

logical) of erectile function by using validate questionnaires in HIV-infected men

with normal serum T.

Methodology

Prospective, cross-sectional, observational study on eugonadal HIV-infected male

patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the

Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15,

IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used to

assess sexual function. Sexual desire was further evaluated through a direct question

during the visit. LC-MS/MS was used to assess gonadal status.

Results

225 HIV-infected patients were enrolled (mean age 45.19G5.36 years). SIEDY

scores at appendix and scale 3 were significantly higher in patients with ED at IIEF-

GP148

(nZ136, 60.4%) compared with those without ED (P!0.001 and PZ0.015,

Impacts of a single ablative dose of radio iodine therapy for

respectively). Conversely, scale 1 (PZ0.448) and 2 (PZ0.503) of SIEDY did not

differentiated thyroid carcinoma on testicular function: results from

differ between patients with or without ED, suggesting a predominance of the

the SAPIRA study

psychological basis of ED in our cohort. The erectile function domain at IIEF-15

Nathalie Bourcigaux¹, Carole Rubino², Isabelle Berthaut³,

was directly correlated with IIEF-5 score (0.778, P!0.001). Similarly, the score at

Bruno Donadille², Marie Elisabeth Toubert⁴, Laurence Leenhardt⁵,

SIEDY appendix was significantly different among ED degrees at IIEF-15

(P!0.001). In particular, lower score was found in HIV-infected men without ED

Catherine Corone⁶, Isabelle Petrot-Keller¹, Sylvie Brailly-Tabard⁷,

compared to those with mild, moderate and severe ED (P!0.001, PZ0.001, and

Julie Beaufaron¹⁰, Tabassome Simon¹, Jean-Pierre Siffroi⁸, Florent De

P!0.001, respectively), confirming the reliability of these tools. Sexual desire was

Vathaire², Martin Sclumberger², Philippe Bouchard⁹ & Sophie

impaired in 73 patients (31.33%) at interview with a good correlation with the

Christin-Maitre¹

specific item of IIEF-15 (P!0.001).

¹Hôpital St Antoine, Greater Paris University Hospitals, Paris, France;

Conclusions

²Institut Gustave Roussy, Villejuif, France;³Hôpital Tenon, Greater

The psychological component impacts in a significant manner on ED in HIV-

University Paris Hospitals, Paris, France;⁴Hôpital St Louis, Greater Paris

infection context. Despite the high prevalence of comorbidities in these patients, the

University Hospitals, Paris, France;⁵Hôpital Pitié Salpétrière, Greater Paris

organic component does not affect erectile function. All the three validated

University Hospitals, Paris, France;⁶Centre René Huguenin, St Cloud,

questionnaires seem to be trustworthy in the diagnosis of ED in this setting.

France;⁷Hôpital Le Kremlin-Bicêtre, Greater Paris University Hospitals, Le

Kremlin-Bicêtre, France;⁸Hôpital Armand Trousseau, Greater Paris

DOI: 10.1530/endoabs.49.GP146

University Hospitals, Paris, France;⁹Hôpital Foch, Suresnes, France;

¹⁰Cabinet Médical, Nouméa, New Caledonia.

Background

Radioactive iodine therapy (RAI) is a classical therapeutic approach in patients

with differentiated thyroid carcinoma (DCT). Few data are currently available on

RAI’s potential impacts on testicular function.

Design

A longitudinal prospective multi-center study (PHRC N8P040419) included male

patients before a single radioiodine dose of 3.7 GBq of I¹³¹ (V0), at 3 months

GP147

(V3) and 13 months (V13) post treatment.

Effects of physical exercise or metformin on testosterone deficiency and

Method and Patients

erectile dysfunction associated to metabolic syndrome

Hormonal assessments (FSH, LH, Testosterone, inhibin B) as well as sperm

Linda Vignozzi^2,3, Sandra Filippi¹, Paolo Comeglio², Ilaria Cellai²,

parameters (number, mobility and morphology), DNA fragmentation and sperm

Francesca Corcetto², Chiara Corno² & Mario Maggi^2,3

FISH analysis in order to detect chromosomal abnormalities were performed at

¹Interdepartmental Laboratory of Functional and Cellular Pharmacology of

V0, V3 and V13.

Reproduction, Department of Neuroscience, Phychology, Drug Research

Results

and Child Care, University of Florence, Florence, Italy;²Sexual Medicine

Thirty six patients were included in the study. At V0, all patients had normal gonadal

and Andrology Unit, Department of Experimental and Clinical Biomedical

function. At V3, FSH median levels were significantly increased as compared to V0,

Sciences, University of Florence, Florence, Italy;³INBB, Rome, Italy.

respectively 9 UI/lG4.8 (N: 3-7 UI/l) versus 4 UI/lG3 (P!0.0001). Between V3 and

V13, FSH levels decreased but remained higher than baseline levels. Inhibin B median

Metabolic Syndrome (MetS) is a cluster of clinical conditions, associated to an

levels decreased significantly at V3 (P!0.0001) and returned to V0 levels at V13. LH

increased cardiovascular and metabolic risk, to hypogonadism and erectile

and T levels were not modified at V3 or V13.

dysfunction (ED). Lifestyle modification (including physical exercise, PhyEx)

Median sperm concentration significantly decreased at V3 as compared to V0 (20 vs 48

and metformin

(MET) are well-known treatments for the condition. We

million/ml; P!0.0001) and returned to V0 levels at V13. In parallel, a statistically

established an animal model of MetS that recapitulates the human phenotype,

significant decrease in sperm morphology was observed at V3. Sperm mobility and DNA

including andrologic derangements.

fragmentation were not modified after RAI. However sperm chromosomal abnormalities

The aim of this study was to investigate in experimental MetS the effect of PhyEx

were increased at V3 (P!0.0005) and V13 (P!0.01), as compared to V0.

or MET on penile erection and on hormonal and metabolic parameters.

Conclusion

Control (RD) and MetS rabbits were treated with MET (the last 18 days) or

In this prospective study, RAI transiently altered FSH, inhibin B and sperm number.

exercise-trained to run on a treadmill for 12 weeks. Penile tissue was collected for

Furthermore, chromosomal abnormalities observed at V3 were found to persist 13

in vitro contractility study or gene expression.

months after RAI. Therefore, our study illustrates that counseling about fertility could

MET, but not PhyEx, induced a reduction in visceral adiposity, blood pressure,

be interesting in male patients with DCT treated by a single dose of radioiodine.

triglycerides, glucose level and tolerance. MET increased testosterone

(T),

DOI: 10.1530/endoabs.49.GP148

whereas PhyEx completely restored it. Ach-induced relaxation, hampered in

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP149

Levels of follicle stimulating hormone were unchanged 2.3 (1.4-4.4) vs 2.2 (1.5-

3.3) U/l (PZ0.47). There were no differences on semen volume 3.0 (1.5-5.0) vs

Presentation, clinical features and long-term follow-up of Leydig cell

3.2

(2.3-4.3) ml (PZ0.33), sperm concentration 35 (6-62) vs 43 (22-73) mill/ml

tumours of the testis: 77 cases from a single center experience

(PZ0.1), or total sperm counts 102 (8-236) vs 136 (65-235) mill (PZ0.09).

Andrea M. Isidori, Vincenzo Giannetta, Daniele Gianfrilli, Rosa Lauretta,

Forty-seven percent of patients and 77% of controls had normal semen quality,

Maria Grazia Tarsitano, Giorgio Fattorini, Riccardo Pofi, Carlotta Pozza &

WHO criteria (volume O1.5 ml, concentrationO15 mill/ml and AB-motile

Andrea Lenzi

spermO42%) (PZ0.001). Three had azoospermia. Testicular size was

unchanged 18 (13-25) vs 20 (19-25) ml (PZ0.46).

Conclusion

Introduction

Patients with acquired pituitary insufficiency had reduced semen quality,

With the improved imaging techniques, Leydig cell tumours

(LCTs) are

supporting the need for early cryopreservation of semen in this group of patients.

frequently found, accounting up to

22% of testicular tumours. The natural

However, despite severe Leydig cell insufficiency almost half of patients had

history of LCTs is relatively unknown, because of the small size and

normal semen quality based on determination of three variables. This finding is in

heterogeneity of available studies. Since LCTs are often removed, long-term

contrast to men with hypergonadotrpic hypogonadism where spermatogenesis is

follow-up is missing. The aim of this study was to report the experience with a

often severely compromised before Leydig cell insufficiency occurs.

large cohort of prospectively collected LCTs.

DOI: 10.1530/endoabs.49.GP150

Materials and methods

Patients with LCTs were enrolled from 2005 to 2016. Clinical and biochemical

features of LCTs were compared with two matched cohorts: patients with

seminomas and patients without testicular lesions (noL) randomly selected among

patients referred in the same period.

Results

Neuroendocrinology & Growth Hormones

77 patients had LCTs, 90 had seminomas, and 1420 had no lesion (noL). Groups

GP151

were matched for age and BMI. Infertility was the reason for referral in more than

Growth hormone-releasing hormone (GHRH) antagonists, MIA-602

half of LCTs. Testicular volumes (PZ0.002), sperm concentration (PZ0.001)

and MIA-690, inhibit survival and proliferation of human pleural

and morphology (P!0.001) were significantly lower in LCTs compared to noL;

mesothelioma cells

gonadotropins were higher (P!0.001) and testosterone was lower (PZ0.008) in

Tania Villanova¹, Iacopo Gesmundo¹, Marina Taliano¹, Ezio Ghigo¹,

LCTs vs noL. No differences were found in gonadal steroid after hCG test,

Andrew V Schally^2,3 & Riccarda Granata¹

between groups. When compared to seminomas, LCTs did not show differences

¹Division of Endocrinology, Diabetology and Metabolism, Department of

in hormonal status except for higher SHBG levels (PZ0.028), LH/Te ratio

Medical Sciences, University of Torino, Torino, Italy;²Endocrine,

(P!0.001), and lower sperm concentration (PZ0.04). LCTs lesions were smaller

Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, Miami,

compared to Sem (P!0.001). Cryptorchidism

(c²Z45.658 P!0.001) and

Florida, USA;³Department of Pathology and Department of Medicine,

gynecomastia (c²Z54.923, P!0.001) were associated with a higher risk of

Divisions of Hematology, Oncology and Endocrinology, University of

LCTs. After a median follow-up of 32.5 months, no metastases have been

Miami Miller School of Medicine, Miami, Florida, USA.

detected. Non-operated LCTs developed subclinical hypogonadism (PZ0.018)

compared to surgically removed LCTs.

Conclusions

Human malignant pleural mesothelioma

(MPM) is a rare but aggressive

LCTs have a good prognosis when correctly recognized. Based on the largest

neoplasm, arising from pleural mesothelial cells, generally due to asbestos

existing series, we showed that infertility, gynecomastia,low testicular volume,

exposure. Different growth factors are involved in the pathogenesis of MPM and

and cryptorchidism are frequently associated with LCTs, supporting the

in resistance to therapy; moreover, chemotherapy with cisplatin and antifolates,

hypothesis that testicular dysgenesis syndrome could play a role. Active

like pemetrexed (PEM), is the first-line treatment for inoperable MPM. Growth

surveillance, as an alternative to surgical removal, appears to be a safe option,

hormone-releasing hormone (GHRH), apart from stimulating GH secretion in the

but monitoring of Leydig cell failure remains necessary.

pituitary, exerts many extrapituitary functions, including stimulation of cell

DOI: 10.1530/endoabs.49.GP149

proliferation and survival. GHRH and GHRH receptor (GHRH-R) are expressed

in different cancer cell types, where they modulate their proliferative effects.

Moreover, GHRH-R antagonists were found to inhibit the proliferation of

different cancer cells in vitro and in vivo; however, the role of GHRH antagonists

in MPM remains unknown. Thus, in the present study, we investigated the effects

of the GHRH antagonists MIA-602 and MIA-690 on survival, proliferation and

apoptosis of human MPM cells. Our results show that MIA-602 and MIA-690

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reduce survival and proliferation of MSTO-211H

(biphasic) and REN

(epithelioid) MPM cells, but have no effect in MeT-5A (human non-malignant

Semen quality in patients with adult-onset hypogonadotropic

mesothelial cells). Moreover, MIA-602 and MIA-690 promoted apoptosis and

hypogonadism

reduced the expression of the antiapoptotic protein Bcl-2 in MSTO-211H and

Mikkel Andreassen¹, Anders Juul², Ulla Feldt-Rasmussen¹ &

REN cells. Cell cycle analysis of REN cells treated with GHRH antagonists

Niels Jørgensen²

showed an increase in the Sub-G1 apoptotic phase and a decrease in the G2 pre-

¹Department of Endocrinology, Rigshospitalet, Faculty of Health Science,

mitotic phase. Furthermore, MIA-602 and MIA-690 inhibited cell migration in

University of Copenhagen, Copenhagen, Denmark;²Department of Growth

REN cells and increased the cytotoxic action of PEM in both MPM cell lines.

and Reproduction Rigshospitalet, Faculty of Health Science, University of

These results suggest a novel therapeutic role for GHRH antagonists in the

Copenhagen, Copenhagen, Denmark.

treatment of MPM, alone or in combination with standard therapies, by reducing

the chemotherapy doses and their associated side effects.

Introduction

DOI: 10.1530/endoabs.49.GP151

Gonadotropins from the pituitary gland are essential for testosterone production

and spermatogenesis. However, little is known about semen quality in patients

with adult onset gonadotropin insufficiency.

Aim

To investigate semen quality in men with adult onset hypogonadotropic

hypogonadism requiring testosterone replacement therapy.

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Patients and method

Somapacitan expected to provide IGF-I levels suitable for once-weekly

A single center study comprising all hypogonadal men with pituitary disease (year

dosing in children

2003-2016, nZ28, (median(IQR) 30 (27-37) years), who accepted cryopreserva-

Rasmus Juul, Michael Rasmussen, Henrik Agersø & Rune Overgaard

tion of semen before initiation of testosterone therapy. On the day semen samples

Novo Nordisk A/S, Bagsvaerd, Copenhagen, Denmark.

were cryopreserved, reproductive hormone levels were measured. Semen

parameters, hormone levels and size of testicles were compared to those of

young men (nZ340, 19 (18-20) years) from the general population.

Somapacitan is a long-acting growth hormone (GH) intended for once-weekly

Results

subcutaneous administration. As for GH, the mechanism of action of somapacitan

Patients vs controls had lower serum testosterone 5.6 (3.5-7.8) vs 19.7 (15.5-

is either directly or indirectly via insulin-like growth factor I (IGF-I). A PK/PD

24.5) nmol/l (P!0.001), free testosterone index 33.3 (18.1-55.1) vs 73.7 (57.8-

model of somapacitan was developed from the pharmacokinetics (PK) and IGF-I

91.7)

(P!0.001), luteinizing hormone

1.5

(1.1-2.1) vs

3.1

(2.3-4.0) U/l

levels from three phase 1 trials data: a single dose/multiple dose trial (0.02-

(P!0.001), and inhibin-B 142 (126-187) vs 229 (176-285) ng/l (P!0.001).

0.24 mg/kg per week) in healthy adults, a multiple dose trial in adults with growth

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

hormone deficiency [GHD] (0.02-0.12 mg/kg perweek) and a single dose trial in

GP154

children with GHD (0.02-0.16 mg/kg). Somapacitan exposure-response was

The effect of chronic hypothalamic-pituitary-adrenal axis activation on

described with a non-linear relationship between dose and exposure and a delay in

hypothalamic glucagon-like peptide-1 action in an animal model of

response observed between C_max PK and C_max IGF-I. Somapacitan PK levels and

depression and in vitro studies

IGF-I response was found to correlate to body weight bridging exposure and

Jan Detka, Anna Kurek, Mateusz Kucharczyk, Joanna Slusarczyk,

response between children and adults. The PK/PD model was based on goodness

Katarzyna Glombik, Wladyslaw Lason & Boguslawa Budziszewska

of fit judged adequate to describe somapacitan exposure and IGF-I levels and

Department of Experimental Neuroendocrinology, Institute of

simulate the expected IGF-I profiles after multiple doses in children. Descriptive

Pharmacology, Polish Academy of Sciences, 12 Smętna Street,

IGF-I exposure-response analysis of single dose data in GHD paediatric patients

31-343, Cracow, Poland.

indicated that the dose range

0.04-0.16 mg/kg provided change in IGF-I

comparable to daily hGH. Based on the PK/PD model of somapacitan, once-

weekly dosing of 0.04 mg/kg per week are expected to provide C_max IGF-I levels

Hypersensitivity of hypothalamic-pituitary-adrenal (HPA) axis is considered to

that match the average daily human GH (hGH) treatment; 0.08 mg/kg per week

be an important factor in the pathogenesis of depression. Interestingly, glucagon-

are expected to provide C_avg IGF-I levels that match the average daily hGH

like peptide-1 (GLP-1) - an incretin hormone involved in the maintenance of

treatment; and 0.16 mg/kg per week are expected to provide higher IGF-I levels

glucose homeostasis in the periphery is known to activate HPA axis. The aim of

than with daily hGH, with average concentrations not exceeding C2 SDS. In

the present study was to investigate whether prenatal stress (an animal model of

conclusion, the PK/PD of somapacitan is well characterised in adults and children

depression) may influence levels of GLP-1 and GLP-1 receptor (GLP-1R) in the

in GHD in support of once-weekly dosing.

hypothalamus. Since prenatal stress may not change the level of the investigated

DOI: 10.1530/endoabs.49.GP152

factors in basal conditions, but may change the response to adverse factors in the

adulthood, our studies were also conducted on animals subjected to acute stress

and oral glucose administration (1 g/kg). In parallel in order to study the direct

influence of GLP-1 receptor agonists on the activity of corticotropin-releasing

hormone (CRH) promoter gene, a hypothalamic cell line mHypoA-2/12 was

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stably transfected with plasmid DNA containing the sequence (from K663 to

Evaluating CHARGE syndrome in CHD7-positive CHH patients:

C124 bp) of human CRH promoter gene conjugated with luciferase reporter

clinical implications

gene. The cells were treated with GLP-1 and exendin-4 (20 and 200 nM) for 6, 24

Cheng Xu¹, Daniele Cassatella¹, Almer van der Sloot², Michael Hauschild¹,

and 48 h. The amount of GLP-1 in the hypothalamus was not altered by prenatal

Richard Quinton³, Christian De Geyter⁴, Christa Fluck⁵, Katrin Feller⁵,

stress in basal conditions, however it was significantly lower in a group subjected

Deborah Bartholdi⁵, Attila Nemeth⁶, Irene Halperin⁷, Sandra

to acute stress. Prenatal stress and glucose loading significantly decreased the

Pekic Djurdjevic⁸, Georgios Papadakis¹, Andrew Dwyer⁹, Laura Marino¹,

concentration of GLP-1R in the hypothalamus. Obtained results suggest that

Duarte Pignatelli¹⁰, Carol Huang¹¹, Nicolas Niederlander¹, James Acierno¹

attenuated central incretin hormone signaling may contribute to metabolic

& Nelly Pitteloud¹

disturbances, evident in depression. In contrast, transfected mHypoA-2/12 cells

¹Lausanne University Hospital, Lausanne, Switzerland;²Institute for

treated with selected GLP-1R agonists displayed no significant differences in

Research in Immunology and Cancer, Quebec, Montreal, Canada;³Institute

reporter gene activity, which may suggest that GLP-1R activation does not

for Genetic Medicine, University of Newcastle-on-Tyne, Newcastle-on

stimulate CRH expression in this experimental model.

Acknowledgments

Tyne, UK;⁴University Hospital, University of Basel, Basel, Switzerland;

This work was supported by the Operating Program of Innovative Economy 2007-

⁵Inselspital, Bern, Switzerland;⁶St John’s Hospital, Budapest, Hungary;

2013, grant No. POIG.01.01.02-12-004/09 and grant 2012/07/N/NZ7/04394;

⁷Hospital Clínic, Universitat de Barcelona, Barcelona, Spain;⁸Institute of

National Science Centre, Poland

Endocrinology, University Clinical Center, Belgrade, Serbia;⁹University of

Lausanne, Lausanne, Switzerland;¹⁰Faculty of Medicine of the University

DOI: 10.1530/endoabs.49.GP154

of Porto, Porto, Portugal;¹¹Alberta Children’s Hospital, Calgary, Canada.

Context

Congenital hypogonadotropic hypogonadism (CHH) and CHARGE syndrome are

clinically and genetically overlapping syndromes, with mutations in the CHD7

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gene presenting in both disorders. However systematic evaluation of CHARGE

A novel purified polyclonal antibody towards T-Pit is a reliable marker

features in CHD7-positive CHH patients is seldom performed.

of corticotroph cell differentiation

Objective

Evelina Sjostedt¹, Jens Bollerslev^3,4, Fredrik Pontén^1,2 &

This study aims to systematically evaluate CHARGE features in CHD7-positive

Olivera Casar-Borota^1,2

patients and explore the phenotype-genotype correlation.

¹Department of Immunology, Genetics and Pathology, Uppsala University,

Design

Uppsala, Sweden;²Department of Clinical Pathology, Uppsala University

Whole exome sequencing was performed on 130 CHH probands to identify

Hospital, Uppsala, Sweden;³Department of Specialized Endocrinology,

mutations in 24 CHH genes, including CHD7. Putative mutations were defined as

Rikshospitalet, Oslo University Hospital, Oslo, Norway;⁴Faculty of

rare sequence variants (RSVs, minor allele frequency !1%) that were either

Medicine, University of Oslo, Oslo, Norway.

protein-truncating variants

(PTVs) or missense variants predicted to be

deleterious by SIFT and/or PolyPhen2. Missense mutations were also evaluated

using Bergman criteria, integrating computational algorithms, population and

Classification of pituitary neuroendocrine tumours (NETs) or pituitary adenomas

segregation data

(Bergman, Human Mutation,

2012). CHD7-positive CHH

is based on the expression of the anterior lobe pituitary hormones (FSH, LH, GH,

patients were evaluated for CHARGE features.

Prolactin, TSH, ACTH and alpha-subunit of the glycoprotein hormones).

Results

Assessment of the transcription factors SF-1, Pit-1

and T-Pit has been a

We identified 16 CHH patients harboring heterozygous mutations (two PTVs and 14

complement to the classification. Tumours negative for both pituitary hormones

missense), of whom 14 were available for re-evaluation. After detailed phenotyping,

and transcription factors have been designated as null-cell adenomas. However,

three probands (one PTV and two missense) were re-classified as CHARGE

lack of sensitive and specific antibodies towards T-Pit has presented difficulties

syndrome. Four probands with missense mutations present additional CHARGE

for the inclusion of these transcription factors into the classification system of

features, while the remaining seven probands exhibit no additional CHARGE feature

pituitary endocrine tumours. Here, we present a novel purified polyclonal

(one PTV and six missense). Both the missense mutations underlying CHARGE

antibody (HPA072686) towards T-Pit and demonstrate its high sensitivity and

syndrome were categorized as pathogenic using Bergman criteria, while the other

specificity for immunohistochemistry-based identification of the cells with

missense mutations were classified as either benign or of unknown significance. Of

corticotroph differentiation. In an immunohistochemical study of a large cohort of

note, 3/4 CHH patients with additional CHARGE features also had mutations in other

pituitary adenomas of different types from

246 patients, a distinct nuclear

CHH genes, contributing to the variable expressivity.

expression of T-Pit was demonstrated in all ACTH-immunolabelled tumours,

Conclusions

silent and clinically functioning, as well as in a proportion of tumours previously

50% of CHD7-positive CHH patients exhibit additional CHARGE features, with

diagnosed as null-cell adenomas. None of the tumours that were immunoreactive

21% meeting the clinical diagnosis of CHARGE syndrome. While the Bergman

for Pit-1, SF-1 or pituitary hormones, other than ACTH, expressed T-Pit. We

criteria accurately predict the most severe mutations resulting in CHARGE

expect that the availability of a reliable T-Pit antibody as a marker of corticotroph

syndrome, it is unable to distinguish isolated CHH from CHH with additional

cell differentiation will contribute to: i) more precise classification of pituitary

CHARGE features. The results of this study have diagnostic and genetic counseling

neuroendocrine tumours, particularly, those with sparse or no hormone

implications for CHD7-positive CHH patients.

expression, ii) better identification of silent corticotroph tumours that may have

DOI: 10.1530/endoabs.49.GP153

more aggressive clinical behaviour than silent gonadotroph tumours, and which

are at the moment difficult to identify in cases with sparse or no ACTH

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

expression, iii) more cost effective immunohistochemical screening of pituitary

DI onset risk (RR 0.264 (0.132; 0.53), PZ0.02). Patients with corticotropinomas

tumours based primarily on the use of the three transcription factors and iv)

and somatotropinomas had higher risk of transient and three-phased DI (RR 0.212

identification of potential corticotroph cell differentiation in non-pituitary NETs.

(0.061; 0.734), PZ0.02, RR 0.459 (0.311; 0.677), PZ0.04, for corticotropino-

DOI: 10.1530/endoabs.49.GP155

mas, respectively; RR 4.559 (1.049; 19.813), PZ0.03, RR 1.977 (1.033; 3.783),

PZ0.07 for somatotropinomas, respectively). Macroadenoma also increased risk

of transient and three-phased DI (RR 5.739 (1.32; 24.962), PZ0.01, RR 2.593

(1.357; 4.955), PZ0.02, respectively).

Conclusions

ACTH- and GH-secreting adenomas, macroadeomas and postoperative adrenal

GP156

insufficiency can be considered as predictors of transient and three-phased

Liraglutide treatment prevented the increased expression of

diabetes insipidus. Panhypopituitarism can be considered as predictor of

proinflammatory cytokines in the hippocampus of male pups in a

permanent diabetes insipidus.

perinatal stress model of food restriction

DOI: 10.1530/endoabs.49.GP157

Yolanda Diz-Chaves¹, Laura Toba¹, Juan Fandin˜o1, Lucas

González-Matías¹, Luis Miguel Garcia-Segura² & Federico Mallo¹

¹University of Vigo, CINBIO, Vigo, Spain;²CSIC, Instituto Cajal, Madrid,

Spain.

GP158

Adverse events during gestation in rodents, results in an enhancement of immune

The effect of chronic tianeptine administration on NLRP3

function, including elevated levels of inflammatory cytokines in the brain.

inflammasome pathway - study in an animal model of depression

Liraglutide is a GLP-1 receptor agonists known to exert neuroprotective effects in

Ewa Trojan, Anna Kurek, Katarzyna Chamera, Joanna Slusarczyk,

brain. The aim of this study was to elucidate if liraglutide given to food restricted

Katarzyna Glombik & Agnieszka Basta-Kaim

(FR) pregnant rats may prevent the deleterious effects of FR in the hippocampal

Department of Experimental Neuroendocrinology, Institute of

inflammatory status of male and female pups at 21 days of age (D21). 20 Sprague-

Pharmacology PAS, Cracow, Poland.

Dawley pregnant rats were included. Controls (CT) were fed ad libitum, whereas

dams in restricted group were fed with 50% (50FR) daily intake of control dams.

Pregnant rats were treated with liraglutide

(100 mg/kg per 12 h; 50FR/LIR,

Introduction

CT/LIR) or vehicle (50FR/VEH, CT/VEH) from gestational day 14 to 21. During

Recently, the immune hypothesis of depression has gained a new dimension

lactation FR was increased to 30%. At D21 and before weaning, pups were

because of inflammasomes. NLRP3 inflammasome is a protein complex and its

sacrificed. The hippocampi were obtained and stored at K80 8C until analysis.

activation leads to stimulation of the enzyme caspase 1 responsible for generation

mRNA expression levels of IL1b, IL6,NFKb,IL 10 and Arginase1 in the

of active form of pro-inflammatory cytokines: IL-1

b and IL-18. Recently

hippocampus were assessed by RT-PCR. Immunohistochemistry analysis for Iba1

postulated ‘inflammasome theory of depression’ assumes that depression is based

(marker of microglia) was performed in dentate gyrus (DG). The FR-mothers

on a disturbance of the mechanisms regulating NLRP3

complexes and

model promoted a proinflammatory state in the hippocampus just in male but not

uncontrolled synthesis of IL-1b.

in female pups. 50FR male rats displayed increased mRNA expression of IL1b,

Aim

IL6

and NFKb compared to control males. LIR treatment decreased the

The aim of present study was to examine whether prenatal stress influence the

expression of these cytokines and increased IL6 in control males. Furthermore,

inflammasome NLRP3 system (subunits: NLR, ASC, protease caspase-1) in the

LIRA treatment increased the anti-inflammatory cytokine IL10 in 50FR male and

frontal cortex and hippocampus of adult rats offspring. Furthermore the impact of

CT female rats and the mRNA expression of the arginase1 (marker of microglia

chronic antidepressant drug - tianeptine administration on the above-mentioned

M2-like phenotype) in 50FR male rats. The number of IBA1 immunopositive

parameters were evaluated.

cells were increased in the DG of 50FR males compared to controls, and were

Methods

reduced by the treatment with LIRA. In conclusion, LIRA prevents the

Pregnant rats were subjected to restraint stress. At 3 months of age, control and

proinflammatory status induced by FR of the mother in male pups and enhanced

prenatally stressed rats were tested for behavioural changes in forced swimming

anti-inflammatory markers.

test. After that male offspring were administered i.p. for 14 days with tianeptine or

DOI: 10.1530/endoabs.49.GP156

vehicle. The animals’ behaviour were tested again and rats were sacrificed. The

protein level of all NLRP3 inflammasome subunits was determined by Western

blot analyses.

Result

Prenatal stress procedure cause long-lasting behavioral alterations expressed as an

increase in immobility and a decrease in swimming and climbing time measured

GP157

in the forced swim test. Chronic treatment of tianeptine normalized all above-

Predictors of permanent, transient and three-phase postoperative

mentioned changes in prenatally stressed offspring. Prenatal stress procedure

diabetes insipidus

increased concentration of all NLRP3 subunits in frontal cortex. In hippocampus

Daria Mikhaylova, Larisa Dzeranova, Ekaterina Pigarova,

prenatal stress affected caspase-1 levels but had no effect on the other NLRP3

Ludmila Rozhinskaya, Andrey Grigoriev, Vilen Azizyan &

inflammasome subunits. Chronic tianeptine treatment attenuated all evoked by

Oksana Ivashenko

stress changes.

Endocrinology Research Centre, Moscow, Russia.

Conclusion

Prenatal stress procedure leads not only to persistent behavioral disturbances but

also malfunction in brain NLRP3 inflammasone pathway. NLRP3 pathway can be

Objectives

indicate as an potential attractive target for antidepressant drug action.

To evaluate predictors of permanent, transient and three-phase diabetes insipidus

Acknowledgement

(DI) in patients undergoing endoscopic endonasal transsphenoidal surgery.

Supported by the grant no. 2015/17/N/NZ7/00924.

Patients and methods

DOI: 10.1530/endoabs.49.GP158

The study included 154 patients undergoing endoscopic endonasal transsphenoi-

dal surgery (122 women and 32 men) age from 18 to 65 years (median 40 (31;52)).

73 patients with Cushing disease, 66 patients with acromegaly, four patients with

prolactinomas, nine patients with non-functioning pituitary adenomas, one patient

with thyrotropinoma, one patient with Nelson’s syndrome and three patients with

multihormonal secreting adenomas we examined. Patients were monitored for

GP159

hormones, balance of fluids, serum electrolytes, plasma and urine osmolality.

Pituitary androgen receptor signalling is a novel negative regulator of

Results

prolactin production

Postoperative permanent DI occurred in 27 patients, among them four as three-

Laura O’Hara, Paul Le Tissier & Lee Smith

phased disturbances. Transient DI occurred in 42 patients, among them nine as

University of Edinburgh, Edinburgh, UK.

three-phased disturbances. Onset arised on the 1th day-2nd month after surgery

(median 1 day (1;5)) for the permanent DI’s and on the 1th day-4th month for

transient DI’s (median 1 day (1;5)). Duration for transient DI was 1 day-1 year

The classical paradigm of lactotroph prolactin production and release is based

and 3 month (median 2 (1;30)), in 38% patients transient DI occurred as single

around tonic inhibition by hypothalamic dopamine and stimulation by factors

polyuria-polydipsia episode. Adrenal insufficiency incrised risk of transient and

such as estrogen. We have recently shown that conditional ablation of pituitary

three-phased DI development (RR 0.516 (0.287; 0.927), PZ0.02, RR 0.056

androgen receptor

(Foxg1-Cre ARKO) surprisingly does not change the

(0.008; 0.42), PZ0.0003, respectively), panhypopituitarism increased permanent

concentration of circulating gonadotrophins but increases circulating prolactin

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

in male mice; highlighting androgen signalling as a novel negative regulator of

vs 639, PZ0.043; nZ22). Postoperative normalization of plasma ACTH was

prolactin production. We aimed to refine our knowledge of the site and

reached more frequently in patients with WT tumors (4/12, 33% vs 1/10, 10%) but

mechanism of action of this control by performing further genetic, pharma-

without statistical significance

(PZ0.323). No differences were observed in

cological and surgical experiments to ablate the production and/or action of

tumor control after surgery.

prolactin and/or androgens. Male mice with a genetic ablation of AR in neurons

Conclusion

(Nestin-Cre ARKO) do not have an increase in circulating prolactin, confirming

Somatic mutations in the USP8 gene are common in Nelson’s syndrome and may

that the increase in prolactin seen in the Foxg1-Cre ARKO mouse is not due to

be related to a more severe hormonal phenotype.

loss of hypothalamic AR, but specifically pituitary AR. However, Foxg1-Cre

DOI: 10.1530/endoabs.49.GP160

ARKO mice treated with the dopamine agonist bromocriptine show a decrease in

circulating prolactin levels suggesting that the mechanism of prolactin increase

originates with the hypothalamic dopamine system that normally controls

prolactin. Male mice with postnatal AR ablation in w50% lactotrophs (Prolactin-

Cre ARKO) do not show an increase in circulating prolactin, suggesting that

Obesity

either the mechanism is not lactotroph-specific or that ablation of AR needs to

GP161

occur earlier or in a greater number of lactotrophs to result in an increase in

circulating prolactin. Mice castrated in adulthood do not show an increase in

The association between olfaction and taste functions with serum

circulating prolactin which suggests that the control mechanism is not an acute

ghrelin and leptin levels in obese women

response to changes in androgens but is programmed during the pre-adult

Burçin Uygun¹, Sinem Kiyici¹, Suay Ozmen², Zulfiye Gul³, Deniz Sigirli⁴ &

development of the pituitary. Further experiments are currently being undertaken

Sinan Cavun³

to ablate AR in other pituitary cell populations and at earlier time points with the

¹University of Health Sciences, Bursa Yuksek Ihtisas Education and

aim of pinpointing the spatio-temporal mechanism of control of prolactin

Training Hospital, Department of Endocrinology and Metabolism, Bursa,

production by androgen receptor signalling.

Turkey;²University of Health Sciences, Bursa Yuksek Ihtisas Education

and Training Hospital, Department of Otorhinolaryngology, Bursa, Turkey;

DOI: 10.1530/endoabs.49.GP159

³Uludag University Medical Faculty, Department of Pharmacology, Bursa,

Turkey;⁴Uludag University Medical Faculty, Department of Bio-statistics,

Bursa, Turkey.

GP160

Aim

Somatic mutations in USP8 are frequent events in pituitary tumors

Olfaction and gustation have great importance on feeding behavior and food

causing Nelson’s syndrome

preferences. Recent published data suggests that olfaction and taste functions are

Luis G Perez-Rivas¹, Marily Theodoropoulou^1,2, Troy H Puar³, Julia Fazel¹,

modulated in response to changing levels of various molecules such as ghrelin and

Mareike R Stieg², Francesco Ferraù⁴, Guillaume Assié⁵, Monica

leptin which are play important roles on feeding and energy balance. We aimed to

R Gadelha⁶, Timo Deutschbein⁷, Maria C Fragoso⁸, Benno Kusters⁹,

investigate the olfaction and taste functions in obese female patients and the

Márta Korbonits⁴, Jérôme Bertherat⁵, Gunter K Stalla², Ad R Hermus³,

association between serum ghrelin and leptin levels compared with healthy controls.

Felix Beuschlein¹ & Martin Reincke¹

Methods

¹Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat

Fifty two obese women who have body mass index O30 kg/m² and 15 healthy

Munchen, Munich, Germany;²Department of Clinical Neuroendocrinology,

women were included in to the study. After 8 h of fasting, blood samples were taken

Max Planck Institute of Psychiatry, Munich, Germany;³Department of

for serum biochemical parameters, ghrelin and leptin levels measurement. For the

Internal Medicine, Division of Endocrinology, Radboud University Medical

quantitative assessment of olfactory function, all participants underwent on

Centre, Nijmegen, The Netherlands;⁴Centre for Endocrinology, William

N-butanol threshold test and odor identification test by using 12 Sniffin’ Sticks

Harvey Research Institute, Barts and The London School of Medicine and

ready-made fragrance sticks. The gustatory function was tested by administering a

Dentistry, Queen Mary University of London, London, UK;⁵Inserm Unité

whole-mouth above-threshold test using sucrose solutions.

1016, Centre National de la Recherche Scientifique Unité Mixte de

Results

Recherche, Institut Cochin, Université Paris Descartes, Paris, France;

The sucrose taste threshold score in obese women was significantly higher than the

⁶Division of Endocrinology, Hospital Universitário Clementino Fraga Filho,

controls (PZ0.004). N-butanol smell threshold was not significantly different between

Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;⁷Division of

the two groups (PZ0.149) while the Sniffin’ Sticks smell test scores were significantly

Endocrinology and Diabetology, Department of Internal Medicine,

lower in obese women compared with the controls (PZ0.007). Serum leptin levels were

Universitatsklinikum Wurzburg, University of Wurzburg, Wurzburg,

also significantly higher in obese women (P!0.001) although there was no significant

Germany;⁸Unidade de Neuroendocrinologia, Laboratório de Hormônios e

difference in serum ghrelin levels between the two groups (PZ0.768).

Genética Molecular/LIM42, Disciplina de Endocrinologia e Metabologia,

Conclusion

Hospital das Clínicas da Faculdade de Medicina da Universidade de São P,

No significant association was observed between olfaction and taste functions and

Sa˜o Paulo, Brazil;9Department of Pathology, Radboud University Medical

serum ghrelin levels of obese individuals. It was found that serum leptin levels were

Centre, Nijmegen, The Netherlands.

increased while taste and smell functions were decreased in obese women. These

results might suggest that leptin, which is an anorexigenic peptide, may have a

negative effect on taste and smell functions.

Recent studies have reported a high prevalence of USP8 mutations in corticotroph

adenomas causing Cushing’s disease. Nelson’s syndrome is a potentially life-

DOI: 10.1530/endoabs.49.GP161

threatening complication of bilateral adrenalectomy in patients with refractory

Cushing’s disease that is caused by the development of an ACTH-secreting tumor

in the pituitary gland. Whether USP8 alterations are also present in Nelson’s

tumors has not been studied in detail so far.

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Methods

Sarcopenic obesity and associated factors in older adults with diabetes: the

We have screened for mutations in the exon 14 of USP8 in tumors from 32

2009-2010 Korean National Health and Nutrition Examination Survey

patients who were diagnosed with Nelson’s syndrome (28 females, four males).

Jin Hwa Kim¹, Hee Jung Ahn¹, Tae Young Yang² & Sang Yong Kim¹

Genomic DNA was extracted from fresh-frozen or FFPE adenomas. The presence

¹Chosun University Hospital, Gwangju, Republic of Korea;²Teayoung21

of mutations was analyzed by Sanger sequencing. Mutational status was

Hospital, Gwangju, Republic of Korea.

correlated to clinical data.

Results

In our cohort, 15/32 tumors presented a mutation in the exon 14 of USP8, a

Objective

prevalence similar to that reported in Cushing’s disease, with c.2159COA

Sarcopenic obesity is a double burden for older people because it carries the cumulative

(p.Pro720Gln) being the most frequent (8/32), followed by c.2155_2157delTCC

risk of functional abnormality, metabolic, cardiovascular risk, and mortality compared

(p.Ser718del, 4/32) and c.2152TOC (p.Ser718Pro, 3/32). Two USP8 WT cases

to either sarcopenia or obesity alone. Diabetes is related to an increase in visceral

were categorized as atypical pituitary tumors and excluded from subsequent

adiposity and is associated with the risk of sarcopenia. The objective was to explore the

analyses. Mutations were found exclusively in females (15/27, 55%; vs 0/3 males).

association between sarcopenic obesity and diabetes and determine the associated

Other variables, such as age at diagnosis of Nelson’s syndrome, BMI,

factors with sarcopenic obesity in older people with diabetes.

hyperpigmentation, visual field defects, adenoma size or mortality did not

Research design and methods

significantly differ between patients with WT and mutant tumors. Regarding the

This study was based on data from the Korean National Health and Nutrition

hormonal status, patients with mutant tumors tended to exhibit higher levels of

Examination Survey (KNHANES), conducted by the Korean Ministry of Health and

plasma ACTH at time of Nelson’s diagnosis (median WT 1335 pg/ml vs mutant

Welfare, from 2009 to 2010. Out of 19,491 participants, the analysis included data for

1668 pg/ml; PZ0.098; nZ25) and significant changes after surgery (median 131

3,206 older people. Multivariate logistic regression analyses were used to identify

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

independent associated factors with sarcopenic obesity. The complex sample analysis

Obesity is one of the major causes of morbidity and mortality worldwide and is

was used for the KNHANES data for weighting all values following the guidance of

considered a risk factor for metabolic syndrome, type

diabetes and

statistics form the Korea Centers for Disease Control and Prevention.

cardiovascular disease

(CVD). miRNAs are epigenetic regulators of several

Results

aspects of metabolism and energy homeostasis and are involved in obesity and

The Prevalence of nonsarcopenic nonobesity, nonsarcopenic obesity, sarcopenic

regulation of insulin sensitivity. miR 26b is among the obesity-related micoRNAs

nonobesity, and sarcopenic obesity were 43.2, 7.7, 23.5 and 25.6%, respectively, in

and is differentially expressed in preadipocytes and mature adipocytes in humans

all subjects. The prevalence of sarcopenic obesity in older people with diabetes was

and is upregulated during adipocyte maturation. Visfatin which is implicated in

significantly higher than those without diabetes (33.9% vs. 23.4%, P-value !0.001).

insulin resistance and metabolic syndrome is a target of miR-26b. The aim of this

Diabetes was an independent associated factor with sarcopenic obesity after fully

study was to investigate the levels of miR-26b levels in obesity and its association

adjusting for confounding factors, including chronic disease, sociodemographic

with insulin resistance and metabolic parameters.

influences, and lifestyle. Among the older people with diabetes, undiagnosed

Methods

diabetes, diabetes duration with more than 10 years, elevated diastolic blood

Seventy children and adolescents (35 controls; 35 obese), between the ages of 8

pressure, known hypertension, increased intake of protein, and number of

and 18 years, were selected and clinically evaluated. The expression of miR-26b

comorbidity were independent associated factors with higher risk of sarcopenic

was measured after microRNA extraction from plasma samples. The extracted

obesity. History of stroke and increased vitamin D level were independently

microRNAs were elongated using poly A polymerase reaction followed by cDNA

associated with a lower risk of sarcopenic obesity.

synthesis. Real-time PCR was performed using SYBR green and delta Ct was

Conclusion

calculated by the formula: Ct (reference gene)-Ct (target gene). miR-16 was used

Diabetes influenced the risk of sarcopenic obesity in older people. Undiagnosed

as the reference gene. Insulin and visfatin levels were measured using ELISA, and

diabetes, diabetes duration with more than 10 years, elevated diastolic blood

insulin resistance was calculated by the homeostasis model of assessment of

pressure, known hypertension, increased intake of protein, number of comorbidity,

insulin resistance

(HOMA-IR). Fasting plasma glucose, triglyceride, total

history of stroke, and vitamin D level were independently associated with

cholesterol, LDL-C and HDL-C were also measured colorimetrically.

sarcopenic obesity in older people with diabetes.

Results

DOI: 10.1530/endoabs.49.GP162

miR-26b expression were significantly lower in obese subjects compared with

control group and were also lower in subjects with insulin resistance compared to

those without insulin resistance. miR-26b was significantly correlated with insulin

levels and HOMA-IR. It also showed a significant negative correlation with

visfatin which was higher in obese subjects compared with control subjects.

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Conclusion

Resistance training reduces skeletal muscle inflammation even after

Decreased miR-26b expression in obese children and adolescents may be

4-week detraining in obese rats

involved in insulin resistance and increased visfatin levels.

Patricia Seraphim¹, Marcelo Freitas¹, Marcos Teixeira¹, Giovana Teixeira¹,

DOI: 10.1530/endoabs.49.GP164

Maria Tereza Nunes² & José Carlos Camargo Filho¹

¹School of Sciences and Technology - Sao Paulo State University/UNESP,

Presidente Prudente/SP, Brazil;²Institute of Biomedical Sciences -

University of Sao Paulo, Sao Paulo/SP, Brazil.

The ingestion of high-fat diet has been considered a crucial factor in the genesis of

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subclinical systemic inflammation and insulin resistance. The resistance training

The effect of FTO polymorphism rs 9939609 on obesity and metabolic

(RTr) can be an effective tool for the prevention and treatment of immune-

disturbances in Polish people from Lower Silesia

metabolic disorders through physiological and morphological adaptations. The

Aleksandra Zdrojowy-Welna¹, Katarzyna Kolackov¹, Katarzyna Zatonska²,

purpose of the present study was to analyze the effects of RTr and cessation of

Malgorzata Tupikowska-Marzec³, Marek Bolanowski¹ &

training on muscle inflammation and expression of genes related to glucose

Grazyna Bednarek-Tupikowska¹

metabolism in obese rats. Thirty male Wistar rats aged 2 months were subdivided

¹Department of Endocrinology, Diabetology and Isotope Therapy, Wroclaw

into three groups: High-Fat Diet

(DH), Trained High-fat Diet

(DHT) and

Medical University, Wroclaw, Poland;²Department of Social Medicine,

Detrained High-fat Diet (DHD). RTr was performed for 12 weeks (wk), 3!/wk,

Wroclaw Medical University, Wroclaw, Poland;³Department of

three sets of 12 repetitions per session. In the 8th wk, DHD group interrupted

Dermatology, Venerology and Allergology, Wroclaw Medical University,

training for 4 wk. RT-PCR was performed to analyze genes code TNFa, AMPK,

Wroclaw, Poland.

GLUT4 and MEF2A, and Western blotting was assayed to analyze the expression

of TNFa in the soleus muscle. Additionally we analyzed the insulin sensitivity by

ITT, and muscle fiber area by HE staining. The results showed that RTr (DH vs.

Background

DHT) caused increase of muscle fiber area (P!0.05), and insulin sensitivity by

The association between fat mass and obesity-associated gene

(FTO)

34% (P!0.05), increased AMPK gene levels by 23% (P!0.05), GLUT4 by 24%

polymorphism rs 9939609 and obesity was found in some European countries.

(P!0.05) and MEF2A by 20% (P!0.05), and reduced protein and gene levels by

However, the data concerning Polish population is insufficient. The relationship

51 and 28% of TNFa (P!0.05), respectively. Detraining (DHD vs DHT)

between FTO and metabolic disorders remains unclear.

increased body weight (P!0.05), and provoked reduction of muscle fiber area

Methods

(P!0.05). However, TNFa expression remained reduced even after cessation of

The study group consisted of 686 women and 418 men from Lower Silesia in

training. We conclude that RTr exerts positive effects on reduction of the local

Poland, aged

30-80 years

(mean age 54.2G9.26 years). The examination

inflammation, and improves the expression of genes related to glucose

included anthropometric measurements, blood pressure, lipid profile and fasting

metabolism in the oxidative skeletal muscle. These adaptations are maintained

blood glucose analysis. The group was genotyped for FTO rs9939609

even after 4-week detraining.

polymorphism.

Results

DOI: 10.1530/endoabs.49.GP163

Mean BMI was 28.2G5.0 kg/m² and was slightly higher in men. Prevalence of

obesity (BMI O30 kg/m²) was around 31% with no sex differences. Minor allele

frequency was 0.44. In whole study group, mean BMI was higher in risk allele

carriers (AA, AT) than TT homozygotes (AA - 28.45 kg/m², AT - 28.41 kg/m² vs

TT - 27.8 kg/m²), but the difference was not statistically significant. The

association between FTO polymorphism and obesity traits were stronger in men

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than in women (p-values, respectively: for body weight 0.0005 vs O0.1, for BMI

miR-26b is decreased in obesity and is associated with insulin resistance

!0.01 vs O0.1, for waist circumference 0.0005 vs O0.1 in co-dominant model).

and visfatin levels

We did not observe any association between FTO polymorphism and

Mitra Nourbakhsh¹, Atieh Hosnieh Farahan⁴, Farideh Yaghmaei⁴,

dyslipidaemia, hypertension or higher blood glucose concentration.

Saeedeh Moradgholi⁴, Fatemeh Ahmadpour¹ & Maryam Razzaghy-Azar^2,3

Conclusions

¹Department of Biochemistry, Faculty of Medicine, Iran University of

FTO polymorphism is one of many factors influencing body mass in Polish

Meical Sciences, Tehran, Iran;²Metabolic Disorders Research Center,

population. The effect on other metabolic disturbances is not significant. The

Endocrinology and Metabolism Molecular-Cellular Sciences Institute,

reasons why the association between FTO and obesity were more pronounced in

Tehran University of Medical Sciences, Tehran, Iran;³H.Aliasghar

men than women remain unclear. Probably age, degree of obesity or other

Hospital, Iran University of Medical Sciences, Tehran, Iran;⁴Department of

hormonal factors modify the clinical presentation of genetic predisposition.

Biology, Science and Research Branch, Islamic Azad University, Tehran,

DOI: 10.1530/endoabs.49.GP165

Iran.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP166

altered sex steroid balance to WT mice, are needed to confirm the causality

between sex steroids, gut microbiota and metabolic disorders.

Role of Elovl6 in brown and beige adipose tissue during b3-adrenergic

receptor activation

DOI: 10.1530/endoabs.49.GP167

Rahul Sharma¹, Takashi Matsuzaka¹, Zao Hui¹, Hiroshi Ohno¹,

Yoshinori Takeuchi¹, kaori Motomura¹, Naoya Yahagi¹, Motohiro Sekiya¹,

Yoshimi Nakagawa¹, Masafumi Muratani² & Hitoshi Shimano¹

¹Department of Internal Medicine, Endocrinology and Metabolism, Faculty

of Medicine, University of Tsukuba, Tsukuba, Japan;²Department of

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Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba,

Effects of short sleep duration on energy metabolism and energy

Japan.

balance in subjects with overweight and obesity

Eleonora Poggiogalle, Lorenzo Donini, Lucio Gnessi, Stefania Mariani,

Marianna Calabretto, Federica Luisi, Andrea Lenzi & Carla Lubrano

Anti-obesity therapeutics based on increasing the amount of brown fat have

received more attention from industry as the biology and regulation of brown fat

are better understood than that of beige fat. Cold exposure and treatment with b3

Introduction

adrenergic receptor agonist are known to activate brown/beige adipose tissue.

The chronic reduction of sleep duration is associated to an increased risk of

Many transcriptional pathways regulating brown/beige adipose tissue have been

weight gain, but mechanistic aspects remain to be fully elucidated. The aim of our

identified, the role of lipid biosynthetic enzymes in brown/beige adipose tissue

study was to examine the relationship between short sleep duration and energy

has been less investigated. In this study, we investigated the role of Elovl6, the

metabolism, fuel selection and energy balance in overweight and obesity.

enzyme responsible for converting C16 non-essential fatty acids (FAs) into C18

Methods: Inclusion criteria were: age 18-65 years, BMI R25 kg/m². Use of any

species, in brown/beige adipose tissue. We have observed upregulation of Elovl3,

CNS medications, any psychiatric disorders and night shift work were considered

4, 6 and 7 in BAT and inguinal WAT of mice treated with b3-adrenergic receptor

as exclusion criteria. Body composition was evaluated by DXA. All participants

agonist CL-316243 as well as cold-expose. These elongases are responsible for

underwent indirect calorimetry. The respiratory quotient (RQ) was calculated

the conversion of C16 FAs into C30 saturated FAs, indicating the relevance of

from gas exchanges. The equations by Weir and by Frayn were used to calculate

very long chain FAs in the activation process of brown/beige adipose tissue. It

the resting energy expenditure

(REE), and carbohydrate and fat oxidation,

was reported that Elovl6 KO mice have impaired mitochondrial function and

respectively. Sleep duration, total daily energy expenditure (TDEE) and the level

hence impaired thermogenic capacity of BAT when exposed to cold temperature

of physical activity (METs/day) were objectively assessed (Sensewear Armband).

(Cell Rep. 13:2039, 2015). When exposed to chronic CL-316243 treatment we

A 3-day dietary record was administered. Participants were divided into two

observed that Elovl6

KO mice compensate its impaired BAT function by

groups,

“regular sleep”

(RS): O300 min/day or

“short sleep”(SS):

%300

increased development of functional beige fat contributing to its increased energy

min/day. Results: 88 women and 30 men were included (age:49.6G12.1 years),

expenditure. Interestingly, these metabolic changes are appearing to be mediated

of whom 30.5% exhibited a short sleep duration. BMI (39.7G7.1 vs. 36.2G

by increased type-2 cytokine signalling and macrophage polarization in the

5.0 kg/m², PZ0.03) and truncal body fat (18.7G6.2 vs. 16.1G4.6 kg, PZ0.04)

inguinal WAT of Elovl6 KO mice, as per our preliminary results. We have

were higher in the SS group than the RS group. Subjects with short sleep had a

observed increased expressions of markers for cell proliferation

(Ki67),

lower RQ (0.71G0.12 vs. 0.76G0.12, PZ0.004) and oxidized more fat (113G55

macrophage (F4/80, CD68, Itgax-1, Arg-1, Clec-10) in the beige fat of Elovl6

vs. 95G56 g/min, PZ0.006) than regular sleepers. The METs/day were higher in

KO mice compared to WT mice stimulated with CL-316243. These results

the SS group compared to the RS group (1.56G0.55 vs. 1.35G1.24, PZ0.04).

suggest that Elovl6-regulated FA chain length is important for beiging and M2

RQ was positively associated to sleep duration (PZ0.04, adj. for age, sex, and

macrophages are playing a mediator role in beige adipogenesis.

body fat). No difference emerged in TDEE or energy intake (SS group: 23G10 vs.

DOI: 10.1530/endoabs.49.GP166

RS group: 25G6 kcal/kg/day, PO0.05).

Conclusion

Short sleep affects energy substrate metabolism and adiposity distribution in

overweight and obese subjects.

DOI: 10.1530/endoabs.49.GP168

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A link between sex hormones, obesity and gut microbiota

Gabriela Martínez-Chacón^1,2, Eveliina Munukka², Himanshu Kumar¹,

Sami Pietila^4,5, Niina Saarinen^2,3, Raine Toivonen², Seppo Salminen¹,

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Arno Hänninen², Leena Strauss^2,3 & Sari Mäkelä^1,2

Blood mercury concentration in relation to overweight or obese among

¹Functional Foods Forum, University of Turku, Turku, Finland;²Institute of

Korean children and adolescents: KNHANES 2009-2013

Biomedicine, University of Turku, Turku, Finland;³Turku Center for

Kyung Hee Park¹ & Jeong-Hyeon Kim²

Disease Modeling, Univesity of Turku, Turku, Finland;⁴Turku Centre for

Biotechnology, University of Turku, Turku, Finland;⁵

˚boAkademi,Turku,

¹Hallym University Sacred Heart Hospital, Anyang, Republic of Korea;

²Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea.

Finland.

Background

Sex steroids are involved in the development of obesity and metabolic disorders.

Harmful effects of mercury on cardiovascular disease have been suggested in

The interrelationship between sex steroid balance and metabolism is complex,

many epidemiologic studies. However, reports on harmful effect of mercury in

and the underlying mechanisms are still unclear. The impact of gut microbiota in

relation to overweight or obesity have shown inconsistent findings.

development of obesity, inflammation and metabolic dysregulation has been

Methods

suggested in humans and demonstrated in mouse models. Less is known about the

A total of 1577 children and adolescents (10-18 years of age) from the Korean

interactions between sex steroids and gut microbiota. Based on available

National Health and Nutrition Examination Survey (KNHANES) 2009-2013.

evidence, it is, however, pertinent to ask if sex steroids participate in the

Overweight or obese group was defined as over the 85th percentile of the age- and

regulation of the composition or function of gut microbiota, or if gut microbes

sex-specific BMI norms or BMI over 25. Subjects were categorized into three groups

regulate sex steroid balance. The aim of the present study was to define the

by age and gender specific blood cadmium, lead, and mercury concentration.

interplay between sex steroid balance and gut microbiota, in the context of obesity

Multivariate logistic regression stratified by gender was performed to estimate the

and metabolic dysregulation. First, we showed that non-obese human aromatase

odd ratio (OR) and 95% confidence interval (CI) for investigate the association.

expressing

(AROMC) male mice, with increased circulating estradiol to

Results

testosterone ratio and impaired liver lipid metabolism, have a female-type

Compared to non-obese group, blood mercury concentration of was higher in obese

intestinal microbiota and higher ratio of Firmicutes to Bacteroidetes. Treatment

group. Blood levels of cadmium and lead were not significantly different according

with aromatase inhibitor restored estradiol/testosterone levels, followed by a

to obese status. After adjustment for confounders, subjects in the highest tertile

slight improvement in their microbiota ecology. Second, in a mouse model

group of blood mercury levels were more likely to have overweight or obesity (OR

reporting the expression of human aromatase (CYP19A1) gene (hARO-Luc

2.65, 95%CI 1.13-6.26) compared to subjects in the lowest tertile group in girls.

mouse), ovariectomy-induced obesity, accompanied with elevated Firmicutes to

No significant association was found in boys.

Bacteroidetes ratio, altered gut homeostasis and increased aromatase reporter

Conclusions

gene expression in the mammary adipose tissue. In conclusion, by applying two

Blood mercury concentration is positively associated with overweight or obesity

gene-modified mouse models, we showed that changes in sex steroid balance are

among Korean children and adolescents. Further longitudinal studies will be

linked to altered gut microbiota composition, and on the other hand, sex steroid -

needed to confirm the causality.

related obesity is linked to increased expression of human aromatase gene

DOI: 10.1530/endoabs.49.GP169

reporter. Further experiments, such as fecal transplantation from mice with

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP170

testosterone

(MDZ6.52, 95%CI (3.09, 9.94), PZ0.0002); estradiol (MDZ

K7.03, 95%CI (K11.05, K3.01), PZ0.0006); luteinizing hormone (MDZ0.92,

Association of the FTO gene rs9939609 polymorphism with obesity in

95%CI (0.64, 1.20), P!0.00001); follicle-stimulating hormone

(MDZ1.29,

the Republic of Tatarstan

95%CI (0.65, 1.94), P!0.0001); sex hormone-binding globulin (MDZ23.85,

Kamilya Khasanova¹, Tatyana Kiseleva¹, Sabina Bogdanova¹,

95%CI (18.44, 29.26), P!0.00001). The changes of sex hormone levels in obese

Elena Valeeva¹, Svetlana Gubaidullina², Ildus Ahmetov¹ & Farida Valeeva¹

female patients before and after bariatric surgery as following: total testosterone

¹Kazan State Medical University, Kazan/Republic of Tatarstan, Russia;

(MDZK0.78, 95%CI (K0.84, K0.71), P!0.00001); free testosterone

²Volga Region Academy of Physical Culture, Sport and Tourism,

(MDZK5.53, 95%CI (K10.47, K0.59), PZ0.03); estradiol (MDZK25.10,

Kazan/Republic of Tatarstan, Russia.

95%CI (K36.92, K13.27), P!0.0001); luteinizing hormone (MDZ4.50, 95%CI

(K1.04, 10.05), PZ0.11); follicle-stimulating hormone

(MDZ1.68, 95%CI

Aim

(0.50,

2.86), PZ0.005); sex hormone-binding globulin (MDZ34.79, 95%CI

To investigate the possible association of the rs9939609 polymorphism in the

(22.63, 46.96), P!0.00001).

FTO gene with obesity in the Republic of Tatarstan (RT).

Conclusion

Materials and methods

This meta-analysis indicates that bariatric surgery has a significant improvement

The study involved 63 adult patients (21 men and 42 women; 38-77 years old)

on the sexual function in both genders.

with overweight or obesity and 515 healthy young people (157 men and 358

DOI: 10.1530/endoabs.49.GP171

women; 16-35 years old) with normal weight. We assessed clinical and

biochemical parameters (blood lipid profile). The analysis of the rs9939609 T/A

polymorphism of the FTO gene in buccal cells was performed using Sintol kits

(Russia) for RT-PCR. All the patients were tested by bioelectrical impedance

analysis.

Results

The distribution of genotypes of the FTO gene polymorphism (TT - 11%, TA -

65% AA - 24%) and alleles (T - 44% A - 56%) in the group of patients with

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overweight and obesity was significantly different from those of the control group

Lipolytic effects of endogenous 3-iodothyronamine (T1AM) and

(TT - 42,9%, TA - 45,4%, AA - 11,7%; T - 65,6%, A - 34,4%; ORZ2.43,

synthetic analog SG-2 in vivo and in cultured adipocytes

P!0.0001), confirming that the A allele is a risk factor for obesity. In the group of

Martina Sabatini¹, Michael P Rogowski², Ebru S Selen Alpergin³,

obese patients we found an additive effect of the A allele on the increase of the

Fariba Assadi-Porter³, Riccardo Zucchi¹ & Grazia Chiellini¹

average waist-hip ratio (lowest value in TT carriers, maximum value in AA

¹Department of Pathology, University of Pisa, Pisa, Italy;²UAB School of

carriers). We found that the number of patients with arterial hypertension and

Medicine-Cardiovascular Disease, Birmingham, AL, USA;³Department of

dyslipidemia was higher in the group with AA and TA genotypes compared with

Zoology, University of Wisconsin-Madison, Madison, WI, USA.

group with TT genotype.

Conclusion

We found a significant association of the T/A polymorphism of the FTO gene

3-Iodothyronamine (T1AM) is a hormone like molecule structurally similar to

with the obesity. Obese patients with the risk allele of the rs9939609 FTO gene

TH, that has been reported to modulate energy metabolism by favoring lipid over

polymorphism have significantly higher values of absolute and relative body fat

glucose catabolism. To better understand the role played by T1AM on the

mass and BMI, total cholesterol, low-density lipoprotein, and triglycerides.

regulation of lipid metabolism, in the present study we administered

DOI: 10.1530/endoabs.49.GP170

spontaneously obese mice with T1AM at two different dosages

(10

and

25 mg/kg per day) for 7 days and the effects on body weight (BW) and lipid

profiles were examined. In addition a fluoro-labeled version of T1AM (FL-

T1AM) was synthesized and utilized to assess T1AM intracellular localization in

3T3-L1 mouse adipocytes.

Administration of 10 or 25 mg/kg per day T1AM showed a BW loss of 10% or

18% of initial BW by day 7 of treatment. T1AM treatment at both dosages

produced a significant increase in total plasma triglycerides (P!0.05) and a

significant decrease in plasma cholesterol (P!0.05), without any significant

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change in glycaemia. At present, the specific mechanism of T1AM entry into the

cell, as well as its internal targets remains unknown. Cellular imaging revealed

Effect of bariatric surgery on sexual function and sex hormone levels in

rapid intercellular uptake of FL-T1AM without localization to the lipid droplet or

obese patients: a meta-analysis

nucleus of mature adipocytes. This rapid rate of uptake was further evaluated via

Junping Wen^1,2, Lingying Wen², Wei Lin^1,2, Liantao Li^1,2, Jixing Liang^1,2,

flow cytometry, with peak detection of FL-T1AM steadily rising until reaching

Huibin Huang^1,2 & Gang Chen^1,2

peak signal and equilibrium at w20 min. We also observed that when 3T3-L1

¹Fujian Provincial Hospital, Fuzhou, China;²Fujian Medical University,

adipocytes were treated with T1AM or its synthetic halogen free analog SG-2 (1-

Fuzhou, China.

10 mM), both compounds decreased lipid accumulation in mature adipocytes,

with SG-2 showing a potency significantly higher than T1AM (IC50_SG-2Z5 mM;

Objective

IC50_T1AMZ20 mM).

The aim of this meta-analysis is to evaluate the effect of bariatric surgery on

In conclusion T1AM and its synthetic analog show a significant lipolytic activity,

sexual function and sex hormone levels in obese patients.

both in cultured adipocytes and in vivo.

Methods

DOI: 10.1530/endoabs.49.GP172

Two independent investigators conducted a literature search of PubMed, Medline

and Cochrane databases using the terms bariatric surgery, sexual function and sex

hormone to identify appropriate human studies published in English about the

effect of bariatric surgery on sexual function and sex hormone levels in obese

patients. The search was restricted to data from January 1, 1990 to December 1,

2016. Bibliographies of recent review articles and systematic reviews were

searched to identify any additional trials. Two investigators according to the

Pituitary

inclusion and exclusion criteria independently select literature, extract data and

evaluate quality, then using RevMan 5.3.5 software for Meta analysis.

GP173

Results

A comparison of single-dose effects of short acting somatostatin analogs:

In all, 31 studies met all criteria, including 1150 patients. The types of bariatric

octreotide vs pasireotide in patients with active acromegaly after

surgery performed included laparoscopic Roux-en-Y gastric bypass, laparoscopic

surgical debulking

gastric banding surgery, laparoscopic adjustable gastric banding, laparoscopic

Agnieszka Majos, Maria Stelmachowska-Banas, Izabella Czajka-Oraniec &

sleeve gastrectomy, Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable

Wojciech Zgliczynski

gastric banding, vertical gastric banding, biliopancreatic diversion. The time to

Department of Endocrinology, Centre of Postgraduate Medical Education,

follow-up after surgery varied from 1 months to 115 months. Of the 31 studies, 5

Bielanski Hospital, Warsaw, Poland.

reported the IIEF in obese men in 154 of 1150 patients (MDZ4.84, 95%CI (2.92,

6.75), P!0.00001); 7 studies reported the FSFI in obese women in 369 of 1150

patients

(MDZ4.10, 95%CI (K0.28, 8.48), PZ0.07). The changes of sex

Acromegaly is a rare endocrine disorder caused by growth hormone (GH)

hormone levels in obese male patients before and after bariatric surgery as

secreting pituitary adenoma. The treatment of choice is transsphenoidal surgery.

following: total testosterone (MDZ8.55, 95%CI (6.59, 10.52), P!0.00001); free

In patients with persistent disease after surgery medical therapy is recommended.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

First-line medical treatment include first generation long-acting somatostatin

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analogs: octreotide LAR and lanreotide autogel. Recently, pasireotide - a second

Resistance to somatostatin analogues is associated with GSTP1 gene

generation somatostatin analog has been investigated in patients with acromegaly.

methylation and AHR rs2066853 variant in acromegaly patients

The aim of this study was to compare the effectiveness of the single-dose of short-

Francesco Ferraù¹, Petronilla Daniela Romeo¹, Soraya Puglisi¹,

acting somatostatin analogs: octreotide vs pasireotide in patients with active

Marta Ragonese¹, Federica Spagnolo¹, Riccardo Ientile², Isa Anna

acromegaly after surgical debulking who were resistant to first generation long-

Maria Picerno², Monica Currò², Giuseppa Visalli², Angela Alibrandi³ &

acting somatostatin analogs.

Salvatore Cannavò⁴

Eighteen patients after debulking surgery without biochemical control of

¹Department of Clinical and Experimental Medicine, University of Messina,

acromegaly on medical therapy were enrolled in the study. All patients had

Messina, Italy;²Department of Biomedical Sciences, Dental Sciences and

short-acting octreotide and pasireotide administered on different days. GH

Morpho-functional Imaging, Messina, Italy;³Department of Economics,

concentration was measured before and

60,

120

and

180 min after drug

Messina, Italy;⁴Department of Human Pathology of Adulthood and

administration. Nadir GH concentrations and decreases in GH concentrations

Childhood, Messina, Italy.

were compared.

Nadir GH values in octreotide test were reached 60 min after drug administration,

while in pasireotide test - 180 min after drug administration. The median nadir

Evidences suggest that environmental contaminants exposure and/or the

GH concentration was 2.765 mg/l (IQR: 1,885-4.07) vs 1.51 mg/l (IQR: 0.95-2.555)

impairment of intracellular xenobiotic metabolizing system could affect pituitary

respectively, P!0.001. The decrease in GH concentration was more significant

pathophysiology. Glutathione-S-transferase-P1 (GSTP1) gene encodes for an

after pasireotide administration compared to octreotide administration

enzyme that is involved in cellular detoxification mechanisms. GSTP1 altered

(P!0.001). The median decrease in GH concentration in octreotide test was

activity or expression has been reported in some tumours.

1.255 mg/l (IQR: 0.918-1.75) vs 2.805 mg/l (IQR: 1.523-5.043) after pasireotide

We aimed to assess the GSTP1 gene promoter methylation status in acromegaly

administration. Octreotide was generally better tolerated than pasireotide.

patients and its contribution to their clinical features.

Short-acting pasireotide is more effective than short-acting octreotide in GH

Seventy-seven WT AIP gene acromegaly patients (50 women) have been screened

supression in patients with uncontrolled acromegaly. Pasireotide may be a

for germline AHR rs2066853 variant and GSTP1 promoter methylation. Epide-

promising alternative for patients resistant to first-generation somatostatin

miologic, clinical, biochemical and radiological parameters at diagnosis have been

analogs.

compared after patients’ stratification according to GSTP1 methylation status and the

DOI: 10.1530/endoabs.49.GP173

presence of AHR rs2066853 variant. We also evaluated the response to somatostatin

analogues (SSA) administered either before or after surgery in 71 cases.

Seventeen patients were found to carry AHR rs2066853 variant and 26 methylated

GSTP1 (GSTP1met). GSTP1met patients showed a higher prevalence of diabetes

mellitus (PZ0.01), colonic polyps (PZ0.05), and were more resistant to SSA

(PZ0.02) as compared to GSTP1 unmethylated patients (GSTP1unmet).

On the basis of GSTP1 methylation status and the presence of AHR rs2066853

variant, we identified four groups: group 1, 40 patients GSTP1unmet and AHR

WT; group 2, 20 patients only GSTP1met; group 3, 12 patients carrying only AHR

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rs2066853 variant; group 4, five patients with both GSTP1 methylation and AHR

Efficacy and safety of switching to pasireotide LAR alone or in

rs2066853 variant. Group 1 patients were more sensitive to SSA than other groups

combination with pegvisomant in acromegaly patients controlled with

(PZ0.02). Patients of group 4 were more resistant to SSA (PZ0.02) and showed

combination treatment of first-generation somatostatin analogues and

higher GH (PZ0.03) and IGF1 (PZ0.04) levels and lower percentage of GH

weekly pegvisomant (PAPE study): a prospective open-label 48 week

decrease (PZ0.04) after SSA than other groups.

study, preliminary results 24 weeks

In conclusion, GSTP1 methylation and AHR rs2066853 variant associate with

Ammar Muhammad, Aart Jan van der Lely, Joop Janssen &

resistance to SSA in acromegaly patients.

Sebastian Neggers

DOI: 10.1530/endoabs.49.GP175

Erasmus MC, Rotterdam, The Netherlands.

Background

Efficacy and safety of combination treatment of pasireotide LAR with

pegvisomant (PEGV) has not been studied yet. Switching to Pasireotide LAR

GP176

in patients previously controlled with long-acting somatostatin analogues (LA-

Minimally Invasive Diagnosis and Direct Transnasal Surgery: a single

SSAs) and PEGV could reduce the required PEGV dose to normalize serum IGF1

centre series of 100 children with Cushing’s Disease with long term

levels, while the effect on glucose metabolism is unknown.

follow-up

Methods

Patricia Crock^1,2, Dieter K Ludecke³, Ulrich Knappe⁴, Joerg Flitsch³ &

We enrolled 60 acromegaly patients O18 years with acromegaly who had normal

Wolfgang Saeger⁵

IGF1 levels (%1.2!Upper Limit of Normal (ULN)) using combination treatment

¹Paediatric Endocrinology, John Hunter Children’s Hospital, Newcastle,

of high dose LA-SSAs and weekly PEGV for R6 months. After enrollment

NSW, Australia;²University of Newcastle, Newcastle, NSW, Australia;

LA-SSA treatment was continued, and the PEGV dose was reduced by 50% for 12

³Department Neurosurgery, University Hospital Eppendorf, Hamburg,

weeks. If IGF1 levels remained normal after 12 weeks, patients were switched to

Germany;⁴Neurosurgical Clinic, Minden, Germany;⁵Department

pasireotide LAR 60 mg monotherapy, every 4 weeks. If IGF1 levels O1.2!ULN

Neuropathology, University Clinic Eppendorf, Hamburg, Germany.

patients were switched to pasireotide LAR 60 mg and continued with the 50%

reduced PEGV dose. The primary endpoint was the percentage of patients

achieving normal IGF1 levels at 24 weeks. The key secondary endpoint was the

Introduction

frequency diabetes at 24 weeks.

Trans-sphenoidal surgery (TSS) with minimally invasive techniques is the first

Results

choice in the treatment of paediatric Cushing’s disease (CD). The question is how

At baseline, median IGF1 was 0.94!ULN with a median PEGV dose of

can high remission rates be achieved with less invasive investigations and TSS.

80 mg/week, and 30.6% of patients had pre-existing diabetes. After the 50% dose

The developments in our centre treating 100 pediatric Cushing patients with long-

reduction of PEGV, median IGF1 levels increased to 1.43 ULN, while IGF1

term follow-up may add some helpful ideas.

remained normal in 33% of patients. At 24 weeks, 73% of patients achieved

Material and methods

normal IGF1 levels with a median IGF1 0.98!ULN. Cumulative PEGV dose

Data from our first series 1 (nZ55) will be compared with new data from the

reduction between baseline and 24 weeks was 66%. At 24 weeks, IGF1 levels

recent series 2 (nZ45) until 2009. All patients were operated by one surgeon by

were normal in 88% of patients on pasireotide LAR monotherapy, and 68% of

direct transnasal microsurgery (TNS). Special diagnostic methods such as inferior

patients on combination treatment. Pasireotide LAR was well tolerated. At 24

petrosal sinus sampling (IPSS) were replaced by ACTH measurement from the

weeks, the most common adverse event was diabetes which occurred in 70.2% of

cavernous sinus (CSS) restricted to unclear cases without increase of salivary

patients. Two patients withdrew prematurely due to hyperglycemia requiring

cortisol in the CRH-test, difficult sella anatomy and/or negative MRI. Multiple

insulin treatment.

direct micro-cytology, micro-doppler and adequate visualization will be

Conclusion

described.

Pasireotide LAR alone or in combination with pegvisomant controls IGF1 in 73%

Results

of patients after 66% reduction in cumulative dose of weekly pegvisomant. The

In our first series of 55 cases, IPSS was performed in 13 (24%) of whom 46% had

frequency of diabetes was 70.2% and is in line with previous studies.

false adenoma lateralization. All adenomas could be removed with extensive

DOI: 10.1530/endoabs.49.GP174

pituitary exploration and all had intraoperative pathology. Two patients had early

successful re-surgery. Recurrence rate 15%. In the second series with more

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

refined MRI and endocrinology: easy repeat CRH saliva tests and CSS sampling

GP178

used in only 7 patients (15%), all micro-adenomas were initially detected. Early

Sleep patterns in patients with non-functional GHRH receptor

repeat-TNS was necessary and successful in three. Recurrence rate 11%. Side

Francielle T Oliveira¹, Roberto Salvatori², José Marcondes³,

effects of TNS were minimal, as such, children and parents readily accepted

Larissa B Macena¹, Alecia A Oliveira-Santos¹, Augusto C N Faro¹,

re-TNS. Thus, including re-TNS in recurrences, 98 of 100 patients had long-term

Viviane C Campos¹, Carla R P Oliveira¹, Ursula M M Costa¹ &

remission. TNS in recurrences had a better outcome in the last series with less

Manuel H Aguiar-Oliveira¹

pituitary dysfunction using more intraoperative minute biopsies.

¹Federal University of Sergipe, Aracaju/Sergipe, Brazil;²The Johns

Conclusions

Hopkins University School of Medicine, Baltimore, MD, USA;³Instituto do

Invasive pre-surgical investigations could be reduced. 98% remission rate could

Sono e Medicina Integrada, Aracaju/Sergipe, Brazil.

be achieved with advanced investigations, refined TNS, early re-TNS and re-TNS

in recurrences. Only two children (2%) were irradiated - only one was indicated

by the senior surgeon.

Hypothalamic GH releasing hormone (GHRH) has hypnotic actions by increasing

DOI: 10.1530/endoabs.49.GP176

slow wave sleep (SWS) (non-rapid eye movement sleep, non-REM), which

account for about 75% of sleep. Conversely, GH may stimulate the rapid eye

movement sleep (REM). Patients with GH deficiency (GHD) often exhibit sleep

problems leading to daytime fatigue and reduced quality of life (QoL). We have

described a cohort of patients with isolated GHD (IGHD) due to GHRH resistance

caused by a homozygous null mutation (c.57C1GOA) in the GHRH receptor

gene. They have normal QoL and no obvious complaints of chronic tiredness. The

aim of this study was to determine objectively and subjectively the sleep quality

in these subjects, who have never received GH therapy. A cross sectional study

was carried out on 21 adult IGHD subjects, and 21 matched controls. Objective

sleep assessment included polygraphic records of the stages wake (W), non-REM:

GP177

N1 (drowsiness), N2 and N3 (already sleeping) and R (REM). Subjective

Octreotide subcutaneous (s.c.) depot, a novel ready-to-use formulation,

evaluation included the Pittsburgh Sleep Quality Index, Insomnia Severity Index,

provides higher exposure and maintains response in patients with

and Epworth Sleepiness Scale. Compared to controls, IGHD subjects exhibited

acromegaly and functioning neuroendocrine tumours (NETs)

lower sleep efficiency (77.7 (27.5) vs 87.5 (10.1) %, PZ0.007), total sleep time

previously treated with long-acting octreotide: Results from a phase 2,

(330.0

(127.5) vs 385.5 (56.0) min, PZ0.028) and higher percentage of the non-

open-label, multicentre, randomized study

REM 1 stage (14.6 (18.9) vs 7.3 (8.1) %, PZ0.022). There was no difference

Diego Ferone¹, Franc¸oise Borson-Chazot2, Anne Cailleux3, Dieter Horsch4,

between the groups in REM sleep and in quality questionnaires. These data show

Harald lahner⁵, Rosario Pivonello⁶, Libuse Tauchmanova⁷,

an extension of the drowsiness period, with a reduction in the total sleep time,

Christelle Darstein⁷, Håkan Olsson⁸, Fredrik Tiberg^8,9 & Marianne Pavel¹⁰

suggesting a preponderant role of GHRH resistance over GHD in the sleep quality

¹Endocrinology, DiMI, IRCCS AOU San Martino-IST, University of

of these IGHD subjects. The objective reduction in the sleep efficiency and total

Genoa, Genoa, Italy;²Fédération d’Endocrinologie, Hospices Civils de

sleep time seem have minimal subjective consequences, as it was not reflected in

Lyon and University Lyon1, Lyon, France;³CHU ouen, Hôpital Charles

differences of quality sleep questionnaires.

Nicolle, 1 rue de Germont, 76031 Rouen cedex, Rouen, France;

DOI: 10.1530/endoabs.49.GP178

⁴Department of Gastroenterology/Endocrinology, Center for Neuroendo-

crine Tumors Bad Berka - ENETS Center of Excellence, Zentralklinik Bad

Berka GmbH, Bad Berka, Germany;⁵Universitaetsklinikum Essen, Zentrum

f. Innere Medizin, Essen, Germany;⁶Dipartimento di Medicina Clinica e

Chirurgia, Università Federico II di Napoli, Naples, Italy;⁷Novartis Pharma

AG, Basel, Switzerland;⁸Camurus AB, Lund, Sweden;⁹Physical

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Chemistry, Lund University, Lund, Sweden;¹⁰Charité Universitatsmedizin

Correction of sustained hyponatremia secondary to SIAD by the use of

Berlin, Campus Virchow-Klinikum, Berlin, Germany.

chronic tolvaptan therapy is associated with a reduction in Emergency

Room visits, hospital admissions and days of hospitalization over a

3-year period

Background

Martín Cuesta Hernández¹, Irene Crespo Hernández¹, Pablo

Octreotide s.c. depot is a novel, ready-to-use formulation administered via a thin

Amich Alemany¹, Emilia Gómez Hoyos², Nancy Sánchez Gómez³,

needle, which may allow self-administration. In a phase 1 study in healthy

volunteers, octreotide s.c. depot provided greater bioavailability with faster onset

Alejandro Santiago¹, Paz De Miguel Novoa¹, Alfonso Luis Calle-Pascual¹

and greater IGF1 suppression than long-acting octreotide. Here, we present data

& Isabelle Runkle de la Vega¹

from a phase 2 study evaluating pharmacokinetics (PK), efficacy, safety, and

¹Hospital Universitario Clínico San Carlos, Madrid, Spain;²Hospital

Universitario Clínico Universitario de Valladolid, Valladolid, Spain;

tolerability of octreotide s.c. depot in patients with acromegaly and neuroendo-

³Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.

crine tumours (NETs).

Methods

Adult patients with acromegaly or functioning, well-differentiated NETs treated

Introduction

with long-acting octreotide 10 mg/20 mg/30 mg every 4 weeks (q4w) for R2

Hyponatremia (HN) is associated with worse clinical outcomes, and longer

months received the last dose of long-acting octreotide in period 0 (P0). Patients

hospital lengths-of-stay than seen in eunatremic patients. The Syndrome of

were randomized 28 days later to receive octreotide s.c. depot 10 mg q2w or

Inappropriate Antidiuresis (SIAD) is the most common cause of hyponatremia in

20 mg q4w for 3 months (period 1 [P1]).

hospitalization. We studied the relationship between correction of sustained

Results

SIAD-induced hyponatremia and visits to the Emergency Room (ERv) as well as

Twelve patients were randomized to receive octreotide s.c. depot 10 mg q2w

hospital admissions (HA) in a case series.

(acromegaly, nZ3; NET, nZ1) or 20 mg q4w (acromegaly, nZ4; NET, nZ4).

Methods

Acromegaly: steady state (SS) PK (for octreotide s.c. depot 10 mg, 20 mg vs long-

Retrospective, cross-sectional study of patients whose HN was corrected with

acting octreotide 10 mg, 30 mg, respectively) - AUC_0-28d(day*ng/l): 95.6, 78.5 vs

chronic tolvaptan therapy (CTV) for a minimum of 3 years. Serum Sodium

6.23, 24.1; C_max(ng/ml): 10.6, 11.3 vs 0.35, 1.41. NETs: SS PK (for octreotide s.c.

levels(SNa) in mmol/l. Descriptive statistics expressed as median (IQR). SPSS

depot 10 mg, 20 mg vs long-acting octreotide 20 mg, 30 mg, respectively) -

15, non-parametric tests (Wilcoxon for paired data), univariate analysis.

AUC_0-28d(day*ng/l): 83.3, 135.0 vs 27.8, 39.9; C_max(ng/ml): 5.61, 15.7 vs 1.68,

Results

2.48. In acromegaly, control of IGF-1 and GH levels was maintained or improved

16/25(64%) patients fulfilled inclusion criteria. Nine patients not completing

in P1 vs P0. In NETs, symptoms of carcinoid syndrome were similar or improved

1 year of follow-up were excluded. Median age: 82 (74-87). Women: 11/16(69%)

in P1 vs P0; symptoms disappeared in two patients in 20 mg group. Adverse

. HN was first detected a median of 51 months (IQR 29-56) prior to initiation of

events (all grade 1-2) were reported in six and eight patients during P0 and P1,

therapy. SIAD etiology: 9/16(56%) idiopathic, 3/16 (19%) drug-induced (19%),

respectively; most common in P1 were GI disorders.

2/16 (3%) respiratory, 1/16 (6%) abdominal, 1/16 (6%) cancer. The year before

Conclusions

HN correction, Nadir SNa:120(115-125) mmol/l, with a median of 2(1-4) ERv/

Octreotide s.c. depot provided higher exposure than long-acting octreotide,

patient, HA:1(1-2) with 18(10-32) days of hospitalization (DH). During year 1 of

maintained biochemical control in patients with acromegaly and symptom control

CTV, Nadir SNa rose to 136(133-137) mmol/l (PZ0.001), ERv dropped to

in patients with functioning NETs, and was well tolerated with a safety profile

1(0-3)(PZ0.03), HA to 0(0-0)(PZ0.003), DH to 0(0,0)(P!0.001). The benefits

consistent with long-acting octreotide.

were sustained when comparing the second and third years to the year prior to HN

DOI: 10.1530/endoabs.49.GP177

correction. Second year: ERv: 0(0-1)(PZ0.004), HA: 0(0-1)(PZ0.001), DH:

0(0-1)(P!0.001). Third year: ERv: 1(0-2)(PZ0.05), HA: 0(0-1)(PZ0.009), DH:

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

(0-4)(PZ0.01). Three years before start of therapy vs 3 years post: Total median

GP181

ERv/patient: 3(1-5), HA: 2(1-4), DH 18(10-34) vs total ERv: 2(1-4) (PZ0.03),

Targeting either GH or IGF-I levels during somatostatin analogue

HA: 1(0-2)(PZ0.006), DH 0(0-4)(PZ0.006). No patient developed hyperna-

treatment in patients with acromegaly: A randomized,

tremia. Tolvaptan doses were lowered if thirst developed or SNa reached

investigator-initiated multicenter study

141 mmol/l. Final weekly TV dose was 34 mg (23-105).

Jakob Dal¹, Marianne Klose⁵, Ansgar Heck⁶, Marianne Andersen³,

Conclusions

Caroline Kistorp⁴, Eigil Husted Nielsen², Jens Bollerslev⁶,

Correction of sustained hyponatremia secondary to SIADH with chronic TV

Ulla Feldt-Rasmussen⁵ & Jens Otto Lunde Jørgensen¹

therapy was safe, and associated with a significant and sustained reduction in ER

¹Aarhus University Hospital, Aarhus, Denmark;²Aalborg University

visits, hospital admissions, and days of hospitalization.

Hospital, Aalborg, Denmark;³Odense University Hospital, Odense,

DOI: 10.1530/endoabs.49.GP179

Denmark;⁴Herlev Hospital, Herlev, Denmark;⁵National University

Hospital, Copenhagen, Denmark;⁶Oslo University Hospital and Faculty of

Medicine, Oslo, Norway.

Context

Assessment of disease control in acromegaly depends on GH and IGF-I, but

discordant values frequently occur. Further, the role of OGTT-suppressed GH

(GH_nadir) in somatostatin analogue (SA) treated patients is debated.

Objective

To evaluate the effect of targeting either IGF-I or GH during SA treatment.

Design

A randomized, investigator-initiated, multicentre trial.

Patients and methods

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84 patients controlled with either SA (nZ61) or surgery-only (nZ23) underwent

Outcome of non-functioning pituitary adenomas that regrow after

a 3 h GH profile including a 2 h OGTT at baseline, after 6 months (SA treated

primary treatment: a study from two large specialist UK centers

patients only) and after

12 months together with IGF-I. SA patients were

Metaxia Tampourlou^1,2, Georgia Ntali³, Shahzada Ahmed⁴, Wiebke Arlt^1,2,

randomized to be monitored by either IGF-I (nZ33) or GH_nadir (nZ28). SA dose

John Ayuk², James Byrne⁵, Swarupsinh Chavda⁶, Simon Cudlip⁷,

increase were allowed at baseline and after 6 months. Symptoms and quality of

Neil Gittoes^1,2, Ashley Grossman³, Rosalind Mitchell⁸, Michael O’Reilly^1,2,

life

(QoL) were assessed by disease-specific questionnaires

(PAQ12 and

Alessandro Paluzzi⁸, Andrew Toogood², John Wass³ & Niki Karavitaki^1,2

AcroQoL).

¹Institute of Metabolism and Systems Research, College of Medical and

Main outcome measures

Dental Sciences, University of Birmingham, Birmingham, UK;²Centre for

GH and IGF-I at baseline and 12 months, symptoms and QoL, and SA dose

Endocrinology, Diabetes and Metabolism, Birmingham Health Partners,

increases.

Birmingham, UK;³Oxford Centre for Diabetes, Endocrinology and

Results

Metabolism, Churchill Hospital, Oxford, UK;⁴Department of Ear, Nose and

IGF-I and fasting GH levels at baseline were comparable between the two groups,

whereas GH_nadir (mg/l) was lower in the surgery group (GH_nadir 0.7G0.1 (SA) vs

Throat, Queen Elizabeth Hospital, University Hospitals Birmingham NHS

0.3G0.1 (surgery), P!0.01). At baseline, 31% of SA patients had concordant

Foundation Trust, Birmingham, UK;⁵Department of Neuroradiology,

controlled GH and IGF-I,

43% had elevated GH and 3% elevated IGF-I.

John Radcliffe Hospital, Oxford, UK;⁶Department of Radiology, Queen

Significantly more patients in the surgery group had concordant controlled values

Elizabeth Hospital, University Hospitals Birmingham NHS Foundation

(65%), P !0.01. SA dose increase was performed in 20 patients in the GH target

Trust, Birmingham, UK;⁷Department of Neurosurgery, John Radcliffe

group as compared to eight patients in IGF-I target group (PZ0.02) and resulted

Hospital, Oxford, UK;⁸Department of Neurosurgery, Queen Elizabeth

in a higher proportion of controlled patients

(PZ0.01). SA patients had

Hospital, University Hospitals Birmingham NHS Foundation Trust,

suppressed insulin levels and elevated glucose and FFA levels during the

Birmingham, UK.

OGTT compared to surgery. QoL was only mildly affected at baseline and did not

change consistently.

Introduction

Conclusions

Despite the significant risk of regrowth of non-functioning pituitary adenomas

i) Discordance between GH and IGF-I is more prevalent during SA treatment

(NFAs) after primary treatment, systematic data on the probability of further

as compared to surgery, mainly due to elevated GH_nadir levels, ii) targeting

tumour progression and the effectiveness of management approaches are lacking.

discordant GH or IGF-I levels in SA patients translates into SA dose increase and

Aims

a higher degree of concordance, iii) Our data suggest that a sizable proportion of

Assess the probability of further regrowth(s), predictive factors and outcomes of

SA patients are undertreated.

management approaches in patients with NFA diagnosed with adenoma regrowth

DOI: 10.1530/endoabs.49.GP181

after primary treatment (surgery combined or not with radiotherapy) in two UK

referral centers.

Methods

The records of the patients with NFA who during their follow-up had adenoma

regrowth were reviewed. The period covered for the primary NFA surgery was

between 1/1963 and 12/2011 and the follow-up period ended in 6/2016.

Results

We identified 237 patients (median follow-up after 1st regrowth of 5.9 years

(range 0.4-37.7)). The 5-year 2nd regrowth rate was 35.3% (36.2% after surgery;

GP182

12.5% after radiotherapy; 12.7% after surgery combined with radiotherapy;

Brain white matter damage and volumes of hippocampus and

63.4% with monitoring). Of those managed by monitoring, 34.8% eventually

hypothalamus correlates to cognitive function in craniopharyngioma

were offered intervention. Type of management and sex were risk factors for 2nd

Sigridur Fjalldal¹, Daniel Svärd², Cecilia Follin¹, Danielle Van Westen²,

NFA regrowth, whereas age at diagnosis of primary NFA and type of adenoma

Sanaz Gabery³,

˚saPetersén3, Magdalena Jansson⁴, Pia Maly Sundgren^2,5,

immunostaining were not. Amongst those with 2nd adenoma regrowth, the 5-year

Isabella Bjorkman-Burtscher^2,5, Jimmy Lätt⁵, Peter Mannfolk⁵,

3rd regrowth rate was 26.4% (24.4% after surgery; 0.0% after radiotherapy; 0.0%

Carl-Henrik Nordstrom⁷, Lars Rylander⁸, Bertil Ekman⁹, Aki Johansson⁴ &

after surgery combined with radiotherapy; 48.3% with monitoring). Overall,

Eva-Marie Erfurth¹

patients with a NFA regrowth had probability of a 3rd regrowth 4.4% at 5 years,

¹Department of Endocrinology, Skåne University Hospital, Lund, Sweden;

and 10.0% at 10 years, and the type of management of the 1st regrowth was the

²Department of Diagnostic Radiology, Clinical Sciences, Lund University,

only risk factor. Malignant transformation was diagnosed in two of 237 patients

Lund, Sweden;³Translational Neuroendocrine Research Unit, Department

(one gonadotroph and one silent ACTH adenoma).

of Experimental Medical Science, Lund University, Lund, Sweden;

Conclusions

⁴Department of Psychology and Psychiatry, Skåne University Hospital,

Patients with regrown NFA after primary treatment continue to carry considerable

Lund, Sweden;⁵Department of Medical Imaging and Physiology, Skåne

risk of tumour progression necessitating long-term follow-up. Management

University Hospital, Lund, Sweden;⁶Lund University BioImaging Center,

approach of the regrowth is the major factor determining this risk; monitoring

Lund University, Lund, Sweden;⁷Department of Neurosurgery, Sk

˚ne

alone is associated with high progression rates and a substantial number of

University Hospital, Sweden, Lund, Sweden;⁸Division of Occupational and

patients will ultimately require intervention.

Environmental Medicine, Lund University, Lund, Sweden;⁹Department of

DOI: 10.1530/endoabs.49.GP180

Endocrinology and Medical and Health Sciences, Linkoping University,

Linkoping, Sweden.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction

GP184

Adult patients with craniopharyngioma (CP) and hypothalamic (HT) damage

Hormonal and metabolic effects of long-term cabergoline withdrawal in

have impaired cognitive function. The white matter (WM) changes behind these

patients with hyperprolactinemia

findings remain to be elucidated. Diffusion tensor imaging (DTI) is a MRI

Renata Simona Auriemma, Chiara Blasio, Ludovica Francesca

technique that quantifies microstructural damage in the WM. This is the first study

Stella Grasso, Mariano Galdiero, Mariarosaria Negri, Claudia Pivonello,

of DTI, hippocampal (HC) and HT volume in relation to cognition in CP patients.

Luciana Granieri, Annamaria Colao & Rosario Pivonello

Methods

Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia,

A cross-sectional study of childhood onset CP was performed at median 22 years

Università Federico II di Napoli, Naples, Italy.

after first operation. After exclusions, 36 patients and 31 controls remained in the

MRI study. Main outcome measures were comparison of cognitive tests, volume

measurements of HC and HT and the DTI parameters median diffusivity (MD)

Hyperprolactinemia is associated with abnormalities in glucose and lipid profile

and fractional anisotropy (FA) between patients and controls.

with development of insulin resistance and metabolic syndrome (MetS), which have

Results

been found to be improved by treatment with cabergoline (CAB). The current study

CP patients have WM damage in the left dorsal cingulum and right uncinate

aimed at investigating hormonal and metabolic effects of long-term CAB

fasciculus. No significant difference was found on DTI measurements of the HC.

withdrawal in patients with prolactinomas. In

46 patients (37 F, 9 M, aged

Correlations were found between DTI results from the right uncinated fasciculus

34.5G11.5 yrs,

36 microadenomas and

10 macroadenomas) anthropometric

(MD, PZ0.035 and FA, PZ0.005) and the left HC (MD, PZ0.035 and FA,

(weight, BMI, waist circumference (WC)) and metabolic (fasting glucose (FG)

PZ0.001) with long term memory reflecting general knowledge. DTI in the

and insulin (FI), total (TCHO), HDL and LDL cholesterol, triglycerides (TG),

cingulum correlated with visual memory (MD, P%0.04 and FA, P%0.04) and

HOMA-IR, HOMA-b, ISI0, VAI, and prevalence of MetS) parameters, and PRL

short term memory (MD, PZ0.004). DTI in the HC correlated with long term

levels were evaluated at baseline, at CAB withdrawal (TWD), and 12 (T12) and 60

memory (MD, PZ0.03 and FA, P%0.046) and short term memory (FA, PZ0.02).

(T60) months after CAB discontinuation. CAB treatment (median durationZ72

HT volume correlated negatively with MD of right uncinate fasciculus

months) induced PRL normalization in all patients, and a significant improvement

(PZ0.015). The CP patients had a smaller HC volume which correlated with

of BMI (P!0.0001), WC (P!0.0001), FI (PZ0.007), HDL (P!0.001), LDL

long term memory (PZ0.016).

(P!0.001), HOMA-IR (PZ0.012) and ISI0 (PZ0.05) compared to baseline. CAB

Conclusions

withdrawal resulted in prolonged and sustained normoprolactinemia, with only 8

A structure to function relationship is established between cognition and WM

(17.4%) patients requiring treatment restarting within 12 months. In 38 patients

damage detected with DTI in CP. CP patients have a smaller HC compared to

permanently discontinuing CAB, compared to TWD BMI (P!0.0001), WC

controls. Whether the cognitive deficits are a direct consequence of HT damage or

(P!0.0001), TCHO (P!0.001) and VAI (P!0.0001) significantly impaired at

an indirect effect on frontotemporal network remains to be elucidated.

T12, and similarly BMI (P!0.0001), WC (P!0.0001), TCHO (P!0.05) and VAI

(P!0.0001) at T60. Compared to TWD no further changes were seen in FI,

DOI: 10.1530/endoabs.49.GP182

HOMA-IR, HOMA-b, ISI0. MetS prevalence significantly increases from T0

(23.9%) to T60 (41.3%, P!0.0001), with 8 patients (17.4%) developing MetS after

CAB withdrawal. In conclusion, CAB discontinuation significantly worsens lipid

profile and MetS prevalence in patients with prolactinomas.

DOI: 10.1530/endoabs.49.GP184

GP183

Copeptin - a sensitive marker of an altered CRH-axis in

pituitary disease

Krzysztof Lewandowski¹, Andrzej Lewinski¹, Elzbieta Skowronska-

Jozwiak¹, Katarzyna Malicka¹, Wojciech Horzelski² & Georg Brabant³

Pituitary & Endocrine Tumours

¹Department of Endocrinology and Metabolic Diseases, “Polish Mother”

Memorial Research Institute and The Medical University of Lodz, Lodz,

GP185

Poland;²Faculty of Mathematics and Computer Science, University of

Localization of benign insulinomas using glucagon-like peptide-1

Lodz, Lodz, Poland;³Experimental and Clinical Endocrinology Med Clinic

receptor (GLP1-R) SPECT/CT and PET/CT and MRI in a prospective

I, University of Luebeck, Lubeck, Germany.

clinical study

Kwadwo Antwi¹, Melpomeni Fani¹, Tobias Heye¹, Guillaume Nicolas¹,

Elmar Merkle¹, Jean Claude Reubi², Beat Gloor³, Damian Wild¹ &

Background

Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin (AVP)

Emanuel Christ^1,4

closely reflects AVP release. Previously it was shown that copeptin is stimulated

¹Clinic of Radiology and Nuclear Medicine, University of Basel Hospital,

in standard pituitary function tests acting through hypothalamic centres.

Basel, Switzerland;²Division of Experimental Pathology, Department of

Furthermore, copeptin has been shown to subtly mirror stress potentially

Pathology, University of Bern, Bern, Switzerland;³Department of Visceral

mediated via CRH. To further test a potential direct interaction of CRH with

Surgery, University Hospital of Bern, Inselspital, Bern, Switzerland;

copeptin release which could augment AVP effects on pituitary function, we

⁴Division of Endocrinology, Diabetology and Clinical Nutrition,

investigated copeptin response in a standard CRH test, both in healthy controls

University Hospital of Bern, Inselspital, Bern, Switzerland.

and patients with pituitary disease.

Patients and methods

Purpose

18 healthy controls and

29 subjects with history of pituitary disease were

We aim at prospectively comparing the detection rate of GLP1-R PET/CT vs

subjected to a standard CRH test and in addition to ACTH and cortisol we

GLP1-R SPECT/CT vs standardized contrast enhanced 3T-MRI in patients with

measured copeptin by standard assays (ThermoFisher).

suspected insulinoma.

Results

Methods

Patients with previous pituitary disease were subdivided in a group passing the test

40 patients with neuroglycopenic symptoms due to endogenous hyperinsulinemic

(P1) and failing (P2). The latter group included five patients with diabetes

hypoglycemia were enrolled.

insipidus. The overall copeptin response was higher in controls than in subjects

3T-MRI was performed. Afterwards patients received SPECT/CT after injection

with pituitary disease (area under the curve, PZ0.04 for P1CP2) with a maximum

of¹¹¹In-DOTA-exendin-4 and PET/CT after injection of⁶⁸Ga-DOTA-exendin-4

increase in controls from 3.84G2.86 pmol/l, to 12.65G24.87 pmol/l, PZ0.04, at

in a randomized order. Three blinded nuclear medicine physicians and three

30 min). In contrast, both groups of pituitary patients lacked a significant CRH

blinded radiologists reviewed the scans.

response. The mean increase in P2 was from 1.93G1.44 pmol/l to 3.37G

Standard of comparison was the histological diagnosis after surgery.

3.49 pmol/l, at 30 min, PZns, and even in P1 where ACTH concentrations

Results

increased four-fold (mean 21.48 vs. 91.53 pg/ml, P!0.01) copeptin did not

Previously performed cross-sectional imaging was negative or inconclusive in

respond (e.g. 4.35G5.81 pmol/l vs. 5.36G6.79 pmol/l, at 30 min, PZns).

27/40 patients. So far 29 patients have been operated. The histological diagnosis

Conclusions

of a benign insulinoma was confirmed in

25 patients, one patient had a

CRH is able to stimulate copeptin release in healthy controls suggesting a direct

nesidioblastosis. In one patient no lesion could be found intraoperatively. In two

interaction of CRH and AVP/vasopressin. Interestingly, this relation is altered

patient symptoms of endogenous hypoglycemia ceased postoperative but

already in the group of pituitary patients who pass the standard CRH test indicating

histological diagnosis did not confirm a benign insulinoma or nesidioblastosis.

i) that the CRH-ACTH-cortisol response is largely independent from the AVP

These two patients were excluded from evaluation as the final diagnosis remained

system, but ii) the CRH-AVP interaction reflected by copeptin may be much more

unclear. Two patients refused surgery. Three patients are awaiting surgery. In five

sensitive to reveal subtle alterations in the regulation of pituitary function.

patients all performed imaging modalities did not find any suspicious lesion and

DOI: 10.1530/endoabs.49.GP183

were thus not operated up to date. One patient showed signs of malignancy in

MRI, thus did not meet the inclusion criteria and was excluded. In this interim

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

analysis of 27 operated patients PET/CT showed an overall pooled sensitivity of

free cortisol (UFC) levels in some patients with Cushing’s disease (CD). Cabergoline is

92%, SPECT/CT at 72 h a sensitivity of 71% and 3T-MRI a sensitivity of 76%.

a dopamine D2 receptor agonist with efficacy in some patients with CD. Most

Conclusion

corticotropinomas co-express SSTR5 and D2, providing rationale for combination

1) These preliminary data suggest that PET/CT performs better as standardized

treatment with pasireotide and cabergoline. Results are reported from a Phase II

MRI imaging and SPECT/CT at lower irradiation dose and much shorter

study of pasireotide alone or combined with cabergoline in patients with CD.

investigation time than the latter.

Methods

2) GLP-1R PET/CT will be a useful diagnostic tool in patients where CT/MRI

Open-label, multicentre, non-comparative study. Patients with persistent/recur-

fails to localize the insulinoma.

rent or de novo (if not surgical candidates) CD who were pasireotide-untreated at

DOI: 10.1530/endoabs.49.GP185

screening were enrolled. Patients initiated treatment with pasireotide (subcutaneous)

0.6

mg bid. If mean UFC (mUFC; from two consecutive 24h collections)

remained OULN after 8 weeks, the pasireotide dose was increased, if tolerated, to

0.9 mg bid for 8 weeks. If mUFC remained elevated, cabergoline 0.5mg qd was

added for 8 weeks, increasing to 1.0mg qd for another 8 weeks if mUFCOULN.

Primary endpoint: proportion of patients with mUFC%ULN at week 35.

GP186

Results

24 hour urinary 5-hydroxyindoleacetic acid (5-HIAA) doubling-time

Sixty-six patients (median 40.5 years; 59 females) were enrolled. Twenty-seven

(DT) is associated with disease-specific mortality (DSM) and

patients received pasireotide monotherapy; 39 received combination therapy. At

progression-free survival (PFS) in patients with neuroendocrine

week 35, mUFC%ULN was achieved in 25 patients (37.9%, 95%CI 26.2-50.7),

tumors (NETs)

13 of whom received pasireotide monotherapy, with a further 12 achieving the

Amit Tirosh^1,2, Naris Nilubol³, Dhaval Patel³ & Electron Kebebew³

primary endpoint after cabergoline addition. The most common (O20%) AEs

¹National Institutes of Health, Bethesda, Maryland, USA;²Sackler Faculty

were hyperglycaemia (51.5%), nausea (47.0%), diarrhoea (45.5%), headache

of Medicine, Tel Aviv University, Tel Aviv, Israel;³Endocrine Oncology

(28.8%), dizziness (24.2%) and cholelithiasis (24.2%). Sixteen (24.2%) patients

Branch, National Cancer Institute, Bethesda, Maryland, USA.

discontinued before week 35 (10 on pasireotide monotherapy); seven (10.6%)

because of AEs (five on pasireotide monotherapy). Two on-treatment deaths

occurred, both unrelated to study treatment.

Background

Conclusions

Biochemical biomarker DT is used clinically for prognosis prediction in several

Pasireotide alone or combined with cabergoline effectively controlled mUFC.

solid malignancies. The aim of the current analysis was to determine whether

Results suggest that addition of cabergoline in patients with persistently elevated

biomarker DT has any prognostic utility in patients with NETs.

mUFC is an effective strategy to enhance the control of CD.

Methods

Patients with NETs

(nZ184) were enrolled in a prospective study with

DOI: 10.1530/endoabs.49.GP187

comprehensive biochemical analysis. The current analysis included subjects

with increasing 5-HIAA levels in at least two consecutive measurements. DTs for

each biomarker were calculated using the formula DT Z [log₁₀(2)*(time interval

between tests)]/[log₁₀(2^nd value)-log₁₀(1^st value)]. Log-rank test was used to

assess differences in DSM or PFS risk by DT. The c-statistic of 5-HIAA predictive

GP188

utility for DSM was calculated using receiver operating characteristic (ROC)

Vertebral fractures are prevalent among patients with acromegaly in

curve analysis. DSM and PFS were compared by 5-HIAA DT using Kaplan-Meier

spite of normal bone mineral density reflecting overall duration of

survival analysis and multivariate analysis was performed using Cox regression.

disease regardless of biochemical control or cure

Results

Marko Stojanovic^1,2, Dragana Miljic^1,2, Sandra Pekic^1,2, Mirjana Doknic^1,2,

91 patients had increasing 5-HIAA levels. Four patients died during a median

Marina Nikolic Djurovic^1,2, Zvezdana Jemuovic¹, Vera Popovic² &

follow-up of

months

(interquartile range,

12). The c-statistic for DSM

Milan Petakov^1,2

prediction by 5-HIAA was 0.76 (95% CI 0.62-0.90), and 5-HIAA DT !434 days

¹Clinic for Endocrinology, Diabetes and Metabolic Diseases,

had positive and negative predictive values for DSM of 75 and 76%, respectively.

Clinical Centre of Serbia, Belgrade, Serbia;²University of Belgrade,

Patients with a 5-HIAA DT !434 days had higher risk for DSM during follow-up

School of Medicine, Belgrade, Serbia.

(Log-Rank test, PZ0.02). In sub-group analysis this difference was found only

among patients with a non-pancreatic NET (PZ0.002). In the entire cohort, PFS

were comparable between patients with 5-HIAA DT longer vs. shorter than

Introduction

434 days. However, patients with small-intestine NET with 5-HIAA DT !

Skeletal complications of acromegaly are among its most persistent and

434 days had a higher risk for progression (PZ0.006), also in multivariate

invalidating impacts. Dual-X-ray absorptiometry

(DXA) alone might be

analysis (Hazard Ratio 15.3, 95% CI 1.01-232.6, PZ0.049).

insufficient or even misleading for bone health assessment in acromegaly.

Conclusions

Patients and methods

Short 5-HIAA DT is associated with increased DSM and lower PFS in patients

Patients with acromegaly

(NZ170) were classified as active

(NZ104),

with NET, and specifically among those with SINET, and can be used as a

operatively cured (NZ34) or medically controlled (NZ32). 57 males and 113

prognostic measure in NET patients.

females were included, 52.8 (22.0-78.5) years old. Bone mineral density (BMD)

DOI: 10.1530/endoabs.49.GP186

was assesed at L1-L4 and Femoral neck (FN) using DXA Hologic Discovery-W-

QDR. BMD results were expressed as Z score, accounting for age and gender.

Vertebral fracture assessment (VFA) on Th4-L4 was performed in 71 patients (24

male, 47 female) to identify number, type, location and degree of severity of

vertebral fractures (VFs).

GP187

Results

Pasireotide alone or in combination with cabergoline effectively

L1-L4 BMD was normal in all patients and not significantly different in active

controls urinary free cortisol levels: results from a prospective study in

(Zsc: 0.61G0.13) cured (Zsc: 0.32G0.25) or controlled acromegaly (Zsc: 0.17G

patients with Cushing’s disease (CAPACITY)

0.32). FN BMD was normal in all and not significantly different in active (Zsc:

Rosario Pivonello¹, Pritam Kadioglu², Marie Bex³, Deyanira

0.61G0.11) cured (Zsc: 0.59G0.19) or controlled acromegaly (Zsc: 0.49G0.22).

González Devia⁴, Cesar Boguszewski⁵, Dilek Gogas Yavuz⁶,

VFs were identified in 23.9% (17/71) of patients. Prevalence in males was

Heather Patino⁷, Federico Campigotto⁷, Alberto Pedroncelli⁸,

significantly higher than in females (33.3% vs. 19.2%; P!0.01). Patients with

Maria Fleseriu⁹, Beverly M K Biller¹⁰ & Richard Feelders¹¹

and without VFs did not differ in BMD L1-L4 Zsc (0.98G0.06 vs. 1.04G0.02) or

¹Università Federico II di Napoli, Naples, Italy;²Istanbul University,

FN Zsc (0.83G0.05 vs. 0.86G0.02). Duration of the disease in patients with VFs

Istanbul, Turkey;³University Hospitals Leuven, Leuven, Belgium;

was significantly longer (14.1G1.9 vs. 9.6G1.2yrs) then in those without VFs

⁴Hospital Universitario Fundación Santa Fé de Bogotá, Bogota, Colombia;

(P!0.05). Prevalence of VFs was significantly higher in controlled (62.5%) and

⁵Federal University of Paraná, Curitiba, Brazil;⁶Marmara University

cured (40.0%) compared to active (17.8%) acromegaly (P!0.01).

Medical School, Istanbul, Turkey;⁷Novartis Pharmaceuticals Corporation,

Conclusion

East Hanover, New Jersey, USA;⁸Novartis Pharma AG, Basel, Switzerland;

Considerable prevalence of vertebral fractures (24%) was identified in a large

⁹Oregon Health and Science University, Portland, Oregon, USA;

cohort of patients with acromegaly, irrespective of normal bone mineral density.

¹⁰Massachusetts General Hospital, Boston, Massachusetts, USA;¹¹Erasmus

Duration of the disease was the main determinator of VFs prevalence, regardless

Medical Center, Rotterdam, The Netherlands.

of the biochemical control or cure. VFs are important, persistent and invalidating

Background

yet often under-recognized complication of acromegaly.

Pasireotide is a multireceptor-targeted somatostatin analogue that predominantly binds

DOI: 10.1530/endoabs.49.GP188

to somatostatin receptor subtype 5 (SSTR5) and provides sustained control of urinary

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP189

Objective and hypotheses

To describe and report safety data and incidence rates (IRs) (events/1000 patient-

Evaluation of pituitary toxicity after radiotherapy for cerebral

years) of adverse drug reactions (ADRs), serious adverse events (SAEs) and

chondrosarcomas in adult patients

serious ADRs (SADRs).

Suzanne Laroche¹, Loïc Feuvret^3,5, Alain Beauchet², Rémi Dendale³,

Method

Philippe Chanson⁴, Eric Bruckert¹ & Christel Jublanc¹

Events were classified by MedDRA Preferred Term/System Organ Class (SOC).

¹Endocrinologie, Hôpital Pitié Salpêtrière, APHP, Paris, France;²Unité de

IRs during GH treatment were calculated.

Recherche Clinique, Département de Santé Publique, Hôpital Ambroise

Results

Paré, APHP, Paris, France;³Centre de Protonthérapie d’Orsay, Institut

Data for 2438 patients (adult-onset, 90.1%; female 44.0%; mean (S.D.) age at

Curie, Orsay, France;⁴Endocrinologie, Hôpital Bicêtre, APHP, Le Kremlin

treatment start, 43.3 (17.8) years; duration of follow-up, 5.8 (4.7) years; GH dose,

Bicêtre, France;⁵Radiothérapie, Hôpital Pitié Salpêtrière, APHP, Paris,

0.41

(0.32) mg/day) were analysed. Overall, 197 adverse events (AEs) were

France.

reported in 150 patients. Among these patients, mean (S.D.) treatment duration to

first AE was 4.7 (4.1) years and GH dose at AE onset was 0.36 (0.31) mg/day.

Pituitary dysfunction can be a consequence of cranial radiotherapy. It usually occurs

After the first AE, GH dose was unchanged in 55.3%, discontinued in 26.4% and

years after the treatment. However little is known on risk factors for pituitary

decreased in 7.6% of patients (not reported/other for 10.7%). IRs were 11.91 for

dysfunction. The object of this study was to evaluate radiation induced pituitary

SAEs, 1.89 for SADRs and 5.52 for ADRs. Most frequently reported (nR10) AEs

toxicity of proton beam therapy in a cohort of adult chondrosarcoma patients.

by SOC (n, %) were nervous system disorders (nZ43, 21.8%), neoplasms

The files of 113 patients were reviewed. Mean age at the beginning of radiotherapy

(benign, malignant and unspecified)

(nZ35,

17.8%), musculoskeletal and

was 43 years old (18-76). Mean dose delivered to the tumor was 67 Gy and mean

connective tissue disorders

(nZ20; 10.2%); general disorders and adminis-

dose delivered to the pituitary gland was 59 Gy. Mean post-radiotherapy follow-up

tration-site conditions or infections and infestations (each nZ15, 7.6%); and

time was 7 years (4-17). Pituitary dysfunction was observed in 78 patients, within the

cardiac disorders (nZ14, 7.1%). Type 2 diabetes was reported as an AE in four

delay of 4 years after radiotherapy. The prevalence of hyperprolactinemia was of

patients. Twelve deaths (one possibly related) were reported.

40%, thyrotrophic insufficiency was 36%, corticotropic insufficiency 31%, and

Conclusions

gonadotropic insufficiency 25%. No significant differences were shown in the delay

IRs of SAEs, ADRs and SADRs were low. Data from NordiNet^w IOS revealed no

of dysfunction between the pituitary axes. In multivariate analysis, risk factors

new safety signals, further supporting the favourable safety profile of GH

known to increase the risk of vascular side-effects of radiation (sex, age, smoking,

replacement in adults with GHD.

high blood pressure, dyslipidemia and diabetes mellitus) were not associated with an

DOI: 10.1530/endoabs.49.GP190

increase of pituitary dysfunction.

Conclusions

Pituitary toxicity of radiotherapy is frequent after 4 years. The high prevalence of

hyperprolactinemia pinpoints a possible hypothalamic origin of post radiotherapy

pituitary insufficiency. A prospective follow up is necessary to complete these

GP191

observations and propose relevant guidelines. Our study analyses the largest cohort

of patients with chondrosarcomas after proton beam therapy. Our results emphasize

GH and IGF-1 levels at 12 weeks predict long-term responses to

the importance of careful and long term endocrine follow-up of these patients.

lanreotide Autogel in treatment-naïve acromegalic patients: post-hoc

analyses from the PRIMARYS study

Philippe Caron¹, Stephan Petersenn², Aude Houchard³, Caroline Sert³ &

John S Bevan⁴

Department of Endocrinology, CHU Larrey, Toulouse, France;²ENDOC

Center for Endocrine Tumors, Hamburg, Germany;³Ipsen Pharma,

Boulogne-Billancourt, France;⁴Department of Endocrinology,

Aberdeen Royal Infirmary, Aberdeen, UK.

Background

In PRIMARYS, lanreotide Autogel (LAN) 120 mg/28 days reduced tumour

volume (TV), and GH/IGF-1 levels in patients with GH-secreting macro-

adenomas. In post-hoc analyses, we investigated predictive factors for treatment

responses.

Methods

PRIMARYS, a 48-week, international, open-label study, involved 90 treatment-

Figure: Kaplan-Meyer curve for pituitary dysfunction.

naïve patients with GH-secreting macroadenomas receiving LAN. Factors

predictive for hormonal control (HC; GH %2.5 mg/LC normal IGF-1) at last

DOI: 10.1530/endoabs.49.GP189

post-baseline value available (LVA) or R20% TV reduction (TVR) at week

48/LVA were investigated using univariate logistic regression. Week-12 GH,

IGF-1 and TV cut-off values for predicting responses were obtained from ROC

curves, maximising the Youden index. Analyses used intention-to-treat

populations and P!0.05 as significant.

Results

GP190

From univariate analyses, HC was more likely in women (odds ratio: 2.9 times

higher for women vs. men), and older patients (2.2 times higher for each 10-year

Safety of long-term growth hormone (GH) treatment in adults with GH

higher age), and with lower baseline IGF-1 (1.1 times higher for each 10% lower

deficiency (GHD): an analysis from the NordiNet^w International

IGF-1 level [% upper limit of normal, ULN]), but no association with GH levels

Outcome Study

was shown. HC was determined by week-12 hormonal response: optimal cut-offs

Jens Otto Jørgensen¹, Vera Popovic-Brkic², Effie Pournara³,

were 1.19 mg/L for GH (sensitivity, 0.79; specificity, 0.89; area-under-the-curve

Birgitte Pedersen⁴, Anita Chudecka³ & Christian Strasburger⁵

[AUC] value, 0.87) and 110% ULN for IGF-1 (0.89, 0.85 and 0.93, respectively).

¹Aarhus University Hospital, Aarhus, Denmark;²University of Belgrade,

Univariate analyses revealed no baseline factors influencing TVR. TVR was,

Belgrade, Serbia;³Novo Nordisk Health Care AG, Zurich, Switzerland;

however, determined by changes from baseline to week 12 in GH, IGF-1 and TV:

⁴Novo Nordisk A/S, Søborg, Denmark;⁵Charité Universitatsmedizin Berlin,

optimal cut-offs were K69% for GH (sensitivity, 0.74; specificity, 0.67; AUC,

Berlin, Germany.

0.74), K61% for IGF-1 (0.58, 0.80, 0.75), and K21% for TV (0.81, 0.97, 0.93).

Conclusions

Background

Based on post-hoc PRIMARYS data, treatment-naïve patients with GH-secreting

Long-term safety data (1998 to mid-2016) are reported for adult patients with

macroadenomas are more likely to achieve long-term hormonal control with LAN

GHD treated with GH (Norditropin^w (somatropin), Novo Nordisk) as prescribed

120 mg/28 days if GH levels are !1.2 mg/L and IGF-1 levels !110% ULN at

by treating physicians in the real-life clinical setting and enrolled in NordiNet^w

12 weeks, and more likely to achieve clinically significant long-term reductions in

International Outcome Study

(IOS)

(NCT00960128), a non-interventional,

TV with O60% reductions in GH/IGF-1 levels by week 12.

multicentre study.

DOI: 10.1530/endoabs.49.GP191

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP192

(68% women) but was also considered as climacteric and result of ageing.

Headache and visual impairment were common causes for referral later on, and

Long-term treatment with pegvisomant (Somavert^w): Observations

hyperprolactinemia was found due to hormonal investigation after MR-visualiza-

from 2090 acromegaly patients followed in ACROSTUDY

tion of pituitary tumor. In some cases with prolactin levels 1300-1900 mMU/l,

Aart Jan vanderLely¹, Beverly Biller², Thierry Brue³, Michael Buchfelder⁵,

differential diagnosis was required between hyperprolactinemia due to pituitary

Ezio Ghigo⁴, kaijie Pan⁸, Peter Jonsson⁹, Joanne Lavenberg⁸, Christian

stalk compression and prolactinomas with moderate secreting activity (“hook”

J. Strasburger⁶, Susan Webb⁷, Cecilia Camacho-Hubner⁸

phenomena was excluded). However, significant tumor shrinkage and (in some

& Judith Hey-Hadavi⁸

cases) restoration of regular menstrual cycle after 3-6 months of cabergoline

¹Erasmus University Medical Center, Rotterdam, The Netherlands;

treatment confirmed prolactinoma.

²Massachusetts General Hospital, Boston, MA, USA;³Universite de la

Conclusion

Mediterranee, Marseille, France;⁴Universita de Torino, Torino, Turin, Italy;

If a woman over 40 has menstrual irregularity or amenorrhea and does not

⁵University of Erlangen-Nurnberg, Erlangen, Germany;⁶Charite-Universi-

experience any vasomotor symptom, it is a reason to prove a natural menopause

tatsmedizin, Berlin, Germany;⁷Universitat Autonoma de Barcelona,

by measuring high FSH levels (O25 MU/l). In cases of lower FSH levels it is

Barcelona, Spain;⁸Pfizer Inc Endocrine Care, New York-Collegeville,

reasonable to consider pathological hyperprolactinemia.

USA;⁹Pfizer Inc ACROSTUDY Endocrine care, Sollentuna, Sweden.

DOI: 10.1530/endoabs.49.GP193

Introduction

Pegvisomant (PEGV) is approved for the treatment of acromegaly since 2003.

This is the second interim analysis of data from ACROSTUDY, with the majority

of patients treated for at least five years (yrs).

GP194

Methods/design

Serotonin, ATRX and DAXX as differential diagnostic markers of

ACROSTUDY is an international, open-label, prospective, non-interventional,

neuroendocrine tumours (NETs) in the sellar region. An

post-marketing surveillance study monitoring the long-term safety and efficacy of

immunohistochemical study in a large series of pituitary adenomas

PEGV. Patients were enrolled in the study on an ongoing basis.

and in a non-pituitary NET

Results

Olivera Casar-Borota^1,2, Johan Botling^1,2, Dan Granberg³,

As of May 31, 2016, data from 2090 patients (51% men) from 15 countries were

Johan Wikstrom⁴, Fredrik Pontén^1,2 & Jacqueline Trouillas^5,6

available. Mean treatment duration was 7.6 yrs (median 8.1 range: 0.0-19.1 yrs).

¹Department of Immunology, Genetics and Pathology, Uppsala University,

Patients were followed in ACROSTUDY for a mean of 6.3 yrs (median 6.8, range

Uppsala, Sweden;²Department of Clinical Pathology, Uppsala University

0.1-12.1). At ACROSTUDY start, there were 12 patients in the 0-18 yrs category

Hospital, Uppsala, Sweden;³Department of Medical Sciences, Uppsala

and 203 patients in the O70 yrs category. At PEGV start, pituitary insufficiencies

University, Uppsala, Sweden;⁴Department of Surgical Sciences, Uppsala

were observed for gonadotrophins (37.9%), TSH (29.1%) and ACTH (28.3%).

University, Uppsala, Sweden;⁵Faculté de Médecine Lyon-Est, Université

54.4% of patients experienced adverse events (AEs) with most common AE being

Lyon 1, Lyon, France;⁶Centre de Pathologie et de Biologie Est,

IGF-I increased

(10.5% of patients), headache(4.9%), vitamin D defici-

Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, Lyon, France.

ency(4.6%) and arthralgia(3.7%). SAEs were experienced in 22% of patients

(2.3% were treatment related, while 7.0% of patients discontinued treatment due

to the SAE). A total of 78 deaths were reported (all non-treatment related).

We present a case of a patient with a locally invasive, serotonin- and ACTH-

Locally assessed MRIs showed that most patients (72.2%) had no change in

reactive tumour in the sellar region, filling the sphenoid sinus and expanding into

tumour size relative to last exam; 16.8% had decrease in tumour size, 6.8% had an

the epipharynx. Clinical examination completed by 68-Gallium-DOTA-TOC

increase, and 4.3% had both increase and decrease. Shift analysis demonstrated

PET revealed tracer uptake in the sellar tumour as well as in a 7 mm lesion in the

that of the

1245 with reported normal LFTs

(AST/ALT) at baseline,

pancreatic tail. A differential diagnosis between silent corticotroph adenoma and

developed elevations O 3xULN. Administration site reactions were reported for

another primary or secondary neuroendocrine tumour

(NET) with ACTH-

3.4% of patients.

expression was difficult.

Conclusions

As serotonin was strongly positive in the tumour cells and its expression in

This second interim analysis of long-term follow up showed that PEGV is an

pituitary endocrine tumours has not been systematically studied, we performed

effective and safe treatment in patients with acromegaly. Data indicate low

immunohistochemical analysis of serotonin in a large series of pituitary adenomas

occurrence of reported pituitary tumor changes, liver test elevations and site

of different hormonal types from 246 patients. In addition, ATRX and DAXX,

administration reactions.

which mutations are associated with a subset of pancreatic NETs have been

DOI: 10.1530/endoabs.49.GP192

studied by using immunohistochemistry in the same cohort of pituitary tumours.

None of the examined pituitary tumours expressed serotonin. There was normal

expression of ATRX and DAXX corresponding to a lack of ATRX/DAXX

mutations in the pituitary tumours.

Thus, serotonin-immunolabelling tumours in the sellar region most probably

represent primary or secondary neuroendocrine tumours of non-pituitary origin.

GP193

ATRX and DAXX do not seem to be involved in the pathogenesis of pituitary

adenomas. Demonstration of ATRX or DAXX mutations in a neuroendocrine

Amenorrhea without vasomotor symptoms in women over 40: A sign of

tumour of the sellar region excludes pituitary adenoma and suggests a non-

pathological hyperprolactinemia?

pituitary NET, probably of pancreatic origin.

Irena Ilovayskaya, Alexader Dreval & Yulia Krivosheeva

Moscow Regional Research & Clinical Institute, Moscow, Russia.

DOI: 10.1530/endoabs.49.GP194

Background

Hyperprolactinemia is often seen in women of reproductive age (20-35 years),

most often due to microprolactinoma. However, prolactinomas do occur in older

GP195

women.

Long-term follow-up of a family with a large AIP gene deletion: variable

Objective

phenotypes and challenges in the management

To analyze clinical features of hyperprolactinemia in women O40 years

Pedro Marques¹, Mary Dang¹, Arla Ogilvie², Helen Storr³, Michael Powell⁴,

Material and methods

Joan Grieve⁴, Jane Evason⁵, Ajith Kumar⁶ & Marta Korbonits¹

Clinical and biochemical data of 185 women with pathological hyperprolacti-

¹Centre for Endocrinology, William Harvey Research Institute, Barts and

nemia were analyzed.

the London School of Medicine and Dentistry, Queen Mary University of

Results

London, London, UK;²West Hertfordshire Hospitals NHS Trust, Watford,

Seventy

(37.8%) patients had microprolactinomas

(MI),

(30.8%)

UK;³Department of Paediatric Endocrinology, Royal London Hospital,

macroprolactinomas (MA), and 58 (31.4%) - non-tumoral hyperprolactinemia

Barts Health NHS Trust, London, UK;⁴The National Hospital for

(NT). Among them, 26(36.1% of corresponding subgroup) with MI, 27(46.6%)

Neurology and Neurosurgery, London, UK;⁵Department of Radiology

with NT and 37(64.9%) with MA were O40 years of age. Menstrual disturbances

Barts Health NHS Trust, London, UK;⁶North East Thames Regional

and infertility issues are key factors for prolactin measurement but among these

Genetics Service, Great Ormond Street Hospital, London, UK.

women, it was a reason to visit doctor only in few cases. In most cases with onset

of hyperprolactinemia within 40-50 years of age, women themselves or their

gynecologists considered amenorrhea as a natural postmenopause, missing the

Introduction

correct diagnosis. It was characteristic for hyperprolactinemic women that they

Germline aryl hydrocarbon receptor-interacting protein

(AIP) mutations are

did not experience vasomotor climacteric symptoms. Weight gain was common

responsible for 15-30% of familial isolated pituitary adenomas (FIPA). We report

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

a 4-generation FIPA kindred with a heterozygous AIP gene deletion in exon 2,

Thyroid 1

highlighting the benefits of genetic screening and management challenges in

GP197

affected subjects and asymptomatic carriers.

Patients

Cognitive functions in primary hypothyroidism on selenium

A 45y woman died of a spinal ependymoma (obligate carrier). Her 18y son

supplementation

showed lethargy over the following months attributed to grief. However,

Marina Nikolic-Djurovic¹, Alberto Pereira², Johannes Smit³,

investigations due to headache revealed hypopituitarism and a clinically non-

Olga Vasovic⁴, Zvezdana Jemuovic¹, Svetozar Damjanovic¹,

functioning PA was diagnosed. Two years later, his 185 cm 18y-brother was

Milika Asanin⁵, Dragan Pavlovic⁶, Dragana Jankovic¹, Sandra Pekic¹,

diagnosed with a sparsely-granulated PA co-expressing PRL&GH. Fourteen-

Dragana Miljic¹, Marko Stojanovic¹ & Milan Petakov¹

years after operation his IGF-1 was repeatedly raised with small increase in his

¹Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical

tumour remnant. Lanreotide treatment was started and surgery is planned. A

Centre of Serbia, University of Belgrade, Belgrade, Serbia;²Department of

Rathke’s cyst was detected in a bulky gland in their eupituitary 17y mutation

Endocrinology and Metabolic Diseases Leiden University Medical Center,

carrier sister when she was first screened, which is now regressed. However, after

Leiden, The Netherlands;³Division of Endocrinology, Department of

8y follow-up a 4 mm-microadenoma became visible, with normal PRL, IGF-1

Internal Medicine, Radboud University Medical Centre, Nijmegen, The

and OGTT-GH nadir 0.38 mg/l. Their 27y second-cousin presented amenorrhoea

Netherlands;⁴Institute for Gerontology and Palliative Care, Belgrade,

after cessation of oral contraceptive, hyperprolactinaemia and 2xULN IGF-1. Her

Serbia;⁵Clinic for Cardiology, Clinical Centre of Serbia, University of

MRI showed 2 pituitary microadenomas, corresponding to a 6 mm-somato-

Belgrade, Belgrade, Serbia;⁶Faculty of Philosophy, University of Belgrade,

tropinoma on the right and a

4 mm-prolactinoma on the left, confirmed

Belgrade, Serbia.

histologically.

Discussion

Introduction

Of 14 subjects with AIP mutations, 4 have PA, 1 ependymoma and 7 are

Selenium (Se) is a trace element that plays key roles in thyroid pathology. In patients

asymptomatic (penetrance 29%). Ependymomas were described with loss of

with Hashimoto thyroiditis (HT), Se supplementation might reduce antibody levels

genetic material at 11q13-locus, but has not been described in patients with AIP

and may provide additional beneficial effects, such as on cognition.

mutations. The slow regrowth of the tumor in the brother suggests that long-term

Aim

follow-up is needed. Bulky pituitary and not fully suppressed GH on OGTT can

To evaluate cognitive function

(cognitive decline) in patients on long-term

represent challenges in AIP mutation carrier teenager females. Multiple PAs with

levothyroxine replacement for primary hypothyroidism with and without selenium

different secretory profiles may arise in the pituitary of these patients. Genetic

supplementation.

screening and baseline review with follow-up of younger subjects is

Design

recommended in AIP mutation-positive families.

Cross-sectional, case-control study.

DOI: 10.1530/endoabs.49.GP195

Patients and methods

Sixty nine patients with HT

(mean age

43.52G14.33

yrs) on long-term

levothyroxine replacement and 57 euthyroid healthy controls, matched for age,

sex, and educational level, were included. HT patients were divided into 2 groups,

25pts with (SeC) and 44pts without selenium supplementation(Se-). Neuropsy-

chological evaluation assessed general cognitive function(cognitive screening:

MMSE, Visual- and Digit Span), attention span in visual and verbal modality

(Numbers from WAIS and Visual span from WMS-R), conceptual tracking (TMT

A and B), verbal divergent thinking (Phonemic fluency test, Listing of animals from

BDEA, TMT B, Verbal fluency test).

Results

Selenium levels were within the normal range in all groups, but significantly higher

in HT(SeC)vs controls (94.88G20.63 vs 86.95G14.95 mcg/l, P!0.05). TSH

GP196

concentrations were higher in patients

(both HT(SeC) and HT(Se-)) when

Diagnosis of acromegaly: Sex and BMI are the major determinants of

compared to controls: (3.01G1.66 and 3.01G1.90 vs 1.77G0.88 mU/l, P!0.000),

growth hormone suppression during oral glucose tolerance test (OGTT)

but FT4 concentrations were not different: (12.81G4.01 vs 12.46G2.64 vs 12.93G

Katharina Schilbach, Shiva Sophia Nicolay, Michael Haenelt,

2.88 ng/l, PO0.05). TPOab concentrations were different, both between HT(SeC)

Andreas Lechner, Christina Gar, Jochen Schopohl, Sylvère Stormann,

and HT(Se-), as well as between patients and controls (1399.25G1968.30 vs

Rita Schwaiger & Martin Bidlingmaier

4290.96G3177.13 vs 20.48G30.73 U/ml, P!0.001). Global cognitive function

Medizinische Klinik und Poliklinik IV, Klinikum der Universitat Munchen,

(MMSE) was not different between groups (29.16G1.31 vs 29.16G1.61 vs

Munich, Germany.

29.54G0.93, PO0.05), but conceptual tracking and verbal divergent thinking was

different between all groups (TMTA:36.40G12.85 vs 40.89G21.89 vs 29.81G

GH suppression during OGTT is the gold-standard test in diagnosis and

11.57, P!0.001, TMTB:89.00G27.88

103.93G48.81

73.02G24.10,

monitoring of acromegaly. However, discrepancies between GH nadir and IGF-I

P!0.001, KF:21.88G5.61 vs 19.07G5.65 vs 21.44G5.11, P!0.05, FF:11.28G

have been described and have triggered search for factors modifying the extent

3.37 vs 9.22G3.69 vs 11.05G3.44, P!0.05).

of GH suppression. Cut-offs at 1.0 or 0.4 ng/ml are currently recommended with

Conclusion

modern, highly sensitive GH assays. To establish assay specific GH nadir cutoffs

Patients treated for primary hypothyroidism according to routine clinical care

for the 22kD GH specific IDS-iSYS assay, we examined 381 subjects (319

guidelines show persistent impairments in cognitive functioning which were, in

females, 62 males) with normal pituitary function. We analyzed the impact of

certain domains, improved with selenium supplementation. Future studies are still

age, body mass index (BMI), menstrual cycle and hormonal contraceptive

needed in order to provide reliable evidence to support selenium supplementation in

therapy.

a clinical practice.

In 96% of all subjects the GH nadir was !0.4 ng/ml (92% !0.3 ng/ml, 81%

DOI: 10.1530/endoabs.49.GP197

!0.2 ng/ml and 56% !0.1 ng/ml). In all sex- and age-groups BMI was the

major determinant, with lower GH nadirs in subjects with higher BMI. In 4

different BMI groups (A: !20 kg/m², nZ30, B: 20-25 kg/m², nZ174, C: 25-

30 kg/m², nZ99 and D: O30 kg/m², nZ77) mean GH nadirs were as follows:

A: 0.29 ng/ml, B: 0.15 ng/ml, C: 0.10 ng/ml and D: 0.07 ng/ml with significant

differences between all groups except group C vs. D (A vs. B: PZ0.0043, A

GP198

vs. C, A vs. D, B vs. C, B vs. D: P!0.0001, C vs D: PZ0.057). While age

had no impact, men exhibited significantly lower mean GH nadirs compared to

Which is the best tool to use when initiating the differential diagnosis of

women (0.09 vs 0.14 ng/ml, P!0.0001). Premenopausal women on estrogen

a thyrotoxic patient? A challenge to current guideline recommendations

containing oral contraception (OC) (nZ20) had significantly higher mean GH

Carolina Perdomo¹, Elisa Gil Ramos¹, Gala Gutiérrez Buey¹,

nadirs (0.36 ng/ml) compared to women not taking estrogen containing OC

María Llavero¹, Javier Gargallo¹, Javier Arbizu², Magdalena de la Higuera¹

(nZ272, 0.13 ng/ml, P!0.044), while the phase of the menstrual cycle had no

& Juan C Galofré¹

impact.

¹Department of Endocrinology. University of Navarra, Pamplona, Spain;

Our findings confirm the need for lower cutoffs for the GH nadir if new

²Department of Nuclear Medicine. University of Navarra, Pamplona, Spain.

sensitive GH assays are used, but also suggest adjustment to sex- and BMI can

improve diagnostic sensitivity and specificity.

Aim

DOI: 10.1530/endoabs.49.GP196

Differential diagnosis (DD) of thyrotoxicosis is critical as the treatment of the

three main causes of this condition (Graves’ disease [GD], Toxic Multinodular

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Goitre [TMG], and Thyroiditis [TS]) differs substantially. Recently published

(rZ0.371, PZ0.004), LDL

(rZK0.325, PZ0.011), ApoB (rZK0.342,

diagnostic algorithms investigating hyperthyroidism embrace the presence of

PZ0.022) and lipoprotein(a)

(rZK0.470, PZ0.001) were revealed in the

thyrotropin receptor (TSH-R) antibodies (TRab) as the first and most cruicial

group TSH 2.5-5.0mUI/ml. Regarding the group TSHO5.0 mUI/ml, we found

diagnostic step. Although TRab measurement has important limitations (some

positive correlations between FT3 and HDL (rZ0.358, PZ0.030), vitamin B12

can block or be neutral to TSH-R, or pass undetected by the assay), Guidelines

(rZ0.398, PZ0.024) and HOMA-IR (rZ0,424, PZ0,031); and between anti-

recommend thyroid radionuclide scan

(TRS) when TRab are absent. Our

thyroglobulin and homocysteine (rZ0.383, PZ0.033).

objective was to compare the TRab vs. TRS values in the DD of hyperthyroidism.

Conclusion

We sought to analyse limitations of the current diagnostic Guidelines which could

We observed significant correlations between thyroid function, thyroid

lead to misdiagnosis and improper treatment of thyrotoxicosis.

autoimmunity, insulin resistance, lipid profile and homocysteine that may

Methods

contribute to an increased cardiovascular risk in AIT.

We conducted a retrospective study of 235 outpatients attended at our Centre

DOI: 10.1530/endoabs.49.GP199

from 2006 to 2016. Inclusion criteria were patients with overt or subclinical

hyperthyroidism from whom TRab and TRS levels were taken at the time of

diagnosis. SPSS 20.0 was used for statistical analysis. Pearson’s correlation was

applied to quantify the relationship between the two diagnostic tools.

Results

We grouped the sample in Gr. A: 89 (37.8%) those with positive TRab; Gr. B: 102

(43.4%) those with diffuse TRS uptake; and Gr. C: 146 (62.2%) those with

negative TRab. All groups were partially overlapped. In Gr. A, the TRS reported a

diffuse increase uptake (consistent with GD) in 63 (70.8%), heterogeneous uptake

GP200

consistent with TMG in 21 (3.6%), and absent or low uptake consistent with TRS

Evaluation of the effectiveness of personalized radioiodine treatment in

in 5 (5.6%). In Gr. B, only 63 (61.8%) had positive TRab. In Gr. C, up to 39

Graves’ disease

(26.7%) of individuals had a diffuse increased uptake in TRS. Pearson’s r analysis

Ana Fernandes¹, Teresa Faria¹, Ana Oliveira¹, Jorge Pereira¹ &

between positive TRab and diffuse increased uptake was: 0.431 (PZ!0.001).

Pedro Coelho²

Conclusions

¹Centro Hospitalar são João, Porto, Portugal;²Universidade Fernando

Provided that a high diffuse uptake by TRS can only be associated with GD, our

Pessoa, Porto, Portugal.

study suggests that the DD of thyrotoxicosis should not rely initially on TRab, as

this approach may leave a third

(29%) of patients misdiagnosed, and

Aim

consequently, improperly treated. Our results support the value of thyroid

Radioiodine activities for the treatment of Graves’ disease hyperthyroidism are

scintigraphy as the first step in the DD of thyrotoxicosis.

still subject to discussion, as is the use of a fixed approach over a dosimetric one.

DOI: 10.1530/endoabs.49.GP198

We aimed to evaluate our success rate using a personalized dosimetric approach:

instead of the “(MBq I-131!g gland mass!100)/(percentage uptake at 24 h)”

activity calculation, we further adjusted for factors such as gender, age, diagnosis,

2 h and 4 h radioiodine uptake, previous medication, and clinical history.

Materials and methods

We reviewed data from all patients treated with radioiodine therapy (RIT) for

hyperthyroidism at our department (nZ179), from January 2008 to January 2016,

selected those with Graves’ disease (nZ118), and excluded the ones without

GP199

follow-up (nZ11). RIT was considered successful if either euthyroidism or

Cardiovascular risk factors in patients with autoimmune thyroiditis

hypothyroidism were achieved. We evaluated success rates differences between

Joa˜o Sérgio Neves2, Catarina Cunha1, Celestino Neves2, Sofia

lower and higher activities. All statistical analyses were carried out using IBM

Castro Oliveira², Oksana Sokhatska³, Camila Dias⁴, César Esteves²,

SPSS version 21.0 for Mac. A type I error 0.05 was considered.

Miguel Pereira², José Luís Medina¹, Luís Delgado³ & Davide Carvalho^1,5

Results

¹Faculty of Medicine, University of Porto, Porto, Portugal;²Endocrinology

107 patients were included (44.346G13.07 years; 89 female). RIT was successful

Service, São Joa˜o Hospital, Faculty of Medicine, University of Porto, Porto,

in 91.6% (nZ98), while 8.4% (nZ9) remained hyperthyroid. If we consider the

Portugal;³Immunology Department, São João Hospital, Faculty of

success after the first RIT, 72.0% (nZ77) succeeded, while 28.0% (nZ30)

Medicine, University of Porto, Porto, Portugal;⁴Department of Biostatistics

remained hyperthyroid. 87 (81.3%) were submitted to a single therapy whereas 20

and Medical Informatics, Faculty of Medicine, Sa˜o João Hospital,

(18.7%) were submitted to multiple RIT. There were no significant outcome

University of Porto, Porto, Portugal;⁵Instituto de Investiga

¸a˜o e Inovação

differences between the lower and higher activities used (PZ0.061).

em Saúde, Faculty of Medicine, University of Porto, Porto, Portugal.

The used activities ranged between

148 MBq and 703 MBq (335.92G

101.60 MBq).

Conclusion

Background

Our results confirm RIT effectiveness in Graves’ disease hyperthyroidism

Overt thyroid dysfunction is associated with an increased cardiovascular risk. The

treatment. Although using inferior activities to those generally prescribed (200-

impact of subclinical hypothyroidism and autoimmunity in the increased

800 MBq), we achieved higher success rates - comparable to the best reposted in

cardiovascular risk remains controversial. Aim: To evaluate the interrelations

the literature. There were no statistically significant outcome differences between

between thyroid function, thyroid autoimmunity and cardiovascular risk factors,

the lower and higher activities used, highlighting the importance of tailored

in patients with autoimmune thyroiditis (AIT).

treatment approaches to warrant the best therapeutic outcome and while avoiding

Methods

unnecessary exposure.

353 subjects with AIT were evaluated. We defined three groups based on TSH

levels: TSH!2.5 mUI/ml, TSH

2.5-5.0 mUI/ml and TSHO5.0 mUI/ml. We

DOI: 10.1530/endoabs.49.GP200

recorded thyroid function tests, thyroid autoimmunity, insulin resistance markers

including Homeostasis Model Assessment for Insulin Resistance (HOMA-IR),

lipid profile, homocysteine, C-reactive protein (CRP) and vitamin B12 levels.

Statistical analysis was performed using Kruskal-Wallis test and Spearman

correlations.

Results

Our sample comprised 94% females with a mean age of 47G16.3 years. The group

TSHO5.0 mUI/ml presented higher levels of HOMA-IR when compared to the

other two groups [2.96(1.76-4.59) in TSHO5.0 mUI/ml vs 1.86(0.97-2.56) in

TSH 2.5-5.0 mUI/ml and 1.58(1.06-2.46) in TSH!2.5 mUI/ml, PZ0.002]. In the

total group we observed positive correlations between free T3 (FT3) and both HDL

GP201

(rZ0.118, PZ0.028) and ApoA1 (rZ0.129, PZ0.024); TSH was positively

correlated with HOMA-IR (rZ0.146, PZ0.018) while free T4 (FT4) was

negatively correlated with homocysteine (rZK0.119, PZ0.041). In the group

Abstract withdrawn.

TSH!2.5 mUI/ml, positive correlations were found between TSH and both HDL

(rZ0.136, PZ0.031) and homocysteine (rZ0.147, PZ0.028), FT4 and CRP (rZ

0.136, PZ0.037) and also anti-thyroglobulin and ApoB (rZ0.165, PZ0.013);

anti-thyroglobulin was negatively correlated with homocysteine (rZK0.186,

PZ0.006). Negative correlations between anti-thyroglobulin, total cholesterol

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP202

activity was mild (VISA %3/10) in 69% and severe in 16% (R7); severity mild

in 47.1% and severe in 20.2%. 1 year data (nZ36) showed mild activity at 1

Citrus flavanones naringenin and hesperetin induced mild functional

year in 95% (38.9% at referral) and 0% severe disease (33% at referral).

alteration in thyroids of old-aged Wistar rats

Intravenous methylprednisolone was administered to 30 patients; 47% required

Marko Miler¹, Vladimir Ajdzanovic¹, Natasa Ristic¹, Branko Filipovic¹,

%1.5 g total with use of SSAs: methotrexate (nZ30), azathioprine (nZ6),

Gordana Uscebrka², Dragana Miljic³, Verica Milosevic¹ &

ciclosporin (nZ10) and Rituximab (nZ8). Orbital decompression surgery was

Branka Sosic-Jurjevic¹

performed in 12.5% (nZ13), squint surgery 12.5%, eyelid surgery 22% and

¹Institute for Biological Research “Sinisa Stankovic”, University of

orbital radiotherapy 8%.

Belgrade, Belgrade, Serbia;²Department of Veterinary Medicine, Faculty of

Conclusion

Agriculture, University of Novi Sad, Novi Sad, Serbia;³Department of

Early use of SSAs has significantly reduced the overall steroid load in patients

Neuroendocrinology, Clinic for Endocrinology, Diabetes and Metabolic

when compared to established European guidance (EUGOGO). This regimen

Diseases, Clinical Center of Serbia, Belgrade, Serbia.

confers a low orbital decompression and orbital radiotherapy rate.

DOI: 10.1530/endoabs.49.GP203

Aging is a complex process characterized by a progressive decline in cellular

function, alterations of the endocrine system and the increased incidence of

thyroid diseases. Citrus flavanones naringenin (NAR) and hesperetin (HES) may

contribute to maintenance of health at old age however they may also affect

thyroid hormone economy. The aim of this study was to test weather NAR or HES

administration alter thyroid functioning. NAR or HES were administrated orally

(15 mg/kg) to male 24-month-old Wistar rats during 4 weeks. Control groups

GP204

received vehicle, sunflower oil. Immunohistochemical staining of thyroglobulin

24-month efficacy of a single radiofrequency ablation on autonomously

(Tg), thyroxine (T₄) bound to Tg (T₄-Tg) and sodium iodide sysmporter (NIS)

functioning thyroid nodules

were performed. Immunopositivity of Tg or T₄-Tg in thyroid follicles were

Stella Bernardi^1,2, Fulvio Stacul², Andrea Michelli¹, Veronica Calabrò²,

measured as intensity of optical density (OD) or relative intensity of fluorescence

Fabiola Giudici¹, Chiara Dobrinja² & Bruno Fabris^1,2

(RIF). Thyroid stimulating hormone (TSH) and total T₄ concentrations were

¹Università degli Studi di Trieste, Trieste, Italy;²ASUITS, Trieste, Italy.

measured in serum. After citrus flavanones treatments, thyroids showed Tg and

T₄-Tg immunopositivity mainly in the colloid of the follicles. The obtained

results showed increased (P ! 0.05) intensity of OD for Tg and T₄-Tg RIF after

Background

both flavanones treatments, while NIS expression did not change. Serum TSH

Radiofrequency ablation has been advocated as an alternative to radioiodine

increased (P ! 0.05) only after NAR, although T₄ remained unchanged after both

and/or surgery for the treatment of autonomously functioning benign thyroid

treatments. In conclusion, citrus flavanones induced stronger expression of

nodules. However, only a few studies have measured radiofrequency ablation

thyroid-specific proteins in gland of old-aged males. However, only NAR

efficacy on autonomously functioning benign thyroid nodules. The aim of this

elevated serum TSH, being more potent than HES. This alteration is in line with

work was to evaluate the 24-month efficacy of a single session of radiofrequency

preserved capacity of the thyroid to compensate the mild interference of

ablation (performed with the moving shot technique) on solitary autonomously

flavanones treatments with thyroid hormone production in old-aged males.

functioning benign thyroid nodules.

Methods

DOI: 10.1530/endoabs.49.GP202

Thirty patients with a single, benign autonomously functioning thyroid nodule,

who were either unwilling or ineligible to undergo surgery and radioiodine, were

treated with radiofrequency ablation between April 2012 and May 2015. All the

patients underwent a single radiofrequency ablation, performed with the 18-gauge

needle and the moving shot technique. Clinical, laboratory, and ultrasound

evaluations were scheduled at baseline, and after 1, 3, 6, 12, and 24 months from

the procedure.

Results

A single radiofrequency ablation reduced thyroid nodule volume by 51, 63, 69,

75%, and 76% after 1, 3, 6,12, and 24 months, respectively. This was associated

with a significant improvement of local cervical discomfort and cosmetic score.

As for thyroid function, 33% of the patients went into remission after 3 months,

43% after 6 months, 50% after 12 months, and 70% after 24 months from the

procedure. This study demonstrates that a single radiofrequency ablation allowed

GP203

us to withdraw anti-thyroid medication in the majority of patients, who remained

The oxford multidisciplinary thyroid eye disease (TED) clinic; can short

euthyroid afterwards.

waiting times and use of steroid sparing agents (SSA) reduce total

Conclusions

steroid dose and requirement for surgery/radiotherapy?

This study shows that a single radiofrequency ablation was effective in 70% of

Helen Turner¹, Joel David² & Jonathan Norris³

patients with autonomously functioning benign thyroid nodules. Most

¹Department of Endocrinology, Churchill Hospital, Oxford, UK;

importantly, patients responded gradually to the treatment, such that it is possible

²Department of Rheumatology, Nuffield Orthopaedic Hospital, Oxford, UK;

that longer follow-up studies might show greater response rates.

³Oxford Eye Hospital, Oxford, UK.

DOI: 10.1530/endoabs.49.GP204

Introduction

The Oxford multidisciplinary thyroid eye disease (TED) clinic comprising an

oculoplastic surgeon, rheumatologist and endocrinologist with access to

orthoptics, neuroradiology and radiotherapy was established in 2013. The aim

was to facilitate rapid referral and treatment in a specialist centre in keeping with

Amsterdam Declaration. Early use of steroid sparing agents (SSA) and recently

rituximab forms part of the treatment regimen.

Methods

A retrospective, 4-year, single-centre, consecutive case series of patients with

GP205

TED audited both outcomes (in terms of severity and activity) derived from

Association of vitamin D levels with thyroid function and

the VISA classification and treatment modalities, at presentation and 1 year

autoimmunity

follow-up.

Luis Raposo^1,2, Sandra Martins^3,4, Daniela Ferreira⁵, João

Results

Tiago Guimarães^4,5 & Ana Cristina Santos^2,5

104 patient records were analysed. Mean wait from referral to first review was 1

¹Grupo de Estudo da Insulino-Resistência da Sociedade Portuguesa de

month with 42% of referrals originating from endocrinology departments. Mean

Endocrinologia, Diabetes e Metabolismo, Portugal, Portugal;²Instituto de

age was 51.2 years. 26.0% (nZ27) of patients were male and 35% were

Saúde Pública da Universidade do Porto - EPIUnit, Universidade do Porto,

current/ex-smokers. Where thyroid biochemistry was available at referral

Porto, Portugal;³Servic¸o de Patologia Clínica, Centro Hospitalar de S. João,

(nZ80): 51% were euthyroid, 45% hyperthyroid and 4% hypothyroid. TSHRAb

Porto, Portugal;⁴Departamento de Biomedicina, Faculdade de Medicina,

was positive in

85% of patients checked compared to

62% of TPO Ab.

Universidade do Porto, Porto, Portugal;⁵Departamento de Epidemiologia

Presenting signs included: ocular surface disease (68%), exophthalmos (53%),

Clínica, Medicina Preditiva e Saúde Pública, Faculdade de Medicina,

diplopia (45%), eyelid retraction (38%) and reduced vision (7%). Presenting

Universidade do Porto, Porto, Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction

TED. This approach results in a significant reduction in disease activity with

Vitamin D is a hormone that acts through the Vitamin D receptor (VDR) not only

reduced total steroid load.

on the skeletal system but on a great number of target tissues, including thyroid

DOI: 10.1530/endoabs.49.GP206

gland. In recent years the association of vitamin D with autoimmune thyroid

diseases (AITD), has been suggested.

VDR gene polymorphisms had been associated with an increased risk of AITD. In

addition a recent meta-analysis showed that AITD patients had lower level of

25-hydroxyvitamin D. However some studies have not confirmed the association

between vitamin D levels and AITD. Furthermore, data on the effects of vitamin

D in thyroid hormones and TSH serum levels are very poor.

The aim of our study was to evaluate the association of vitamin D levels with

GP207

thyroid function and positivity for thyroid antibodies.

Prediction of response to methimazole based on clinical symptoms in

Material and methods

new onset graves’ patients, using neural networks

PORMETS is a nationwide, cross-sectional study in Portugal comprising a

Hoon Sung Choi¹ & Won Sang Yoo²

sample of 4095 adults. Five hundred participants were randomly selected to be

¹Kangwon National University Hospital, Chuncheon-si, Republic of Korea;

included in the present study. A fasting venous sample was collected and serum

²Dankook University Hospital, Cheonan-si, Republic of Korea.

calcium, PTH, 25-hydroxyvitamin D [25(OH)D], TSH, FT₄, FT₃ and thyroid

antibodies were measured.

Introduction

Results

Anti-thyroidal drug (ATD) therapy is a treatment of choice for Graves’ disease

Our study included 286 women and 214 men with a mean age of 53.4 years.

because of its effectiveness and low rate of adverse effect. Response to ATD or

Free thyroxine (FT₄), free triiodothyronine (FT₃), TSH and thyroid antibody

remission rate varies among individuals, although there were few useful clues for

levels did not present any significant linear correlation with 25(OH)D levels.

prediction of treatment response. We applied neural network model to predict

After adjustment for sex and age, TSH, FT₄ and FT₃ levels did not present any

response to methimazole, based on clinical symptoms at initial clinical symptoms.

significant association with 25(OH)D levels or with low vitamin D status.

Methods & Design

Logistic regression analysis did not show any significant association of low

We reviewed 20 new onset Graves’ patients and used their symptoms at initial

vitamin D status with thyroid antibodies positivity, even after adjustment for

diagnosis. A total of 12 symptoms were classified into 5 categories (general,

several possible confounding variables.

cardiac, neuromuscular, psychologic, and gastrointestinal). In each category, the

Conclusion

number of positive symptoms was considered the score of the category. Response

Our results do not confirm the association of vitamin D levels with thyroid

to methimazole was defined as whether serum TSH normalized within 3 months.

function and positivity for thyroid antibodies.

A total of six variables, 5 symptom categories and sex, were used for a 2-layer

DOI: 10.1530/endoabs.49.GP205

neural network model. Among 20 subjects, 15 subjects used in training set, and

the other 5 subjects were use in model validation.

Results

The mean age of subjects was 49.3G12.2 years and male subjects were 6 (30%).

Our neural network model with 15 subjects as a training set showed sensitivity of

1.0 and specificity of 0.545 with AUC of 0.75 to predict normalization of serum

TSH within 3 months. With same model, the estimated scores of the other 5

subjects corresponded to their actual outcomes.

Conclusion

Thyroid 2

Despite the limitation of small sample size, our neural network model showed

GP206

promising performance to predict response to methimazole with patients’ clinical

symptoms in new onset Graves’ patients.

Early use of steroid-sparing agents in treatment of moderate-to-severely

active thyroid eye disease

DOI: 10.1530/endoabs.49.GP207

Zuzana Sipkova¹, Joel David², Helen Turner³ & Jonathan Norris¹

¹Oxford Eye Hospital, Oxford, UK;²Nuffield Orthopaedic Centre, Oxford,

UK;³Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford,

UK.

Introduction

The management of active thyroid eye disease (TED) remains controversial. High

GP208

dose intravenous methylprednisolone (IVMP) is the current recommended first-

Serum Interleukin-37 (IL-37) levels were increased and correlated with

line treatment based on EUGOGO guidance. Such therapy has the potential for

oxidative stress parameters in Hashimoto’s Thyroiditis (HT) patients

serious adverse effects. We present the outcomes of an alternative approach in the

Rosaria Maddalena Ruggeri¹, Teresa Manuela Vicchio¹, Angela Alibrandi²,

management of moderate-to-severely active TED, using steroid-sparing agents

Salvatore Giovinazzo¹, Rosaria Certo¹, Giuseppe Giuffrida¹,

(SSAs) in conjunction with IVMP. Methotrexate is used as the first-line SSA

Francesco Trimarchi³, Sebastiano Gangemi⁴ & Mariateresa Cristani⁵

alongside ciclosporin and rituximab depending on activity score.

¹Division of Endocrinology, Department of Clinical-Experimental Medicine

Methods

and Pharmacology, University of Messina, Messina, Italy;²Department of

Presented is a retrospective, 4-year, single-centre, consecutive case series of

Economy, University of Messina, Messina, Italy;³University of Messina,

patients with moderate-to-severe TED treated using the Oxford protocol.

Accademia Peloritana dei Pericolanti, Messina, Italy;⁴Division of Clinical

Treatment modality, disease activity (derived from the VISA classification) and

Immunology and Allergology, Department of Human Pathology, University

adverse effects are reported at initial presentation, 6- and 12-month follow-up.

of Messina, Messina, Italy;⁵Department of Pharmaceutical Sciences and

Results

Health Products (SCIFAR), University of Messina, Messina, Italy.

104 consecutive case notes were reviewed of TED patients treated by the TED

MDT. 24 patients with moderate-to-severely active disease were identified (mean

age 46.8 years; 12 female) with a mean pre-treatment VISA activity score of

Background

5.5/10 (S.D.Z1.98; range 1-9). IVMP and an SSA was commenced in all patients.

IL-37, member of the IL-1 family, is a natural suppressor of immune and

Mean total steroid dose was 2.72 g (S.D.Z1.4; 1.0-6.9). 38% of patients (nZ9)

inflammatory responses. Increased serum IL-37 levels were observed in several

received 1.5 g of IVMP or less. Only two patients required O4.5 g of IVMP

autoimmune diseases, including Graves’ disease. No data on TH are available

equating to the EUGOGO treatment protocol dose for this patient group. There

from the literature.

was significant improvement in VISA activity score both at the intermediate

Materials and methods

review (mean score 2.7; S.D.Z2.8; P!0.001; mean follow up 25.2 weeks) and at

We enrolled 45 euthyroid HT patients (5 M e 40 F, mean age 38.5G12.6) and

one year or last follow up (mean score 1.4; S.D.Z1.5; P!0.001; mean follow up

age- and sex-matched healthy controls. None was on LT-4

therapy.

48.0 weeks). Three patients stopped methotrexate due to a non-specific chronic

Smokers, subjects with kidney failure, history of cancer or autoimmune,

cough, deranged liver function or nausea. No serious or long-term adverse effects

inflammatory and infection comorbidities were excluded. Serum IL-37 levels

were reported.

were measured by ELISA (kit IL-37 DuoSet Elisa, R&D System, Minneapolis,

Conclusion

USA; minimum detectable dose

10 pg/ml). Specific serum tests, such as

Based on our experience and outcomes, the initiation of an SSA with limited

d-ROMs (derived Reactive Oxygen Metabolites) test and BAP (Biological

adjuvant IVMP is as an effective and safe therapy for moderate-to-severely active

Antioxidant Potential) test (Diacron International, Italy), were performed in all

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

subjects to investigate the changes in oxidative balance, and AGEs (Advanced

GP210

Glycation End Products) were determined as a specific marker of oxidative

Laser ablation of benign thyroid nodules without anesthesia: clinical

stress.

tolerance, hazards and complications

Results

Pablo Vidal-Ríos, Teresa Jiménez, Antonio Rodríguez, Laura Villas &

IL-37

levels were significantly higher in TH

(meanG S.D.:

999.59G

Sebastian Vidal-Ríos

1064.93 pg/ml) than in controls

(448.02G498.96 pg/ml; PZ0.018). In both

Coruna Endocrinology Center, La Coruna, Spain.

groups, these values correlated negatively with age

(TH, RSZK0.377

PZ0.016; controls, RSZK0.404; PZ0.06) and were tendentially higher in

men than in women (PZ0.063). Furthermore, there was a positive correlation

Laser ablation of thyroid nodules has been used for the last two decads (Pacella

between serum IL-37 levels and TSH, statistically significant in TH (RSZ

et al,

2000). Surprisingly, complications are less frequent in patients treated

0.412 PZ0.008; in controls, RSZ0.418; PZ0.053). The regression analysis

without anesthesia, probably because eventual pain is an useful alarm symptom,

showed a significant positive association between IL-37

and d-ROMs

leading the operator to repositioning the fiber during the procedure (Pacella et al.,

(PZ0.029) and AGEs

(PZ0.014): if serum d-ROMs and AGEs levels

2015).

increased, serum IL-37 levels also increased. A significant direct correlation

Material and methods

between serum IL-37

levels and AGEs was also observed

(RSZ0.578;

A total of 32 patients were included, without using local anesthesia. Nodules

PZ0.006).

were solid, 5-72 ml volume, age 36-84 years, gender female (84%). Procedure

Conclusion

included three phases:

(1) Preparation

30 min (informed consent and final

Serum IL-37 levels were significantly increased in TH patients and correlated

decision about anatomic approach); (2) Laser ablation 30 min (usually

3-8

with oxidative stress parameters. Given the anti-inflammatory properties, IL-37

paths, 3-5 illuminations each and total energy of 50-500 joules/cc); and (3)

could be an innovative research strategy for TH pathogenesis and therapy.

Observation

60 min

(with ice collar and vital constants monitoring). A

DOI: 10.1530/endoabs.49.GP208

1064 nm Nd-YAG laser from an EchoLaser generator (Elesta, Florencia-Italy)

was used. Triple thyroid image (Ultrasound, Doppler and Elastography) was

monitored using an Acusson

2000

Hellix platform

(Siemens, Forchheim-

Germany).

Results

30 of 32 patients (93.75%) would accept another ablation if necessary. Pain was

refered as 1-6 of 10 (arithmetic mean 3.5; median 2). Difficulties were: cervical

discomfort (4), excessive time of manipulation because short neck (1), transient

mild hypertension

(1), mild vasovagal reaction

(1), small intra-thyroid

hematoma (1) and a partial and transient Horner syndrome (1) resolved 3

months later.

Discussion

Clinical tolerance in general was spectacular. Major complaints were postural.

Complications were mild and transient, although potentially risky. No cases of

severe pain, voice change, fever, skin burn or cough were observed. In the future,

GP209

preventive specific strategies (like careful identification of risky patients, laser

cauterization of large feeding vessels or protective hydrodissection to protect vital

The increased immunohistochemical expression of IL-23 in Hashimo-

organs) will be considered before laser ablation.

to’s thyroiditis but not in Graves’ disease patients

Conclusions

Tatjana Zake^1,3, Sandra Skuja³, Ieva Kalere², Ilze Konrade^1,2 &

Clinical tolerance was very good. Complications were few, mild and transient, but

Valerija Groma³

potentially risky. This highlights the importance of identifying properly risky

¹Riga East University Hospital, Riga, Latvia;²Department of Internal

patients as well as the need of including preventive strategies.

Medicine, Riga Stradins University, Riga, Latvia;³Institute of Anatomy and

Anthropology, Riga Stradins University, Riga, Latvia.

DOI: 10.1530/endoabs.49.GP210

Introduction

Recently, Th17 cells and their cytokines were identified to play an important role

in the pathogenesis of thyroid autoimmunity. IL-23, produced by antigen

presenting cells, is required for survival and differentiation of Th17 cells, and is

known to guide T cells toward the Th17 phenotype. Its serum levels are increased

in several autoimmune diseases, including Hashimoto’s thyroiditis

(HT),

however, the expression level of IL-23

within thyroid tissue assessed by

immunohistochemistry has not been addressed thoroughly before. The aim of our

study was to estimate the levels of immunoexpression and distribution of IL-23

within thyroid tissue of patients with HT and Graves’ disease (GD) and compare

them with controls.

GP211

Materials and Methods

Forty seven adult patients presenting 21 cases of HT, 8 of GD, and 18 cases of

Orbital ectopic thyroid mistaken for mestastases

ordinary colloidal goiter without autoimmune component, which served as

Greta Jagucianskaite^1,2, Agne Petrenaite^1,2, Rasa Ziukaite² &

control group, were enrolled in this study. Immunostaining was performed using

Zydrune Visockiene^1,2

an anti-IL-23 antibody (Santa Cruz Biotechnology, CA, dilution 1:50). Levels of

¹Vilnius University Faculty of Medicine, Vilnius, Lithuania;²Vilnius

immunopositivity for IL-23 were defined semiquantitatively.

University Hospital Santariskiu Klinikos, Centre of Endocrinology, Vilnius,

Results

Lithuania.

In HT patients the expression of IL-23 was detected both in the abundant

Introduction

inflammatory lymphocytic infiltrates characteristic of HT and follicular

Ectopic benign thyroid tissue outside the normal migration path of the thyroid is

epithelial cells, whereas tissues obtained from GD patients demonstrated the

an extremely rare condition that, to our knowledge, has never been described in

weak thyrocytic expression predominantly. Majority of patients in controls

the orbit.

showed negative or occasional expression of IL-23. The highest IL-23

Clinical case

immunopositivity was observed in HT patients, furthermore, it was significantly

75-year-old woman with nodular thyroid was referred to Vilnius University

higher compared to the control group and GD

(P!0.001; PZ0.043,

Hospital Santariskiu Klinikos for fine needle aspiration biopsy. Her complaints

respectively). No difference was found between the expression of IL-23 in

were palpitations, difficulty swallowing, diplopia, exophthalmos with medial and

GD patients and the control group (PZ0.324). Additionally, weak expression of

-superior dislocation. Symptoms were progressing for

years, although

IL-23 was observed in connective tissue septae and blood vessels in most HT

laboratory testing always showed euthyreosis. Her thyroid-stimulating hormone

patients.

(TSH) was 1.04 mU/l (normal 0.4-4.1 mU/l), anti-TPO antibodies - 1.9 kU/l

Conclusion

(!5.61 kU/l) on admission. Fine needle aspiration biopsy and histological

Overexpression of IL-23 might play a role in the pathogenesis of HT, guiding T

examination suggested diagnosis of Hurthle cell carcinoma and subject was

cells towards the Th17 phenotype and promoting the autoimmune inflammation

referred to surgery.

of the thyroid gland.

Management and Outcome

DOI: 10.1530/endoabs.49.GP209

After thyroidectomy histology revealed nodular thyroid hyperplasia and follicular

adenoma. To exlude orbital malignancy head MRI was performed. Imaging

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

showed 18!14 mm in size, non-homogenic, contrast accumulating mass with

higher in patients with AITD compared with controls (P!0.001) but TNF-a

well-defined margins in the inferior -lateral part of the orbit. Orbital tumor

levels were not significantly different in the groups of different genotypes of the

excision was performed and histological examination revealed tumor composed

selected polymorphism of the Period3 gene.

of micro-/macrofolicules with colloid. Folicular epithelium had no atypical

Conclusion

changes, as confirmed by three independed pathologists. These criteria supported

This study provides the first evidence for a genetic association between AITD and

diagnosis of ectopic thyroid tissue. Due to patients noncompliance further

the Period3 gene, highlighting the possible relevance of polymorphisms in clock

postoperative period is unknown. A 5-year follow-up showed normal TSH levels

genes in the etiopathogenesis of AITD.

3.07 mU/l, with 75 mcg/day levothyroxin therapy, anti-TPO antibodies -

DOI: 10.1530/endoabs.49.GP212

0.2 kU/l, thyroglobulin 0.91 mgk/l (normal 0.83-55 mgk/l). Once no primary or

secondary tumors were detected we concluded that the thyroid tissue in the orbit

of our patient was ectopic.

Conclusion

Ussualy ectopic benign thyroid tissue could be found in the normal migration path

of the thyroid. However, we are presenting the extremely rare case of benign

thyroid tissue located in the orbit, suggesting the extensive diagnostic approach in

unclear cases.

DOI: 10.1530/endoabs.49.GP211

GP213

IgG4-related fibrous variant of Hashimoto thyroiditis in a non-Asian

woman

Sónia do Vale^1,2, Ana Filipa Martins¹, Cristiana Costa¹, Lucas Batista³ &

Margarida Mendes de Almeida⁴

Endocrinology Department, Santa Maria Hospital, North Lisbon Hospital

Center, Lisbon, Portugal;²Endocrinology Department, Lisbon Medical

School, Lisbon, Portugal;³Surgery Department, Santa Maria Hospital,

North Lisbon Hospital Center, Lisbon, Portugal;⁴Pathology Department,

GP212

Santa Maria Hospital, North Lisbon Hospital Center, Lisbon, Portugal.

Association of the Period3 clock gene polymorphism with autoimmune

thyroid diseases

Nafiye Helvaci¹, Seda Oguz¹, Serkan Kabacam², Erdem Karabulut³,

Introduction

Filiz Akbiyik⁴, Mehmet Alikasifoglu² & Alper Gurlek¹

First described in

2009, IgG4-related thyroid disease includes several

¹Division of Endocrinology and Metabolism, Hacettepe University Faculty

subcategories: Riedel’s thyroiditis, fibrous variant of Hashimoto thyroiditis

of Medicine, Ankara, Turkey;²Department of Medical Genetics, Hacettepe

(FVHT), IgG4-related Hashimoto thyroiditis (HT) and Graves’ disease with

University Faculty of Medicine, Ankara, Turkey;³Department of

elevated IgG4. It is rare, with most cases described in Japan and characterized by

Biostatistics, Hacettepe University Faculty of Medicine, Ankara, Turkey;

increased IgG4 plasma cells at immunostaining.

⁴Department of Medical Biochemistry, Hacettepe University Faculty of

Case Report

Medicine, Ankara, Turkey.

A 59-year-old Caucasian women, without known Asian ancestry, was observed at

the endocrinology department due to neck swelling over the previous 4 months.

She reported dyspnea at some neck positions, fatigue and constipation. She

Background

presented a diffusely enlarged very hard thyroid, with some nodules and reduced

Circadian rhythmicity is generated by a set of genes including Period3. Changes

mobility. Laboratory evaluation revealed primary hypothyroidism, very elevated

in the expression of Period3 and other clock genes have been linked with

titles of anti-thyroglobulin and anti-peroxidase antibodies, elevated erythrocyte

regulation of the immune system. Period3 polymorphisms have been associated

sedimentation rate and G immunoglobulins (3400 mg/dl, reference range, RR:

with circadian disruption and so immune system dysregulation and altered

751-1560), elevated IgG4 (267 mg/dl, RR: 4-86) and k-dominant light chains.

secretion of several cytokines, which can lead to inflammatory and autoimmune

There was no monoclonal band; IgA and serum calcium levels were normal.

disorders.

Ultrasound confirmed an enlarged heterogeneous thyroid, with nodules and small

Aim

calcifications. Cytology was compatible with lymphocytic thyroiditis. The CT

To investigate the influence of a polymorphism in Period3 gene on susceptibility

scan additionally revealed multiple latero-cervical ganglia, esophageal diversion,

and severity of autoimmune thyroid diseases (AITD).

airway impression and reduction of the nasopharynx lumen. There was no

Methods

evidence of malignancy, infection, other autoimmune disorders or non-neck

A total of 125 unrelated patients (mean age 35.94G9.9 years) with AITD (GD,

involvement. Euthyroid state was obtained with levothyroxine reposition and

69; HT, 56) and 115 unrelated healthy controls (mean age 31.3G8.7 years) were

total thyroidectomy was performed. Histology revealed a FVHT with elevated

included. Serum levels of IL-6 (pg/ml) and TNF-a (pg/ml) were determined by

IgG4-positive plasma cells and IgG4/IgG ratio. After surgery, serum IgG levels

ELISA method. Period3 gene polymorphism rs2797685 was identified by PCR-

decreased and IgG4 levels became normal.

RFLP.

Discussion

Results

The very hard rapidly enlarging thyroid, short disease duration, high antibody

Subjects expressing the GACAA genotype of the selected polymorphism in

titers, hypothyroidism, diffuse thyroid involvement, no evident extrathyroidal

Period3 gene demonstrated a significantly higher risk of AITD compared to the

invasion, increased inflammatory parameters, IgG and k dominant profile and

population expressing the GG genotype (ORZ1.83, CI: 1.04-3.20; PZ0.033). No

elevated IgG4 that normalized after surgery, suggested a fibrous IgG4-HT.

significant associations of genotypes were detected with the age of onset of

Histology and immunostaining confirmed an IgG4-related FVHT. Although

disease, presence and severity of orbitopathy in GD and thyroid function status at

very rare in non-Asian countries, it is important to suspect and confirm an

diagnosis and daily dose of thyroxine per kg body weight in HT. AITD and

IgG4-related thyroid disease, allowing an adequate diagnosis, treatment and

control groups were similar in terms of mean IL-6 levels, but mean serum IL-6

follow-up.

level was significantly lower in the group with GA genotype than in the group

DOI: 10.1530/endoabs.49.GP213

with GG genotype in GD (PZ0.013). Mean level of TNF-a was significantly

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP214

Aim of the study

To evaluate the impact of HT on the progression of HF during a long-term

Thyroid hormones deficiencies and poor outcome in chronic heart

follow-up.

failure outpatients

Methods

Vincenzo Triggiani¹, Brunella Licchelli¹, P Terlizzese², D Grande²,

From 2006 to 2015, we evaluated 675 consecutive CHF outpatients (523 males,

C Rizzo², MS Lattarulo², T Leopizzi², I Gioia², Vito Angelo Giagulli¹,

64G13 years) in stable clinical conditions (O1 month) and in conventional

Edoardo Guastamacchia¹ & Massimo Iacoviello³

therapy. They underwent a clinical evaluation, 12-lead ECG, echocardiogram,

¹Endocrinology and Metabolic Diseases Unit, Interdisciplinary Medicine

blood pressure measurement and a routine chemistry. They have been carefully

Department, University of Bari, Bari, Italy;²School of Cardiology,

evaluated for the presence of thyroid diseases. The follow-up was extended on a

University of Bari, Bari, Italy;³Cardiology Unit, Cardiothoracic

median value of 47 months, for a maximum of 123 months. Thyroid function has

Department, Polyclinic Hospital of Bari, Bari, Italy.

been evaluated every 4 months, more frequent (every 6 weeks) for patients

receiving levothyroxine. The onset of HT during follow-up was defined as

detection of TSH values above the upper limit. When HT was detected, thyroid

Background

replacement therapy was started according to guidelines. During follow-up were

Hypothyroidism and low T3 syndrome frequently occur in HF patients.

also evaluated hospitalizations related to exacerbation of HF and death.

Aim of the study

Results

To evaluate in a large sample of CHF patients the association between thyroid

Four hundred and fifty-five patients (67.7%) were euthyroid at the enrolment and

hormone deficiencies and poor outcome.

showed a normal thyroid function during the follow-up; in 80 patients (11.8%)

Methods and results

there was a previous diagnosis of HT; in 40 patients (5.9%) the HT was detected

From 2006 to 2015, we screened 712 consecutive CHF outpatients (551 males,

at the time of enrolment; 52 patients (7.7%) developed HT during the follow-up.

64G14 years, left ventricular ejection fraction (LVEF) 33G10%, NYHA class

To avoid confounding factors, we compared patients in euthyroid status at the

2.3G0.6, NTproBNP 2153G4696 pg/ml, GFR-EPI 71G25 ml/min*1.73 m²) in

enrolment and during follow-up and patients with HT at the enrolment. At

stable clinical conditions (O1 month) and in conventional therapy. All patients

univariate Cox regression analysis, a significant association between HT and the

underwent assessment of thyroid function. A total of 34 patients were excluded

events, i.e. mortality for all causes (HR: 1.60; 95% CI: 1.08-2.38; P:0.019) and

for hyperthyroidism; among the remaining 678, 58 (9%) showed a TSH level

hospitalization for HF worsening (HR: 2.13; 95% CI: 1.54-2.96; P:!0.001) was

above the upper normal limit, but below 10 microU/ml, 23 (3%) a TSH value

found. At multivariate Cox regression analyses, HT remained associated only

above 10 microU/mL, and 20 patients (3%) low fT3 (LT3) levels without changes

with HF hospitalization (HR: 1.58; 95% CI: 1.09-2.29; P:0.015), but not with

in TSH levels. During a mean follow-up of 38 months, 122 patients died (101 for

mortality (HR: 1.05;95% CI:0.67-1.65; P:0.819), after correction to LVEF!

cardiovascular causes) and 202 experienced at least one admission for acute

35%, GFR!60 ml/min/m², NTproBNPO1000 pg/ml, NYHAIII, PA 95 mmHg.

decompensated heart failure. TSH O10 microU/mL (HR:2.96; 95%CI: 1.54-

Conclusion

5.68; P: 0.001) and LT3 (HR: 3.79; 95%CI: 1.91-7.54; P!0.001), but not high

In a long-term follow-up, HT is independently associated with hospitalization due

TSH!10 microU/mL (HR: 1.59; 95%CI: 0.871-2.91; P: 0.13), were associated

to HF worsening, but not with mortality. We hypothesise that HT is able to induce

with an increased risk of death at univariate analysis. At multivariate Cox

hemodynamic instability leading to hospitalization, but, probably, its correction

regression analysis, after correction for the presence of NYHA class 3, LVEF!

with thyroid hormone therapy could in part blunt its impact on patients’ survival.

35%, NTproBNP O1000, systolic arterial pressure !100 mm Hg and GFR-EPI

DOI: 10.1530/endoabs.49.GP215

!60 ml/min, only LT3 remained significantly associated with events (HR: 2.75;

95%CI:1.38-5.49; P: 0.004). When the occurrence of heart failure hospitalization

was considered, high TSH levels with a value !10 microU/ml (HR 1.82; 95% CI:

1.18-2.83; P!0.01), TSHO10 microU/ml

(HR 2.84;

95%CI:1.61-5.01;

P!0.001) and LT3 (HR:

3.33;

95%CI:

1.89-5.88; P!0.0001) were all

associated with events at univariate regression analysis. At multivariate

regression analysis TSHO10 microU/ml (HR: 1.91; 95%CI:1.06-3.46; P:0.03)

and LT3 (HR: 2.39; 95%CI: 1.36-4.24; P:0.002), but not high TSH with value

!10 microU/ml, remained associated with HF hospitalization.

Conclusions

GP216

In this observational study on a large cohort of CHF outpatients, we found

The correction of TSH with thyroid replacement therapy is associated

that impaired thyroid function, particularly when high levels of TSH

with a better outcome in chronic heart failure patients

(O10 microUI/ml) and low T3 levels are considered, has an independent adverse

V Triggiani¹, B Licchelli¹, D Grande², C Rizzo², P Terlizzese²,

impact on CHF events.

VA Giagulli¹, M.S Lattarulo², T Leopizzi², I Gioia², E Guastamacchia¹ &

M Iacoviello³

Endocrinology and Metabolic Diseases Unit, Interdisciplinary Medicine

Department, University of Bari, Bari, Italy;²School of Cardiology,

University of Bari, Bari, Italy;³Cardiology Unit, Cardiothoracic

Department, Polyclinic Hospital of Bari, Bari, Italy.

Background

It has been previously demonstrated that thyroid hormone deficiency is associated

with a worse outcome in patients affected by chronic heart failure

(CHF).

However, few data are available about the effects of thyroid replacement therapy

on the prognosis of patients.

DOI: 10.1530/endoabs.49.GP214

Aim of the study

The aim of the study was to evaluate the relationship among thyroid replacement

therapy, correction of thyroid stimulating hormone (TSH) serum levels and

outcome of a series of CHF outpatients.

Methods

We screened CHF outpatients in stable clinical conditions (O1 month) and in

conventional therapy. All patients underwent a baseline clinical evaluation, a

GP215

12-lead ECG, an echocardiogram and routine blood tests. Thyroid hormones were

Hypothyroidism and heart failure outcome: a study with a long-term follow-up

assessed at the enrolment and routinely during follow-up (every 3-4 months or

V Triggiani¹, B Licchelli¹, C Rizzo², D Grande², P Terlizzese², T Leopizzi²,

every 6-8 weeks if TSH level was altered at the previous control). All patients

I Gioia², VA Giagulli¹, E Guastamacchia¹ & M Iacoviello³

with history or newly diagnosed hypothyroidism were managed by endocrinol-

¹Endocrinology and Metabolic Diseases Unit, Interdisciplinary Medicine

ogists. We considered hypothyroidism corrected when TSH serum levels were

Department, University of Bari, Bari, Italy;²School of Cardiology,

normalized by thyroid replacement therapy (levothyroxine).

University of Bari, Bari, Italy;³Cardiology Unit, Cardiothoracic

Results

Department, Polyclinic Hospital of Bari, Bari, Italy.

Hypothyroidism was diagnosed in 180 patients (121 males, 67G12 years, left

ventricular ejection fraction, LVEF,

33G10%, NYHA class 2.5G0.5,

Background

NTproBNP 2125G2975 pg/ml, GFR-EPI 64G22 ml/min*1.73 m²) out of 712

Hypothyroidism (HT) has been demonstrated to be associated to heart failure

patients. Twenty-four patients were excluded because they were lost at follow-up

(HF) progression.

or died within the first 3 months or because endocrinologists did not prescribe

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

levothyroxine for TSH values not high enough. Among the remaining 156

GP218

patients in which levothyroxine was prescribed, in 111 patients a normal TSH

STAT6 deficiency ameliorates Graves’ disease severity by suppressing

value was obtained. During a mean follow-up of 38 months, 29 patients died (25

thyroid epithelial cell hyperplasia

for cardiovascular causes) and 62 experienced at least one admission for acute

Bingbing Zha

decompensated heart failure. The failure in TSH correction was associated with

Department of Endocrinology, Fifth People’s Hospital of Shanghai Fudan

an increased risk of all cause of death (HR: 3.31; 95% CI: 1.59-6.86; P: 0.001)

University, Shanghai, China.

and of heart failure hospitalization (HR: 2.27; 95% CI: 1.36-3.79; P: 0.002). At

Cox multivariate analysis the failure in TSH correction remained associated with

all cause mortality (HR: 2.57; 95% CI: 1.20-5.51; P: 0.002) and with heart failure

hospitalization (HR: 1.78; 95% CI: 1.05-3.01; P: 0.03) after correction for NYHA

Signal transducer and activator of transcription 6(STAT6) is involved in

class 3, LVEF!35%, NTproBNPO1000, systolic blood pressure !100 mmHg

epithelial cell growth. However, little is known regarding the STAT6

and GFR-EPI!60.

phosphorylation status in Graves’ disease (GD) and its role in thyroid

Conclusion

epithelial cells (TECs). In this study, we found that STAT6 phosphorylation

Our results support the possibility that hypothyroidism correction could improve

(p-STAT6) was significantly increased in TECs from both GD patients and

the prognosis of CHF patients, although randomized controlled trials should be

experimental autoimmune Graves’ disease mice and that STAT6 deficiency

designed in order to demonstrate this hypothesis.

ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the

DOI: 10.1530/endoabs.49.GP216

phosphorylation of STAT6 via IL-4R engagement, and the downstream

targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-

xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD.

More importantly, in vitro and in vivo experiments demonstrated that

STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyper-

plasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our

study reveals that in addition to the traditional pathogenesis of GD, in which

autoantibody TRAb stimulates thyroid-stimulating hormone receptors and

Thyroid 3

consequently produces T3, T4, TRAb could also trigger TECs producing IL-

GP217

4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling

Thyroid function in heart failure with preserved ejection fraction

and stimulate unrestricted cell growth, thus aggravating GD. These findings

(HFpEF) - evaluation of serum and myocardial thyroid hormones in an

suggest that STAT6 inhibitors could be potent therapeutics for treating GD.

animal model of HFpEF

DOI: 10.1530/endoabs.49.GP218

Joa˜o Sérgio Neves1,2, Catarina Vale2, João Almeida-Coelho2,

Soledad Bárez-López^3,4, Maria Jesus Obregon³, Ana Isabel Oliveira¹,

André Lourenço², Inês Falca˜o-Pires2, Davide Carvalho1,5 &

Adelino Leite-Moreira²

¹Department of Endocrinology, Diabetes and Metabolism, São João

Hospital Center, Porto, Portugal;²Departamento de Cirurgia e Fisiologia,

Unidade de Investigac¸ão Cardiovascular, Faculdade de Medicina,

Universidade do Porto, Porto, Portugal;³Department of Endocrine and

Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas

Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC)-

Universidad Autónoma de Madrid, Madrid, Spain;⁴Department of

Endocrine, U-708, Center for Biomedical Research on Rare Diseases

(Ciberer), Instituto de Salud Carlos III, Madrid, Spain;⁵Instituto de

Investigação e Inova

¸a˜o em Saúde da Universidade do Porto, Faculdade de

GP219

Medicina, Universidade do Porto, Porto, Portugal.

Delayed TSH recovery after dose adjustment during TSH-suppressive

levothyroxine therapy in patients with differentiated thyroid cancer

Hye In Kim, Tae Hyuk Kim, Young Nam Kim, Hosu Kim, So Young Park,

Introduction

Yun Jae Chung, Jae Hoon Chung & Sun Wook Kim

Thyroid hormones play a central role in the regulation of the cardiovascular

¹Samsung Medical Center, Seoul, Republic of Korea;²Chung-Ang

system. Heart failure with preserved ejection fraction (HFpEF) is responsible for

University Hospital, Seoul, Republic of Korea.

more than 50% of all heart failure cases and its main pathophysiological alteration

is diastolic dysfunction. Diminished thyroid function is known to predominantly

impair diastolic function, however the thyroid hormone status in HFpEF remains

Background

largely unknown.

Delayed thyroid-stimulating hormone

(TSH) recovery during treatment of

Methods

Graves’ disease is caused by long-term excessive thyroid hormone, which results

We evaluated an animal model of HFpEF, ZSF1 Obese rats (ZSF1-Ob, nZ13),

in down-regulation of pituitary thyrotropic cells. However, it is unknown whether

and their control group, ZSF1

Lean rats

(ZSF1-Ln, nZ11), with serial

delayed TSH recovery exists after levothyroxine

(LT4) dose adjustment in

echocardiography followed by invasive hemodynamic recordings and tissue

patients with differentiated thyroid cancer (DTC) who are taking a suppressive

collections at 20 weeks. Serum TSH was quantified by ELISA. Thyroxine (T4)

dose of LT4.

and triiodothyronine (T3) were quantified in serum, left ventricle and visceral

Methods

adipose tissue by radioimmunoassay (RIA).

We retrospectively reviewed 97 DTC patients who had a reduced LT4 dose while

Results

receiving excessive LT4 for TSH suppression. TSH levels at baseline (point 1),

At 20 weeks of age, ZSF1-Ob group developed HF with diastolic dysfunction, as

6 months (point 2), and 12-18 months (point 3) after LT4 dose adjustment were

shown by an increased E/E’ on echocardiography, a prolonged time constant of

compared with each other. A delayed TSH recovery group whose TSH levels

isovolumetric relaxation, an elevated end-diastolic pressure and upward shifted

exceeded target TSH levels (according to recent guidelines) between points 2 and

end-diastolic pressure-volume relationship on invasive hemodynamic evaluation.

3 was identified.

Serum levels of thyroid hormones were significantly decreased in ZSF1-Ob rats

Results

(T3: 5.96G4.65 vs 35.85G9.39 ng/dL in ZSF1-Ln, P!0.001; T4: 1.51G0.64 vs

In patients with LT4 reduction, the median TSH level at point 3 was significantly

3.49G1.35 mg/dl in ZSF1-Ln, P!0.001), while the levels of serum TSH were not

higher than that at point 2 [0.17 vs 0.09 mIU/ml; P!0.001). The delayed TSH

significantly different between the two groups (0.65G0.38 ng/ml in ZSF1-Ln vs

recovery group (44.3%, 43 of 97 patients) showed increased body weight during

0.79G0.57 ng/ml in ZSF1-Ob, PZ0.531). Left ventricle levels of thyroid

follow-up (60.84-62.73 kg; PZ0.01), although TSH levels remained in the target

hormones were significantly decreased in ZSF1-Ob rats (T3: 3.87G0.85 vs

range. A lower LT4 dose per body weight (LT4 dose/weight) after reduction [HR

10.51G7.91 ng/g in ZSF1-Ln, PZ0.012; T4: 0.99G0.43 vs 2.02G0.60 ng/g in

(95% CI), 0.01 (0.00-0.54); PZ0.03], greater changes in the LT4 dose/weight

ZSF1-Ln, PZ0.016). The levels of T3 and T4 in visceral adipose tissue were not

[1.10 (1.00-1.22); PZ0.04], and higher BMI before surgery [1.19 (1.03-1.38);

significantly different between the two groups.

PZ0.01] predicted the occurrence of delayed TSH recovery.

Conclusion

Conclusions

We observed a decrease in serum and myocardial thyroid hormone levels in an

Delayed TSH recovery was commonly observed after LT4 dose adjustment was

animal model of HFpEF. This may contribute to impaired diastolic function and,

performed as recommended by dynamic risk stratification. Six months may not be

therefore, may constitute an interesting therapeutic target in HFpEF.

enough time to evaluate real thyroid hormone status by TSH levels.

DOI: 10.1530/endoabs.49.GP217

DOI: 10.1530/endoabs.49.GP219

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP220

mediated by the autophagic/lysosomal pathway. The core autophagic machinery

is composed of ATG (autophagy-related) proteins. One ATG family member,

Analysis of a large cohort of subjects with thyroid hemiagenesis (THA)

Atg7, activates enzyme facilitating microtubule-associated protein-light-chain3

reveals random seasonality in the dates of birth

(LC3)-phosphatidylethanolamine conjugation. The presence of T3 was able to

Ewelina Szczepanek-Parulska¹, Ariadna Zybek-Kocik¹, Marek Niedziela²,

significantly reduce ATG7 mRNA expression, moreover the hormone signi-

Agata Czarnywojtek¹ & Marek Ruchala¹

ficantly reduces LC3II/LC3I protein expression, when compared to STV mice

¹Department of Endocrinology, Metabolism and Internal Medicine, Poznan

(P!0,05). On the whole our results suggest that T3 treatment can reduce fasting

University of Medical Sciences, Poznan, Poland;²Department of Paediatric

induced skeletal muscle atrophy by counteracting the autophagic process.

Endocrinology and Rheumatology, Poznan University of Medical Sciences,

Poznan, Poland.

DOI: 10.1530/endoabs.49.GP221

Introduction

In the etiology of thyroid dysgenesis (TD) an interplay between genetic and

environmental factors is thought to play a crucial role. Data from previous studies

on association between the season of birth and the incidence of TD causing

GP222

congenital hypothyroidism (mainly agenesis and ectopy) are conflicting. To date,

Will it be useful to measure PTH at 4 hours post thyroidectomy to

seasonality of births have not been analysed yet in regard to congenital absence of

decide for calcium replacement? 1^st result of a prospective study

one thyroid lobe (thyroid hemiagenesis, THA).

Sílvia Silva¹, Ana Rafael¹, Ricardo Marques¹, Luisa Moniz¹, Carlos Costa¹,

Patients and Methods

Ricardo Capita˜o2, Catarina Saraiva2, Clotilde Limbert2, Luis Fernandes1 &

Dates of birth of 102 patients diagnosed with THA were analysed and compared

Rogério Matias¹

to 102 control subjects with no thyroid pathology matched for age and gender.

¹Surgery, Egas Moniz Hospital, Lisboa, Portugal;²Endocrinology,

Both groups were subdivided according to the month of birth (I-XII), season of

Egas Moniz Hospital, Lisboa, Portugal.

birth

(spring, summer, autumn, winter) and quarter (1-4) of the year. The

differences were analysed statistically.

Introduction

Results

Calcium replacement after Thyroid surgery has been changing along times. The

Distribution of the months of birth in the group of patients with THA was

aim for this replacement is to avoid hypocalcaemia effects after thyroid surgery

asymmetric; smaller number of patients were born in the 4th (X-XII) quarter of

but not all the patients seem to need it. Parathyroid hormone (PTH) has a short

the year (19 patients) vs 1st (28 patients), 2nd (29 patients) and 3rd (26 patients).

half-life after its release into the bloodstream, making it a good marker of calcium

Similarly, smaller number of patients were born in autumn (IX-XI) - 19 patients if

metabolism in short time after surgery.

compared to other seasons of the year (winter - 27 patients, spring - 27 patients,

Method

summer - 29 patients). However, if the studied group was compared to the control

Prospective study of Endocrine Surgery Multidisciplinary group of one Centre

group, the difference in the distribution of the months of birth was at the border of

between March and December of 2016. Calcium replacement was done according

statistical significance (P!0.0923). Furthermore, if the studied and control group

to a protocol defined by multidisciplinary group after PTH measurement. PTH

were subdivided into four quarters or seasons, and then compared, the difference

values were considered normal above 15 pg/ml. Data were analyzed using SPSS.

was definitely not statistically significant.

Results

Conclusions

96 patients underwent total thyroidectomy vs totalization of thyroidectomy.

An analysis of the largest so far reported cohort of patients with THA indicate that

5 were excluded since they were admitted at ICU and protocol was not

environmental factors including intrauterine exposure to maternal seasonal viral

implemented. PTH was measured 4 hours after surgery.

infections or variable vitamin D availability seem not to play a significant role in

From the 91 patients, 74 had normal PTH levels. The remaining patients (17)

pathogenesis of THA.

started calcium replacement according to established protocol and showed no

DOI: 10.1530/endoabs.49.GP220

symptoms of hypocalcaemia.

Considering group with normal PTH, at day one after surgery, 41 had normal

calcium levels (P 0,01 on correlation analysis) and 33 had low levels. This last

group started the protocol of calcium replacement and at day two after surgery

were observed higher calcium levels (P 0,001 at linear analysis) and didn’t refer

hypocalcaemia symptoms.

GP221

Our Sample has a significance of 0.05 in the non-parametric, Q-square and

Thyroid hormone T3 protects mice from fasting induced skeletal muscle

Kolmogorov-Smirnov test.

atrophy by counteracting autophagy

Conclusion

Sarassunta Ucci¹, Valentina Russi¹, Maria Giulia Santaguida²,

Measuring PTH 4 hours after surgery is helpful to decide which patients should

Marco Centanni², Viviana Moresi³ & Cecilia Verga Falzacappa^1,2

start calcium replacement, using PTH value cut-off of 15 pg/ml.

¹Pasteur Institute, Rome, Italy;²Sapienza, University of Rome, Medical

DOI: 10.1530/endoabs.49.GP222

Surgical Sciences and Biotechnologies Department, Rome, Italy;³Sapienza,

University of Rome, Department of Anatomy, Histology, Forensic Medicine

and Orthopedic, Section of Histology, Rome, Italy.

Purpose

GP223

Skeletal muscle has been recognized as a thyroid hormones (THs) target for

Endogenous TH metabolite 3-iodothyronamine (T1AM) and synthetic

contractile function, regeneration, metabolism and glucose disposal. Despite a

thyronamine-like analogues SG-1 and SG-2 induce autophagy in human

role in regulating muscle development has been described, little is known about

glioblastoma cells (U-87MG)

the role of THs in regulating muscle homeostasis in a pathological state such as

Lorenza Bellusci¹, Martina Sabatini¹, Giulia Nesi², Simona Rapposelli²,

food deprivation induced atrophy. The purpose of this study is to evaluate whether

Leonardo Rossi³, Paola Lenzi⁴, Francesco Fornai⁴, Riccardo Zucchi¹ &

thyroid hormones may hamper the fasting induced skeletal muscle atrophy and to

Grazia Chiellini¹

investigate the mechanisms involved.

¹Department of Pathology, University of Pisa, Pisa, Italy;²Department of

Methods

Pharmacy, Pisa, Italy;³Department of Clinical & Experimental Medicine,

Preliminary data on C2C12 myotubes have suggested that T3 could counteract the

Pisa, Italy;⁴Department of Translational Research and New Technologies in

starvation induced atrophy in vitro. Based on these results, BALB/C male mice

Medicine and Surgery, Pisa, Italy.

(8-10 weeks) were used for in vivo experiments. Animals were food-deprived

(STV) for

24 and 48 hours to induce muscle atrophy and daily injected

intraperitoneally with T3 (100 ug/kgBW) or vehicle (NaCl 0,95%) as controls.

Endogenous TH metabolite 3-iodothyronamine (T1AM) and recently developed

Tibialis anteriors were taken at the end of the experiments. Morphological

thyronamine-like synthetic analogues SG1

and SG2

have emerged as

analyses were performed on hematoxylin/eosin stained sections. ATG7-Mrna was

neuroprotective agents. Autophagy has proved to be an effective therapeutic

evaluated by Sybr-Green qRT-PCR and LC3II/Lc3I was evaluated by western

approach for neurodegenerative diseases. Therefore we investigated whether

blot.

these compounds can induce autophagy in human glioblastoma cells (U-87MG).

Results and conclusions

Cultured U-87MG cells were initially treated with 1 mM T1AM, SG-1, SG-2 or

As a sign of skeletal muscle atrophy, the STV group showed a significant

vehicle for 30’, 4, 8 and 24 h and autophagy was monitored morphologically by

(P!0.001) reduction in the Cross-Sectional-Area of the myofibers, compared to

assessing the presence of autophagic vacuoles and LC3-II puncta formation

the control group; on the contrary the T3 treated group (STVT3) ensures the

with transmission electron microscopy (TEM) and immunofluorescence (IF)

maintenance of the fiber size. Protein degradation in skeletal muscle cells is

microscopy, respectively. In addition, cellular lysates were subjected to western

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

blotting to assess the accumulation of microtubule-associated protein 1 light chain

Introduction

(LC3). This protein is widely used as a marker for autophagy because it is a

The aim of this study was to examine prognostic significance of patient-related,

structural protein vital in autophagosome formation. TEM and IF microscopy

tumor-related and treatment-related factors for intrathyroidal papillary thyroid

showed a significant time dependent increase of autophagy-like vacuoles density and

carcinomas (PTC), via multivariate analysis.

LC3 punta formation in U-87MG cells exposed to the treatment with test compounds,

Materials and methods

with T1AM and SG-1 being the most effective. Along with extensive cytoplasmic

This study included

153 patients with intrathyroidal PTCs

(pT1/pT2/pT3)

vacuolization, western blotting analysis revealed significant up regulation of LC3-II

surgically treated in our Institution during two-decade period. Patients with

expression (P!0.01). Finally, we extended our analysis to examine the role played

locally invasive tumors (pT4) and initial distant metastases (M1) were excluded.

by our test compounds on the PI3K-AKT-mTOR pathway that has been suggested

Parameters of interest were: gender (male; female), age (%45; O45 years), tumor

to play an important role in the regulation of autophagy in mammalian cells. We

size (pTNM classification WHO 1984), multifocality (no; yes), histological type

carried out WB for Akt, phosphorylated Akt (pAkt) and we calculated the ratio

of PTC (pure; microcarcinoma; follicular; poorly differentiated), presence of

pAkt/Akt in vehicle-treated cells following test compounds administration. We

lymphonodal metastases

(pN1a; ipsilateral-pN1b; contralateral-pN1b; total),

found that 1 mM T1AM, SG-1 and SG-2 decreased such a ratio after 30’ and 4 h

surgery extent

(total thyroidectomy; total thyroidectomy with lymphonodal

treatment, suggesting that they might induce autophagy through the modulation of

dissections). Univariate and multivariate analysis of all parameters was

pAkt level. In conclusion, T1AM and synthetic analogues induce autophagy in a

performed in order to distinguish factors of significance for disease-free (DFS)

glioblastoma cell line. The potential pathophysiological and/or therapeutic

and cancer-specific overall survival (cs-OS).

implications of this finding remain to be determined.

Results

DOI: 10.1530/endoabs.49.GP223

In the follow-up, 10% of patients had locoregional or distant relapse, while 5.2%

died due to PTC. Univariate analysis distinguished older age, male gender, tumors

over 4 cm in diameter, multifocality and poorly differentiated PTC-types as

unfavorable prognostic factors for cs-OS. DFS was significantly shorter in males

vs. females, as well as in patients with multifocal vs. solitary PTC. Tumor

multifocality was unfavorable prognostic factor for both DFS and cs-OS.

Independent prognostic factors for intrathyroidal PTCs, based on Cox multi-

variate analysis, were multifocality and gender for DFS, and multifocality and age

at diagnosis for cs-OS.

GP224

Conclusion

Prognostic factors define risk groups within population of differentiated PTCs

Impact of chronic high fat diet consumption on the expression of

providing timely, adequate treatment and opportunity for longer quality life of

organic nutrients carriers in the small intestine of mice: role of thyroid

patients with PTCs.

hormones in these processes

Mariana Losacco Cerqueira, Carolina Fernanda Theodora Almeida,

DOI: 10.1530/endoabs.49.GP225

Paula Bargi-Souza, Maria Tereza Nunes, Patricia Gama &

Francemilson Goulart-Silva

Institute of Biomedical Sciences - University of São Paulo, São Paulo-SP,

Brazil.

Products of carbohydrates, proteins and lipids hydrolysis are absorbed by specific

carriers located at the enterocytes apical membrane, but little is known about the

mechanisms related to their regulation by own nutrients, especially considering

the high consumption of fats. Carbohydrates are transported by SGLT1, GLUT5

GP226

and GLUT2 and peptides are transported by PEPT1. Cholesterol is transported by

NPC1L1 and long chain fatty acids occur through FAT-CD36 and FATP4.

Malignancy Rate in Thyroid Nodules: Cytology versus Histology in

Thyroid hormones have important effects on organic nutrients metabolism, but

challenging categories

little is known about their role on the intestine, which led us to evaluate thyroid

Catarina Silvestre, Rita Luís, Maria Joa˜o Bugalho, Margarida Mendes de

hormone effects on intestine organic nutrients carriers of mice fed high fat diet

Almeida & Raquel Carvalho

(HFD) or standard diet. C57BL/6 mice were fed standard diet (control) or high fat

Santa Maria Hospital, Lisbon, Portugal.

diet (HFD) for 12 weeks. Afterwards, both mice were treated with saline, PTU

(antithyroid drug) or T3 for 30 days. They were killed and the jejunum was

Background

removed for histological analysis or inverted for intestinal epithelium separation

To stratify the risk of malignancy, thyroid fine-needle aspiration cytology

from the mucosa for protein analysis by Western blotting technique. FAT-CD36,

(FNAC) is an important and cost-effective method to evaluate nodules. The

NPC1L1 and GLUT2 protein contents reduced in mice fed HFD compared to

Bethesda System for Reporting Thyroid Cytopathology III, IV and V categories

control mice. SGLT1, PEPT1

and FATP4

remained unchanged among

are diagnostic challenges, falling between benign and malignant.

experimental groups. On the other hand, NHE3

protein content, which is

Objective

important for sodium and peptides absorption, increased significantly in the small

Determinate the malignancy rates of thyroid nodules classified as Bethesda

intestine of mice fed HFD. PTU or T3 treatment did not affect these parameters.

Categories III-V.

High fat compared to standard diet did not show any alteration of the villus length,

Methods

but mice fed standard diet and treated with PTU or T3 showed an increased villus

Retrospective study of patients’ records with thyroid nodules classified as III-V

length compared to treated-vehicle mice, however this finding have no association

by the Bethesda system, between January 2014-June 2016.

with the changes of nutrient carriers described above. Thus, we can infer that HFD

Results

affects the expression of some organic nutrient carriers in the small intestine,

Of a total of 2791 cytologies, 176 (6%) were classified as III-V, with the following

independently of thyroid hormones treatment.

distribution: 93 (3%) atypia of undetermined significance (AUS, III); 50 (1,8%)

DOI: 10.1530/endoabs.49.GP224

suspicious for follicular neoplasm

(SFN, IV) and

(1%) suspicious for

malignancy (SM, V). Malignancy rates for IV and V FNAC diagnostic groups

were 27% (10/37) and 85% (22/26), respectively. Among patients in group III, 27

patients underwent surgery after a single AUS report

(final diagnosis of

malignancy

- 33%), 39 repeated the FNAC and the remaining are under

surveillance. The second cytology report was as follows: 24 benign, 9 AUS, 4

SM, 1 SFN and 1 unsatisfactory; surgery was performed in 9 patients (5AUSC

1SFNC3SM) and the final diagnosis of malignancy was 44%. The malignancy

Thyroid Cancer

rate based on histology was not statistically different between patients with one or

two cytologies (PZ0,693).

GP225

Conclusions

Prognostic factors for intrathyroidal papillary carcinomas - a

Incidences of III-V diagnostic categories in our study resemble the predicted by

multivariate analysis

the Bethesda System. The malignancy rate for the AUS category was higher than

Nada Santrac¹, Ivan Markovic^1,2, Merima Goran¹, Marko Buta^1,2,

expected and similar to the one found in SFN. Repeating the FNAC in the former

Igor Djurisic¹ & Radan Dzodic^1,2

group offered minimal additional benefit.

¹Surgical Oncology Clinic, Institute for Oncology and Radiology of Serbia,

Belgrade, Serbia;²Medical Faculty, University of Belgrade, Belgrade,

DOI: 10.1530/endoabs.49.GP226

Serbia.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

GP227

structural disease). Groups were compared for age at diagnosis, nodule

dimensions, multicentricity, capsule presence and extrathyroidal involvement

Fine needle aspiration biopsy in pediatric patients with thyroid nodules

as well as the presence of node or distant metastasis.

Maria Manuel Costa^1,3, Rita Santos Silva^2,4, Cintia Castro-Correia^2,4,

Results

Maria Bom Sucesso^2,4, Tiago Henriques Coelho^2,4, Helena Barroca⁶ &

A total of 814 patients was included, 82.9% of which were female. The median

Manuel Fontoura^2,4

age at diagnosis was 47 years old (min. 11; max. 89). Five hundred patients had

¹Department of Endocrinology, Diabetes and Metabolism of Centro

criteria for remission (Group 1) and 314 didn’t (Group 2 [36 with cancer related

Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, University of

death,

55 with persistent or recurrent disease and

223 with indeterminate

Porto, Porto, Portugal;³Instituto de Investiga

¸a˜o e Inovação da Saúde da

response]). Median follow up was 10 years (min. 3; max. 50) in Group 1and 9

Universidade do Porto, Porto, Portugal;⁴Department of Pediatrics of Centro

years (min. 3; max. 57) in Group 2. Patients in group 1 were significantly younger

Hospitalar de São Joa˜o, Porto, Portugal;5Department of Pediatric Surgery of

(median 44.5 vs 49.5; P!0.001) had more multicentricity (45,7% vs 37.7%;

Centro Hospitalar de São João, Porto, Portugal;⁶Department of Pathology,

PZ0,041) and less local (22.7 vs 30.6%; PZ0,016) and distant metastasis (0.4%

Centro Hospitalar de São João, Porto, Portugal.

vs 5.7%; P!0,001). No differences were found in nodule dimensions, capsule

presence or extrathyroidal involvement.

Introduction

Conclusion

Although thyroid nodules (TN) are less common in children than in adults, the

Among patients with differentiated thyroid cancer, the older ones, with unicentric

risk of malignancy is much higher in pediatric age and therefore representing

tumours, local or distant metastasis at presentation seem to have worst outcome.

greater concern in this age group.

DOI: 10.1530/endoabs.49.GP228

Objective

Evaluate a cohort of pediatric patients with TN and search differences between

subjects with malignant and benign TN regarding sex, age, compressive

symptoms, cervical ultrasound characteristics, family history of differentiated

thyroid cancer (FHDTC), radiation exposure and previous/coexisting thyroid

GP229

disease.

Methods

Trends in papillary microcarcinoma prevalence in North of Portugal

Retrospective review of patients under 18 years of age with the diagnosis of TN

Teresa Alves Pereira¹, Ana Amado¹, Patrícia Gouveia², Rosa Castro²,

submitted to fine needle aspiration biopsy (FNAB) from 2010 to 2016.

António Moreira da Costa³, André Couto de Carvalho¹, Cláudia Freitas¹ &

Results

Fátima Borges¹

Seventy-three patients [21% males; mean age 13.8(3.2) years] were included.

¹Endocrinology Department, Centro Hospitalar e Universitário do Porto,

46.6% had palpable nodules. 84.9% were euthyroid and 12.3% had hypothyroid-

Porto, Portugal;²Nuclear Medicine Department, Centro Hospitalar e

ism.

31.5% of the patients had positive anti-thyroid antibodies. Ultrasound

Universitário do Porto, Porto, Portugal;³Surgery Department,

showed that TN had a diameter range of 15.9G9.8 mm, 47.9% patients had a

Centro Hospitalar e Universitário do Porto, Porto, Portugal.

solitary nodule, 31.5% TN were hypoechoic, 5.5% had increased intranodular

flow, 10.9% had microcalcifications and 5.5% had irregular margins. We found

Introduction and Objectives

that 5.5% of patients had undergone previous cervical irradiation and 12.3% had

The incidence of thyroid cancer has increased worldwide. This increase has been

FHDTC. 84.9% of the patients had a conclusive FNAB at first: benign in 39

attributed to more diagnosed papillary thyroid microcarcinomas. The purpose of

(colloid

(nZ25), chronic lymphocytic thyroiditis

(nZ12), granulomatous

this study was to analyse the growing trend of first appointments in our Thyroid

thyroiditis

(nZ1), thymus tissue

(nZ1)), FLUS in 4, suspected follicular

Cancer Unit, namely patients with papillary microcarcinomas.

neoplasia in 3, suspected malignancy in 1 and papilar carcinoma in 15 patients.

Methods

Thyroidectomy was performed in 43.8% of the patients. In histology, 71.9% were

We performed a retrospective study based on the patients diagnosed with thyroid

diagnosed as malignant. One patient developed permanent hypoparathyroidism

cancer between 1960 and 2016. We divided these patients into groups, based on

after surgery. We verified that the FHDTC was more frequently present in the

the year of first surgical treatment: 1960 to 1996, 1997 to 2001, 2002 to 2006,

malignant nodules (26% vs 6%, PZ0.024), while for the other factors mentioned

2007 to 2011 and 2012 to 2016. We calculated the relative frequency of papillary

above there were no statistically significant differences.

microcarcinomas comparing to the total cancer diagnostics in each group.

Conclusion

Results

In most patients a conclusive diagnosis was achieved with FNAB. The high

The total count of patients with registered thyroid cancer dimensions was 1146.

prevalence of malignancy was similar to that described in the literature. FHDTC

The mean age was 48.2G15.3 years old. 81.9% were female. We have found that

was the only factor found associated with an increased risk of malignancy.

papillary microcarcinoma frequency increased steeply from 11.2% [35/313, 95%

DOI: 10.1530/endoabs.49.GP227

confidence interval (CI) 8.2-15.2%] in 1960-1996 to 30.9% (42/136, 95% CI

23.7-39.1%) in 1997-2001. From that time onwards it stabilised around 1/3 of

thyroid cancer cases evaluated - 34.0% (54/159, 95% CI 27.1-41.6) in 2002-

2006; 34,6% (93/269, 95% CI 29.1-40.4%) in 2007-2011 and 30.5% (82/269,

95% CI 25.3-36.2%) in 2012-2016.

Conclusions

GP228

The prevalence of papillary microcarcinomas has increased until the end of the

Differentiated thyroid cancer - comparison between patients with and

last century. After 2002 our data showed a somewhat stabilised rate of 1/3 of all

without remission

diagnosed thyroid cancers.

Ana Amado¹, Patrícia Gouveia², Teresa Alves Pereira¹, Rosa Castro²,

DOI: 10.1530/endoabs.49.GP229

António Moreira da Costa³, André Carvalho¹, Cláudia Freitas¹ &

Fátima Borges¹

¹Endocrinology Department, Centro Hospitalar e Universitário do Porto,

Porto, Portugal;²Nuclear Medicine Department, Centro Hospitalar e

Universitário do Porto, Porto, Portugal;³Surgery Department,

Centro Hospitalar e Universitário do Porto, Porto, Portugal.

GP230

Radioiodine (RAI) refractory differentiated thyroid cancer (DTC):

outcome and prognostic factors for DISEASE progression

Introduction

Katerina Saltiki, George Simeakis, Elli Anagnostou, Michalis Apostolakis,

Differentiated thyroid cancer

(DTC) is one of the most frequent forms of

Evangelia Zapanti, Eleni Anastasiou & Maria Alevizaki

malignancy. Because of its favourable outcome and low mortality rates,

Endocrine Unit, Department Medical Therapeutics, Alexandra Hospital,

identifying prognostic factors has been a challenge. Several risk stratification

Athens University School of Medicine, Athens, Greece.

systems have been developed. Most of them include demographic and tumour

specific features, as well as extrathyroidal extension. Our objective was to

compare clinical characteristics between DTC patients with and without

Introduction

remission.

Patients diagnosed with DTC have excellent prognosis. A small percentage of

Methods

patients with disease persistence do not respond to treatment with RAI (RAI-

Data from patients followed for DTC between 1956 and 2016 was retrieved.

refractory DTC) and have low median survival (3.5 years). We investigated the

Patients with less than

2 years of follow up, those submitted to subtotal

prognostic factors and the disease course in patients with RAI-refractory DTC.

thyroidectomy or with positive antithyroglobulin antibodies were excluded. They

Methods

were divided in two groups, according to the presence or absence of remission

Of all DTC patients (nZ1160) followed-up in our department in recent years, 800

criteria (undetectable TSH-suppressed thyroglobulin levels and no evidence of

received RAI treatment and were classified in 2 groups: RAI-refractory DTC

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

(5.8%) and RAI responsive DTC (94.2%). Clinical and histological charac-

in the real life, the use of bone active drugs is currently limited to zoledronate in

teristics were compared between the 2 groups.

patients with pre-existing SREs. In this specific clinical setting, RAI therapy, but

Results

not zoledronate, prevented progression of SREs and mortality. Future studies are

The incidence of RAI-refractory DTC was higher in patients R45yrs and

needed to clarify the effectiveness of anti-resorptive drugs in primary prevention

particularly in those R65yrs (3% vs 7.4% vs 17.4%, PZ0.001). Men had RAI-

of SREs and possible advantages of denosumab versus zoledronate in the

refractory DTC more frequently than women (PZ0.02). RAI-refractory DTC

treatment of BM from DTC.

patients presented higher incidence of capsular, lymph node and extra-thyroid

DOI: 10.1530/endoabs.49.GP231

invasion (P!0.004), larger size (P!0.001), worse histological type (high risk

papillary:

34.9% vs 12% and features of poor differentiation:

14%vs0.6%

respectively, P!0.001,). They presented more frequently distant metastases at

follow-up (73.3% vs 1.5%, P!0.001). 12 RAI-refractory patients had local

persistence. 5/12 had no distant metastasis; all underwent multiple surgeries and 3

locoregional external radiation therapy. The

10-year probability of lack of

GP232

progression of disease was

27.9% vs 98.8% (x²Z297, P!0.001). In Cox

Germ-line mutations in RET-790 and RET-791 codons (exon 13) among

proportional hazard analysis, the only predictor for disease progression was

subjects with sporadic medullary thyroid cancer

resistance to RAI (HR 0.032, 95% CI 0.007-0.146, P!0.001). Within the RAI-

Darko Katalinic¹, Miljenko Solter² & Nora Nikolac²

refractory DTC subgroup, when age at diagnosis, gender, tumor size, histological

¹Department of Internal Medicine, Faculty of Medicine, Josip Juraj

type, lymph node, capsular and tissue invasion were taken into account, the only

Strossmayer University of Osijek, Osijek, Croatia;²UHC Sisters of Charity,

predictor for disease progression and occurrence of distant metastases was tumor

Faculty of Medicine, University of Zagreb, Zagreb, Croatia.

size (PZ0.008 and PZ0.015 respectively).

Conclusions

Background

Patients with RAI-refractory DTC present disease progression at high percentage

Medullary thyroid carcinoma (MTC) is a rare calcitonin producing neuroendo-

(72.7%). In these patients, tumor size is the most important unfavorable factor

crine tumour that originates from parafollicular C-cells of the thyroid gland. RET

predicting disease progression and occurrence of distant metastases. These data

proto-oncogene germline mutations are crucial for the onset and the progression

may be useful in designing treatment strategy.

of MTC, and the occurrence of single nucleotide polymorphisms could predispose

DOI: 10.1530/endoabs.49.GP230

the clinical course of disease. The objective of this study was to evaluate possible

differences in clinical presentation among patients with/without RET codon 790

and codon 791 (exon 13) mutations.

Methods

A non-isotopic polymerase chain reaction based single strand confirmation

GP231

polymorphism analysis and heteroduplex gel electrophoresis method was used to

screen tumour DNA extracted from

132

formaldehyde fixed and paraffin

Management and outcome of bone metastasis from differentiated

embedded MTC specimens. We analysed clinical data from

patients

thyroid carcinoma in the real life: the M.OS.CA.TI. study

harbouring RET codon 790 and codon 791 mutations (exon 13) (group A)

Gherardo Mazziotti¹, Maria Beatrice Panarotto^2,3, Emanuela Arvat⁵,

compared with 63 patients with “wild-type” genotype (group B). The study was

Arturo Chiti⁶, Alberto Cuocolo⁷, Massimo Dottorini⁸, Rossella Elisei¹⁰,

conducted according to the Declaration of Helsinki, the protocol was reviewed

Sebastiano Filetti⁹, Angelina Filice¹¹, Anna Maria Formenti^2,12,

and approved by the institutional independent ethics committee. All patients were

Leonardo Pace¹³, Teresa Pellegrino¹⁴, Marcello Nodari⁶,

provided with written informed consent.

Massimo Salvatori¹⁵, Cristina Tranfaglia⁸, Annibale Versari¹¹,

Results

Stefano Frara¹⁶, Alfredo Berruti⁴, Andrea Giustina¹⁶ & Raffaele Giubbini^2,3

Mean age for the group A was 56.2G11.4 years (range, 44.8-67.6) vrs. 49.4G9.7

¹Endocrine Unit, ASST Carlo Poma, Mantua, Italy;²Nuclear Medicine,

(range 39.7-59.1) for the group B. Lymph node metastases were found in all

ASST Spedali Civili of Brescia, Brescia, Italy;³Nuclear Medicine,

patients (group A, nZ46 vrs. group B, nZ31; P!0.001), and distant metastases

University of Brescia, Brescia, Italy;⁴Clinical Oncology, University of

in 11 patients (group A, nZ7 vrs. group B, nZ4; PO0.001). Postoperatively,

Brescia, Brescia, Italy;⁵Oncological Endocrinology, University of Turin,

62% of patients in group A vrs. 78% of patients in group B were biochemically

Turin, Italy;⁶Nuclear Medicine, Humanitas, Milan, Italy;⁷Nuclear

cure (P!0.001). In the group A, pT-category was: T₀, nZ21; T₁, nZ16; and T₂,

Medicine, University Federico II of Naples, Naples, Italy;⁸Nuclear

nZ9. In the group B, pT-category was: T₀, nZ22; T₁, nZ7; and T₂, nZ2

Medicine, “Maria della Misericordia” Hospital, Perugia, Italy;⁹Internal

(P!0.001).

Medicine, University Sapienza of Rome, Rome, Italy;¹⁰Endocrinology,

Conclusions

University of Pisa, Pisa, Italy;¹¹Nuclear Medicine, Arcispedale S. Maria

Nuova A.O. Reggio Emilia, Reggio Emilia, Italy;¹²Department of

Patients with RET codon 790/791 (exon13) mutations have a more aggressive

clinical course and lower biochemic cure rate in comparison with patients with

Molecular and Translational Medicine, University of Brescia, Brescia, Italy;

‘wild-type’ genotype. This information should be considered by genetic

¹³Department of Medicine and Surgery, University of Salerno, Salerno,

counseling or by operative therapy and could have clinical importance when

Italy;¹⁴Institute of Biostructure and Bioimaging of the National Research

specific targeted therapy is discussed.

Council of Italy - CNR, Naples, Italy;¹⁵Nuclear Medicine, Catholic

University of Rome, Italy, Rome, Italy;¹⁶Endocrinology, San Raffaele

DOI: 10.1530/endoabs.49.GP232

Vita-Salute University, Milan, Italy.

Although differentiated thyroid cancer (DTC) has the third highest propensity to

spread to the bone after breast and prostate cancer, there is a paucity of data

concerning the treatment of bone metastasis (BM) in this setting. The MOSCATI

GP233

(Metastasi OSsee da Carcinoma TIroideo) was a multicenter, retrospective study

Comparison of clinicopathological features in patients with familial and

investigating the real-life outcome and management of BM in 143 patients (80 F,

sporadic papillary thyroid cancer

63 M; median age 60 years) with DTC involving 10 specialized centers in Italy.

Fatma Dilek Dellal¹, Didem Ozdemir^1,2, Cevdet Aydin^1,2, Berna Ogmen¹,

One or more skeletal related events (SREs) were diagnosed in 58% of patients in

Aydan Kilicarslan^1,2, Mehmet Kilic^1,2, Reyhan Ersoy^1,2 & Bekir Cakir^1,2

significant association with more aggressive tumor histotype (OR 5.39), higher

¹Ataturk Training and Research Hospital, Ankara, Turkey;²Yildirim

number of BM (OR 1.36), localization of BM to thoracic spine (OR 2.7), cervical

Beyazit University, Ankara, Turkey.

spine (OR 7.47) or skull (OR 2.28), and lack of radio-iodine (RAI) uptake (OR

6.03). RAI treatment was performed in 93% of patients. Bone active drugs were

Introduction

used in 32 patients with SRE (22.4%; zoledronate in 31 and denosumab in one).

Although, familial medullary thyroid cancer is a known condition, familial

Bone active drugs were used more frequently in patients with more aggressive

papillary thyroid cancer (PTC) is a rare and less well described clinical entity.

histotype of DTC (P!0.001), with RAI-refractory BM (P!0.001) who did not

While some studies suggest more aggressive features in familial PTC, some do

receive RAI therapy (P!0.001) and/or in those with multiple BM (PZ0.006),

not support these findings. We aimed to compare ultrasonographical,

malignant hypercalcemia (PZ0.001), pathological fractures (PZ0.02) and in

cytopathological and histopathological results of patients with familial and

those undergoing radiotherapy (P!0.001). After treatment, 13.5% of patients

sporadic PTC.

developed new SREs and 39 patients (27.3%) died. RAI treatment significantly

Methods

prevented the second SRE (HR 0.01) and decreased mortality (HR 0.12) as

Data of 194 patients diagnosed with PTC histopathologically between 2007-2016

compared to patients treated with anti-resorptive drugs alone. Patients treated

were retrospectively reviewed. PTC in R2 members of the family was defined

with RAI plus anti-resoptive drugs showed less efficacy in preventing second SRE

as familial PTC. Thyroid functions, ultrasonography features, cytological and

and decreasing mortality as compared to treatment with RAI alone. In conclusion,

histopathological findings were compared in familial and sporadic PTC.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

retrospective multicenter study of

871 patients at 11 centers in Spain with

There were 35 tumor foci in 20 familial and 253 foci in 174 sporadic PTC

papillary thyroid cancer followed after total thyroidectomy and radioactive iodine

patients. Gender, thyroid functions, thyroid autoantibody positivity, mean nodule

remnant ablation. 685 patients were re-stratified during the first year of follow-up

number, thyroidectomy indications and surgical approach were similar in two

based on response to therapy: excellent (73% of the patients), indeterminate (8%),

groups. Preoperative ultrasonography features were available in 20 familial and

biochemical incomplete (6%) and structural incomplete (13%). Clinical outcomes

112 sporadic nodules. There was not any difference in mean nodule diameter,

were obtained in each group and no evidence of disease (NED) was seen in 95%,

echogenity, texture, microcalcification, macrocalcification, presence of hypo-

47%, 32% and 24% respectively for a median follow-up of 57 months. BRAF

echoic halo, taller than wide shape, margin irregularity and vascularization

mutation prevalence was 51% and was significantly associated with patients who

pattern. Cytological results were distributed similarly in two groups (PZ0.433).

had no excellent response (31.4% vs 22.9%; HR 1.53 (95% CI, 1.080 a 2.188)).

In histopathological examination, mean tumor number was 1.79G0.98 in familial

This association remained significant with biochemical incomplete response but

and 1.46G0.77 in sporadic patients (PZ0.09). Mean tumor diameters were

not with structural incomplete response. Moreover, BRAF positive tumors were

6.26G4.10 mm and 9.87G11.62 mm in familial and sporadic tumors, respect-

less likely to have distant metastasis compared with BRAF negative tumors.

ively (PZ0.074). Multifocality, microcarcinoma rate, variants of PTC, vascular

Patients with excellent response and BRAF negative tumors, almost 100% had

invasion and extracapsular extension were similar

(PZ0.155, PZ0.239,

NED at the end of follow-up. Patients with indeterminate and biochemical

PZ0.094, PZ0.617 and PZ0.743, respectively). Capsular invasion was

incomplete response and BRAF positive tumors, were less likely to have NED

significantly increased in sporadic group (19.8% vs 5.9%, PZ0.049).

compared with BRAF negative, although the difference was not significant due to

Conclusion

the small number of patients in each group. Our data show that indeterminate and

Whether familial PTC is more aggressive than the sporadic form of the disease

biochemical incomplete response may not have such favourable clinical outcome

is controversial. Clinical, ultrasonographical, cytological and most of the

as previously shown. In addition, BRAF status informs about the way papillary

histopathological features of familial and sporadic PTC were identical in our

carcinomas disseminate (locoregional vs distant metastasis) and may help to

study. Early detection of cases other than index patients might cause diagnosis at

better assess risk estimates that change over time based on response to therapy.

an earlier stage of the disease in familial form.

DOI: 10.1530/endoabs.49.GP235

DOI: 10.1530/endoabs.49.GP233

Thyroid Cancer & Thyroid Case Reports

GP234

GP236

Lobectomy as a treatment option for well differentiated thyroid cancer

A rare case of medullary thyroid cancer, mesothelioma and

(WDTC) between 1-4 cm: which results should we expect?

meningioma, due to APC and RASAL1 mutations

Ana Fareleira, Patrícia Andrea Ferreira, L Matos Lima & J Costa Maia

Charalampos Lyssikatos¹, Martha M Quezado², Fabio R Faucz³,

Centro Hospitalar S. João, E.P.E., Porto, Portugal.

Anna Angelousi^1,4, Narjes Nasiri-Ansari⁵, Constantine A Stratakis¹ &

5,6

Eva Kassi

Introduction

¹Section on Endocrinology and Genetics, Eunice Kennedy Shriver National

The ATA guidelines 2015 suggests lobectomy as an option for low risk thyroid

Institute of Child Health and Human Development (NICHD), National

tumors between 1-4 cm, although there remains some controversy once some

Institutes of Health (NIH), Bethesda, MD, USA;²Laboratory of Pathology,

characteristics become apparent only on pathologic examination.

National Cancer Institute, Bethesda, MD, USA;³Section on Endocrinology

Objective/methods

& Genetics, NICHD, National Institute of Health, Bethesda, MD, USA;

Retrospective analysis of patients who underwent thyroid surgery in 2014 and

⁴Department of Pathophysiology, Unit of Endocrinology, Kapodistrian

2015, with a histologic diagnosis of WDTC 1-4 cm in size and revision of the

University of Athens, Athens, Greece;⁵Laboratory of Biochemistry,

proportion of patients eligible for lobectomy with indication for completion

National and Kapodistrian University of Athens, Athens, Greece;

thyroidectomy according to the ATA guidelines 2015.

⁶Endocrine Unit of Clinical and Translational Research, National and

Results

Kapodistrian University of Athens, School of Medicine, Athens, Greece.

Three hundred and eighty eight patients who underwent thyroidectomy were

analysed. Of these, 85 (21,9%) were include for final analysis. Exclusion criteria:

Introduction

history of cervical radiation, tumors !1 and O4 cm, macroscopic extrathyroidal

Patients with “mixed” phenotypes are common among patients with multiple

extension (ETE), cNC, and bilateral thyroid nodules.

endocrine and non-endocrine neoplasias. Their diagnoses do not fit a given

The mean age of the cohort was 49 years, 83,5% are females, none had an

pattern making ge netic counseling difficult and testing impossible to guide. Most

aggressive histology, 12 (14,1%) had vascular invasion, 5 (5,9%) had microscopic

of these patients end up getting genome-wide studies for the identification of any

ETE, 3 (3,5%) had positive margins and 1 (1,2%) patient had positive lymph node

predisposing genetic defect. We present a rare case of a 57 year old female who

metastasis.

presented clinically with medullary thyroid cancer (MTC), mesothelioma and

Conclusion

meningioma. As part of our diagnostic work-up for this category of patients, we

(20%) of the patients with apparently ‘low risk’ WDTC who are eligible for

performed a SNP microarray (comparative genomic hybridization; CGH) and

lobectomy would have indication for completion total thyroidectomy according

whole exome sequencing (WES). CGH did not reveal any abnormalities; WES

to the ATA guidelines 2015.

revealed two variants of unknown significance (VUS) in two separate genes,

DOI: 10.1530/endoabs.49.GP234

namely APC and RASAL1.

Case presentation

The patient, a 57 year old female patient, was diagnosed with AML at 41y old,

peritoneal mesothelioma at 43y old, meningioma at 53y old and medullary

thyroid cancer with lymph node metastasis at 53y old. She also suffers from

GP235

autoimmune atrophic gastritis, alopecia universalis and relapsing perichondritis

of the ear.

Clinical Utility of response to therapy in combination with BRAF in risk

Results

assessment of thyroid cancer

WES was performed by DNA extracted from blood and revealed two specific VUS,

Laura Pérez Fernández¹, Antonio De la Vieja Escolar², Carles Zafón³, Juan

in the APC gene: p.R1103W, c.3307 AOT and in the RASAL1 gene: p.R538H,

Carlos Galofré⁴, Garcilaso Riesco-Eizaguirre⁵ & Spanish Task Force for the

c.1613 GOA. The APC gene (OMIM #17500) is a tumor suppressor gene involved

study of BRAF SEEN^4,5

in Wnt / b catenin signaling pathway; mutations have been reported in Familial

¹Hospital del Tajo, Aranjuez, Madrid, Spain;²Instituto de Salud Carlos III,

Adenomatous Polyposis (FAP), brain tumors and Turcot syndrome. Mutations in

Majadahonda, Madrid, Spain;³Hospital Universitari Vall d’Hebron,

the RASAL1 gene (OMIM#604118) have been found in thyroid cancer (both

Barcelona, Catalun˜ a, Spain;4Clinica Universitaria de Navarra, Pamplona,

papillary and medullary) and Cowden syndrome. The above two variants found in

Navarra, Spain;⁵Hospital Universitario de Móstoles, Móstoles, Madrid,

this patient have not been reported previously as pathogenic. The mutations in the

Spain.

APC and RASAL1 genes are probably involved in thyroid cancer development. In

addition, the mesothelioma and meningioma are likely related to mutations in the

Response to therapy re-stratification approach has been recently included in the

APC gene. This unique clinical presentation has not been reported before and is

2015 ATA guidelines as a risk-adapted approach to management of thyroid

being proven by additional immunostaining and molecular studies.

cancer. Our aim was to investigate the clinical utility of response to therapy

Conclusion

variables obtained during early follow-up in combination with BRAF, a

Patients with unique phenotypes may present with a list of clinical manife stations

prominent oncogene in thyroid cancer with prognostic value. This was a

that do not fit any given diagnosis. These patients deserve genome-wide testing

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

that is often rewarding but also complex. In our patient with MTC, mesothelioma

undertreated AH (TSH 31.4 mU/mL, fT4L 0.97 ng/dL) and Levothyroxine dose was

and meningioma two new gene defects were identified that are probable

increased. At 24^th GW, blood tests showed a mild hyperthyroidism (TSH 0.05 mU/mL,

responsible for the phenotype.

fT4 1.53 ng/dL) and LT4 dose was reduced. Fetal ultrasound (US) at 25^th GW showed

DOI: 10.1530/endoabs.49.GP236

a male fetus with bilateral cerebral ventriculomegaly without other alterations.

TORCH serologies were negative, amniocentesis revealed a normal karyotype and

fetal MRI showed bilateral cerebral ventriculomegaly and fetal goiter.

To study the fetal thyroid function a blood sample by cordocentesis was obtained

and a maternal blood test to examine TSH-R-ABs levels was performed.

Meanwhile, fetal US at 26^th GW showed tachycardia, mild pericardial effusion,

GP237

hydrothorax, cardiomegaly, hepatomegaly and splenomegaly. Fetal blood sample

Thyrotoxic Periodic Paralysis due to Graves’ disease: a mandatory

showed fetal hyperthyroidism (TSH!0.008, fT4 4.03, fT3 9.92) while maternal

differential diagnosis in Asian patients presenting with paralysis and

TSH-R-ABs were elevated (O40 mUI/mL). Unfortunately, fetal death occurred

hypokalemia

before knowing the results and antithyroid drugs could not be started. As far as we

David Barbosa¹, Carolina Faria¹, Ana Sofia Osório¹, Ema Nobre¹,

know, this is the second reported case of TSH-R-ABs-induced fetal thyrotoxicosis

Ana Paula Vilas² & Maria Joa˜o Bugalho1

in an AH woman.

¹CHLN - Hospital de Santa Maria, Endocrinology, Diabetes and

Conclusion

Metabolism Department, Lisbon, Portugal;²CHLN - Hospital de Santa

TSH-R-ABs plasma determination should be mandatory in pregnant women with

Maria, Medicina 2B, Lisbon, Portugal.

any previous autoimmune thyroid disease and fetal goiter or thyrotoxicosis.

Antithyroid drugs should be started as soon as fetal hyperthyroidism is suspected.

Introduction

DOI: 10.1530/endoabs.49.GP238

Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication

of hyperthyroidism that is underdiagnosed and frequently missed. It is relatively

common in Asian men with Graves’ disease. TPP attacks are frequently

associated with hypokalemia.

Case presentation

GP239

We describe a 26-year-old Asian male with an unremarkable past medical history

Renal cell carcinoma metastasis to thyroid tumor: a case report

who was admitted following sudden onset of flaccid paralysis of the lower

Carolina Faria, David Barbosa, Ana Sofia Osório, Ema Nobre &

extremities. Signs and symptoms such as weight loss, diaphoresis, palpitations

Maria Joa˜o Bugalho

and mild diffuse goitre were present. The electrocardiogram showed a sinus

Hospital de Santa Maria, Lisboa, Portugal.

tachycardia and the laboratory evaluation revealed markedly low potassium and

phosphorus levels (K^C1.5 mmol/l; PO_3K 1.8 mg/dl). The patient was managed

with intravenous potassium chloride with markedly improvement of the

Introduction

neurological deficits, despite a rebound hyperkalemia shortly after replacement.

Subacute thyroiditis (SAT) association with papillary thyroid carcinoma (PTC)

A thyroid profile was taken due to the suspicion of TPP in the context of Graves’

has been rarely reported in the literature. Metastatic neoplasms to the thyroid are

disease, and the diagnosis was made (TSH 0.01 mU/ml; free T4 5.21 ng/dl; free

rare in clinical practice. Renal cell carcinomas (RCC) are the most frequent site of

T3 15,64 pg/ml; TRABs 37,64 U/l). The patient then started on oral propranolol

origin of thyroid metastases (12 to 34%). Tumor-to-tumor metastases, in which a

and tiamazol, with complete remission of the symptoms and sustained

thyroid neoplasm is the recipient of a metastasis, are exceedingly rare. Tuberous

normalization of serum potassium.

sclerosis (TS) is associated with several renal manifestations (80-85% of the

Conclusion

patients) including angiomyolipomas (AMLs) (80%), renal cysts (30%) and RCC

TPP is an alarming and potentially lethal complication of hyperthyroidism

(2-4%)

characterized by muscle paralysis and hypokalemia due to a massive shift of

Case report

potassium into cells. This condition mainly affects male patients of Asian descent.

A 19-year-old male, with personal history of TS, presented in the emergency

With increasing population mobility and admixture, TPP as the presenting feature

department complaining of edema, jitteriness and pain in cervical region. SAT

of hyperthyroidism is now more common in Western countries. Early diagnosis

diagnosis was established based on complaints, physical examination and

not only aids in definitive management with nonselective beta-blockers and

laboratory results. After the resolution of SAT, thyroid ultrasonography (US)

correction of hyperthyroidism, but also prevents the risk of rebound hyperkalemia

revealed 2 suspicious nodules. The major nodule was submitted to fine needle

due to excessive potassium replacement. We report this case to emphasize the

aspiration cytology and the report was suspected of malignancy. Total

importance of recognizing TPP to avoid missing a treatable and curable condition.

thyroidectomy was performed. Postsurgical pathology evaluation showed a

DOI: 10.1530/endoabs.49.GP237

bilateral PTC/follicular variant (pT3N0). Within the PTC were a few nests of a

morphologically distinct neoplasm. Immunoperoxidase stains of these cells were

positive for CK8/18 and CK7 and were negative for thyroglobulin, calcitonin,

vimentin, CK20, CD10 and racemase thus suggesting metastases of RCC. The

body CT showed bilateral renal lesions likely to be angiolipomas without

distinctive criteria. Suspicious lesions in the liver, lungs and bones were also

GP238

reported without uptake in a 18F-FDG PET-CT.

A fatal case of fetal goiter: autoimmunity is the key

Conclusion

Irene Berges-Raso¹, Lara Albert¹, Assumpta Caixàs¹, Ismael Capel¹,

This case illustrates an extremely rare occurrence of tumor-to-tumor metastasis

Albert Cano¹, Isabel Mazarico¹, Laura Serra², Manuel Corona²,

where the recipient was a PTC and the donor likely to be an occult RCC.

Cesar Martín Martínez³ & Mercedes Rigla¹

DOI: 10.1530/endoabs.49.GP239

¹Endocrinology and Nutrition Department. Parc Taulí Hospital Universitari.

Institut d’Investigació i Innovació Parc Taulí I3PT. Universitat Autònoma

de Barcelona., Sabadell, Barcelona, Spain;²Obstetrics and Gynecology

Department. Parc Taulí Hospital Universitari. Institut d’Investigació i

Innovació Parc Taulí I3PT. Universitat Autònoma de Barcelona., Sabadell,

Barcelona, Spain;³SDI-UDIAT. Parc Taulí Hospital Universitari. Institut

GP240

d’Investigació i Innovació Parc Taulí I3PT. Universitat Autònoma de

Giant goiter with intrathyroid arteriovenous fistula as a cause of severe

Barcelona, Sabadell, Barcelona, Spain.

pulmonary hypertension

Elena Márquez Mesa, Estefanía González Melo, Cristina Lorenzo González,

Pilar Olvera Márquez, Ricardo Darias Garzón, María Teresa

Introduction

Herrera Arranz, Bruno Francisco García Bray, Yolanda Zambrano Huerta &

Fetal goiter is an infrequent and potentially life-threating condition derived from

Enrique Palacio Abizanda

either fetal hypothyroidism or hyperthyroidism. TSH-receptor stimulating

Hospital Universitario Nuestra Sen˜ora de la Candelaria,

antibodies (TSH-R-ABs) can cross the placenta and induce fetal hyperthyroidism

Santa Cruz de Tenerife, Spain.

and goiter. We describe a rare case of TSH-R-ABs-induced hyperthyroidism in a

woman with autoimmune hypothyroidism (AH) without previous hyperthyroidism.

Case Report

Introduction

A 28 years old pregnant woman under treatment with Levothyroxine (LT4) for

Hyperthyroidism has been described as a rare cause of pulmonary hypertension

6 years because of AH was referred during pregnancy. She had history of

(PH) as well as systemic arteriovenous fistulas. However, we describe a case of

2 miscarriages: fetal death at 28^th gestational week (GW) two years before and

pulmonary hypertension secondary to an intrathyroid arteriovenous fistula, not

fetal loss in 2015 because of corioamnionitis. Blood tests at 12^th GW showed

previously described in the literature.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Case report

GP242

A 56 year old woman followed in our consultations with multinodular goiter and

False negative fine needle aspiration thyroid cytology: an institutional

a long standing hyperthyroidism, secondary to Graves Basedow disease with

experience

difficult management. She required methimazole and low doses of levothyroxine

Anabela Martins, Evelina Mendonc¸a, António Garrão, Hugo Marques,

simultaneously to achieve hormonal control, needing multiple admissions for

Maria Cid, Francisco Rosário, Ricardo Veiga & Ana Catarino

heart failure (HF). In her last admission to Cardiology, she had right HF stage III-

Hospital da Luz, Lisbon, Portugal.

IV of NYHA, and physical examination revealed grade III goiter with murmur

auscultation and thrill palpation. The blood tests revealed that she was euthyroid.

The echocardiogram showed dilatation of both ventricles, ejection fraction 57%,

Introduction

moderate-severe biauricular dilatation, moderate mitral and tricuspid insuffi-

Fine needle aspiration cytology (FNA) is the most accurate diagnostic method for

ciency, PAPs 73 mmHg. Cervical thoracic CT evidenced large multinodular

thyroid malignant nodule diagnosis. According to the literature, the percentage of

goiter with intrathoracic extension and tracheal compression, multiple hypervas-

false negative results (FN-FNA) is less than 1.5%, in tertiary health care centers.

cular nodules and cervico-vascular venous congestion. Right cardiac catheteriza-

In this study we describe the cases reported in this Hospital, between 2014 and

tion showed moderate precapillary PH with high saturations in the venous

2016, of benign cytology, histologically characterized as malignant. All

territory explored and cardiac output 8.1 l/m. These findings were consistent with

pathologic specimens were reviewed.

the diagnosis of PH secondary to intrathyroid arteriovenous fistula. Definitive

Results

treatment was made by performing total thyroidectomy. The pathologic study of

From a total of 299 benign FNA cases submitted to surgery, 6 cases with

the piece was reported as multinodular thyroid goiter (12!13!5 centimeters and

malignant histopathology were detected (2.0%). FN-FNA was identified in 5

140 grams) with signs of diffuse hyperplasia and arteriovenous fistula. Two

males and 2 females, with ages ranging from 42 to 72 years old. The nodules size

months after surgery the patient had improved her functional class and the PAPs

varied between 41 to 95 mm.

had decreased to 30 mmHg.

The ultrasound malignancy risk was between 5 and 20% (ATA 2015 Risk

Conclusions

Stratification System).

This is the first case described in which pulmonary hypertension is secondary to

The benign FNA were described as hyperplasic nodule in 3 cases, cystic

an arteriovenous fistula in a giant goiter. Surgery was a successful treatment, and

hyperplasic nodule in 1 case, cystic colloid nodule in 1 case and colloid nodule in

one year after, the patient has a disease free survival.

the remaining.

DOI: 10.1530/endoabs.49.GP240

In all the cases the histological diagnosis was of follicular variant of papillary

carcinoma, with macrofollicular areas, either predominant or focally, and with a

heterogeneous distribution of the distinctive nuclear features of papillary

carcinoma.

Four patients were recommended for radioiodine therapy. One of these patients

was diagnosed with pulmonary and bone metastases.

Four patients were available for follow-up (mean time Z1.5 years; 9-24 months).

GP241

There is no imaging evidence of disease in any of the patients.

Thyroid-related adverse events in patients treated with Nivolumab

Conclusions

I Peiró¹, L San Martín², A Simó-Servat², J Otero², JC Ruffinelli³, E Nadal³,

In our institution, the percentage of FN-FNA was 2.0%, in accordance with that

P Iglesias⁴, JJ Díez⁴ & C Villabona²

described in the literature.

¹Clinical Nutrition Unit, Institut Català d’Oncologia (ICO), Hospitalet de

The ultrasound risk assessment did not significantly change the risk assessed

Llobregat, Spain;²Department of Endocrinology, Hospital Universitari de

by FNA.

Bellvitge, Hospitalet de Llobregat, Spain;³Department of Oncology, ICO,

In all the cases the histological diagnosis was follicular variant of papillary

Hospitalet de Llobregat, Spain;⁴Department of Endocrinology, Hospital

carcinoma. The presence of macrofollicular areas, cystic areas and a

Ramón y Cajal, Madrid, Spain.

heterogeneous expression of the typical nuclear features of papillary carcinoma

may explain the occurrence of FN-FNA.

DOI: 10.1530/endoabs.49.GP242

Introduction

Nivolumab is an antibody that binds to and blocks the activation of programmed-

death-receptor 1(PD-1), promoting the activation of T-cells against tumor cells.

Thyroid dysfunction (TD) is one of the most common immuno-related adverse

events, with incidence up to 10% in patients treated with PD-1/PD-L1 blockade.

Objective

To report our experience of Nivolumab-TD in patients with advanced cancer.

Methods

All patients diagnosed of nivolumab-induced TD during 2016 were included.

GP243

Data from thyroid function tests, autoimmunity and imaging study before and

during nivolumab therapy were recorded.

Risk factors associated with malignancy in thyroid nodules classified as

Results

Bethesda category IV (follicular neoplasm/suspicious for follicular

Twelve cancer patients (5 lung, 4 melanoma, 3 Hodgkin lymphoma) were

neoplasm)

evaluated. 75% women, mean age: 56.7 year (19-77). Ten patients were treated

Bekir Kuru & Mehmet Kefeli

with nivolumab 3 mg/kg (with or without chemotherapy) every 15 days, 2

Ondokuz Mayis University School of Medicine, Samsun, Turkey.

patients received combined immunotherapy (nivolumab 1 mg/kg plus ipilimumab

3 mg/kg). Three patients had previously well-controlled thyroid disease (1 overt

Background

primary hypothyroidism, 2 subclinical hypothyroidism). Baseline serum TSH and

Thyroid nodules diagnosed as Bethesda category IV (follicular neoplasm/suspi-

free thyroxine were evaluated in eleven patients, being normal in ten whereas one

cious for follicular neoplasm (FN/SFN)) are recommended for surgery. However,

showed minimal subclinical hypothyroidism. During follow-up,

patients

only 25% of these nodules turn to be malignant on histopathology. Therefore,

(58.3%) developed hyperthyroidism (4 overt and 3 subclinical). Six of them

selection of nodules for surgery diagnosed as Bethesda category IV is important.

after cycle(C) 2, and 1 after C3. Thyroid antibodies were positive in 3 patients.

We aimed at to define the predictive factors for malignancy and predictive risk

One overt hyperthyroidism was treated with high dose steroids (prednisone

indices for selection of surgery.

0.8 mg/kg per day) and nivolumab was temporarily withdrawn. Four of seven

Method

hyperthyroid patients became hypothyroid later, needing levothyroxine. Primary

The records of all patients with nodules that underwent fine needle aspiration

hypothyroidism occurred in 5 patients (41.7%) (3 overt and 2 subclinical),

biopsy (FNA) and classified by Bethesda reporting system as FN/SFN between

between C4-C7. Autoimmunity was positive in 3 hypothyroid patients. No patient

2011 and 2017 at our institution were reviewed. Univariate and multivariate

discontinued nivolumab due to hypothyroidism.

analysis were performed to select independent factors associated with thyroid

Conclusions

cancer. Using independent risk factors for malignancy predictive indices were

In our series, hyperthyroidism is more frequent and appears earlier than

created.

hypothyroidism. A pattern consistent with a transient thyroiditis followed by

Results

hypothyroidism is seen in one-third of patients. Monitoring thyroid function at

Among 6,217 nodules which underwent FNA, 163 (2.6%) were diagnosed as

baseline and before each therapeutic cycle is warranted to detect and treat TD

FN/SFN. Of the 163 patients classified as FN/SFN, 126 underwent surgery with

promptly.

an associated malignancy rate of 36% (45/126). Age under 45, solid structure,

DOI: 10.1530/endoabs.49.GP241

microcalcification, hypoechogenicity and increased vascularization were found to

be significant and independent risk factors associated for malignancy. The risk

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

indices were created by classifying nodules with 0, 1, 2, 3, and R4 risk factors as

(57.9%) were shown to be positive. Subsequently, DNA samples from Rc-PTC

risk indices 0, 1, 2, 3, and 4. There were 17 (14%), 41 (33%), 27 (21%), 22 (17%),

and NR-PTC groups were analysed for BRAF^V600E mutation and this mutation

and 19 (15%) patients in risk indices 0, 1, 2, 3, and 4, respectively. The estimated

was found in 54.8% (17/31) of Rc-PTC samples and 59.0% (49/83) of NR-PTC

malignancy risk in patients with 0, 1, 2, 3, and 4 risk indices were 0% (0/17), 12%

samples. There was no signifficant difference between these groups (PZ0.686).

(5/41), 26% (7/27), 64% (14/22), and 100% (19/19), respectively.

Conclusion

Conclusions

These results suggest that miRNA-21, miRNA-222, miRNA-146b might be

Using predictive factors for malignancy in Bethesda IV category a small, but

potential biomarkers for PTC recurrence. BRAF mutation is not associated with

important proportion of patients 14% who had nodules without any risk factors

PTC recurrence.

could be spared unnecessary surgery. Predictive indices should be considered for

DOI: 10.1530/endoabs.49.GP244

informing the patients about the malignancy risk and for selection of surgery in

Bethesda IV category.

DOI: 10.1530/endoabs.49.GP243

GP245

A statistical, in silico model predicts polygenic thyroid cancer risk

Livio Casarini^1,2, Marco Marino^1,2, Federico Nuzzo¹, Manuela Simoni^1,3 &

Giulia Brigante^1,3

Unit of Endocrinology, Department Biomedical, Metabolic and Neural

GP244

Sciences, University of Modena and Reggio Emilia, Modena, Italy;²Center

Expressions of miRNAs and BRAF^V600E mutation detection in papillary

for the Genomic Research, University of Modena and Reggio Emilia,

thyroid carcinoma

Modena, Italy;³Azienda Ospedaliero-Universitaria di Modena, Modena,

Vaida Simanaviciene¹, Aiste Kondrotiene², Daina Pamedytyte¹,

Italy.

Valdas Sarauskas³, Dalia Dauksiene⁴, Albertas Dauksa⁵,

Aurelija Zvirbliene¹ & Birute Zilaitiene¹

¹Institute of Biotechnology, Vilnius University, Vilnius, Lithuania;

Introduction

²Lithuanian University of Health Sciences, Medical Academy, Kaunas,

The detection of a unique genetic marker is not possible for multifactorial

Lithuania;³Department of Pathological Anatomy, Lithuanian University of

diseases, such as thyroid cancer (TC), where the pathological phenotype is given

Health Sciences, Kaunas, Lithuania;⁴Institute of Endocrinology, Medical

by the contribution of multiple genes, environmental factors and lifestyle. We

Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania;

found a mathematical model for inferring the risk of thyroid cancer, an example of

⁵Institute of Digestive Research, Medical Academy, Faculty of Medicine,

multifactorial disease.

Lithuanian University of Health Sciences, Kaunas, Lithuania.

Methods

Genetic data represented by 184 SNPs associated to thyroid tumors were used for

Bayesian clustering of 2504 individuals from the 1000 Genomes database, by

Introduction

STRUCTURE software. Numerical values representing the inferred genetic

Papillary thyroid carcinoma

(PTC) is the most common type of thyroid

structure of each individual is provided in the output file of the software and were

malignancy. For the majority of patients with PTC, the prognosis is very good;

matched with environmental and lifestyle parameters associated to thyroid

however, up to 20% of patients suffer disease recurrence. Currently, the risk

functions, i.e. iodine exposure and obesity, by principal component analysis

stratification for PTC recurrence is based on clinicopathological features which

(PCA). Data analysis was performed using labels such as geographic origin of

have limited prognostic value. Identification of molecular biomarkers of PTC

individuals, population, sex and thyroid cancer incidence.

recurrence such as protooncogene BRAF and miRNAs may help to improve risk-

Results

stratified patient management.

We found that seven thyroid tumor-related genetic clusters are differently

Objective

represented among human populations. The matching of genotype, iodine and

The aim of this study was to detect BRAFV600E mutation and identify miRNA

obesity data resulted in individuals’ gradient distribution by thyroid cancer

biomarkers for PTC recurrence.

incidence, revealing that all these components are required to infer the disease

Methods

risk. Genetic background and, to a lesser extent, environmental factors and

We selected 3 miRNA (miRNA- 146b, -222 and -21) and measured the expresion

lifestyle, are not related per se to a specific range value of cancer risk. An

levels of these miRNAs in patients with recurrent PTC (Rc-PTC) and without

exception is provided by individuals from Tuscany, Italy, which deviates from the

recurrence

(NRc-PTC). 106 NR-PTC and 60 Rc-PTC FFPE samples were

overall distribution, preserving high cancer risk independently from obesity or

analysed for selected miRNAs. 114 FFPE PTC samples (31 Rc-PTC and 83

iodine. This could result from a peculiar genetic setting or from the exposure to

NR-PTC) were analysed for BRAF^V600E mutation.

environmental factors not considered in the analysis.

Results

Discussion

The expression levels of all three miRNAs were significantly increased in PTC

We demonstrated that TC risk may be detected a priori by applying polygenic

when compared to healthy thyroid tissue. miRNA-146b expresion was extremely

model to specific population or individuals.

elevated with 55.6-fold over-expression in PTC (P!0.001). miRNA-222 and -21

Conclusion

were over-expressed 13.8-fold and 3.7-fold, respectively (PZ0.001 and PZ0.16).

This study provides a novel mathematical approach to infer the polygenic disease

In Rc-PTC and NRc-PTC groups miRNA-21, -146b and -222 were significantly

risk, as a promising diagnostic tool for personalized medicine.

differently expressed with 1.4- fold (PZ0.006), 1.8-fold (PZ0.007) and 2.1-fold

DOI: 10.1530/endoabs.49.GP245

(P!0.001) higher expresion in NRc-PTC compared with Rc-PTC tissues. 114

FFPE PTC samples were analysed for BRAF^V600E mutation and 66 of them

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Adrenal Cortex (to include Cushing’s)

Conclusions

In our study we found a correlation between salivary and serum cortisol values in

EP1

both samples, at the morning and at the midnight to all participants; in healthy

Confirmatory tests for diagnosis of primary aldosteronism among

people, patients with Cushing’s disease.

Chinese hypertensives

Keywords: salivary cortisol; serum cortisol; correlation

Minchun Jiang¹, Dujuan Ma², Hailun Lin¹, Ying Lin¹, Yajuan Deng³,

DOI: 10.1530/endoabs.49.EP2

Juying Tang¹, Shaoling Zhang¹ & Ying Guo¹

¹Department of Endocrinology and Metabolism, Sun Yat-sen Memorial

Hospital, Sun Yat-sen University, Guangzhou, China;²Department of

Endocrinology and Metabolism, Guangzhou Panyu Central Hospital,

Guangzhou, China;³Shenzhen Hospital of Southern Medical University,

Shenzhen, China.

EP3

Adrenocortical virilizing tumor in an adult woman in remission after

surgical therapy performed more than 12 years ago

Objective

Terroba Larumbe, Crespo Soto, Citores Pascual, Benito Fernandez,

Primary aldosteronism (PA) has emerged as the most frequent form of secondary

Calero Aguilar, Anacabe Goyogana, Urbon Lopez De Linares,

hypertension. For the diagnosis of PA, confirmatory testing is indispensable and

Ventosa Vin˜ a, Cuellar Olmedo & Palacio Mures

different tests are recommended by guidelines, including captopril challenge test

Hospital Universitario Rio Hortega, Valladolid, Spain.

(CCT) and saline infusion test (SIT). However, there are sparse studies evaluating

and comparing CCT and SIT in Chinese population. Hence, we investigate the

diagnostic efficiency of CCT and SIT for PA in Chinese hypertensives in our study.

Introduction

Methods

Adrenocortical carcinomas (ACCs) are rare, frequently aggressive tumors. Pure

In total, 183 patients with essential hypertension and 105 patients with PA were

virilizing carcinomas are infrequent, constituting 5 to 10% in most series.

recruited in the study, and their clinical data were analyzed by constructing the

Clinical case

receiver operating characteristics (ROC) curve to compare the accuracy of CCT

A 36-year-old female consults for 5 years evolution of amenorrhea associated

and SIT.

with hirsutism attributed to polycistic ovary syndrome (PCOS) and treated with

Results

oral contraceptives during the previous 2 years. There was no other data on

(1) A total of 277 patients underwent CCT. The AUC of post-CCT aldosterone,

virilization, changes in body weight, hypertension or gastrointestinal symptoms.

aldosterone suppression rate and post-CCT aldosterone/renin ratio (ARR) were

In the biochemical exam the following were observed: total testosterone 405 ng/dl

0.877

(95% CI 0.833 to 0.921, P!0.001), 0.683 (95% CI 0.617 to 0.748,

(15-110), free testosterone 26.9 pmol/l (0.19-8.9), DHEA-sulphate 1000 mg/dl

P!0.001) and 0.929 (95% CI 0.896 to 0.963, P!0.001), and accuracy of ARR

(35-430), FSH 2.9 mU/ml and LH 11.4 mU/ml. Basal and urinary cortisol,

post-CCT is highest (P!0.001). For post-CCT ARR, at the optimal cut-off value

prolactin, beta-estradiol,

17-OH-progesterone, thyroid, hepatic and renal

of 30 ng†dl-1/ng†ml-1†h-1, the sensitivity and specificity were 67.6% and

function, ions, were normal. The response to LHRH and ACTH and ovarian

96.2% respectively. (2) The SIT was performed in 116 patients. The AUC of post-

ultrasound were compatible with PCOS and ruled out late onset congenital

SIT aldosterone and post-SIT ARR were

0.829

(95% CI 0.731 to 0.928,

adrenal hyperplasia. The imaging tests showed a solid adrenal mass in the left

P!0.001) and 0.923 (95%CI 0.860 to 0.985, P!0.001), and post-SIT ARR has

10!13!14 cm, with prominent vascular structures inside it, which were

higher accuracy

(P!0.05). The best cut-off value of post-SIT ARR for

embolized prior to surgical excision performed by bilateral subcostal laparotomy.

identifying PA was 60 ng†dl-1/ng†ml-1†h-1, with sensitivity and specificity of

The histological diagnosis of the tumor which weighed 1.152 kg and measured

81.8% and 95.2%, respectively. (3) 110 patients underwent both CCT and SIT. In

20!12.5!8.5 cm, proved to be an adrenocortical tumor of low degree

the consistency check of CCT and SIT, kappa value was 0.714, P!0.001. The

malignancy, without invasion of the capsule or adjacent tissues. Menstruation,

AUC of post-CCT ARR, post-SIT ARR, serial test of post-CCT ARR and post-

hormonal tests and ovarian ultrasound became normal after surgery. The patient

SIT ARR were 0.937 (95% CI 0.885 to 0.990, P!0.001), 0.921 (95% CI 0.858 to

did not receive any therapy and the follow-up has not shown recurrence.

0.984, P!0.001) and 0.939 (95% CI 0.881 to 0.881, P!0.001), there is no

Discussion

statistical difference among the three indices.

Overall, survival is poor for ACC. Five-year survival is approximately 45-60%

Conclusions

for early stage disease, and 10-25% for advanced stage disease. For patients with

With a good consistency, CCT and SIT are both efficient confirmatory tests for

stage I to III disease, complete surgical resection as initial therapy is the only

PA, and applying ARR post-CCT or ARR post-SIT make it feasible to diagnose

potentially curative treatment and open surgery remains the standard approach.

PA more accurately. However, combining two tests fails to further improve the

Despite the large tumor size, the patient had a good prognosis based on the

accuracy for diagnosis of PA.

absence of invasion of the surrounding tissues, the histological grade of

DOI: 10.1530/endoabs.49.EP1

differentiation and the complete tumor resection. The interest of her case is due

not only to the prolonged survival with an optimal quality of life, but also is a

representative example of PCOS secondary to hyperandrogenism that disappears

from the functional and morphological point of view after the suppression of its

cause.

DOI: 10.1530/endoabs.49.EP3

EP2

The correlation of salivary cortisol values with serum cortisol values

Blertina Dyrmishi¹, Taulant Olldashi¹, Ema Lumi³, Entela Puca⁴,

Emirvina Kolici⁴, Dorina Ylli² & Thanas Fureraj²

¹Hygeia Hospital Tirana, Tirana, Albania;²UHC Mother Teresa, Tirana,

Albania;³Regional Hospital Korca, Korca, Albania;⁴Neo Style Clinic,

EP4

Tirana, Albania.

Investigation of atrophic adrenal glands in Cushing’s syndrome model

rats induced by the administration of dexamethasone

Toshiro Seki¹, Atsushi Yasuda¹, Natsumi Kitajima¹, Masami Seki²,

Aim

Masayuki Oki¹, Atsushi Takagi¹ & Masafumi Fukagawa¹

The aim of the study was to evaluate the correlation between salivary and serum

¹Tokai University School of Medicine, Isehara-shi, Kanagawa, Japan;

cortisol values to the healthy people and patients with Cushing’s syndrome.

²Seirei Numazu Hospital, Numazu-shi, Shizuoka, Japan.

Methods

33 cases: 21 healthy people aged 22 to 53 years old; 12 patients with Cushing’s

syndrome values were included to our study. All the participiants of control group

Cushing’s syndrome is a disease caused by excessive glucocorticoids from

were healthy without known disease. Two samples of salivary and serum cortisol

adrenocortical tumors. In most cases, impaired adrenocortical function is likely

was taken to all the participiants of the study in the morning and in the midnight.

caused by atrophy of the normal adrenal tissue as a result of chronic suppression

All the subject respect the rolls of salivary collected samples.

by the low ACTH levels in the hypercortisolism state. Secondary adrenal

Results

insufficiency causes with surgical resection of cortisol-secreting tumors.

The mean age of the healthy subjects was 31G4.8 years old. Basal salivary

Therefore, we thought that it was necessary to prepare Cushing’s syndrome

cortisol was significantly correlated with serum salivary cortisol in the morning

model rats for establishment of a new treatment method to promote improvement

and at the midnight; P!0.05 in the morning and PZ0.052 at the midnight.

of the function of the remaining adrenal glands after adrenalectomy. Cushing’s

Pearson coefficients were 0.45 in the morning and 0.42 at the midnight (2300 h).

syndrome model rats have already been published and they describe changes in

The sensitivity of salivary cortisol values in diagnoses of Cushing’s syndrome

blood pressure and body weight. Regarding atrophy of tissues, it is considered that

was 100% for cut off values 2.18 ng/dl and for cut off values 3.14 ng/dl the

the atrophy of cells and the appearance of apoptosis are observed in such tissues.

sensitivity was 100% and specificity 83%. ACU 0.97.

However, the weight and histological changes of the adrenal glands are not

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

described. In this study, we investigate ACTH, the ratio of adrenal cortex to

stimulates the adrenal gland and induces the release of glucocorticoids. Many

medulla and number of apoptotic cells as evaluation of atrophic adrenal glands in

studies have shown their effects on several physiological functions such as

dexamethasone-treated rats (nZ5) compared to control rats (nZ5). In the group

immunity, inflammation as well as the cardiovascular system whose action is

treated with dexamethasone, an increase in blood pressure (135G24 mmHg),

controlled by ACTH. For this purpose, the study carried out in the wistar rat

suppression of plasma ACTH (20G12 pg/ml) and the low serum corticosterone

revealed the effects of a treatment with Cortrosyn (ACTH of synthesis) on the

levels (7.5G1.1 ng/ml) were observed as compared with the control group. In

weight and the adrenal structure in the wistar rat. The work was carried out on a

addition, adrenal gland weight decreased (13.6G1.2 mg), and the low ratio of

lot of rat wistar divided into two lots: one batch of control rat (T) and one batch of

adrenal cortex to medulla and an increase of apoptotic cells were observed.

treated rat (S) receiving a daily intramuscular injection of Cortrosyn at the rate of

Compared with control rats, dexamethasone-treated rats showed a significant

0.01 mg/100 g of weight Body for 20 days. After sacrifice of the animals, the

decrease in hormonal secretory ability both endocrinologically and histologically.

adrenals are taken, weighed and immediately immersed in the fixing liquid in

Our group is currently conducting experiments to investigate the levels of

order to carry out the histological techniques. The results show that the

mRNAs for c-fos in adrenal glands as assessment of the recovery of adrenal

intramuscular injection of Cortrosyn resulted in a very significant increase in

atrophy.

absolute and relative adrenal weights in treated rats as compared to controls as

DOI: 10.1530/endoabs.49.EP4

well as an increase in the number of cells

(hyperplasia), a different cell

distribution and The appearance of optically empty space. These results to be

investigated and could explain why the activation of the adrenal cortex during

20 days by the Cortrosyn would be in favor of an important structural and

functional modification of the adrenal gland whose indirect trophic effect of this

hormone could be regulated by several factors.

EP5

Keywords: Cortosyn; adrenal; ACTH

Long-term assessment of AddiQoL and patient diaries may identify

DOI: 10.1530/endoabs.49.EP6

Addison patients at high risk for adrenal crises

Maike Koch¹, Klaus Badenhoop¹, Eva Herrmann² & Gesine Meyer¹

¹Department of Internal Medicine 1, Endocrinology, Goethe-University

Hospital, Frankfurt, Germany,²Institute for Biostatistics, Goethe-University

Hospital, Frankfurt, Germany.

Introduction

Several studies have shown a reduced quality of life (QoL) in patients with

Addison’s disease (AD). However, by now there are no data investigating the

changes of QoL over a long-term course. Adrenal crises (AC) are frequent and

potentially life-threatening complications in patients with AD. Since no reliable

laboratory indicator can predict impending crises it is difficult to detect patients at

EP7

increased risk. The purpose of this study was to test whether the repeated use of

questionnaires for self-assessment over longer periods can detect possible

Molecular variability determines subtle adrenal biosynthetic defect in

prodromal periods of an AC.

non-classical congenital adrenal hyperplasia due to 21-hydroxylase

Methods

deficiency

137 patients with AD were included. They were asked to complete the disease

Livia Mermejo¹, Fernanda Coeli-Lacchini¹, Wendy Turatti¹,

specific-quality of life questionnaire AddiQoL once monthly over a period of ten

Marcia Elamid², Renata Parente², Carlos Martinelli², Sonir Antonini²,

months. In addition they also completed a short questionnaire about adverse

Margaret Castro¹ & Ayrton Moreira¹

events during the last month. AC was defined if at least two of the following

¹Department of Internal Medicine Ribeirao Preto Medical School,

symptoms were reported: a) hypotension, b) nausea or vomiting, c) severe fatigue,

University of Sao Paulo, Brazil, Ribeirao Preto/SP, Brazil;²Department of

d) documented hyponatremia, hyperkalemia, or hypoglycemia, and subsequent

Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Brazil,

parenteral glucocorticoid administration was carried out.

Ribeirao Preto/SP, Brazil.

Results

110 patients completed the study by fulfilling at least 9 of the 10 required sets of

There is a clinical spectrum of non-classical congenital adrenal hyperplasia due to

questionnaires and not exceeding a time-lag over more than three months. Seven

21-hydroxylase deficiency (NC-CAH). In addition, CYP21A2 gene mutations

patients suffered an AC, resulting in 7.6 crises/100 patient years. AddiQoL scores

analysis present in homozygosis or as compound heterozygosis.

in patients with adrenal crises showed a trend (PZ0.058) to a wider fluctuation

Objectives

over the ten months. 19 Patients reported about severe adverse events not

To evaluate the relationship between the genotype and biochemical profiles and

fulfilling the named criteria of AC. In these patients we found a significantly

also compare with clinical severity in NC-CAH.

lower median (PZ0.017) of the AddiQoL scores compared to patients not

Patients and methods

suffering a pre-crisis.

Clinical, hormonal and molecular data of 57 patients (47 female,10 male; 47

Conclusions

children,10 adults) with NC-CAH were retrospectively analyzed.

These are the first data showing the course of QoL during a period of ten months

Results

in patients with AD. Prevalence of AC lay by 7.6 per 100 patient years, in

The majority of children

(76%) presented with premature pubarche at the

accordance with previous data. Our data show, that relevant medical adverse

diagnosis and 12% showed clitoromegaly. Among adult patients, hirsutism (90%)

events in patients with AD are associated with a lower QoL. Furthermore, such

and menstrual abnormalities (66%) were observed at diagnosis. The basal and

events affect intraindividual AddiQol-scores over time with a trend to a stronger

ACTH-stimulated 17OHP mean levels were 1115G919 (97-4125) and 4245G

fluctuation. Long-term assessment of AddiQol and assessment of adverse events,

2059

(1115-10648) ng/dl. The most frequent mutation was p.V281L (68% of

e.g. via patient diaries, may be applied as an additional clinical tool to identify

alleles) being 42% in homozygosis and 39% of the patients were compound

patients at risk for critical events.

heterozygotes for one classic and one non-classical mutation (C/NC).The severe

DOI: 10.1530/endoabs.49.EP5

mutations were p.I172N, IVS2-13A/COG, D8, CL6, p.Q318X, p.R356W and

LGC. Basal and ACTH-stimulated 17OHP values were higher in patients carrying

the C/NC genotype group compared to NC/NC genotype (1549G250 vs 806G

162; PZ0.01

and

4740G577 vs 3355G345 ng/dl; PZ0.04, respectively).

Moreover, ROC curve analyses showed that the basal and ACTH-stimulated

17OHP levels of 610 and 3,913 ng/dl were the best cutoffs to identify NC-CAH

patients carrying compound heterozygosis with severe mutations. We observed a

EP6

higher DHEAS

(182G150

85G69 mg/dl, PZ0.03) and a bone age

advancement trend (PZ0.05) in C/NC genotype group compared to NC/NC.

Impact of Cortrosyn treatment on weight and adrenal structure in the

There were no differences in age, height, weight, androstenedione and

wistar rat

testosterone levels at diagnosis.

Samira Akdader-Oudahmane, Zohra Hamouli-Said &

Conclusion

Fatma Hadj-Bekkouche

Although no phenotype difference was observed between NC/NC and C/NC

University of Algiers, Algiers, Algeria.

genotypes, the present study showed graded severities of adrenal biosynthetic

defect reflecting the molecular variability in NC-CAH.

The corticotropic hormone (ACTH) mainly secreted by the anterior lobe of the

DOI: 10.1530/endoabs.49.EP7

pituitary gland which, following a physiological or psychological stress situation,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP8

Discussion

The presence and type of hyperlipemia prior to therapy is likely to affect the

Corticoids-therapy related complications in patients with primary

adverse effects of mitotane on lipids and in this patient, TG levels have varied

adrenal insufficiency

according to mitotane doses and levels despite lipid-lowering therapy. On the

Juan Carlos Romero Rodríguez, María Calatayud Gutiérrez, Laura

other hand, dyslipidemia may induce an overestimation of plasma mitotane

Mola Reyes, Carlos Silva Vaca, Sonsoles Guadalix Iglesias & Guillermo

measurements, so it is necessary to closely monitor the lipid profile in all patients

Martínez Díaz-Guerra

treated with this drug.

Hospital Universitario 12 de Octubre, Madrid, Madrid, Spain.

DOI: 10.1530/endoabs.49.EP9

Introduction

Patients with primary adrenal insufficiency

(PAI) require lifelong corticoids

replacement and they are at risk of therapy-related osteoporosis and cardiovascular

complications.

Objectives

EP10

Determine the prevalence of cardiovascular risk factors, osteoporosis, and other

Addison’s disease presenting as severe hypoglycaemia and cachexia

toxicities related with corticoids treatment.

Ana Cláudia Martins, Paula Bogalho & Ana Agapito

Material and methods

Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,

Retrospective, descriptive study in patients with PAI follow up in our service

Portugal.

during the last 30 years. Information was collected from clinical histories.

Results

Addison’s disease (AD), also known as primary adrenal insufficiency, is caused

Identified 30 patients with PAI. Clinical characteristics: 21 were women, mean

by destruction or dysfunction of the adrenal cortex, resulting in hypocortisolism.

age at diagnosis of 36.72G5.3 years and mean time since diagnosis 263.8G57.5

The usual clinical features of chronic AD are non-specific and include fatigue,

months. Etiology: 15 (50%) autoimmune disease; 7 (23.3%) post-surgery; 5

nausea, vomiting and hyperpigmentation. We describe the case of a 58-year-old

(16.6%) congenital adrenal hyperplasia; 2 (6.7%) tuberculosis and 1 (3.3%)

African black male with AD presenting with recurring severe hypoglycaemia.

metastatic disease.

The patient was admitted several times to the emergency department with

Steroid replacement: 26 (86.7%) used hidrocortisone (HC), 3 (10%) dexameta-

hypoglycaemia

(blood glucose between

and

50 mg/dl) and loss of

sone, 1 (3.3%) prednisone. 25 patients were on treatment with fludrocortisone.

consciousness, managed with intravenous dextrose. These episodes were

Mean glucocorticoid dose

(HC or equivalent):

20.58G1.5 mg/day, mean

associated with anorexia, dizziness, fatigue and progressive weight loss over

fludrocortisone dose 0.066G0.008 mg/day.

two years prior to presentation. His past history was significant for pulmonary

Possible therapy-related complications: 23(76.7%) patients developed at least

tuberculosis, and there was no family history of note. Physical examination

1complication during follow-up: osteoporosis

11(36.7%), dyslipidemia

revealed a cachectic habitus, depressed mood and hyperpigmentation of palmar

(33.3%), prediabetes 8(26.6%), hypertension 7(23.3%), type 2 diabetes 6(20%),

creases and oral mucosa. He had a body mass index of 14.9, blood pressure

1(3.3%) cardiovascular event.

88% patients with osteoporosis,

78.6% with

98/57 mmHg and regular pulse of 64 bpm, with no other remarks on systemic

diabetes or prediabetes, 85.7% hypertension and 70% with dyslipidemia used HC

examination. Biochemical analysis revealed Hb

11 g/dl, mild hyponatremia

dose R20 mg/d.

(134 meq/l), normokalemia (4.1 meq/l), hypoalbuminemia (32.4 g/l), and normal

Conclusions

renal and hepatic function tests. Morning serum cortisol level was 2.3 mg/dl and

Osteoporosis and cardiovascular complications are frequents in patients with PAI.

ACTH 52.2 pg/ml, with normal levels of other pituitary hormones. ACTH

Patients on treatment with higher corticoid dose are at risk of development

stimulation test was performed and confirmed adrenal insufficiency. Compu-

therapy-related complication. Adjustment in corticoid to minimal necessary dose

terised tomography scan of the abdomen showed normal shaped and sized adrenal

could prevent these complications.

glands. HIV screening was negative and there were no clinical or radiological

DOI: 10.1530/endoabs.49.EP8

signs of active tuberculosis. He started treatment with hydrocortisone and

fludrocortisone, and his symptoms readily improved. This case illustrates an

unusual presentation of Addison’s disease and points out the need for a high index

of suspicion so that morbidity and mortality can be decreased by a prompt

EP9

diagnosis.

Severe hypertriglyceridemia in relation to toxic levels of mitotane in a

DOI: 10.1530/endoabs.49.EP10

patient with stage IV adrenocortical carcinoma (ACC)

Terroba Larumbe, Crespo Soto, Anacabe Goyogana, Urbon López De

Linares, Amon Sesmero, Ventosa Vin˜ a, Cuellar Olmedo, Marcos García,

Otero Roussel & Almendros Mu

˜ oz

H. U. Rio Hortega, Valladolid, Spain.

EP11

Posterior reversible encephalopathy syndrome (PRES) in a patient with

Introduction

primary aldosteronism

The use of mitotane as ACC therapy is associated with multiple adverse effects

Julia Silva-Fernández¹, Florentino Del Val-Zaballos¹, Francisco

including hypercholesterolemia due to increased levels of LDL cholesterol. There

Javier Gómez-Alfonso¹, Paloma González-Lázaro¹, Belvís Torres-Arroyo¹,

are no reported cases of severe hypertriglyceridemia (HTG).

Rafael García-Ruiz², Álvaro García-Manzanares Vázquez de Agredos¹,

Clinical case

María López-Iglesias¹ & Inés Gómez-García¹

A 59-year-old male with a personal history of dyslipidemia phenotype IV and

¹Endocrinology Service, Hospital La Mancha Centro, Alcázar de San Juan,

pulmonary emphysema, former smoker and drinker was diagnosed with non-

Spain;²Neurology Service, Hospital La Mancha Centro, Alcázar de San

functioning left-sided ACC. Left adrenalectomy C left nephrectomy and

Juan, Spain.

subsequently right adrenalectomy and atypical segmentectomy of the upper

right lung lobe due to the presence of metastases was performed. One month later,

low-dose

(2 g/day) mitotane therapy was initiated in combination with

Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder

hydrocortisone and oral fludrocortisone replacement therapy. In the first post-

characterized by varied neurological symptoms. There are two leading theories

mitotane control, triglycerides

(TG) level which previously was

325 mg/dl

regarding the pathophysiology: hypertension crisis and endothelial dysfunction.

increased to 953 mg/dl, coinciding with serum mitotane of 13.8 mg/l. Other

Case report

factors that could increase it were overruled. Fenofibrate

145 mg/day was

We report the case of a 42-year-old patient with history of hypertension. She

prescribed but in the following control TG were 880 mg/dl with serum mitotane

presented to the emergency department with headache and bilateral loss of vision.

of 14.3 mg/l. The dose of mitotane was then reduced to 1 g/day, its level dropped

She described one previous episode of witnessed generalised tonic-clonic seizure

to 10.5 mg/l and TG were 939 mg/dl. Consequently ezetimibe 10 mg/day was

at home. She was found to have an elevated blood pressure (BP) of 210/105 mm

added to the therapy and the mitotane dose was increased to 1.5 g/day and

Hg. An ocular examination revealed a diminished vision and perception of hand

subsequently to 2 g/day because the level was very low and a 4.5 cm unresectable

movement on both eyes. Laboratory findings were within normal range except for

metastatic adenopathy that received radiotherapy appeared in the mediastinum.

potassium, which was 2.7 mEq/l (normal range 3.5-5). Brain MRI showed

Coinciding with a mitotane level of 33.8 mg/l, the patient presented severe

bilateral posterior parietooccipital hyper densities in the cortex and subcortical

asthenia attributable to mitotane toxicity and TG of 1,528 mg/dl, without data of

white matter consistent with PRES. Antihypertensive therapy was started. The

pancreatitis, what required a drastic decrease in the dose of drug. In the last

patient’s headache rapidly resolved and her vision improved. The patient was

review, the mitotane level was 6.7 mg/l, TG were 344 mg/dl, the symptoms

discharged symptom-free on potassium supplements and antihypertensive

disappeared and the mitotane dose was again raised while those of fenofibrate,

therapy. After discharge the patient was referred to the Endocrinology service.

ezetimibe, hydrocortisone and fludrocortisone remained the same.

Aldosterone concentration/plasma renin activity ratio was positive and the saline

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

infusion test confirmed the diagnosis of hyperaldosteronism. Abdominal MRI

Methods

revealed a two-centimetre adenoma of the left adrenal gland. The patient

Hair samples were collected from 12 study subjects (four with PA, two with PA

underwent surgery to remove the adenoma. After surgery, hypokalemia and

and cortisol co-secretion, and six controls), with mean age 40.1G21.4 years,

hypertension resolved.

mean BMI 28.1G5.3 kg/m². Diurnal serum cortisol and ACTH measurements,

Conclusions

24-h-urinary free cortisol corrected by body surface area

(UFC/BSA) and

Although primary aldosteronism (PA) is not included among the reported causes

17-hydroxysteroids, corrected for creatinine (17OHS/Cr) were measured. Patients

of PRES, it is important to consider its existence in PRES patients, particularly in

underwent step-wise diagnosis, with measurement of serum aldosterone and

those with hypokalemia. The occurrence of PRES in patients with PA might be

plasma renin activity followed by saline suppression and/or oral salt loading tests.

independent of hypertension since the direct action of aldosterone on the

Patients without PA or CS were excluded as controls, if midnight serum cortisol

mineralocorticoid receptor may cause endothelial dysfunction.

O1.8 mg/dl. Segmental hair samples from each patient were processed and

DOI: 10.1530/endoabs.49.EP11

analysed for cortisol according to the methods described by Meyer et al. (2014).

Results

Age, blood pressure, urinary and midnight cortisol levels were higher (P!0.05)

in the PA group compared to the controls. Average hair cortisol values in the

groups with PA and controls were 30.0G31.0 pg cortisol/mg hair (median:

EP12

16.3 pg/mg; interquartile range: 12.6-37.4 pg/mg) and 22.9G27.6 pg cortisol/mg

hair

(median:

11.3 pg/mg; interquartile range

7.9-26.6 pg/mg), respectively

Evaluation of cardiovascular risk in patients with adrenal

(PO0.05). No correlation between hair cortisol and serum and urinary markers of

incidentaloma

hypercortisolemia was seen in the six patients with PA.

Goknur Yorulmaz¹, Aysen Akalin¹ & Burcu Yagiz²

Discussion

¹Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey;

We found that no statistically significant difference in hair cortisol between

²Uludag University School of Medicine, Bursa, Turkey.

groups and no significant correlation of hair cortisol with urinary or serum cortisol

evaluations. We speculate that the lack of correlation may be due to insufficient

Introduction

power. More research is needed on the use of hair cortisol in patients with PA.

Recent studies indicate that patients diagnosed with adrenal incidentaloma may

DOI: 10.1530/endoabs.49.EP13

present with cardiovascular disease. The aim of this study was to investigate

markers of subclinical cardiovascular disease in patients with adrenal

incidentaloma and healthy control group.

Methods

This study included 50 patients with non-functional adrenal adenoma and 30

EP14

healthy controls. BMI and waist circumference of the patients were measured.

The lipid parameters, glucose, insulin, C-peptide, erythrocyte sedimentation rate,

Salivary steroid levels during diagnostic tests for adrenal insufficiency

fibrinogen, homocysteine, hsCRP levels and carotid intima media thickness were

Michaela Dušková¹, Kateřina

ˇ im

˚ nková^1,2, Jana Vítk

˚¹,

measured. HOMA levels of the patients were calculated.

Lucie Kolátorová¹, Hana Jandíková¹, Hana Pospíšilová¹,

Results

Monika Sˇ rámková1, Mikuláš Kosák2 & Luboslav Stárka1

Patients with non-functional adrenal adenomas were compared with obese and

¹Institute of Endocrinology, Praha, Czech Republic;²Third Department of

non-obese control groups. Carotid intima media thickness and erythrocyte

Medicine, General University Hospital and First Faculty of Medicine,

sedimentation rate levels of the patients with adrenal incidentaloma were

Charles University, Praha, Czech Republic.

significantly higher than the healthy controls. There was not statistically

significant difference between lipid parameters, glucose, insulin, C-peptide,

Diagnostic tests of the hypothalamic-pituitary-adrenal axis

(HPA axis),

fibrinogen, homocysteine, hsCRP levels of the patients and control group.

measuring of free cortisol and use of other adrenal steroids are the subject of debate.

Conclusion

We investigated 15 healthy men with mean/median age 27.4/26 (G4.8) years, and

In patients with nonfunctional adrenal adenomas the carotid intima media

mean/median BMI 25.38/24.82 (G3.2) kg/m². All subjects underwent four

thickness, which is a cardiovascular risk indicator, was found to be thicker than

dynamic tests of the HPA axis, specifically 1, 10, and 250 mg synacthen tests and an

the normal population. At the same time, erythrocyte sedimentation rate, another

insulin tolerance test (ITT). Salivary cortisol, cortisone, pregnenolone, and DHEA

indicator of cardiovascular risk, was also higher in the adrenal incidentaloma

were analysed using liquid chromatography-tandem mass spectrometry.

group. These findings suggest that patients with adrenal adenomas have a higher

During the ITT maximum salivary cortisol levels of over 12.5 nmol/l were found at

risk for subclinical cardiovascular disease and close follow-up may be necessary.

60 min. Maximum cortisol levels in all of the Synacthen tests were higher than

DOI: 10.1530/endoabs.49.EP12

stimulation in the ITT. Cortisone reacted similarly as cortisol, i.e. we did not find

any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were

higher during the ITT, and their peaks preceded the cortisol peak. There was no

increase of pregnenolone or DHEA in any of the Synacthen tests.

Our results indicate that a 10 mg Synacthen dose is a safe and cost-effective choice.

EP13

This study was supported by the project MZCR for conceptual development of

Hair cortisol in patients with primary aldosteronism

research organization 00023761 Institute of Endocrinology and grant 17-28692A.

Aaron Hodes^1,3, Maya Lodish¹, Amit Tirosh^1,3, Jerrold Meyer⁵,

DOI: 10.1530/endoabs.49.EP14

Elena Belyavskaya¹, Charalampos Lyssikatos¹, Kendra Rosenberg⁵,

Andrew Demidowich¹, Jeremy Swan¹, Nichole Jonas¹,

Constantine Stratakis¹ & Mihail Zilbermint^1,2

¹Section on Endocrinology and Genetics, Eunice Kennedy Shriver National

Institute of Child Health and Human Development, National Institutes of

Health, Bethesda, Maryland, USA;²Johns Hopkins University School of

EP15

Medicine, Division of Endocrinology, Diabetes, and Metabolism, Balti-

Assessment of quality of life of patients with Cushing’s syndrome

more, Maryland, USA;³Sackler Faculty of Medicine, Tel Aviv University,

depending on the disease course

Tel Aviv, Israel;⁴Albert Einstein College of Medicine, Department of

Gulchekhra Narimova, Zamira Yusupovna, Ravshan Fayzullaev &

Radiology, Jacobi Medical Center, Bronx, New York, USA;⁵Department of

Iskandar Arifjanov

Psychological and Brain Sciences, University of Massachusetts, Amherst,

Republican Specialized Scientific and Practical Medical Center of

Massachusetts, USA.

Endocrinology Uzbekistan, Tashkent, Uzbekistan.

Context

Aim of the study

Primary aldosteronism (PA) is a common cause of secondary hypertension, and

To evaluate effectiveness of pituitary transsphenoidal surgery (TSS) in patients

some PA adrenal tumors co-secrete glucocorticoids, causing subclinical or overt

with ACTH-dependent Cushing’s syndrome

(ACTH-DCS) in Republic of

Cushing syndrome (CS). We recently reported correlations between hair cortisol

Uzbekistan (RUZ).

concentration (HCC) and serum and urinary levels of cortisol in patients with CS.

Materials and methods

Objective

Patients who included in CS register monitored in 2015. All data from 2000 to

To determine correlations of segmental hair cortisol and biochemical markers of a

2015 analyzed including outpatient, inpatient examines, tests and treatment. To

referred cohort of patients for the evaluation of PA and to compare to patients

present, 158 patients with ACTH-DCS registered and monitored. Of these 158

with normal cortisol secretion. This pilot study was conducted at the National

patients, 41 males (26%) and 117 females (74%). Mean age of patient varied from

Institutes of Health Clinical Center.

12 to 38 years old. Mean age was 26.38G3.4 and 27.58G3.4 years old for males

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

and females respectively. Duration of the condition varied from 4 months to 25

EP17

years. 73 patients who had TSS were evaluated in 1, 3, 6 and 12 months period of

Frequancy of diabetes and prediabetes in patients with adrenal

time and the every 3 months for the follow-up period. TSS was performed initially

incidentaloma without hormonal activity

in 73 patients and in ten patients it was carried out after medical treatment.

Elzbieta Bandurska-Stankiewicz, Katarzyna Myszka-Podgórska,

Results

Joanna Rutkowska & Wojciech Matuszewski

Of 158 patients, 86 patients (54%) had surgery including 73 cases who underwent

Endocrinology, Diabetology and Internal Diseases Clinic, University of

TSS. Pituitary surgery performed as a monotherapy in 32 patients (44%) and in 41

Warmia and Mazury in Olsztyn, Olsztyn, Poland.

cases

(56%) patients received combination therapy. Of

patients who

underwent TSS, in 60 cases (82%) patients had cured, while repeat surgery

performed in ten cases (13.7%). After repeat surgery all ten patients (13.7%) had

Aim of the study

remission, however, four of them relapsed in 15 months in average. After TSS

Estimation of the frequancy of diabetes and prediabetes in patients with adrenal

remission was achieved in 82% of patients who included 62 patients with

incidentaloma (AI) without hormonal activity.

microadenomas (84.9%) and 12 cases with macroadenimas (16.6%). After 3 years

Material and methods

of follow-up five patients (6.8%) who had total hypophisisectomy procedure

The study comprised patients with AI without hormonal activity, verified by CT.

developed no relapse, whereas of

patients

(84.9%) with selective

The hormonal function of adrenal glands was determined according to the

adenomectomy and of six patients (6.8%) who had hemihypophysisectomy

circadian rhythm of cortisol and/or dexametasone suppression test, ACTH,

recurrent disease observed in 5 (8.1%) and 1 (16.7%) cases respectively while

aldosterone, plasma renin activity, DHEAS, androstenedione,

17hydroxy

remission has not developed in 6 (9.7%) and 1 (16.7%) respectively (PZ0.03).

progesterone, metanephrines in urine.

Conclusion

Physical examination included: the BMI, the waist circumference (norm !80 cm

Of 73 patients with CS who had pituitary surgery, remission observed in 60

women, !94 cm men), blood pressure. The biochemical assays: fasting

patients (82%), whereas six patients (8.2%) relapsed and in seven cases (9.6%)

glycemia, OGTT (excluded patients with diabetes), fasting insulin and lipids

remission has not developed. TSS remains as first treatment choice in CS and

level (total, HDL and LDL cholesterol, triglycerides).

contributes to a steady remission in 82% according to our results.

Results

DOI: 10.1530/endoabs.49.EP15

125 patients were examined, aged 61.3G8.8 years, 72 (57.6%) women. Size of

tumors were 27.6 mm G15 mm. Carbohydrates disorders were observed in 62

(49.6%) persons aged 62.9G7.5 years, including 32 (25.6%) women. Abdominal

obesity was diagnosed in 87 (69.6%), 56 (44.8%) women and 31 (24.8%) men.

Diabetes was regonised in 16 (13%) patients, IFG in 24 (19.2%), IGT in 34

(27.6%). The concentration of fasting insulin was 8.9C/K5.5 mU/ml, higher in

men then in women

(9.16C/K5.65

8.71C/K4.70; PO0.01). The

concentration of total cholesterol was 218G49.7 mg/dl, HDL-cholesterol 59G

21.1 mg/dl, LDL cholesterol 134G44.1 mg/dl, triglycerides 116G60 mg/dl; 83

(66.6%) of the patients had been diagnosed positive for dyslipidemia or were

administered hypolipemic medications. Additionaly arterial hypertension was

diagnosed in 99 (79.2%) patients, with the arterial systolic BP 131G15 mmHg,

diastolic BP 80G9 mmHg.

EP16

Conclusions

1) Diabetes was observed more often in patients with AI without hormonal

Paraneoplastic Cushing’s syndrome and nephrotic syndrome in a

activity then in the entire Polish population.

patient with bronchial carcinoid

Patients with AI without hormonal activity are a risk group of prediabetes and

Daniel Grigorie^1,2, Andra Caragheorghopol², Carmen Iordachescu²,

diabetes.

Dan Hortopan², Ionela Pascanu³, Livia Hara⁴, Iulian Brezean¹,

Nicolae Galie¹, Florina Vasilescu⁵, Eugen Mandache⁶ & Alina Sucaliuc^1,2

DOI: 10.1530/endoabs.49.EP17

¹Carol Davila University of Medicine, Bucharest, Romania;²National

Institute of Endocrinology, Bucharest, Romania;³University of Medicine,

Targu Mures, Romania;⁴Matei Bals Hospital, Bucharest, Romania;⁵Central

Military Hospital, Bucharest, Romania;⁶Carol Davila Nephrology Hospital,

Bucharest, Romania.

Introduction

We report a case of Cushing’s syndrome association with nephrotic syndrome in a

EP18

patient with occult ectopic ACTH (EAS) secretion by a bronchial carcinoid and

To big to work! Lymphoma presenting with primary adrenal

resolution of both disorders after bilateral adrenalectomy.

insufficiency

Case report

Joel Capraro, Hanna Giessen & Beat Muller

A 42-year-old man was admitted to our department with the suspicion of EAS. He

Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau,

was in a very good health until several months ago when he developed suddenly

Aarau, Switzerland.

nephrotic syndrome, severe hypertension, severe hypokalemia, hyperglicemia

and rapidly progressive the full blown picture of severe hypercortisolism: severe

mental changes, muscle weakness, bruising, pigmented moon facies, no striae,

Background

distal muscular atrophy and weight loss. A renal biopsy showed podocyte foot

Primary adrenal lymphoma (PAL) is a rare cause of primary adrenal insufficiency

process effacement and no inflammation/sclerosis; renal function was normal.

(PAI). Most often patients present with unspecific symptoms. Bilateral adrenal

Serum cortisol was frankly elevated and variable (21-97 mg/dl), because of the

enlargement with signs and symptoms of PAI are clues, percutaneous biopsy after

heavy and variable proteinuria

(1.7-7.5 g/24 h), urinary free cortisol

having excluded pheochromocytoma in a situation of high suspicion is diagnostic.

37.071 nmol/24 h. Serum cortisol did not supress with both low -dose and

Most of PAL are highly malignant B-cell lymphomas with a bad prognosis.

high-dose dexamethasone and serum ACTH was high (238 pg/ml). A pituitary

Case

MRI was normal. Chest CT scan revealed a round subpleural nodule 8-9 mm in

A 71-year-old patient was sent for endocrine workup because of a 2-month history

the right lung. SRS (111-indium-pentetreotide) and 18-FDG-PET CT scans were

of intermittent dyspnea, thoracic discomfort, weight loss and abdominal pain. An

negative. Bilateral laparoscopic adrenalectomy was performed. Postoperative

ambulant CT scan to exclude pulmonary embolism showed bilateral adrenal

course was marked by sepsis and he was treated with antibiotics for three months.

enlargement (right 77!31!55 mm, left 63!38!41 mm, native 25-29HE),

All the sign and symptoms of hypercortisolism gradually disappeared but the

which were new compared to a CT scan done one year earlier. On clinical

pigmentation remained; surprisingly the resolution of the nephrotic syndrome was

examination, the patient was orthostatic and in an im-paired general condition. He

noted. One year later he was in good clinical condition with adrenal replacement

had hyperpigmented hand lines. Laboratory evaluation showed a slight

therapy. Chest CT scan confirmed the presence of a stable pulmonary nodule and

hyponatremia (131 mmol/), potassium in the upper normal range (4.2 mmol/l),

he underwent thoracic surgery. A bronchial typical carcinoid tumour with positive

pathologic ACTH-stimulation test (peak cortisol level: 153 nmol/l) and elevated

immunostaining for ACTH was diagnosed. Postoperative course was uneventful.

ACTH levels (231 ng/l, normal range !46 ng/l). Antibodies for 21-hydroxylase

Conclusion

were negative, as well as free metanephrines in plasma, aldosterone-renin ratio

This is a rare case of the association of severe occult EAS with nephrotic

was decreased (aldosterone 122 pmol/l, renin 39 mU/l). 17-hydroxyprogesterone

syndrome, which has been cured by the resolution of the severe hypercortisolism.

was low

(3.3 nmol/l, normal range

1.9-6.5 nmol/l). Quantiferon test was

DOI: 10.1530/endoabs.49.EP16

negative, and the CT scan did not raise suspicion for tuberculosis. We diagnosed

PAI and started substitution with hydrocortisone

(initial dose

50 mg/d) and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

fludrocortisone (0.1 mg/d). Histology of a CT-guided needle biopsy revealed

EP20

infiltration of a highly malignant B-cell lymphoma. The patient was sent for

Cofilin is a cAMP effector in mediating actin cytoskeleton reorgan-

oncological evaluation and start of chemotherapy with rituximab, cyclopho-

ization and steroidogenesis in mouse and human adrenocortical

sphamide, doxorubicin, vincristine and prednisone (R-CHOP).

tumor cells

Discussion

Rosa Catalano^1,2, Erika Peverelli^1,2, Elena Giardino^1,2,

PAL is a rare manifestation of primary extranodal lymphomas (1/3 of all lymph

Donatella Treppiedi^1,2, Valentina Morelli^1,2, Iacopo Chiodini^1,2,

node neoplasms, PAL!1% of all extranodal lymphomas). Only about 100 cases

Lorenzo Marcon^1,2, Cristina L Ronchi³, Jérôme Bertherat⁴,

are published in the literature worldwide. Conversely, secondary spreading of a

Felix Beuschlein⁵, Maura Arosio^1,2, Anna Spada^1,2 & Giovanna Mantovani.

lymphoma to the adrenals is quite common (in autopsy studies up to 25%). Other

¹Endocrine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore

reasons for bilateral adrenal enlargement are adrenal hyperplasia (any cause),

Policlinico;²Department of Clinical Sciences and Community Health,

metastasis of lung, breast and stomach

(O50% of metastasis), bilateral

University of Milan, Milan, Italy;³Department of Internal Medicine I,

pheochromocytoma, adrenal hemorrhage, adrenal involvement with granuloma-

Division of Endocrinology and Diabetes, University Hospital, University of

tous diseases, histicytosis and primary pigmented nodular adrenal dysplasia

Wuerzburg, Wuerzburg, Germany;⁴Institut Cochin, Inserm U1016, CNRS

(PPNAD). Symptoms of PAL are unspecific (asthenia, weight loss, vague

UMR8104, Descartes University, Department of Endocrinology, Reference

abdominal pain, fever). Diagnosis is made by percutaneous biopsy. In nearly 70%

Center for Rare Adrenal Diseases, Hôpital Cochin, Paris, France;

of cases PAL are bilateral, causing primary adrenal insufficiency. Average age of

⁵Medizinische Klinik und Poliklinik IV, Endocrine Research Unit,

affected patients is around

70 years. Most of PAL are diffuse large B-cell

Klinikum der Universitat Munchen, LMU, Munich, Germany.

lymphomas with BCL6 gene rearrangement and poor prognosis, as in our case.

Therapy consists of R-CHOP.

Conclusion

The cAMP signaling pathway plays a major role in the pathogenesis of cortisol-

Patients with bilateral adrenal enlargement and PAI need immediate replacement

producing adrenocortical adenomas (CPA). In adrenocortical cells cAMP induces

of glucocorticoid (including instructions about dosing in stressful situations) and

dramatic changes in cell morphology accompanied by actin cytoskeleton

mineralocorticoid hormones. While PAL is rare, it has a poor prognosis, thus

rearrangements that precede steroidogenesis, the causal relationship between

rapid induction of treatment is necessary.

these events being still undefined. In this study we investigated cAMP effects on

DOI: 10.1530/endoabs.49.EP18

cytoskeleton rearrangements and steroidogenic response in mouse (Y1) and

human adrenocortical tumor cells, focusing on the role of the actin-severing

protein cofilin, whose inactivation is regulated by phosphorylation on Ser3.

Moreover, we tested possible alterations in cofilin phosphorylation status and

expression in human CPA vs endocrine inactive adrenocortical adenomas (EIA).

We demonstrated that forskolin induced cell rounding and reduced phosphory-

lated (P)-cofilin/total cofilin ratio in Y1 (K52G16%, P!0.001) and primary

human CPA cells (K53G18%, P!0.05). Cofilin silencing in Y1 cells reduced

both forskolin-induced morphological changes (37G8% rounded cells vs 63G

7% in control cells, P!0.05) and progesterone production (1.3-fold increase in

EP19

silenced cells vs 1.8-fold in control cells, P!0.05), whereas transfection of wild

type or S3A (active) cofilin, but not S3D (inactive) cofilin, potentiated forskolin

Specificity of the posture test for subtyping of primary aldosteronism, a

effects on cell rounding (80G6% and 85G14% rounded cells, respectively, vs

10 year nationwide summary in Iceland

69G6% in control cells) and increased about threefold progesterone synthesis

Hrafnhildur Gunnarsdottir¹, Gudbjorg Jonsdottir^1,2, Jon Gudmundsson³,

with respect to control cells (P!0.05). Furthermore, cofilin dephosphorylation by

Gudjon Birgisson⁴ & Helga Sigurjonsdottir^1,5

Y27632, a selective inhibitor of ROCK, the kinase that phosphorylates cofilin,

¹Faculty of Medicine, University of Iceland, Reykjavik, Iceland;

potentiated forskolin induced cell rounding

(about

90% rounded cells) and

²Department of Internal Medicine, University of Iowa Hospitals and Clinics,

steroidogenesis (about twofold increase vs forskolin alone).

Iowa City, Iowa, USA;³Department of Radiology, Landspitali University

Finally, western blot analysis showed a reduced P-cofilin/total cofilin ratio and an

Hospital, Reykjavik, Iceland;⁴Department of Surgery, Landspitali

increased total cofilin expression in CPA vs EIA (P-cofilin/total cofilin ratio 0.76

University Hospital, Reykjavik, Iceland;⁵Department of Endocrinology,

and 2.44 respectively, P!0.05, total cofilin/GAPDH 1.20 and 0.54, respectively,

Landspitali University Hospital, Reykjavik, Iceland.

P!0.01).

Overall, these data identified cofilin as a mediator of cAMP effects on both

Introduction

morphological changes and steroidogenesis in mouse and human adrenocortical

The posture test (PT), developed to distinguish idiopathic adrenal hyperplasia

tumor cells.

(IAH) from aldosterone producing adenoma (APA), has been postulated as

DOI: 10.1530/endoabs.49.EP20

inaccurate. In

2007, standardized diagnostic methods, including PT for

subclassification, were introduced in Landspitali University Hospital (LUH),

housing the only endocrine department in Iceland. The aim of this study is to

review the results of PT performed in LUH in 2007-2016.

Methods

Charts for all patients R18 years old, diagnosed with primary aldosteronism (PA)

during 2007-2016 in LUH, were retrospectively reviewed. After screening,

verification of PA was made with saline infusion test. During PT, s-aldosterone,

EP21

s-renin and s-potassium were measured after a 10-h bed-rest and again after

Primary Aldosteronism in Iceland, nationwide results from 2012-2016

subsequent 4-h upright-position. If s-aldosterone increased by O50%, the test

Hrafnhildur Gunnarsdottir¹, Jon Gudmundsson², Gudjon Birgisson³ &

was considered positive. Thereafter, patients underwent a CT-scan and adrenal

Helga Sigurjonsdottir^1,4

venous sampling (AVS). Adrenalectomy was offered if PA was found unilateral

¹Faculty of Medicine, University of Iceland, Reykjavik, Iceland;²Depart-

by AVS.

ment of Radiology, Landspitali University Hospital, Reykjavik, Iceland;

Results

³Department of Surgery, Landspitali University Hospital, Reykjavik,

Out of 49 PA-patients undergoing PT during the period, 22 had unilateral disease

Iceland;⁴Department of Endocrinology, Landspitali University Hospital,

and 27 bilateral. The unilateral group (UG) consisted of 14 patients with APA and

Reykjavik, Iceland.

4 with IAH. Three are awaiting surgery and one histopathological examination

was inconclusive. Average increase of s-aldosterone during PT in the bilateral

group (BG) was 217G127%, significantly higher than 88G26% in the UG

Introduction

(PZ0.008). A greater proportion of the BG had a positive PT, 81% (22/27) versus

Primary aldosteronism

(PA) is an important, potentially curable cause of

55% (12/22) of the UG, PZ0.04. Positive predictive value of the PT with regards

hypertension (HT) with higher risk of cardiovascular events than essential HT. In

to bilateral disease was 0.65 (22/34), sensitivity 0.81 (22/27) and specificity 0.45

2007, a standardized PA work-up protocol was introduced in Landspitali

(10/22).

University Hospital (LUH), housing the only endocrine department in Iceland.

Conclusions

The aim of this study is to review characteristics, test results and histopathology

In this nationwide study we found the PT to have fairly high sensitivity but low

for patients diagnosed with PA in 2012-2016 in LUH.

specificity in subclassifying PA, supporting previous reports of inaccuracy.

Methods

Although the PT is not conclusive, it could be informative in addition to CT-scan

Charts for PA-patients aged R18, diagnosed in 2012-2016 in LUH, were

for treatment decision if a patient is unable to undergo AVS for practical reasons.

retrospectively reviewed. Screening was considered positive if s-aldosterone

DOI: 10.1530/endoabs.49.EP19

and/or 24-h urinary aldosterone excretion was increased and s-renin decreased.

Diagnosis was confirmed if s-aldosterone increased by O140 pmol/l on saline

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

infusion test (SIT) performed by a 4-hour intravenous infusion of isotonic saline,

EP23

500 ml/h. Thereafter, patients underwent a CT-scan and adrenal venous sampling

Bilateral adrenal incidentaloma: a diagnostical and therapeutical

(AVS) for distinguishing unilateral

(UD) from bilateral disease

(BD).

challenge

Adrenalectomy was offered if UD was diagnosed.

Ines Bilic-Curcic^1,2, Tatjana Bacun^1,2, Marija Tripolski² & Biljana Zulj²

Results

¹Faculty of Medicine, University J.J. Strossmayer, Osijek, Croatia;²Clinical

Thirty-six patients were diagnosed with PA during the period; 19 males and 17

Hospital Center, Osijek, Croatia.

females. All had s-aldosterone O300 pmol/l on morning screening and 12 had an

elevated 24-h urinary aldosterone (nZ23). Median (range) s-aldosterone after

SIT was 311 pmol/l (202-1715). By the end of 2016, 10 had a confirmed UD

Incidentally discovered adrenal masses (incidentalomas) present challenges both

(32%), 21 BD (68%) and 5 were awaiting AVS. Six out of 10 UD underwent

in diagnosis and management. The bilateral adrenal mass carries a risk of

adrenalectomy by the end of

2016

and all had a cortical adenoma on

hormone hypersecretion, but it could also present a metastasis from another

histopathological examination. CT-scan showed unilateral adrenal nodule in 15

primary carcinoma or be a part of genetic syndrome.

patients, 8 of whom had UD by AVS on that same side (positive predictive value

We report a 68 year old patient with bilateral adrenal incidentalomas (revealed

0.53).

accidentally on US, confirmed by abdominal CT in 2015.) left 29 mm, right

Conclusions

33 mm in diameter, radiological characteristics indicating adenoma. Initial

This study indicates that PA is an important cause of HT in Iceland with equal

diagnostical work up showed subclinical Cushing syndrome with osteoporosis

gender distribution. Bilateral hyperplasia proved to be a more frequent cause than

and arterial hypertension as part of clinical presentation. One year later,

cortical adenoma which is consistent with prior Icelandic results from 2007-2011.

abdominal CT showed significant enlargement of both adrenal masses (left

Interestingly, no-one was diagnosed with unilateral hyperplasia during the study

50 mm, right 45 mm), still adenomas according to CT characteristics, but post

period.

contrast imaging could not be performed due to chronic renal impairment. Her

DOI: 10.1530/endoabs.49.EP21

laboratory results were still consistent with subclinical Cushing syndrome, now

presenting with osteoporosis, hypertension and glucose impairment with no signs

of other excessive hormone secretion but now her chest x-Ray revealed a lesion in

her left lung 27 mm in diameter of unknown etiology (although she mentioned

lung tuberculosis in her youth). As she did not have any signs of metastatic

disease and her tumor markers were normal we decided to perform left

adrenalectomy to provide definite diagnosis. Histological finding confirmed

adrenal adenoma and hormone reevaluation showed possible excessive cortisol

secretion with osteoporosis, but now blood glucose was normal, and anti-

hypertensive agents were discontinued due to normal blood pressure. There was

no change in the size of the lung lesion on her chest X ray (6 months after) and no

signs of metastatic lesions. Thoracic CT and bronchoscopy are planned.

While the initial diagnostic approach is similar to the unilateral incidentaloma,

additional testing should be considered in the case of the bilateral adrenal mass

and as oppose to unilateral incindentalomas surgery remains the mainstay of

treatment in most cases.

EP22

DOI: 10.1530/endoabs.49.EP23

Cardiovascular risk factors do not play a role in the risk factor profile of

adrenal crisis

Marcus Quinkler¹, Robert D. Murray², Pinggao Zhang³, Pierre Zelissen⁴ &

Bertil Ekman⁵

¹Endocrinology in Charlottenburg, Berlin, Germany;²St James’s University

EP24

Hospital, Leeds, UK;³Shire, Lexington, MA, USA;⁴University Medical

Are we missing patients with primary aldosteronism (PA) if we require

Center Utrecht, Utrecht, The Netherlands;⁵Linkoping University, Linkop-

both elevated aldosterone: renin ratio (ARR) and elevated aldosterone

ing, Sweden.

levels?

Troy Puar, Joan Khoo & Meifen Zhang

Changi General Hospital, Singapore, Singapore.

Introduction

Adrenal crises (ACs) are life-threatening events in patients with primary (PAI) or

secondary (SAI) adrenal insufficiency, occurring w4-10 times per 100 patient-

Introduction

years. Major causes of ACs are infections, especially gastroenteritis and

Although the Endocrine Society guidelines recommend using aldosterone: renin

tonsillitis/laryngitis. Risk factors for ACs remain ill defined, but could include

ratio (ARR) to screen patients for primary aldosteronism (PA), whether to include

concomitant endocrine diseases (diabetes mellitus, premature ovarian failure) in

a cut-off for aldosterone levels remains controversial. In Singapore, most centres

PAI, diabetes insipidus in SAI, and concomitant non-endocrine diseases (obesity,

require both an ARR O550 (ng/dl)/(ng/ml per h) and aldosterone R15 ng/dl.

asthma, cancer, and cardiac and neurological diseases) in both groups.

However, it has been shown that patients with PA may have aldosterone

Design

levels!15 ng/dl, and also respond well to mineralocorticoid antagonists. We

We analysed data from the European Adrenal Insufficiency Registry (EU-AIR;

examined the prevalence of Asian patients with high ARR, and influence of

NCT01661387) with centres across Germany, the Netherlands, Sweden and the

including patients with unsuppressed aldosterone levels O5 ng/dl.

UK. Clinical and biochemical data at enrolment were compared for patients with

Methods

frequent (nR2) and infrequent ACs (n!2) in each AI subset; 1969 patients were

We determined the prevalence of patients with high ARR O550 (aldosterone,

included (727 PAI, 1172 SAI) in the current analysis. Patients with congenital

ng/dl; plasma renin activity, ng/ml per hr) in a multi-ethnic Asian population with

adrenal hyperplasia or tertiary AI were excluded.

hypertension being screened for PA in a single tertiary centre, and stratified them

Results

by aldosterone levels.

To November 2016, 27 patients with frequent ACs were identified (19 PAI, 8

Results

SAI). The number of adverse events/patient was significantly higher in the

A total of 786 patients were screened for PA from 2015-2016, with 219 of 786

frequent than the infrequent AC group in both subsets (PAI, 15.3G14.0 vs 3.9G

(27.8%) patients having a high ARR. Amongst these 219 patients with a high

6.5; SAI,

19.6G18.5 vs

2.2G4.3, respectively; PZ0.0024). Patients with

ARR, 68 of 219 (31.1%) had an aldosterone levels R15 ng/dl, 51 (23.3%) had

frequent ACs were more likely to be female (PAI, 78.9% vs 65.1%; SAI, 75.0%

aldosterone levels

10-14.9 ng/dl,

(27.4%) had an aldosterone levels

vs 47.9%), and less likely to have hypertension (PAI, 5.3% vs 21.0%; SAI, 25.0%

9.9 ng/dl, and 40 (18.3%) had aldosterone levels !5 ng/dl. When both ARRO

vs 34.4%), with a lower BMI (PAI, 24.2G4.7 vs 26.2G4.9 kg/m²; SAI, 26.0G

550 and aldosterone R15 ng/dl are required, only 68 of 786 (8.6%) patients will

5.7 vs 28.7G5.1 kg/m²). There were no differences in daily glucocorticoid dose,

proceed for confirmatory tests as per current practice. However, if all patients

frequency of diabetes mellitus, HbA1c levels, lipid profiles or use of statins.

with ARRO550 and unsuppressed aldosterone levels R5 ng/dl are included, then

Interestingly, disease duration was shorter in patients with frequent compared

179 of 786 (22.8%) of patients should be considered for the diagnosis of PA.

with infrequent ACs in PAI (12.8G13.2 vs 18.9G14.5 years), whereas the

Conclusion

opposite was true in SAI (15.6G12.3 vs 13.8G11.2 years).

Current practice of requiring a high aldosterone level in addition to a high ARR

Conclusions

may underdiagnose patients with PA. However, potential benefit of working-up

Data suggest that known cardiovascular risk factors appear not to feature in the

all patients with a high ARR has to be weighed against increased cost. A possible

AC risk profile.

alternative would be a trial of mineralocorticoid therapy in these patients.

DOI: 10.1530/endoabs.49.EP22

DOI: 10.1530/endoabs.49.EP24

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP25

in the Addison group than in ACC patients, both in baseline conditions

(PZ0.036) than following CRH (PZ0.041).

Severe hypoglycaemic ketoacidosis in a patient with adrenal crisis

In conclusion, measurement of salivary cortisol did not add useful information for

Azmi Mohammed, Giridhar Tarigopula, Paul Peter, Praveen Partha &

assessing AI in mitotane-treated ACC patients. Assessment of ACTH levels may be

Shafie Kamaruddin

of some aid, since levels that are not frankly elevated may herald over-replacement.

Darlington Memorial Hospital, Darlington, UK.

The observation of lower ACTH levels in ACC patients than in patients with

Addison, both in basal conditions and after CRH stimulation, suggests that

We present a case of a 26 years old female who was rushed to hospital with 4 days

mitotane may play an inhibitory effect on ACTH secretion at the pituitary level.

history of abdominal pain, vomiting and dizziness. She also had one episode of

However, an effect of high-dose cortisol replacement should not be ruled out.

diarrhoea. Further history revealed that she had lost 32 kilograms of weight over

DOI: 10.1530/endoabs.49.EP26

the last 18 months through diet and exercise. There were no signs suggestive of an

eating disorder.

On examination she was peripherally cold, tachycardic (117/min), hypotensive

(86/50 mmHg) and sweaty. Her Glasgow Coma Scale was 15. Her chest was clear

and she had mild epigastric tenderness. She was fluid resuscitated with 0.9%

sodium chloride. Blood test results: pH 7.01, pCO2 (3.2), pO2 (14.6), blood

EP27

glucose (2.1 mmol/l), HCO3 (12), Na (126), K (5.6), ketones (7.6 mmol/l), urea

Extra-gastrointestinal stromal tumor in the retroperitomeum which

15.1 mmol/l and creatinine (79) and CRP (76). 10% Dextrose infusion was started.

had difficulty in differential diagnosis with adrenal cancer

An adrenal crisis was suspected and she was commenced on IV hydrocortisone.

Naotetsu Kanamoto, Makiko Nagatsuji, Keiko Yamagami,

A possible trigger was thought to be gastroenteritis. Her serum cortisol was

Shinya Tokunaga & Masayuki Hosoi

13 mmol/l, no baseline ACTH was checked. She remained hypotensive despite

Osaka City General Hospital, Osaka, Japan.

aggressive fluids and was subsequently transferred to ITU. Over the next 24 hours

her blood pressure was maintained on inotropes however her acidosis was

Extra-gastrointestinal stromal tumors

(EGISTs) in the retroperitomeum are

refractory to treatment (pH!7.2 after 8 hours). She was started on sodium

extremely rare. A 44-year-old man was referred from a private clinic suspicious

bicarbonate 1.26%; however, the effect was not sustained as her pH continued to

of an adrenal tumor that was incidentally detected by abdominal ultrasound.

drop. Her ketones also remained high (5-6 mmol/l) despite a normal glucose

Computed tomography (CT) scan showed a retroperitoneal mass of

12 cm

(4-7 mmol/l). She was subsequently commenced on 5%Dextrose infusion to halt

harboring a feeding artery from the left adrenal gland contiguous with the left

ketogenesis. Her HbA1c was 35 mmol/mol. Following 5% Dextrose infusions, her

adrenal gland, which enhanced heterogeneously on post-contrast imaging. By

acidosis started to improve with normalisation of ketones. Learning points:

magnetic resonance imaging, the tumor demonstrated heterogeneous low intensity

1. Adrenal crisis should be treated promptly

in T₁ weighted images and an extremely heterogeneous lesion composed of high

2. Euglycaemic or hypoglycemic ketosis can complicate prolonged starvation,

and low signal intensity in T₂ weighted images. PET CT imaging with fluorine-

vomiting and eating disorders, so detailed and collateral history is important

18-fluorodeoxyglucose (¹⁸F-FDG) demonstrated¹⁸F-FDG accumulation in the

3. Although very rare, type 1 diabetes can be masked by adrenal insufficiency and

tumor in the early and late phase. Iodine-123-metaiodobenzylguanidine and iodine-

present with euglycemic ketoacidosis. It should be considered in similar scenarios.

131-adosterol scintigram did not detect any accumulation in the tumor. The results

DOI: 10.1530/endoabs.49.EP25

of all conducted serum and urinary examinations of adrenocortical hormone and

catecholamine were within the normal range. Adrenalectomy was performed.

Histopathological diagnosis of the tumor was GIST. Immunohistochemical findings

revealed that the neoplastic cells were positive for c-kit and CD34 and negative for

S100 protein, alpha-SMA, and desmin. Mitotic activity (2-3/50 high power field)

and the labeling index for MIB-1 (about 3.2%) were low. The GIST was diagnosed

EP26

as a high-risk tumor because its diameter was over 5 cm. We started imatinib

Assessment of the hypothalamic pituitary adrenal axis in patients

400 mg/day according to the Japan GIST guideline 1 month after operation.

receiving adjuvant mitotane treatment after radical resection of

DOI: 10.1530/endoabs.49.EP27

adrenocortical carcinoma

Giuseppe Reimondo¹, Soraya Puglisi², Barbara Zaggia¹, Vittoria Basile¹,

Laura Saba¹, Paola Perotti¹, Silvia De Francia³, Maria Chiara Zatelli⁴,

Salvatore Cannavo² & Massimo Terzolo¹

¹Internal Medicine 1, Department of Clinical and Biological Sciences,

University of Turin, Orbassano, Italy;²Endocrinology Unit, Department of

EP28

Clinical and Experimental Medicine, University of Messina, Messina, Italy;

Perceptions of medical practitioners’ management of addison’s disease

³Pharmacology, Department of Clinical and Biological Sciences, University

across Africa: an on-line survey

of Turin, Orbassano, Italy;⁴Section of Endocrinology and Internal

Ian Louis Ross¹, Thabiso RP Mofokeng², Fazleh Mahomed² &

Medicine, Department of Medical Sciences, University of Ferrara,

Salem Beshyah³

Ferrara, Italy.

¹University of Cape Town, Cape Town, South Africa;²University of the

Free State, Bloemfontein, South Africa;³Sheikh Khalifa Medical City,

Abu Dhabi, United Arab Emirates.

Mitotane, used in the treatment of adrenocortical cancer (ACC), is able to inhibit

multiple enzymatic steps of adrenocortical steroid biosynthesis, potentially

causing adrenal insufficiency (AI). Recent studies in vitro have also documented a

Objectives

direct inhibitory effect of mitotane at the pituitary level.

Addison’s disease diagnostic and management challenges in Africa are not well

The aim of the study was to assess the hypothalamic pituitary adrenal (HPA) axis

documented. We aimed to identify the specific needs of patients with established

in patients receiving mitotane as adjuvant treatment after radical resection of

Addison’s disease, across Africa.

ACC getting insights on how mitotane affects the HPA axis and looking for

Methods

markers to assessing AI.

An online survey of a large pool of medical practitioners was undertaken. The

We prospectively enrolled 16 patients on adjuvant treatment with mitotane after

questionnaire covered patient demographics, aetiology, therapy and limitations of

radical surgical removal of ACC, who were on stable mitotane dose and cortisol

diagnosis and treatment.

replacement therapy for at least 6 months and were disease free at the time of

Results

evaluation. Patients underwent standard hormone evaluation and stimulation test

Of the 36,203 recipients; 661 responded; 246 completed the questionnaire. 151

with h-CRH. A group of 10 patients with Addison’s disease served as controls for

were actively treating Addison’s disease. The total number of patients identified

the h-CRH test.

with Addison’s disease in this study was 1134 (530 males; 604 females). The

At the time of the study, six patients had mitotane levels within the therapeutic

highest number were reported from South Africa (748; 66%). Majority of patients

range, one had levels O20 mg/l, while nine had levels !14 mg/l. The median

were in the age groups of 16-60 years with a slight excess of females (334 vs 403).

dose of cortisone acetate was 62.5 mg daily. Basal serum cortisol was reduced in

Associations were reported with hypothyroidism in 15.3%, type 1 diabetes in

14 patients, being undetectable in 7 of them, and in the normal range in only two

11.6%, pernicious anaemia in 6.5%, premature ovarian insufficiency in 4.6% and

patients (12.5%); one of them had low mitotane concentrations. Only a non-

Graves’ disease in 3.0%. Presentation in crisis was reported in 12.1% of cases,

significant trend between mitotane dose and either serum or salivary cortisol was

otherwise classical symptoms were seen fairly consistently. Over 60% of patients

evident. We demonstrated a close correlation between CBG levels and plasma

received hydrocortisone only and the remainder received combination of

mitotane levels

(PZ0.003) and between serum cortisol levels and salivary

hydrocortisone and fludrocortisone. Fixed doses of steroid replacement were

cortisol levels (PZ0.005), while ACTH levels were inversely correlated with the

used by 35.3% of physicians, whereas 57.9% of respondents adjust doses on basis

daily dose of cortone acetate (PZ0.006). ACTH levels were significantly higher

of body weight. Appropriate diagnostic investigations, proved to be the greatest

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

limitation in making the diagnosis, with 73.2% of responders relying on the

aldosterone to renin ratio was compatible with diagnosis. A CT scan revealed a

combination of clinical grounds and compatible electrolytes alone and only 27.9%

right adrenal nodule suggestive of adenoma (21!19 mm). He was submitted to

having access to an ACTH stimulation test. There were few therapeutic options

laparoscopic unilateral adrenalectomy. Pathology confirmed an adrenal adenoma.

available to the responders outside of South Africa, with overall, 53% indicating

At discharge, all anti-hypertensive drugs were suspended.

non-availability of medication and 58% not having access to a CT scan.

3 weeks after surgery he complained of asthenia, anorexia and diarrhea. Blood

Conclusions

tests showed severe hyperkalaemia (7.8 meq/l), metabolic acidosis and acute renal

This first continent-wide survey highlighted some challenges in diagnosis and

failure (creatinine 4.2 mg/dl). The serum aldosterone was low (43 ng/dl) and renin

treatment of Addison’s disease. Awareness and resources are required for timely

(4.7 pg/ml) normal. We assume the diagnosis of hyporeninemic hypoaldosteron-

recognition and optimal management of Addison’s disease in Africa.

ism and he was treated with fludrocortisone (0.1 mg id), sodium bicarbonate and

DOI: 10.1530/endoabs.49.EP28

fluids, with improvement in serum creatinine and normalization of potassium

levels. 3 months after discharge he remained asymptomatic but fludrocortisone

dependent, with stable potassium and creatinine levels and mild hypertension.

Conclusion

Despite uncommon, hypoaldosteronism after unilateral adrenalectomy is known

to occur. Usually mild and transitory, it can also be severe, persistent and life-

EP29

threatening. Long term hypertension and impaired renal function, both present in

Improved metabolic outcomes for patients with subclinical Cushing’s

our patient, are associated with persistent disease. A close and regular follow-up

syndrome treated with surgery: Ten year experience in a tertiary centre

is essential for earlier detection, especially in high risk patients.

Lih Ming Loh, Du Soon Swee, Wei Lin Tay & Peng Chin Kek

DOI: 10.1530/endoabs.49.EP30

Department of Endocrinology, Singapore General Hospital, Singapore,

Singapore.

Introduction

Subclinical Cushing’s syndrome (SCS) occurs in up to 12% of patients with

EP31

incidentally found adrenal masses. Optimal management remains controversial.

The role of CYP11B2 polymorphism in the pathogenesis of

We report our experience of nine patients with SCS managed at our institution

hypertension in patients with adrenal incidentaloma

from 2007 to 2016.

Lukasz Zukowski^1,2, Natalia Wawrusiewicz-Kurylonek¹,

Methods

Janusz Mysliwiec² & Maria Gorska¹

All patients were referred for adrenal incidentalomas

(AI) and had no

¹Department of the Endocrinology, Diabetology and Internal Medicine,

discriminatory clinical features of Cushing’s syndrome. SCS was defined using

Medical University of Białystok, Poland;²Department of Nuclear Medicine,

cortisol levels O 138 nmol/l after overnight 1-mg dexamethasone suppression

Medical University of Białystok, Poland.

test and one additional abnormal biochemical test. ACTH was suppressed in all.

Urinary free cortisol measurements were normal in the majority.

Patients and results

Background

The median age of our patients was 53 years (range 36-63) and all but one were

Significant prevalence of hypertension in the world’s population and its

female. Mean size of the adenomas was 2.65C0.52 cm. Majority of our patients

consequences tend to an intensive search for pathogenesis and etiology of this

had metabolic comorbidities of overweight, hypertension, glucose intolerance or

disease. Epidemic of hypertension is accompanied by an epidemic of adrenal

diabetes and dyslipidemia. One patient initially followed up as a non-functioning

incidentaloma and grows in direct proportion to patients age. Polymorphism of

AI developed SCS over 8 years of surveillance as her adenoma grew. Another

aldosterone synthase (CYP11B2) in -344th region of promoter seems to have

patient had bilateral adrenal adenomas. All our patients underwent surgical

much in common with hypertension and adrenal incidentaloma.

resection. The patient with bilateral nodules underwent bilateral subtotal

Aim

adrenalectomy. All but one required a period of postoperative corticosteroid

The aim of this study was to assess what role may play CYP11B2 polymorphism

support. Following withdrawal of steroids, there was observable median weight

in the phenotype of hypertension with associated adrenal incidentaloma. In this study,

loss of 3.85 kg (0.5-10.7) compared to presurgical weight. Four patients had an

the analysis of alleles and genotypes focused on incidence of adrenal tumour and

improvement of their BMI category from overweight to normal. All six patients

impact on the number of antihypertensive medications required to proper control.

with hypertension had sustained improvement in their blood pressure: two

Subjects and methods

became normotensive and the remainder had reduction of doses of antihyperten-

Study was performed on 106

hypertensive patients with diagnosed adrenal

sives. However there was no change to glycemic and lipid status.

incidentaloma (HAI), on 44 hypertensive patients without adrenal incidentaloma

Conclusions

(HWAI) and on 63 healthy individuals forming control group. Groups matched to

In our small series of patients with SCS, surgical intervention resulted in

each other in terms of age, gender. Related patients and those who suffered from

improved metabolic outcomes. We therefore suggest that if patients are surgically

disease that may falsely affect the results were excluded. Severity of hypertension

fit, surgery should be considered for SCS.

was determined by number of antihypertensive medications used to control. The

DOI: 10.1530/endoabs.49.EP29

significance of differences between the groups was evaluated through chi-square

and Student’s t-test.

Results

TT genotype and T allel occurred significantly less frequently in HAI in comparison

with Control Group (respectively: PZ0.049; PZ0.04). Patients with TT genotype

needed more medication to control hypertension in comparison with CC genotype

EP30

(3,080 vs 2,361, PZ0.0439). Lack of significant differences between HWAI to the

Severe hypoaldosteronism after unilateral adrenalectomy for primary

rest groups.

hyperaldosteronism

Conclusions

Joa˜o Ananias Gonçalves1, Rui Barrros1, Betânia Ferreira1 &

Cláudia Amaral^1,2

† The presence of the C allele in the region of -344 aldosterone synthase

¹Hospital da Luz Arrábida, Vila Nova de Gaia, Portugal;²Centro Hospitalar

promoter predisposes to adrenal tumour, the TT genotype reduced that risk.

do Porto - Hospital de Santo António, Porto, Portugal.

† Hypertension in patients with CC genotype is less severe, regardless of its

phenotype.

Introduction

DOI: 10.1530/endoabs.49.EP31

Primary hyperaldosteronism is a known cause of arterial hypertension, classically

with hypokalaemia. About

30-40% of the cases are caused by unilateral

aldosterone-producing adenoma, and the recommended treatment is adrenalect-

omy. Hypoaldestoronism is an uncommon complication of unilateral adrena-

lectomy, but it can be life-threatening. We present a case of severe

hypoaldosteronism after unilateral adrenalectomy for the treatment of primary

EP32

aldosteronism.

Case presentation

Primary aldosteronism: more common than once thought:

A 66 years old male with long term hypertension on triple drug therapy, chronic

Two clinical cases

kidney disease and persistent hypokalaemia was diagnosed with primary

Nadine Monteiro, Eduarda Comenda, Joana Costa, Helena Vitorino,

hyperaldesteronism. He had increased aldosterone - 3426 pg/ml (normal 34.7-

Sofia Santos, Filipa Moleiro, Claúdia Jesus, Ana Afonso & Helena Cantante

275 pg/ml) and low renin - 4 uUI/l (normal 4.4-46.1 uUI/l). An elevated plasma

Lusiadas, Lisboa, Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction

EP34

Estimated prevalence of hypertension (HT) in Portugal is 42%. It is a major risk

The treatment with dual release hydrocortisone in patients with adrenal

factor for coronary heart disease and cerebrovascular disease, the leading

insufficiency: correlation between change of the evening cortisol

mortality cause in Portugal. Primary aldosteronism (PA) was once recognized as

exposure time profile and change in metabolic profile, depression status

rare cause of secondary hypertension and hypokalemia a condition present in all

and quality of life

cases. Nowadays, prevalence of this condition is about 10% in HT patients, being

Chiara Simeoli, Rosario Ferrigno, Claudia Pivonello, Renata

the commonest form of secondary HT. Secondary forms of HT should be

Simona Auriemma, Mariarosaria Negri, Gilda Di Gennaro,

excluded in young patients, severe increase in blood pressure, sudden onset or

Davide Iacuaniello, Maria Cristina De Martino, Annamaria Colao &

worsening of HT, poor blood pressure response to drugs and organ damage

Rosario Pivonello

disproportionate to the duration of hypertension.

Dipartimento Di Medicina Clinica E Chirurgia, Sezione Di Endocrinologia,

Case 1

Università Federico Ii Di Napoli, Naples, Italy.

A 69 years old female with a past medical history of HT for the last 20 years,

presented with poor blood pressure control on bisoprolol 10 mg id perindopril

10 mg id and nifedipine 30 mg ER id at outpatient department. She had normal

Conventional glucocorticoids (CGCs) are unable to mimic physiological cortisol

electrolytes. Screening tests for PA revealed high plasmatic aldosterone and

rhythm in adrenal insufficiency (AI), resulting in increased metabolic morbidity

suppressed renin plasmatic activity with a ratioO25 ng/ml per h. Diagnosis was

and impaired quality of life

(QoL). Non-physiological cortisol pattern and

confirmed after saline infusion test. CT adrenal scan suggested left adrenal diffuse

elevated evening cortisol levels may be responsible for the increased risk of

hyperplasia.

metabolic disorders observed in AI patients under CGCs. Once daily dual-release-

Case 2

hydrocortisone (DR-HC), which better reproduces physiological daily cortisol

A 48 years old female presented at the emergency room complaining of severe

profile, significantly improves metabolic parameters and QoL in primary AI (PAI)

headache and four limbs’ muscle weakness. There was a past medical history of

and secondary AI (SAI) patients. The aim of the current study was to evaluate

eclampsia and hypertension diagnosed at the age of

30, and euthyroid

cortisol profile and its impact on metabolism, depression status and QoL in PAI

multinodular goiter. Labs revealed hypokalemia and she was started on oral

and SAI patients switched from CGCs, including cortisone acetate and

KCl 600 mg bid. After electrolytes correction, she was screened for PA. High

immediate-release hydrocortisone, to DR-HC. Fourteen AI patients underwent

plasmatic aldosterone and low renin plasmatic concentration with a ratioO3.8

daily cortisol sampling, at 3 h intervals, at baseline (CGCS treatment) and 12

was detected. Diagnosis was confirmed after saline infusion test.

months after switching to DR-HC. Mean cortisol (24 h, 7-7am) AUC was 15.61%

Conclusion

lower with DR-HC than with CGCs. In particular, mean (7am-1pm) and (1-7am)

PA is an important cause of secondary hypertension, with a higher cardiovascular

were 15.61% and 2.1% higher whereas mean (1-7pm), (7pm-1am) and (7pm-

event rate than essential hypertension. It is frequently underdiagnosed and a

7am) AUC were 18.8% (PZ0.057), 58.39% (P!0.001) and 41.87% (PZ0.004)

potentially curable form of hypertension.

lower with DR-HC than with CGCs, respectively. After 12 months of treatment,

DR-HC induced a significant improvement in waist circumference (PZ0.002),

DOI: 10.1530/endoabs.49.EP32

depression status (PZ0.05) and QoL (PZ0.05). Moreover, the change (D) in

cortisol 7pm-1am and 7pm-7am AUC appeared significantly correlated with the

change (D) in glucose 120’ after load (P!0.005), depression score (P!0.05) and

QoL score (P!0.05). The change (D) in cortisol 7pm-1am AUC appeared also

significantly correlated with the change (D in fasting insulin (PZ0.045) and

HOMA index (PZ0.045). In conclusion, the switch from CGCs to DR-HC in AI

EP33

patients induces a significant improvement of waist circumference, depression

Rapid reduction in left ventricular mass in primary aldosteronism after

status and QoL, and a significant decrease of late afternoon, evening and night GC

treatment; a prospective cardiac MRI study

overexposure; this reduction is significantly correlated with the improvement in

Marianne Aardal Grytaas^1,2, Kjersti Sellevåg¹, Hrafnkell

metabolic profile, depression status and QoL.

Baldur Thordarson^1,2, Eystein Sverre Husebye^2,1, Kristian Løvås^1,2 &

DOI: 10.1530/endoabs.49.EP34

Terje Hjalmar Larsen^1,2

¹Haukeland University Hospital, Bergen, Norway;²University of Bergen,

Bergen, Norway.

Background

EP35

Primary aldosteronism (PA) patients have increased left ventricular mass (LVM)

and increased cardiovascular morbidity compared with those with essential

Treatment of adrenal insufficiency with hydrocortisone dual-release

hypertension. Echocardiographic studies have demonstrated that adrenalectomy

formulation: glycometabolic profile and health-related quality of life

or spironolactone decreases LVM. The aim of the present study was to use MRI to

Laura Maria Mongioì, Rosita Angela Condorelli, Laura Cimino,

Sandro La Vignera & Aldo Eugenio Calogero

assess both LVM and cardiac function before and during stress testing, at baseline

Unit of Andrology and Endocrinology, Department of Clinical and

and after treatment with adrenalectomy or spironolactone, compared with healthy

Experimental Medicine, University of Catania, Catania, Sicily, Italy.

subjects (HS).

Material and methods

Fifteen recently diagnosed PA patients and

24 age- and sex-matched HS

Introduction

performed a baseline cardiac MRI with a 3.0 Tesla scanner. Imaging was

Treatment of adrenal insufficiency (AI) in the last years has been object of

performed at rest and during stress-testing with adenosine 140 mg/kg per min.

important changes due to the development of a dual-release preparation of

Short-axis images were used for quantifications of LVM and left ventricular

hydrocortisone (Plenadrenw). Hydrocortisone dual-release therapy contemplates

volumes. A follow-up MRI was performed in 20 of the HS and 14 of the PA

a once-daily tablet that allows more closely mimicking the physiological

patients, at least one year after starting specific treatment.

circadian rhythm cortisol, thus avoiding overexposure.

Results

Objective

Nine patients (60%) had unilateral PA, the remaining bilateral (nZ5, 33%) or not

The aim of the study was to value effects of Plenadren administration on the 24-h

representative (nZ1, 7%) adrenal vein sampling. The PA and HS did not differ in

urinary free cortisol (UFC), the glycometabolic profile and health-related quality

age or sex. PA patients had higher baseline blood pressure (BP) than the HS

of life of patients with AI.

(median BP

138/90

118/75, P!0.001). At follow-up,

8/14

PA were

Methods and materials

adrenalectomized (median 18 months). The remaining 6/14 were on spirono-

We enrolled seven adults with secondary AI caused by panhypopituitarism

lactone (median 21 months). LVM at baseline differed significantly between the

(55.9G3.6 years) and seven adults with primary AI

(36G6.2 years). We

PA and HS groups (median 145 vs 97 g; P!0.001). At follow-up, the PA group

evaluated BMI, UFC levels, the glycometabolic profile and health-related quality

had a significant reduction in LVM (median -18 g, P!0.001), but no difference in

of life (estimated by AddiQol questionnaire) before and 3, 6, 9 and 12 months

cardiac output (CO) response to stress compared with baseline (follow-up PA

after Plenadren administration. One patient dropped out the study for personal

median stress CO/rest CO 1.4 vs baseline 1.5, PZns).

reasons.

Conclusion

Results

Cardiac MRI showed rapid reduction in LVM in PA after treatment with

All patients, except one, reported a significant improvement of the quality of life

adrenalectomy or spironolactone. CO response to stress remained unchanged after

after 3 months of treatment, whereas after 1 year everyone reported individual

treatment. Our results underline the importance of early diagnosis and treatment

wellness. After 12 months of treatment, all parameters evaluated improved,

of PA.

though not in statistically significantly manner. The parameters for which there

DOI: 10.1530/endoabs.49.EP33

was evidence of a greater improvement were total cholesterol, low-density

cholesterol and glycosylated hemoglobin levels.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

Transduction of HAC15

cells with shRNA for Vsnl1

that reduced Vsnl1

The once-daily oral hydrocortisone dual-release therapy is a valid option for the

expression decreased their basal and A-II stimulated aldosterone synthesis. The

treatment of patients with AI. It allows a good glycometabolic balance in the

Vsnl1 has a myristoylation consensus sequence at the N-terminal domain. Site

absence of side effects and improving compliance.

directed mutagenesis of Vsnl1 at the 2 position (G2A) lentivirus transduced in

DOI: 10.1530/endoabs.49.EP35

HAC15 cells resulted in a significant decrease in the aldosterone response to A-II.

In summary, the Vsnl1 is a zona glomerulosa protein that participates in calcium

mobilization and increases the various secretagogue-induced aldosterone synthesis.

DOI: 10.1530/endoabs.49.EP37

EP36

Transformation from Addison’s disease to adrenocortical carcinoma

presented as Cushing’s syndrome with androgenisation

Antonela Sabati Rajic, Kristina Groti Resman, Tomaž Kocjan &

EP38

Marija Pfeifer

Metabolic syndrome is common among patients with adrenal

Department of Endocrinology, University Medical Centre Ljubljana,

incidentalomas, but not associated with functional adrenal status

Ljubljana, Slovenia.

Charalampos Tsentidis, Andreas Bampilis, Vasiliki Ntova, Grigoria Betsi &

Georgia Kassi

Department of Endocrinology, Metabolism and Diabetes, Nikaia General

We present a female patient 56 years old, who was treated at the endocrinology

Hospital ‘Ag. Panteleimon’, Athens, Greece.

department from the year

2006. The diagnosis of Addison’s disease was

established and she was properly treated. At the same time primary

hypothyroidism was diagnosed, also started treating it properly. She was

Background

regularly controlled more often at the first time, than yearly at outpatient clinic. In

Adrenal incidentalomas (AI) have an increasing prevalence during last decades,

September 2015 she was in menopause. A few months before she noticed

probably due to the extended use of new imaging techniques and longer life

oedematous legs and arms and diffuse bruising. Hypertension was also noticed for

expectancy. Adrenal hormonal hypersecretion, even subclinical, is probably

the first time and needed therapy. Her voice was different (became deep), she

related to cardiovascular disease (CVD).

noticed hair loss and hirsutism, as well. She thought it was all in correlation with

Methods

menopause. At the control examination she had hypokalemia, hypernatremia,

We evaluated 100 patients with adrenal masses, incidentally discovered in

hypertension, osteopenia with clear clinical aspect of Cushing. The abdominal

imaging techniques performed for non adrenal disorders (67 Female, 33 Male,

ultrasound, CT scan and FDG-PET scan showed huge (13.8 cm in diameter)

mean 58.1G12.9 years, median 60.5y), according to NIH criteria of 2002 and

heterogeneous tumour mass in the right adrenal gland. The tumour infiltrates

ESE 2016. IDF 2006 criteria were used for metabolic syndrome (MS) definition.

inferior vena cava and liver. Pelvic bone metastases were diagnosed also. CT

Results

angiography showed tumour thrombus and pulmonary embolism. Tumour biopsy

Mean incidentaloma size was 35.5G20 mm. 20% were bilateral, while 41% were

showed adrenocortical carcinoma. The hormonal tests showed co-secretion of

located to the right and 39% to the left adrenal. The majority (70%) was found to

cortisol and androgens (Cushing’s syndrome and androgenisation). Tumour was

be non functional and 30% to be functional. Autonomous cortisol secretion (ACS)

inoperable so tumour arterial embolisation was performed with idea of debulking.

was found in 15%, pheochromocytoma (Ph) in 7% and hyperaldosteronism (HA)

The patient was treated with mitotane in combination with systemic

in 8% of all cases. Non functioning lesions were defined as non functioning

chemotherapy (EDP regiment: etoposide, doxorubicin), antiandrogen therapy

adenomas (62%), non malignant cysts (2%), myelolipomas (2%), metastases

per os and metirapon. Because of the important hepatotoxicity mitotane was

(1%) and bilateral teratoma (1%). MS prevalence was higher in study group

discontinued soon. She needed also hydrocortisone supplementation transitory,

compared with general population (65% vs 23%, P!0.001). There was no

for the short time. The patient died due to the disease progression after one year.

difference in MS prevalence between patients with functional and non functional

DOI: 10.1530/endoabs.49.EP36

tumors (63.3% vs 64.7%, PZ0.53), while no difference was found between

functional tumors (ACS60% vs Ph57% vs HA75%, PZ0.78). Hypertension had

the greatest proportion in cases with hyperaldosteronism, while no difference in

central obesity, hyperlipidemia and abnormal glucose metabolism was found

between functional tumors.

EP37

Conclusions

Visinin-Like Protein-1 in the regulation of aldosterone biosynthesis

The prevalence of metabolic syndrome was found to be high in patients with AI.

Celso Gomez-Sanchez¹, Maniselvan Kuppusamy¹, Jeanne Ishimwe¹,

A common pathophysiologic pathway (probably hyperinsulinaemia) must be the

Tracy Williams², Paolo Mulatero² & Elise Gomez-Sanchez¹

underlying mechanism between AI and MS, associated with an increased risk for

¹University of Mississippi Med Center, Jackson, MS, USA;²University of

CVD.

Turin, Turin, Italy.

DOI: 10.1530/endoabs.49.EP38

Visinin-Like Protein-1 (Vsnl1) is a member of the EF-hand calcium sensor

protein family that is expressed in the zona glomerulosa of the rat and human

adrenal and upregulated in aldosterone-producing adenomas.

We studied the expression pattern of Vsnl1

and co-localization with the

EP39

CYP11B2 enzyme and the zona glomerulosa (ZG) marker Dlk1 (ZOG) using

The clinical course of patients with adrenal incidentaloma: Ba¸kent

double and triple immunofluorescence in the adrenal of rats on a normal, high and

University experience

low sodium diets. We also studied the role Vsnl1 in aldosterone biosynthesis and

Nazli Gulsoy Kirnap¹, Ozlem Turhan Iyidir¹, Yusuf Bozkus¹,

calcium in the HAC15 cell.

Lala Ramazanova¹, Asli Nar¹, Altug Kut² & Neslihan Tutuncu¹

In the rat adrenal, Vsnl1 was expressed only in cells of the ZG and in cells

¹Department of Endocrinology, Baskent University Hospital, Ankara,

expressing Dlk1, including undifferentiated cells between the ZG and zona

Turkey;²Department of Family Medicine, Baskent University Hospital,

fasciculata. Nearly all of the ZG cells from adrenals of rats on a low sodium diet

Ankara, Turkey.

expressed both Vsnl1 and CYP11B2. However in adrenals of rats on a normal and

high sodium diet the staining for Vsnl1 was in many more ZG cells than those

expressing CYP11B2. Vsnl1 and Dlk1 immunoreactivity was found not only cells

The prevalance of incidentally discovered adrenal masses increased in last three

that are steroidogenically active and producing aldosterone, but also in ZG and

decades. The major clinical concern is the risk of malignancy and hormone

undifferentiated cells in the rat adrenal subcapsular area.

overproduction but most of them are non-fonctional and benign. Current practices

Human adrenal cortical carcinoma cell line HAC15 was transduced with a

in the management of adrenal incidentalomas reevaluated the follow-up

lentivirus carrying Vsnl1. Three days after transduction cells were incubated with

suggestions considering low probability of the transformation of a benign and

vehicle, angiotensin II (A-II) 10 nM, Forskolin 10 mM and potassium 16 mM and

non-functional adrenal mass to a malignant or functional one. Therefore, in the

compared with control cells transduced with an empty lentivirus. Aldosterone and

present study we analysed the clinical course of patients with adrenal

cortisol were measured after 24 h. The basal secretion of aldosterone was not

incidentaloma. We evaluated

203

consecutive patients

(139

females,

increased, but that of cortisol was. Aldosterone and cortisol secretion were greater

males:mean age 55.8G0.8 years) who were referred to the Department of

after A-II, forskolin and potassium stimulation in cells overexpressing Vsnl1.

Endocrinology, Ba¸kent University Hospital, between January 2007 and 2017.

Proliferation of the HAC15 cells measured by the XXT and crystal violet methods

Among the 203 patients examined 171 had unilateral, 32 had bilateral adrenal

and intracellular calcium, as measured by the Fluo-4 AM dye, were also increased

masses. Mean size of tumors was 22.7G10.8 mm. In 157 (%77.3) patients’

after transduction with Vsnl1.

adrenal mass was benign and non-functional, 21 (%10.3) had autonomous cortisol

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

secretion, 9 (%4,4) had Cushing syndrome, 5(%2.5) had pheochromocytoma, 9

Introduction

(%4,4) had primary hyperaldosteronism and,

2(%1) had adrenocortical

Pheochromocytomas are rare tumors arising from adrenomedullary chromaffin

carcinoma. Twentyone patients went adrenelectomy. Median follow up time

cells. Pheochromocytomas are a serious clinical condition and undiagnosed cases

was 3 (1-10) years. During the follow up the change in the size of adrenal mass

are associated with increased unexpected cardiovascular mortality.

was non significant (PZ0.12) and there were no changes either in metanephrines

Case report

and normetanephrines or in the activity of renin-aldosterone axis. There was a

A female Caucasian patient aged 52-year-old was referred to the endocrine

significant correlation between adenom size and cortisol levels after dexametha-

department of a public central hospital because of an incidental right adrenal mass

sone supression test in patients with autonomous cortisol secretion. As a result our

first found 3 years before during the work out of non specific tiredness. Annual CT

study suggests that the risk of an adrenal adenoma initially diagnosed as benign or

CT scans documented significant growth (34, 40 and 62 mm) of a hypodense

non-functional becoming malignant or hormonally active is low.

lesion (less than 10 Housefield units). Presently the patient denied gastrointestinal

DOI: 10.1530/endoabs.49.EP39

or abdominal complaints and did not present clinical evidence for hypercorti-

solism, hyperaldosteronism, hyperandrogenism or for excessive catecolamine

production. Past medical history revealed chronic gastritis treated with

omeprazole daily. She reported three uneventful pregnancies 25, 20 and 19

years ago. Physical examination was unremarkable, with normal blood pressure

and no orthostatic hypotension. Analytic evaluation excluded hypercortisolism

EP40

and hyperaldosteronism. Urinary metanephrine and normetanephrine were high

Predictive baseline morning P-cortisol levels for the response to a

(12 and 16 times higher than the upper limit of the reference range) and dopamine

Synacthen test in prednisolone treated patients

1.5 times over the upper limit. Serum calcium and calcitonin were in the reference

Stina Willemoes Borresen¹, Marianne Klose¹, Henning Locht³,

range.

¹²³I-MIBG scintigraphy presented increased right adrenal uptake.

Toke Laursen³, Bente Jensen³, Linda Hilsted⁶, Bo Baslund²,

˚se

Uneventful laparoscopic right adrenalectomy was performed after preoperative

Krogh Rasmussen¹, Lennart Friis-Hansen⁷, Annette Hansen⁴, Merete

treatment with doxazosin 8 mg, 2 l normal saline ev and propranolol 30 mg daily.

Lund Hetland⁵ & Ulla Feldt-Rasmussen¹

Histologic evaluation confirmed a 55 mm pheochromocitoma, with no signs of

¹Department of Medical Endocrinology, Copenhagen University Hospital,

malignancy. No genetic study was conducted.

Rigshospitalet, Copenhagen, Denmark;²Center of Rheumatology and Joint

Discussion and conclusion

Diseases, Copenhagen University Hospital, Rigshospitalet Blegdamsvej,

About 7% of adrenal incidentalomas are pheochromocytomas. Although rare,

Copenhagen, Denmark;³Center of Rheumatology and Joint Diseases,

clinically silent pheocromocytomas are recognized. Possible mechanisms may

Copenhagen University Hospital, Frederiksberg Hospital, Frederiksberg,

include

1) vasodilator peptides co-secreted by pheochromocytomas such as

Denmark;⁴Center of Rheumatology and Joint Diseases, Copenhagen

dopamine; 2) desensitization of target organs due to high catecholamine long-

University Hospital, Gentofte Hospital, Gentofte, Denmark;⁵Center of

term exposure, 3) low circulatory volume in these patients and 4) malignancy with

Rheumatology and Joint Diseases, Copenhagen University Hospital,

undifferentiation and minimal catecholamine production. This case highlights the

Rigshospitalet Glostrup, Glostrup, Denmark;⁶Department of Clinical

need to exclude catecholamine producing tumors in all adrenal incidentalomas,

Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenha-

even if they are asymptomatic.

gen, Denmark;⁷Department of Clinical Biochemistry, Copenhagen

DOI: 10.1530/endoabs.49.EP41

University Hospital, Nordsjællands Hospital Hillerød, Hillerød, Denmark.

Introduction

Evaluation of glucocorticoid production generally requires a dynamic test. Cut-

off levels for baseline cortisol concentrations predicting the outcome of a

Synacthen test have been proposed for different cortisol assays. With introduction

of the new Roche Elecsys Cortisol II assay, P-cortisol concentrations are expected

to decrease by 20%. We have investigated cut-off levels for baseline P-cortisol

concentrations measured with the Roche Elecsys Cortisol II assay that could

EP42

predict the response to a Synacthen test in patients at risk of glucocorticoid-

induced adrenal insufficiency.

LH and adrenal tumor size correlate with insulin resistance in

Methods

menopausal patients with adrenal incidentalomas and (possible)

In a cross-sectional study, 110 prednisolone treated rheumatologic patients had a

autonomous cortisol secretion

250 mg Synacthen test performed, fasting, in the morning, starting between 0800

Ljiljana Marina^1,2, Miomira Ivovic^1,2, Milina Tancic-Gajic^1,2,

and 1030 h, 36-48 h after the last prednisolone dose. P-cortisol was measured

Zorana Arizanovic¹, Dragana Rakovic¹, Jelena Milin-Lazovic^1,2,

before and 30 min after Synacthen injection. The locally validated assay specific

Aleksandra Kendereski^1,2, Dragan Micic^1,2, Srdjan Pandurevic² &

cut-off for normal adrenal function was 30 min P-cortisol R420 nmol/l.

Svetlana Vujovic^1,2

Results

¹Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical

Forty-six patients

(42%) had an insufficient response to the Synacthen test.

Centre of Serbia, Belgrade, Serbia;²Faculty of Medicine, University of

Baseline and

30 min P-cortisol correlated positively

(P!0.0001, rZ0.86).

Belgrade, Belgrade, Serbia;³Institute of Medical Statistics and Informatics,

Receiver-operator curve analysis showed an area under the curve of 0.94 (95%

Belgrade, Serbia.

CI: 0.90-0.98). All patients with baseline P-cortisol !139 nmol/l also failed the

Synacthen test (positive predictive valueZ100%). All patients with baseline

High prevalence of insulin resistance (IR) has been shown in patients with adrenal

P-cortisol O310 nmol/l had a normal response to the Synacthen test (negative

incidentalomas (AI) and it has been demonstrated that an increase in IR is related

predictive value Z100%). Applying these cut-off values baseline P-cortisol

to the adrenal tumor size (ATS). Also, responsive adrenal pathologies are well

measurements predicted the response to the Synacthen test in 58/110 (53%) of

documented in patients with chronically elevated LH. The aim was to investigate

cases; P-cortisol O310 nmol/l (33%); P-cortisol !139 nmol/l (20%).

the association between LH and IR and ATS and IR in AI patients. The case-

Conclusion

control study was conducted in Clinic for endocrinology, diabetes and metabolic

We have presented assay specific baseline P-cortisol concentrations that could

diseases, Belgrade, Serbia. The total studied group consisted of 105 menopausal

predict the response to a Synacthen test in half of patients at risk of

women: 75 AI patients (mean age 60.13G7.28 years, mean BMI 27.60G

glucocorticoid-induced adrenal insufficiency and potentially reduce the number

4.66 kg/m², mean menopause duration 10.86G7.79 years, mean LH 31.82G

of needed Synacthen tests in the worldwide many glucocorticoid treated patients.

14.17 IU/l and mean ATS 31.25G10.72 mm) and 30 age, BMI, menopause

Baseline morning cortisol measurements might become a valid diagnostic

duration and LH matched healthy control (HC) women. Based on level of cortisol

screening tool in the future.

after

1 mg-dexamethasone suppression test AI patients were divided in two

DOI: 10.1530/endoabs.49.EP40

groups: !50 nmol/L, 27 with nonfunctional AI (NAI) and O50 mmol/l, 48 with

(possible) autonomous cortisol secretion ((P)ACS). To estimate IR we used

homeostasis model assessment (HOMA-IR). There was no significant difference

between AI subgroups in terms of age, BMI, menopause duration, LH and

HOMA-IR. HC subjects had significantly lower HOMA-IR when compared to

EP41

NAI (PZ0.017). There was a significant positive correlation between LH and

HOMA-IR in AI group (rZ0.230; PZ0.047) and in (P)ACS subgroup (rZ0.353;

Silent pheochromocitoma - a rare case of adrenal incidentaloma

PZ0.017), but not in patients with NAI (rZK0.097, PZ0.623). The correlation

Ana Filipa Martins¹, Sónia do Vale^1,2 & João Martin Martins^1,2

of ATS and HOMA-IR was significant in AI group (rZ0.341; PZ0.003) and both

¹Hospital de Santa Maria-CHLN, Lisboa, Portugal;²Faculdade de Medicina

NAI (PZ0.018, rZ0.445) and (P)ACS (PZ0.012, rZ0.362). After adjusting

de Lisboa, Lisboa, Portugal.

for age and BMI both LH and ATS were significant predictors of HOMA-IR,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

(r²Z0.196, PZ0.004). There was no significant correlation between LH and

Methods

HOMA-IR in HC. Our data suggest that not only insulin, but also the interplay

Three group of subjects were studied: healthy volunteers, suspected CS and

between LH and insulin may contribute to the adrenal tumorigenesis.

proven CS. All patients collected saliva at 23.00 h using a Salivette. Salivary

DOI: 10.1530/endoabs.49.EP42

Cortisol was measured using an automated electrochemiluminescence assay -

Elecsys 2010-Roche. The functional sensitivity of the assays is 0.018 mg/dl.

Diagnostic cut-off level was defined by Receiver operating characteristic (ROC)

curve and Youden’s J index.

Results

We studied 127 subjects: 57 healthy volunteers, 39 patients with suspected CS

and 31 with proven CS (ACTH-dependent: 22 pituitary, two ectopic; ACTH-

independent: two adrenal adenoma, five adrenal carcinoma).

EP43

The 2.5th-97.5th percentile of the LNSC concentrations in normal subjects was

A case of recurrent Cushing’s disease after total bilateral

0.054-0.1827 mg/dl, respectively. The meanGS.D. LNSC concentration in

adrenalectomy

patients with proven CS (0.6798G0.52 mg/dl) was significantly higher than

Ivan Vicic¹, Ivan Kruljac², Miroslav Cacic², Bozidar Peric²,

those in normal subjects (0.0642G0.03 mg/dl; P!0.0001) and suspected CS

Maja Filipovic-Grcic², Gorana Mirosevic², Vatroslav Cerina³,

group (0.1803G0.19 mg/dl; P!0.0001).

Leo Pazanin⁴ & Milan Vrkljan²

ROC curve analysis showed an AUC of 0.9881 (P!0.0001) and a cut-off point of

¹University of Zagreb School of Medicine, Zagreb, Croatia;²Department of

0.1 mg/dl provides a sensibility

(S) of

96.77% (95%CI 83.3-99.92%) and

Endocrinology, Diabetes and Metabolic Diseases ‘Mladen Sekso’,

specificity (E) of 91.23% (95%CI 80.7-97.09%).

University Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia;

There were significant correlations between LNSC and late-night serum cortisol

³Department of Neurosurgery, University Hospital Center ‘Sestre Milosrd-

(LNSeC) levels (rZ0.6977; P!0.0001) as well as with Urinary Free Cortisol

nice’, Zagreb, Croatia;⁴Department of Pathology ‘Ljudevit Jurak‘,

(UFC) levels (rZ0.5404; P 0.0025) in proven CS group.

University Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia.

Conclusion

Our results give to LNSC an excellent accuracy and reaffirm that can be used as a

Bilateral adrenalectomy usually results in lifelong primary adrenal insufficiency.

highly reliable noninvasive screening tool for outpatient assessment. In our

Evidence exists that up to 34% of patients with Cushing’s disease (CD) have some

population, the LNSC reference cut-off was 0.1 mg/dl with S 96.77% and E

degree of endogenous cortisol secretion after bilateral adrenalectomy due to

91.23% for CS diagnosis. Given its convenience and diagnostic accuracy, LNSC

ACTH driven hyperplasia of residual cortical tissue. We present a case of a

may profitably be added to traditional screening tests such as LNSeC and UFC.

patient with atypical corticotropinoma/carcinoma and recurrence of CD after

DOI: 10.1530/endoabs.49.EP44

bilateral adrenalectomy.

A 59-year-old man presented with Cushing’s disease (CD) in 2010. An MRI

revealed intrasellar mass 8!8 mm suggestive of a microadenoma. After the

surgery pathohistological evaluation was suggestive of atypical corticotropinoma

(Ki-67 proliferation index 7%, positive nuclear staining for p53). CD recurred

eight months after the surgery. Total hypophysectomy led to complete remission,

followed by recurrence 5 months later. We performed radiosurgical treatment of

EP45

the remnant tumor mass, along with bilateral two-stage adrenalectomy.

Pathohistological evaluation confirmed complete removal of the left adrenal

Adrenal involvement in MEN1 families

gland, and was inconlusive about the right one. Postoperatively, patient required

Mara Ventura, Miguel Melo, Leonor Gomes, Joana Saraiva, Luisa Barros,

replacement therapy. Two years after the adrenalectomy patient was diagnosed

Dírcea Rodrigues, Diana Oliveira, Diana Martins, Adriana Lages,

with Nelson’s syndrome due to enlargement of the pituitary mass. Fractionated

Nelson Cunha & Francisco Carrilho

radiotherapy was performed, after which ACTH slightly decreased, but UFC

University and Hospital Center of Coimbra, Coimbra, Portugal.

levels continued to increase, while taking hydrocortisone replacement.

Replacement therapy was stopped, but urinary free cortisol increased to

Introduction

1400 nmol/24 h 3 years after the bilateral adrenalectomy, accompanied by the

MEN1 is a rare autosomal dominant syndrome typically characterized by

recurrence of signs and symptoms of CD. Computed tomography showed 4-cm

neoplastic lesions of parathyroid glands, anterior pituitary gland and endocrine

large mass in the left adrenal bed suggestive of an adrenal tissue, along with the

pancreas. Several other tumours are associated with this syndrome, including

multiple liver lesions and without the signs of another primary tumor. Patient died

adrenal lesions, but their prevalence and clinical characteristics

(endocrine

five years after the initial diagnosis and his family refused an autopsy.

secretion and aggressiveness) are largely unknown.

This is the first case of a recurrent CD after bilateral adrenalectomy. This report

Objective

highlights the importance of long-term monitoring of the patient and individual

To determine the prevalence, clinical characteristics and the possible

dosing of replacement therapy.

genotype/phenotype association of adrenal lesions in MEN1 patients, as well as

DOI: 10.1530/endoabs.49.EP43

their global impact on patients’ outcome.

Material and methods

We retrospectively studied 16 patients belonging to six families of individuals

with MEN1. Adrenal involvement was evaluated clinically, biochemically and

imagiologically based on clinical records.

Results

Adrenal lesions were identified in 9 of 16 (56.3%) patients. This group comprises

seven women and two men with a mean age of 55.6 years. The mean age at

diagnosis of MEN1 was 46.3 years (18-68) and adrenal involvement was detected

EP44

between 0 and 16 years after the syndrome was diagnosed. Among the 16 patients

Late-night salivary cortisol: cut-off definition and diagnostic value in

evaluated, a total of nine adrenal nodules were founded, with a median of two

Cushing’s syndrome

nodules per patient. Only three patients had unilateral involvement. The mean

Adriana Lages¹, João Frade¹, Isabel Paiva¹, Patrícia Oliveira¹,

adrenal lesion diameter at diagnosis was

17.5 mm (6-30 mm). Hormonal

Diana Oliveira¹, Diana Martins¹, Mara Ventura¹, Nelson Cunha¹,

hypersecretion - autonomous cortisol secretion - was founded in one patient.

Alexandre Rebelo-Marques², Susana Antunes¹, Fátima Leitão¹ &

None of the patients was submitted to adrenalectomy. Adrenal lesions were

Francisco Carrilho¹

evenly distributed between the different germline mutations.

¹Coimbra Hospital and University Center, Coimbra, Portugal;²Faculty of

Conclusion

Medicine University of Coimbra, Coimbra, Portugal.

Adrenal tumours are a common feature of MEN1 that can affect more than half of

the patients. Most of the tumours are bilateral non-functional lesions, but

Background

hormonal secretion may occur and should be promptly identified in order to

The diagnosis of Cushing’s syndrome (CS) remains a challenge in clinical

reduce the morbidity/mortality of the syndrome. Adrenal evaluation should be

endocrinology. Several screening tests have been proposed to establish

considered in patients with MEN1.

hypercortisolism. Late-night salivary cortisol (LNSC) is used as screening tool,

DOI: 10.1530/endoabs.49.EP45

however, individualized cut-off levels for each population must be defined.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP46

Comment

In the case of Cushing’s syndrome, the adrenal glands on one side or on both

Differential effects of aldosterone excess on potassium homeostasis and

adrenal glands are not diagnostic in terms of diagnosis.

blood pressure in Asian subjects

Du Soon Swee, Peng Chin Kek & Lih Ming Loh

Department of Endocrinology, Singapore General Hospital, Singapore,

Table 1

Singapore.

Cushing’s

Unilateral mass

Bilateral Masses

Syndrome

(n:20)

(n:15)

Introduction

Hypokalemia is considered as a late manifestation of primary aldosteronism (PA),

Age

58.2G2.4

63.5G2.5

0.7

long preceded by hypertension. However, there have been reports of

1 mg DST

5.9G1.6

5.8G1.8

0.9

normotensive PA patients presenting with hypokalemia. This study aims to

(median:3.3)

(median:3.1)

examine the relationship of hypokalemia and blood pressure in patients with

Liddle test

4.8G1

4.2G0.7

0.2

hyperaldosteronism.

24 h urine cortisol

138.2G28.8

184G26.5

0.5

Methods

A retrospective review of patients who underwent saline infusion test (SIT) from

2014 to 2016 was conducted. All patients had screening plasma aldosterone

DOI: 10.1530/endoabs.49.EP47

concentration (PAC): plasma renin activity (PRA) ratio of O20. Postinfusion

PAC level !5 ng/dl (139 pmol/l) indicated normal aldosterone suppression, PAC

O10 ng/dl

(277 pmol/l) confirmed PA, whereas PAC

5-10 ng/dl

(139-

277 pmol/l) was regarded as indeterminate. Hypokalemia was defined as serum

potassium !3.5 mmol/l.

Results

EP48

Over a 3-year period, 52 patients referred for hypokalemia had non-suppressible

Late night salivary cortisol measurement may help in excluding

postinfusion PAC (O5 ng/dl). They comprised of 36 men and 16 women, with a

Cushing’s syndrome in patients with chronic kidney disease

mean age of 58.4G9.1 and 57.3G13.2 years respectively.

Urszula Ambroziak¹, Agnieszka Kondracka¹, Jadwiga Rojek-Tre˛bicka2,

In the PA group consisting of 26 men and 11 women, the mean serum potassium

Paweł Gajkowski¹, Agnieszka Stan´ czyk1, Malwina Stępor1 &

were 2.9G0.3 mmol/l and 2.7G0.5 mmol/l respectively. Eighteen (69.2%) men

Tomasz Bednarczuk¹

and 10 (90.9%) women were on %2 antihypertensive agents, including two

¹Department of Internal Medicine and Endocrinology, Medical University

women (age 48 and 51) with severe hypokalemia (!2.5 mmol/l) who were

of Warsaw, Warsaw, Poland;²Department of Internal Medicine and

normotensive and rendered normokalemic after adrenalectomy and spironolac-

Nephrology, Medical University of Warsaw, Warsaw, Poland.

tone treatment separately.

In the indeterminate group comprising of ten men and five women, the mean

serum potassium were 3.1G0.2 mmol/l and 3.0G0.2 mmol/l respectively. Five

Objective

(50%) men and 4 (80%) women were on %2 antihypertensive agents.

The diagnosis of Cushing’s syndrome may be challenging, especially in cases of

In all patients with moderate to severe hypokalemia (%2.9 mmol/l), 7/11 (63.6%)

patients with chronic kidney disease (CKD).

men and 8/9 (88.9%) women were on %2 antihypertensive agents.

Aim

Conclusion

The assessment of late night salivary cortisol concentration, serum and salivary

In our cohort of Asian patients, majority with hypokalemia secondary to

concentration in overnight dexamethasone suppression test in patients with CKD

autonomous aldosterone production required only 0-2 antihypertensive agents,

stage III-V and a control group.

even in those with more severe degree of hypokalemia. This suggests possible

Patients and methods

differential effects of aldosterone excess on potassium homeostasis and blood

37 patients mean age 66G12 (MZ13) with CKD stage III-V according to

pressure.

KDIGO and 28 controls mean age 45.3G15 years (MZ6) were enrolled to the

study. Patients were recruited in the nephrology clinic during their routine control

DOI: 10.1530/endoabs.49.EP46

visits. Serum and salivary cortisol were measured by Roche ECLIA cortisol test

(Cobas E411). Two samples of late night salivary cortisol (LNSC) from each

subject were obtained from home. 1 mg dexamethasone suppression test (DST)

was done in patients and controls with serum and saliva measurement at 0800 h.

Serum creatinine assessment was done no longer than 1 week prior to cortisol

measurement. GFR was obtained from the CockcroftKGault calculator.

EP47

Results

The mean GFR in patients was

33.89 ml/min

(8.4-54) while in controls

Effect of adrenal mass lateralization on diagnostic tests in patients with

125 ml/min (73-230) (P!0.0001). The mean serum DST cortisol in patients

Cushing

was 2.62 mg/dl (0.46-7.42). In 19 (51.4%) patients serum DST cortisol was

Ozlem Ustay Tarcin, Emre Pehlevan, Eren Imre, Melin Uygur,

O1.8 mg/dl. In all controls serum DST cortisol was !1.8 mg/dl (mean, min-max

Oguzhan Deyneli & Dilek Gogas Yavuz

0.70, 0.36-1.48). The mean DST salivary cortisol in patients was 0.88 mg/dl

Marmara University Pendik Hospital, Endocrinology and Metabolism,

(0.11-0.88) while in controls 0.18 mg/dl (0.02-0.69) mg/dl. Although there was a

Istanbul, Turkey.

significant difference between controls’ and patients’ salivary cortisol concen-

tration in DST (PZ0.01), all but one patient’s salivary measurement were within

The frequency of adrenal masses is increasing in parallel with the progress of the

control ranges. The mean LNSC in patients was 0.26 mg/dl (0.10-0.65) while in

technology. Most of these masses, which are detected by chance, are not

controls 0.29 mg/dl (0.04-0.80), PZ0.4. All patients’ LNSC measurements were

functional, and only a part of them are exposed to an excess of hormone. The most

within control ranges. In the patients’ group the negative correlation between

common dysfunction in masses with hormonal activity is hypercortisolism.

GFR and DST serum cortisol was detected, rZK0.6, PZ0.001 (the higher

However, the diagnosis of Cushing’s disease is based on more than one test. In this

cortisol the lower GFR).

study, we intended to compare the values of screening tests to determine whether

Conclusion

the presence of a unilateral mass or bilateral mass would help in the diagnosis.

LNSC may be helpful in excluding Cushing’s syndrome in patients with CKD.

Materials and methods

DOI: 10.1530/endoabs.49.EP48

Adrenal masses were detected in our clinic and 143 patients who were followed

up were evaluated. 112 of these patients have unilateral adrenal mass, 31 have

bilateral adrenal masses. Twenty (17.8%) of 112 unilateral adrenal masses and 15

(51.6%) of the patients with bilateral adrenal masses were diagnosed as Cushing.

The 1 mg overnight dexametasone suppression test

(DST),

days

2 mg

EP49

dexametasone suppression test (Liddle test), and 24-h urine cortisol levels used

for diagnosis in these patients were compared. Averages of tests were taken

The short Synacthen test revisited - reevaluation of the normal

multiple times.

reference range using LCMSMS

Conclusion

Grethe

˚strømUeland1,2, Paal Methlie^1,2, Marianne Øksnes^1,2,

The mean age of the patients with bilateral and unilateral adrenal masses was

Kristian Løva˚s1,2, Hrafnkell Thordarson2 & Eystein Husebye1,2

around 60. When the mean values of 1 mg DST, Liddle test and 24 h urine were

¹Department of Clinical Science, University of Bergen, Bergen, Norway;

compared, no statistically significant difference was found between the two

²Department of Endocrinology, Haukeland University Hospital, Bergen,

groups.

Norway.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

EP51

The Synachten test is used to diagnose for adrenal insufficiency (AI) and non-

Education sessions in patients with adrenal insufficiency

classical congenital adrenal hyperplasia (CAH). The cut-off levels for s-cortisol

Aldora Távora, Ema Lemos, Isaura Duarte, Joaquim Sobral,

and s-17-hydroxyprogesterone are derived from immunoassays that were not well

Catarina Machado, Patrícia Tavares, Gustavo Rocha, Sara Monteiro,

standardized and are no longer in use. Introduction of liquid chromatography

Ana Sousa, Pedro Rodrigues & Maria Joa˜o Oliveira

tandem mass spectrometry (LCMSMS) could resolve the lack of standardization

Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.

of steroid hormone assays and enable increased diagnostic accuracy.

Aim

Define cut-off values for s-cortisol and s-17OH-progesterone by LCMSMS after

Introduction

intravenous administration of 250 mg tetracosactide acetate (Synachten).

Adrenal insufficiency (AI) is a rare and potentially life-threatening disease. The

Methods

most common causes are primary adrenal insufficiency (Addison’s Disease), due

The Synachten test was performed in healthy individuals (nZ60) and patients

to an adrenocortical disease, and secondary insufficiency, due to disorders of the

referred for evaluation of adrenocortical function (nZ42). Steroids were assayed

pituitary gland. Chronic glucocorticoid replacement is vital and patients should be

by LCMSMS. Cut-off level for s-cortisol was defined as the 2.5% percentile in

educated about how to act in acute stress situations, in order to avoid adrenal

healthy subjects not using oral estrogens (nZ55), and for 17-OH-progesterone as

crisis. Taking this into account, we organized education sessions, aimed at

the 97.5% percentile in the healthy women.

patients with AI.

Results

Discussion

Cortisol cut-off levels were 415 and 493 nmol/l at 30 and 60 min, respectively.

We realized group sessions of about 90 minutes duration each, with maximum 8

All controls had higher cortisol at 60 compared to 30 min. Applying the current

patients with AI; the presence of a family member or caregiver was strongly

cut-off of 550 nmol/l, 27 healthy controls would have had a false negative test at

advised. A multimedia presentation was performed, focusing on basic knowledge

30 min, and six at 60 min. For s-17-OH-progesterone the cut-off levels were 10.5

on adrenal insufficiency, management of the disease during stress situations and

and 11.1 nmol/l at 30 and 60 min, respectively. Forty-two patients performed the

early recognition of signs and symptoms of an adrenal crisis. At the end of each

test for suspected AI or non-classic CAH. Applying the new cut-offs, seven who

session, patients were given an emergency hydrocortisone kit and taught how and

had AI according to old criteria, now scored normal.

when to use it. In addition, three brochures with written information with general

Conclusions

information about the disease, specials situations and how to prepare and

Cut-off levels for s-cortisol after Synacthen test are lower than the commonly

administer emergency medication were available to take home. The identification

recommended discriminating levels when cortisol is analyzed by LCMSMS.

card of disease carrier (European Society of Endocrinology) was also provided to

When applied, a significant proportion of patients can be re-categorized from

those who didn’t have it. Patient adherence was 100% and a second session will

adrenal insufficiency to healthy. We recommend using the 60 min value as

be scheduled in order to access the effectiveness of the first session and to

standard, as cortisol increased from 30 to 60 min in all controls.

reinforce patient education.

Conclusions

DOI: 10.1530/endoabs.49.EP49

AI is a chronic disease with a significant burden in both patients and its partners.

A careful and repeated education is the best strategy to avoid life-threatening

emergencies.

DOI: 10.1530/endoabs.49.EP51

EP50

Cushing’s syndrome in pregnant woman

Anastasiia Chekanova, Irina Komerdus, Tatiana Shestakova,

EP52

Fatima Burumkulova, Timur Britvin & Alexander Dreval

Characteristics of aldosterone-producing adenomas: a tissue

Moscow Regional Research Clinical Institute n.a. M.F.Vladimirsky,

microarray study

Moscow, Russia.

Yara Rhayem¹, Annette Feuchtinger², Christine Woischke³,

Philippe Ludwig¹, Thomas Kunzke², Thomas Schwarzmayr⁴,

Background

Stefanie Hahner⁵, Celso E. Gomez-Sanchez⁶, Tim M. Strom⁴,

Pregnancy occurs rarely in Cushing’s syndrome (CS), slightly over 150 cases

Thomas Kirchner³, Martin Reincke¹, Axel Walch² & Felix Beuschlein¹

have been reported in the literature. The risk of maternal morbidity and a poor

¹Department of Endocrine Research, Klinikum der Universitat Munchen,

fetal outcome is significant when CS coexists with pregnancy. CS may be difficult

Ludwig-Maximilians University, Munich, Germany;²Research Unit of

to detect clinically and laboratory because of the hormonal changes and

Analytical Pathology, Institute of Pathology, Helmholtz Zentrum Munchen,

pathological comorbidities associated with normal pregnancy.

Neuherberg, Germany;³Institute of Pathology, Klinikum der Universitat

Material and methods

Munchen, Ludwig-Maximilian University, Munich, Germany;⁴Institute of

A case of CS that was diagnosed and treated during pregnancy.

Human Genetics, Helmholtz Zentrum Munchen and Technische Universitat

Case

Munchen, Munich, Germany;⁵Endocrinology and Diabetes Unit, Depart-

Woman Y., 30y.o., since she was 18 had menstrual irregularities and since she

ment of Medicine I, University Hospital Wurzburg and Comprehensive

was 28 an arterial hypertension, type

2 DM. She was on supervision of

Heart Failure Center, University of Wurzburg, Wurzburg, Germany;

therapeutist and take metformin for her DM and hypotensive medication.

⁶Division of Endocrinology, G.V.(Sonny) Montgomery VA Medical Center

Unexpected pregnancy occurs in December 2016. She was referred in our clinic in

and Department of Medicine-Endocrinology, University of Mississippi

15 weeks of her pregnancy because of uncontrolled DM and hypertension.

Medical Center, Jackson, MS, USA.

Examination revealed increased blood pressure, fatigue, easy bruising, excessive

hair growth on the face and body, swelling and rounding of the face, edema of legs

Background

and feet. Laboratory evaluation: UFC-1475.0 and 1511.0 nmol/24 h (N 138.0-

Sporadic aldosterone-producing adenomas (APA) are relevant cause of endocrine

524.4), serum cortisol

- at

0800 h K868 nmol/l

(190-650), at

2300 h

related hypertension in Primary Aldosteronism (PA). Next generation sequencing

K995 nmol/l (50-350)), suppressed ACTH level. HbA1c-7.7%. Insulin therapy

techniques have identified somatic mutations in APA harbored in KCNJ5,

initiated to treat DM. MRI data: adenoma in left adrenal (32!30 mm). 13.05.16.-

ATP1A1, ATP2B3, CACNA1D, CTNNB1 and PRKACA genes. Yet, a number

unilateral adrenalectomy was done. Adrenal insufficiency developed post-

of APA harbor no mutations in candidate genes (designated as wild type, WT) and

operatively and glucocorticoid therapy was started. She was under close

little is known about genotype/phenotype correlation.

supervision of gynecologist. At 38 weeks gestation surgical delivery performed

Objectives

(boy,

1900 g, 44 cm, 7/8 Apgar score, with three degrees of fetal growth

We investigated the tissue-based molecular and histopathological characteristics

retardation and two degrees of malnutrition). Insulin was cancelled after delivery,

of 132 APAs after laparoscopic unilateral adrenalectomy in PA-patients and

and hydrocortisone and antihypertensive therapy cancelled 2 months postpartum.

studied genotype/morphometry and histopathology correlation.

Conclusion

Methods

High clinical suspicion of the CS during pregnancy can help for the diagnosis and

Tumor-DNA was screened for somatic mutations in candidate genes by targeted

leads to better outcomes for the mother and the fetus. Multidisciplinary approach

(nZ84) or whole-exome (nZ48) sequencing. Accurate characterization of 179

needs for these patients with careful supervision during pregnancy and

morphometric parameters and of immunohistochemistry

(IHC) results for

postpartum.

steroidogenic enzymes CYP11B1, CYP11B2, CYP17, HSD3B1 and HSD3B2

DOI: 10.1530/endoabs.49.EP50

was performed on tumor tissue microarrays from all samples by digital image

analysis.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

¹Department of Endocrinology, Diabetes and Metabolism, São João

Prevalence of WT APA in our cohort was 34% and affected men more frequently. In

Hospital Center, Porto, Portugal;²Departamento de Cirurgia e Fisiologia,

8/48 APA, non-recurrent somatic mutations (NR) were identified. H&E analysis

Unidade de Investiga

¸a˜o Cardiovascular, Faculdade de Medicina, Uni-

demonstrated that 6 morphometric parameters correlated negatively with WT status

versidade do Porto, Porto, Portugal;³Faculty of Medicine University of

whereas those same parameters correlated positively with the presence of KCNJ5 or

Porto, Porto, Portugal;⁴Department of Medical Oncology, São Jo

˜o

NR (P!0.01). The same reversed pattern between WT and KCNJ5 mutated APA was

Hospital Center, Porto, Portugal;⁵Instituto de Investigac¸ão e Inovação em

found in

10 cytoplasmic parameters, including mainly color-based features

Saúde da Universidade do Porto, Porto, Portugal;⁶Department of Infectious

(P!0.01). KCNJ5 mutation status was negatively correlated with CYP11B1 and

Diseases, São Jo

˜o Hospital Center, Porto, Portugal;⁷Servic¸o de Medicina

HSD3B1 expression (P!0.01). On the contrary, WT, CACNA1D and NR APA

Interna. Centro Hospitalar Entre Douro e Vouga, Santa Maria da Feira,

significantly correlated positively with CYP11B1. ATP1A1 mutated APA correlated

Portugal.

positively with CYP11B2 (P!0.01) and not with CYP11B1 or HSD3B2.

Conclusion

Introduction

Our findings in NR APA point towards a KCNJ5-like morphometric pattern

Adrenal tumors are usually detected due to clinical manifestations of hormonal

associated with a WT-like steroidogenic enzymes expression pattern. WT APA

hypersecretion or incidental findings on imaging evaluation. Although most

presented an opposed morphometric pattern in comparison to mutated APA,

incidentalomas are non-functioning adenomas, it is important to appropriately

indicating that in absence of detectable somatic mutations APA cells are driven

evaluate such masses to exclude hormonal excess or malignancy.

towards a different cellular fate.

Case description

DOI: 10.1530/endoabs.49.EP52

An 81-year old male was admitted to our hospital for fever with 15 days of

evolution. The patient also presented chills and loss of 3 kg in the last 4 weeks.

Regarding past medical history, the patient had type 2 diabetes, hypertension,

coronary artery disease, heart failure, cerebrovascular disease (stroke 8 years

before), vertebral fractures (3 years before), deep vein thrombosis (3 months

EP53

before), renal lithiasis and a right adrenal mass

(3 cm in the abdominal

Adrenal cushing’s syndrome surprisingly unveiling breast cancer

tomography 16 months before; no functional study available). An elevated

Joa˜o Sérgio Neves1,2, Ana Isabel Oliveira1, Pedro Souteiro1,3, Sofia

C-reactive protein (142 mg/l) was observed, with negative blood and urinary

Castro Oliveira^1,3, Helena Baldaia⁴, Daniel Melo⁴, Celestino Neves^1,3,

cultures and no other signs of infection. The abdominal ultrasound shown a right

Paula Freitas^1,5 & Davide Carvalho^1,5

adrenal mass of 13 cm. On magnetic resonance, the mass was heterogenous with

¹Department of Endocrinology, Diabetes and Metabolism, Sa˜o João

invasion of inferior vena cava. The patient had no stigmas of Cushing’s syndrome.

Hospital Center, Porto, Portugal;²Departamento de Cirurgia e Fisiologia,

Plasma catecholamines, urinary catecholamines and metanephrines, and renin

Unidade de Investigac¸ão Cardiovascular, Faculdade de Medicina, Uni-

and aldosterone levels were normal. The midnight salivary cortisol was normal

versidade do Porto, Porto, Portugal;³Faculty of Medicine University of

and the plasma cortisol level after 1 mg overnight dexamethasone suppression test

Porto, Porto, Portugal;⁴Department of Pathology, São João Hospital Center,

was 3.7 mg/dl. Given the risk for a surgical approach, the fast growth of the tumor

Porto, Portugal;⁵Instituto de Investiga

˜o e Inova

¸a˜o em Saúde da

and the imaging characteristics suggestive of adrenal carcinoma, a decision to

Universidade do Porto, Porto, Portugal.

preclude biopsy was made. The patient started mitotane and two months later the

mass has 15 cm and the patient is still on follow-up in outpatient setting.

Conclusions

Introduction

The authors present a case of adrenal carcinoma in a patient with previous adrenal

Cushing’s syndrome is an endocrinopathy characterized by glucocorticoids

mass not completely studied at presentation. Adrenal incidentalomas are frequent.

excess. Adrenalectomy is the recommend treatment for unilateral adrenal

This case highlights the importance of prompt evaluation of adrenal

Cushing’s syndrome and is usually associated with resolution of the disease.

incidentalomas to early recognize rapidly growing adrenal carcinomas.

Clinical Case

DOI: 10.1530/endoabs.49.EP54

A 54-year old woman with central obesity (BMI 34.3 kg/m²), diabetes and

hypertension had a left adrenal mass of 15 mm and characteristics suggestive of

adenoma (Hounsfield unit of !10). On CT reevaluation, five years later, there

was evidence of mass growth (28 mm) and the characteristics were suspicious of

malignant lesion (Hounsfield unit of 38 and absolute contrast washout of 35%).

She was then referred to our department for evaluation. Urinary catecholamines

EP55

and metanephrines were normal, ACTH level was 4.2 pg/ml and the cortisol

The relative risk of developing Addison’s disease among patients

following 1 mg overnight dexamethasone suppression test was 11.0 mg/dl. The

with type 1 diabetes mellitus: a nationwide, matched, observational

24 h urinary-free cortisol, late-night salivary cortisol and two-day low-dose

cohort study

dexamethasone suppression test were consistent with ACTH-independent

Dimitrios Chantzichristos^1,2, Anders Persson³, Bjorn Eliasson^1,2,

Cushing’s syndrome. A left adrenalectomy was performed. At pathological

Mervete Miftaraj³, Stefan Franzén³, Ann-Marie Svensson³ &

evaluation, there was a neoplasm of solid pattern, with vascular invasion and a

Gudmundur Johannsson^1,2

immunohistochemical pattern suggestive of a breast carcinoma metastasis.

¹Department of Internal Medicine and Clinical Nutrition, Institute of

Mammography revealed a 15 mm nodule with spiculated contours that on breast

Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg,

biopsy revealed a NST (no special type) breast carcinoma. The patient was

Sweden;²Department of Endocrinology-Diabetes-Metabolism, Sahlgrenska

submitted to neoadjuvant chemotherapy and surgical tumorectomy. Five months

University Hospital, Gothenburg, Sweden;³Department of Medicine,

after surgery she was admitted in Endocrine department for adrenal insufficiency.

National Diabetes Register, Centre of Registers, University of Gothenburg,

Ten months after the adrenalectomy, the patient presents an adrenal insufficiency

Gothenburg, Sweden.

(compensated with replacement therapy) and maintains follow-up on endo-

crinology and multidisciplinary breast cancer appointments.

Background

Conclusion

Both prevalence and incidence of type 1 diabetes (T1DM) is increasing. T1DM is

The authors present a case of Cushing’s syndrome of adrenal origin, with a

associated with other autoimmune diseases, such as Addison’s disease (AD). This

concomitant metastasis of a breast carcinoma. The find of a metastasis in an

combination is rare, with estimated prevalence in Norway 20 per million. Having

adrenal mass, is consistent with a tumor-to-tumor metastasis, a rare finding in

both DM & AD is associated with marked excess mortality.

adrenal masses that, in this case, allowed the diagnosis of a previously unknown

Objectives

breast cancer.

To study prevalence and incidence of AD among patients with and without

DOI: 10.1530/endoabs.49.EP53

T1DM.

Methods

Nationwide, observational study cross-referencing the Swedish National Diabetes

controls from the general population (matched 1:5 for age, sex and country).

EP54

Demographics at baseline, group proportions and time to AD diagnosis using a

Giant adrenal tumor in a patient admitted for fever

Cox proportional hazards model were assessed.

Joa˜o Sérgio Neves1,2, Luís Teles7, Pedro Souteiro1,3, Sofia

Results

Castro Oliveira^1,3, Ana Isabel Oliveira^1,3, Ana Catarina Fernandes⁴,

Prevalence: Between 1987-2012, 105 subjects were diagnosed with AD among

Margarida Damasceno⁴, Luísa Grac¸a6, Elisabete Rodrigues1,3,

30,685 patients with T1DM, while 32 among 153,918 controls. The odds ratio

Celestino Neves^1,3, Paula Freitas^1,5 & Davide Carvalho^1,5

for AD in T1DM patients vs controls was therefore 16.5 (95% CI 11.1-24.5).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

The prevalence of AD in patients with and without T1DM was 3400 and 200 per

Introduction

million, respectively. Incidence: Between 1998-2013, 67 subjects were diagnosed

Primary adrenal insufficiency (PAI) is a rare but severe and potentially life-

with AD at a mean age of 36.7 years (SD 13.1) among 36,705 patients with

threatening condition. There are no studies characterizing portuguese patients

T1DM, while 33 were diagnosed with AD at a mean age of 43.1 (SD 15.1) among

with PAI.

184,304 controls. The estimated relative risk increase to develop AD in T1DM

Aims

patients was therefore 10.7 (95% CI 7.0-16.2). The incidence of AD for a patient

To characterize the clinical presentation, diagnostic workup, treatment and

with and without T1DM was 195 and 18 per million patient-years, respectively.

follow-up of patients with confirmed PAI.

Conclusion

Methods

This nationwide study shows that prevalence of AD is higher than previously

A multicentre retrospective study of PAI patients followed in 12 portuguese

reported and that the incidence of AD for a patient with T1DM is 195 per million

hospitals.

patient-years. T1DM patients have a more than 10-fold higher risk of developing

Results

AD than matched controls and their AD develops at a younger age.

We investigated 278 patients with PAI (55.8% were females) with mean age of

DOI: 10.1530/endoabs.49.EP55

diagnosis of 33.6G19.3 years, 7.3 years after the beginning of the symptom

presentation. The most frequently reported symptoms and signs were asthenia

(60.1%), hyperpigmentation (55.0%), weight loss (43.2%), hypotension (42.8%)

and hypoglycaemia (8.6%). Hyponatremia was documented in 36.3% of cases

and hyperkalaemia in 25.9%; 29.1% of patients were diagnosed in adrenal crisis.

In 122 patients the diagnosis was established using morning cortisol !5 g/dl and

plasma ACTH 2-fold the upper limit of the reference range and in 39 cases by the

corticotropin stimulation test. The main causes were autoimmune adrenalitis (140

EP56

cases), idiopathic

(48 cases), congenital adrenal hyperplasia

(27 cases) and

The frequency of incidental liver and renal masses in patients with

tuberculosis (17 cases). Concerning associated autoimmune diseases, the most

adrenal incidentalomas

common were autoimmune thyroiditis (81 patients) and type 1 diabetes mellitus

Narin Nasiroglu Imga, Yasemin Tutuncu, Mustafa Unal, Mazhar

(25 patients). Seventy-nine percent were treated with hydrocortisone (mean dose

Muslum Tuna, Bercem Aycicek, Serhat Isik, Dilek Berker & Serdar Guler

26.3G8.3 mg/day) in three (57.5%), two (37.4%), one (3.7%) or four (0.5%)

Department of Endocrinology and Metabolism, Ankara Numune Education

daily doses; the remainder with prednisolone (10.1%), dexamethasone (6.2%) and

and Research Hospital, Ankara, Turkey.

methylprednisolone (0.7%); 66.2% were medicated with fludrocortisone (median

dose of 100 mg/day). Since diagnosis 33.5% have been hospitalized due to disease

Purpose

decompensation. At the last consultation, 17.2% of the patients had complaints

Adrenal incidentalomas (AIs) are adrenal masses, which are found on imaging

(7.6% asthenia and

6.5% depression) and

9.7% presented changes in the

ionogram.

studies not performed related to an adrenal problem. Hepatic incidental masses

Conclusion

and renal incidental masses are usually seen in abdominal imaging methods. We

This is the first multicentre Portuguese study about PAI. As described in

aim to investigate the frequency and the kind of hepatic and renal incidental

international studies a significant number of PAI patients continue to have

masses in patients with AIs.

symptoms of over or under-substitution despite optimal steroid replacement.

Methods

Retrospective evaluation of 381 (245 female and 136 male) AI patients and 285

DOI: 10.1530/endoabs.49.EP57

(168 female and 117 male) controls were done. Adrenal masses were divided into

two groups according to Hounsfield Units (HU) %10 and O10, also classified as

right, left and bilateral sided. The comparisons were made between hepatic and

renal and both hepatic and renal incidental masses in AIs patients.

Results

Renal incidental mass and both hepatic and renal mass frequency were found

higher in AIs group than controls. InAIs patients who had left sided

unilateraladrenal mass HU O10, the frequency of both hepatic and renal

incidental mass was found more than left sided unilateral adrenalHU %10 group

EP58

(PZ0.001). Also in patients who had bilateral sided adrenal mass HU O10 the

Adrenal incidentaloma: a challenging dilemma!

frequency of both hepatic and renal incidental mass was found more than bilateral

Caoimhe Bonner, Usman Shah, Anna Hawkins, Anthony Pittathankal,

sided unilateral adrenal HU %10 group (PZ0.049).

Imran Syed, Edel Casey & Khash Nikookam

Conclusions

King George Hospital, London, UK.

Increased incidence of both hepatic and renal incidental masses were detected in

AIs patients which adrenal mass HU greater than 10. We consider that the

physicians should carefully evaluate these cases. Large studies are needed to

The prevalence of adrenal incidentaloma on abdominal Computed Tomography

define the incidence and follow-up of AIs patients with hepatic and renal

(CT) is around 4.4%. This prevalence is increased in obese, diabetic, hypertensive

incidentalomas.

patients, and could be as high as 10% in older patients. Unilateral adrenal masses

larger than 4 cm should be considered for surgical removal to avoid missing

DOI: 10.1530/endoabs.49.EP56

adrenal carcinoma, particularly in younger patients.

This is the case of a 67 year old gentleman with Type 2 diabetes mellitus, known

to have hypertension, hypercholesterolaemia, ischaemic heart disease with six

coronary stents, and iron deficiency anaemia. He was on polypharmacy including

aspirin, clopidogrel, bisoprolol, amlodipine, oral hypoglycaemic agents, insulin

and iron supplementation. He presented with increased urinary frequency and

pain in the right flank. Urinalysis and examination of all systems were

unremarkable.

EP57

An ultrasound of kidney, ureter, and bladder (KUB) was performed showed a

Primary adrenal insufficiency: a Portuguese multicentre study by the

well-defined solid echogenic mass superior to the right kidney measuring 98!

adrenal tumour study group

76!85 mm with no vascularity. CT of the adrenals and abdomen revealed a 7 cm

Lia Ferreira¹, João Silva², Ana Martins³, Carlos Belo⁴, Diana Oliveira⁵,

right adrenal mass, most likely myelolipoma, multiple bilateral small renal cysts,

Hélder Simo˜ es6, Isabel Paiva5, Joana Guimarães7, Marta Ferreira8,

and an extensively calcified atherosclerotic abdominal aorta. Phaeochromocy-

Rita Silva⁹, Susana Garrido¹⁰, Tiago Silva¹¹, Vera Fernandes¹² & Maria

toma and Conn’s syndrome were ruled out following normal 24 hour urinary

Lopes Pereira¹²

metanephrines and normal renin aldosterone ratio. It was rather unlikely for

¹Centro Hospitalar do Porto, Porto, Portugal;²Hospital das Forças Armadas,

Cushing’s in view of normal 24 hour urinary cortisol and lack of the clinical

Lisboa, Portugal;³Centro Hospitalar Lisboa Norte, Lisboa, Portugal;

stigmata of excess cortisol.

⁴Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal;⁵Centro Hospitalar e

Conclusion

Universitário de Coimbra, Coimbra, Portugal;⁶Instituto Português de

Is it best to leave it alone, bearing in mind his multiple co morbidities or to operate

Oncologia Lisboa, Lisboa, Portugal;⁷Centro Hospitalar do Baixo Vouga,

in view of right flank pain, the size of tumour, and the risk of bleeding in this type

Aveiro, Portugal;⁸Centro Hospitalar Leiria, Leiria, Portugal;⁹Centro

of tumour?

Hospitalar São João, Porto, Portugal;¹⁰Hospital Tâmega e Sousa, Penafiel,

Portugal;¹¹Hospital Garcia da Orta, Lisboa, Portugal;¹²Hospital de Braga,

DOI: 10.1530/endoabs.49.EP58

Braga, Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP59

between conventional therapy and Plenadren. Currently, the median follow-up is

9 months (range 3-24 months). In one obese and diabetic patient body weight

Assay of steroids with Liquid chromatography tandem mass

decreased as well as fat mass while lean mass increased and HbA1c improved. In

spectrometry is superior to immunoassays in monitoring patients

one patient with osteoporosis T score improved and accordingly cross laps

with 21-hydroxylase deficiency

decreased and BAP increased. All study parameters did not show significantly

Ingrid Nermoen^1,2, Sandra Rinne Dahl¹, Ingeborg Brøndstad^1,3, Eystein

changes in the remaining patients.

S Husebye^3,4, Per M Thorsby¹ & Kristian Løvås^3,4

Conclusions

¹Oslo University HospitalHrmone Laboratory, Oslo, Norway;²Akershus

Treatment with Plenadren provides a more physiological cortisol profile and in

University Hospital, Lørenskog, Norway;³University of Bergen, Bergen,

some patients shows a beneficial effect on glucose metabolism and bone and body

Norway;⁴Haukeland University Hospital University, Bergen, Norway.

composition without increasing adrenal crisis and/or infections.

DOI: 10.1530/endoabs.49.EP60

Objective

Immunoassays of steroids are still used in the diagnosis and biochemical

monitoring of patients with congenital adrenal hyperplasia due to 21-hydroxylase

deficiency (21 OHD). However, high levels of steroid intermediates can promote

cross-reactivity between steroids giving rise to falsely elevated levels.

Design

Fifty-nine patients with classic 21OHD (38 women) were studied. Blood samples

EP61

were collected in the morning after overnight medication fasting. Immunoassay

Autoimmune Addison disease - data from long-term follow-up of

and liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitation

patients from a tertiary hospital’s Endocrinology Department

of the following steroids were performed:

17OH-progesterone

(17OH),

Diana Oliveira, Isabel Paiva, Adriana Lages, Diana Martins, Mara Ventura,

21-deoxycortisol (21DF, an 11-hydroxylated derivative of 17OHP), 11-deox-

Nelson Cunha, Sandra Paiva & Francisco Carrilho

ycortisol, testosterone and androstenedione.

Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital

Results

and University Center, Coimbra, Portugal.

Concentrations of testosterone, androstenedione and 17OHP were lower when

measured with LC-MS/MS compared with immunoassays, with exception of

testosterone levels in men. Testosterone results differed by 30.0% in females and

Introduction

only a small difference in men (C1.1%). The difference was even larger for

Autoimmune Addison disease requires lifelong glucocorticoid and mineralo-

androstenedione (31.3%) and 17OHP (57.0%).

corticoid replacement. Optimal therapy is not standardized and must balance

The correlation between 21DF and 17OHP was good (rZ0.87), but three patients

adequate hormone substitution with prevention of treatment-related compli-

did not have measurable 21DF which indicate that 21DF is not superior to 17OHP

cations.

to monitor replacement therapy. Subjects with no enzyme activity had

Objective

significantly lower mean 11-deoxycortisol concentrations compared with subjects

Assessment of patients followed at our department: epidemiology, associated

with severe enzyme failure, analyzed by LC-MS/MS. Levels of other steroid

conditions, treatment, cumulative hydrocortisone dose and comorbidities.

hormones did not differ significantly between the genotypes and methods.

Methods

Conclusions

Review of clinical records of patients currently followed at our department,

LC-MS/MS is superior to immunoassays in monitoring patients with 21-OHD on

diagnosed from 1975 until 2015. Statistical analysis using SPSS v. 23.0.

corticosteroid replacement therapy as they are more specific and can be

Results

multiplexed. Immunoassays seems to overestimate high levels of 17OHP and

A total of 27 records were evaluated, 17 were women, 10 men. Mean age at

androstenedione considerably.

diagnosis was 32G9.7 years, mean follow-up 19.7G13.8 years. Disease duration

DOI: 10.1530/endoabs.49.EP59

was 20 or more years in 55.6%. Mean current age 51G13 years. The most

frequently associated immune system disorder was autoimmune thyroiditis

(42.3%). Regarding glucocorticoid replacement,

92.6% were treated with

hydrocortisone (HC), 2 patients with prednisolone. Mean daily dose of HC

31.2G10.0 mg

(range

5.0-47.5 mg). Mineralocorticoid replacement with

fludrocortisone, mostly 0.1 mg/d. Osteoporosis/osteopenia was found in 33.3%

EP60

(nZ9), hypertension (HT) in 25.9% (nZ7), diabetes in 14.8% (nZ4), treatment

for depression or anxiety in 40.7% (nZ11) and dyslipidemia in 51.9% (nZ14).

Treatment of patients with primary and secondary adrenal insufficiency

Mean cumulative HC dose was higher in patients with osteoporosis/osteopenia

with hydrocortisone modified-release (Plenadrenw)

and in those with HT, dyslipidemia and diabetes, although not reaching statistical

Tania Pilli, Raffaella Forleo, Sandro Cardinale, Valeria Cenci &

significance. Tendency remained when adjusted for age.

Furio Pacini

Discussion and conclusion

Section of Endocrinology, Department of Clinical&Surgical Sciences and

Our sample shows a long follow-up time, associated with lifelong need of

Neurosciences, University of Siena, Siena, Italy.

Endocrinology assessment. A significant number of patients developed

comorbidities possibly related to long-term glucocorticoid therapy (osteoporosis,

Introduction

HT, dyslipidemia and diabetes). All of these were related to higher cumulative

Adrenal insufficiency is a life-threatening disease. Conventional treatment

HC dose. Absence of statistical significance was likely due to sample size. To

requires multiple daily doses of immediate-release hydrocortisone or cortisone

reduce the risk of complications, replacement therapy in autoimmune Addison

acetate causing non-physiological peaks and nadir of cortisol and it has been also

disease should be individually adjusted and overtreatment avoided.

associated with premature mortality, high frequency of infections, reduced quality

DOI: 10.1530/endoabs.49.EP61

of life, altered metabolic profile and reduced bone mineral density. A modified-

release hydrocortisone

(Plenadrenw, Shire) by combining a rapid with an

extended-release of the hormone can mimic the normal circadian rhythm of

cortisol and may be administered as a single daily dose. Plenadren has been also

associated with a reduction of body weight and blood pressure and improvement

of the glyco-metabolic parameters.

Purpose

EP62

The study objectives are: (1) to compare the area underr the curve (AUC) of

Effect of GH treatment on coagulation and fibrinolysis parameters in

cortisol under conventional therapy and Plenadren and (2) to evaluate clinical

prepubertal children with growth hormone deficiency

(body weight, body composition, blood pressure), glyco-metabolic (HbA1c)) and

Feneli Karachaliou¹, Maria Kafetzi², Maria Drakopoulou³,

bone (T score, BMD, serum bone alkaline phosphatase (BAP) and cross laps)

Elpis Vlachopapadopoulou⁴, Sofia Leka-Emiris⁴, Aspasia Fotinou² &

parameters at 3, 6 and 12 months of treatment with Plenadren.

Stefanos Michalakos⁴

Materals and Methods

¹Pediatric Endocrinology Unit, 3rd Department of Pediatrics, University

Thirteen patients

M/6 F; age 53G17 (mG S.D.)) with primary adrenal

General Hospital Attikon, Athens, Greece;²Biochemistry-Hormonology

insufficiency in seven subjects and secondary in six cases were prospectively

Department, P & A Kyriakou Children’s Hospital, Athens, Greece;

enrolled in the study.

³Endocrine Unit, Choremis Research Laboratory, A Pediatric Department,

Results

Athens University Medical School, Aghia Sophia Children’s Hospital,

Daily cortisol profiles were more physiological on Plenadren and body exposure

Athens, Greece;⁴Endocrinology Department, ‘P. & A. Kyriakou’ Children’s

to cortisol, calculated as area under the curve, was not statistically significant

Hospital, Athens, Greece.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

EP64

Increased fibrinogen levels have been reported in prepubertal children and

Cushing’s Syndrome During Pregnancy mimicking preeclampsia -

adolescents with growth hormone deficiency (GHD), which were reduced after

case report

rhGH treatment. rhGH treatment has also been shown to exert a beneficial effect

Danijela Radojkovic^1,2, Milan Radojkovic^1,3, Milica Pesic^1,2,

on the amount of aPAI-1 in children with GHD.

Slobodan Antic^1,2, Sonja Kostic², Sanja Curkovic², Vojislav Ciric² &

Aim

Ivan Ilic^1,4

Of the study was to evaluate whether prepubertal GH deficient (GHD) children

¹Medical Faculty, University of Nis, Nis, Serbia;²Clinic of Endocrinology,

showed any impairment in coagulation- and fibrinolysis-related parameters and

Diabetes and Metabolic Disorders, Clinical Center Nis, Nis, Serbia;

the effect of GH therapy on these parameters.

³Surgery Clinic, Clinical Center Nis, Nis, Serbia;⁴Pathology Institute,

Patients and methods

Clinical Center Nis, Nis, Serbia.

Fifteen prepubertal children (10 girls and five boys) of a mean (S.D.) age of 9.8

(0.4) years with GH deficiency were included in this hospital based prospective

study. Serum levels of PT, APTT, fibrinogen, VII, VIII, AT, PC, D-dimers, Plg,

Introduction

and PAI-1 were measured before and after 6-12 months of GH treatment.

Physiological changes of pregnancy could be similar with classical presentation

Results

and biological confirmation of Cushing’s Syndrome (CS). To diagnose CS in

At baseline all studied parameters were within normal ranges. A significant

pregnancy is very difficult especially in previously healthy women. Since the

increase in PT values was noted after a mean (S.D.) interval of 9.3 (0.4) months of

hypercortisolemia in the pregnancy increase maternal and foetal morbidity it is a

treatment: 12.46 (0.2) s vs 12.1(0.15) s, PZ0.045. A significant decrease in PAI-1

concern for endocrinologists, gynaecologists, and paediatricians.

levels (3.04 (0.1) U/ml vs 2.28 (0.3) U/ml, PZ0.018) was noted at the same time.

Patient case report

No significant changes in the rest of parameters were found during the study

Herein, we present young woman (23 years old) admitted to the Genecology

period.

Clinic, with uncontrolled hypertension and gestational diabetes. The pregnancy

Conclusion

was terminated with an emergency caesarean section at 28 weeks of gestation due

GH replacement therapy for 6-12 months led to a significant increase in PT

to sever preeclampsia. Five months after delivery hypertension, weight gain, poor

values, while fibrinogen levels did not change. Moreover, GH treatment reduced

glycaemic control, irregular menstrual cycles and cushingoid features persisted.

PAI-1 levels in GHD children, suggesting a beneficial effect of GH treatment on

She was admitted to the Endocrinology Clinic for further evaluation. Computed

possible risk of future atherothrombosis. Further evaluation of the clinical

tomography revealed right adrenal adenoma, size

32!41 mm. Endocrine

significance of these changes is needed.

evaluation verified increased cortisol and decreased ACTH. There was no plasma

cortisol suppression after low- and high-dose dexamethasone suppression tests.

DOI: 10.1530/endoabs.49.EP62

Vanillylmandelic acid in 24 h diuresis, plasma catecholamine and chromogranin

serum level, were normal. Potassium was decreased, but other electrolytes

(sodium, calcium, phosphorus, magnesium) were in normal range. After

adequately preoperative preparation, right adrenalectomy was performed. The

procedure and postoperative course were uneventful. The histopathological

examination confirmed a benign adrenocortical adenoma.

Conclusion

Even though CS in pregnancy is very rare, it is worthy to be considered when

pregnant women develop hypertension and gestational diabetes. Delayed

diagnosis and treatment could lead to maternal-foetal complications.

EP63

DOI: 10.1530/endoabs.49.EP64

Treatment with modified-release hydrocortisone for 6 months: A

clinical audit in 15 patients with adrenal insufficiency

Charlotte Steffensen¹, Marianne Andersen², Ulla Feldt-Rasmussen³,

Caroline Kistorp⁴ & Jens Otto L Jørgensen¹

¹Department of Endocrinology and Internal Medicine, Aarhus University

Hospital, Aarhus, Denmark;²Department of Endocrinology and Internal

Medicine, Odense, Denmark;³Department of Endocrinology and

Metabolism, Rigshospitalet, Copenhagen, Denmark;⁴Deparment of

Endocrinology and Internal Medicine, Herlev, Denmark.

EP65

Potentially aggressive adrenal oncocytoma during pregnancy: about

Background

one case

Patients with adrenal insufficiency (AI) exhibit increased morbidity, mortality and

Mouna Mezoued^1,2, Maissa Smaili¹ & Djamila Meskine^1,2

impaired quality of life (QoL) and conventional hydrocortisone replacement does

¹Laboratoire Endocrinologie et Metabolisme, Algiers, Algeria;²EPH

not mimic the endogenous circadian pattern and may compromise adherence. A

Bologhine, Algiers, Algeria.

modified - release hydrocortisone formulation (Plenadren) for once-daily use is

licensed in order to meet these needs.

Objective

Oncocytary cells adrenal adenoma or adrenal oncocytoma is an extremely rare

To audit the effects of treatment change from HC to Plenadren in an out-patient,

tumor, mainly composed by oncocytomes. The diagnosis is exclusively confirmed

daily-life clinical setting.

on histological findings. There are about 50 cases published in the scientific

Patients and methods

reviews, of which only one case described a pregnant woman.

Fifteen consecutive patients with AI and problems with adherence and/or QoL

We report an observation about a 31 years old patient, with no personal

were shifted from HC to Plenadren treatment. The effect of treatment was

antecedent, explored in our unit for an adrenal masse, measuring 71!58!46 mm

assessed by clinical biochemistry, DEXA scanning and QoL (AddiQol) before

discovered during an abdominal CT scan done for low back pain.

and after 6 months.

Patient did not present obvious signs of adrenal hypersecrtion at clinical exam, we

Results

noticed some sympathic signs associated to an amenorrhea, and a pregnancy of 8

Fifteen patients (10F/5M) were included in the audit of whom 8 had primary AI

weeks of amenorrhea was then diagnosed. At CT scan the adrenal masse did not

with a mean age of 49.5 years. The mean daily HC dose was 21.4 mg and the

match with the characteristics of an adenomatous one, having a spontaneous

mean daily plenadren dose was 20 mg. No significant changes were recorded in

density of 40 HU, and an absolute washout up to 33%.

fasting lipid levels, morning salivary cortisol, serum electrolytes, HbA1c, or CRP

Methoxylated drift and hormonal exploration were normal.

before and after plenadren treatment. Likewise, body composition and BMD were

Regarding to the size of this mass and its radiological characteristics with a strong

unchanged. The AddiQol questionnaire showed a trend towards improved sleep,

suspicion of malignancy, Surgical management was decides, and patient was

less muscle pain and better concentration at 6 months. Fourteen of the 15 patients

treated at 12 weeks of amenorrhea with simple post-operative issues. Histological

continued on Plenadren after 6 months.

findings concluded to an adrenal adenoma with oncocytary cells presenting

Conclusion

malignant potential (according to BISCEGLIA criteria).

Plenadren treatment for 6 months in patients with AI was well received but did not

Pregnancy was leaded to its term, with birth of a healthy new-born. The patient

translate into detectable changes in clinical biochemistry or body composition.

was followed for more than one year without recurrence.

Longer treatment duration and a larger patient group are needed to evaluate the

Treatment of adrenal oncocytoma should always be surgical, with an exert as

long term benefit of plenadren.

large as possible.

DOI: 10.1530/endoabs.49.EP63

DOI: 10.1530/endoabs.49.EP65

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP66

sample of patients the over-substitution of these patients should be reconsidered

regarding the consequences.

Primary hyperparathyroidism associated with Cushing syndrome and

primary hyperaldosteronism

DOI: 10.1530/endoabs.49.EP67

Fatma Mnif, Hamza Elfekih, Mouna Elleuch, Faten Hadjkacem,

Dorra Ghorbel, Nabila Rekik, Mouna Ammar, Mouna Mnif &

Mohamed Abid

Hedi-Chaker University Hospital, Sfax, Sfax, Tunisia.

Introduction

EP68

The simultaneous occurrence in the same patient of more than one

endocrinological condition is rare and was described in the multiple endocrine

The role of dehydroepiandrosterone sulphate (DHEAS) in the

neoplasia (MEN). Here, we report a patient with an unusual combination of

evaluation of autonomous cortisol secretion in adrenal incidentalomas

primary-hyperparathyroidism, papillary thyroid microcarcinoma, primary-hyper-

Fotini Adamidou, Thomas Georgiou, Gesthimani Mintziori, Efrosini Tsirou,

aldosteronism and ACTH-independent Cushing’s syndrome.

Panagiotis Anagnostis, Athanasios Panagiotou & Marina Kita

Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece.

Case description

A 54-year-old women with a primary-hyperparathyroidism was admitted to our

hospital to undergo a parathyroidectomy for a single adenoma and total

Introduction

thyroidectomy for suspicious nodules in which one of it was confirmed

Subclinical hypercortisolism (SH) has been reported in 5-20% of patients with

histopathologically to be a

3 mm papillary thyroid microcarcinoma. An

adrenal incidentalomas (AIs), with various cardiometabolic consequences. We

exploration of a resistant hypertension associated with hypokalaemia was done

intended to investigate the contribution of DHEAS to standard testing, as another

and the co-secretion excess of aldosterone (aldosterone-renin ratio O23 ng/ng

indicator of autonomous cortisol secretion in AIs.

twice) and cortisol (negative overnight and low-dose Dexamethasone suppression

Materials and methods

with low ACTH level) was confirmed with an abdominal CT-scan showing a

Ninety consecutive patients (nZ90) with AIs were included in a prospective

19 mm left adrenal adenoma. The patient has also multiple lipomas.

cohort study. SH was diagnosed if R2 criteria were fulfilled: an overnight

Conclusion

dexamethasone suppression test (DST) R1.8 mg/dl, a 24 h urinary free cortisol

The multiple endocrine hypersecretion exists and the MEN1 should be considered

(UFC) above the upper limit of normal, midnight/morning serum cortisol R0.5

since there is a considerable number of atypical MEN1 syndrome thus the DNA

and plasma ACTH !10 pg/ml. Age- and sex-specific DHEAS ratios were

testing is scheduled.

calculated and a ratio of 1.25 was considered the cut off. Data are expressed as

DOI: 10.1530/endoabs.49.EP66

median (interquartile range).

Results

Ten cases of SH were found among the 90 patients (11%), harboring 112 AIs.

DHEAS ratio in patients with SH was 1.55 (2.5) and 1.85 (2.67) in non-functional

AIs. A DHEAS ratio %1.25 was not predictive of SH.

Conclusion

DHEAS failed to prove a useful screening tool for SH in patients with AIs in this

study. Further study is needed to evaluate its potential as an adjunct to DST.

DOI: 10.1530/endoabs.49.EP68

EP67

Comparison of biochemical and hormonal parameters in patients with

primary adrenal insufficiency of autoimmune and no-autoimmune

cause

Anna Angelousi, Aggeliki Karapanagioti, Giorgos Nikolopoulos,

Panagiotis Moschouris, Marina Tsoli, Vasiliki Mavroeidi,

EP69

Michalis Kokkinos, Nikolaos Assonitis, Fotini Petychaki, Gregory Kaltsas

& Eva Kassi

Adrenocortical carcinoma in pregnancy

Kapodistrian University of Athens, Athens, Greece.

Goknur Yorulmaz¹, Nur Kebapci¹, Funda Canaz², Betul Aydin Buyruk¹,

Sevil Alaguney¹, Bartu Badak³ & Mahmut Kebapci⁴

¹Division of Endocrinology, Eskisehir Osmangazi University School of

Introduction

Medicine, Eskisehir, Turkey;²Department of Pathology, Eskisehir

Primary adrenal insufficiency (PAI) can be of autoimmune origin (AI), non-

Osmangazi University School of Medicine, Eskisehir, Turkey;³Department

autoimmune origin (bilateral adrenalectomy, acute hemorrhage, infection) (NAI)

of General Surgery, Eskisehir Osmangazi University School of Medicine,

or pharmaceutical (mitotane) origin. Studies have shown that these patients

Eskisehir, Turkey;⁴Department of Radiology, Eskisehir Osmangazi

develop long-term morbidities and increased mortality due to excessive

University School of Medicine, Eskisehir, Turkey.

glucocorticoid tissue exposure. Data about differences concerning hydrocortisone

(HC) needs, cortisol hormonal levels and metabolic parameters in these patients

are scarce.

Introduction

Methods

Adrenocortical carcinoma (ACC) is a very rare tumor. The mean age at onset is

This retrospective analysis included patients with PAI with follow-up more than

between 40 and 50 years. Patients with nonfunctioning ACC report symptoms of

5 years (mean follow-up: 9G6.9 years). Patients had two different day curves of

abdominal discomfort or back pain due to the large tumor size. Surgery for ACC

cortisol (F) measurements and 24 h urinary cortisol levels (UFC) and were on oral

should be performed by an expert surgeon.

HC replacement treatment (total mg/day).

Case

Results

A 29-year-old patient with 25 weeks of pregnancy admitted at our clinic with

We included 12 patients with Addison disease (AD), 8 patients under therapeutic

right side pain. 10!11 cm solid mass on right adrenal gland was detected by

mitotane levels (O13 mg/l) and six patients with PAI of other causes (NAI). BMI

ultrasonography. The lactate dehydrogenase level of the patient was 10 times

increases in all groups in the follow up and it is positively correlated with daily

higher than normal ranges. The urinary metabolits were within normal limits.

HC substitution (PZ0.017, rZ0.5). Mitotane group had statistical significant

Because of the increase in the size of the mass, the patient underwent operation

higher BMI at diagnosis compared to the two other groups (PZ0.015). This

urgently. The histopathological report indicates an adrenocortical carcinoma and

difference among groups in the BMI disappears in the follow-up thus probably

tumor weighting 376 g and measuring 10!9!7 cm. The patient gave birth on

due to ‘Cushing effect’. NAI group had higher HC substitution compared to AD

the 32nd gestational week. The patient was evaluated after delivery and liver,

group (PZ0.01) and higher Hb1Ac and cholesterol levels during follow up

pulmonary and brain metastases were detected. One week after delivery patient

compared to AD group (PZ0.02) and mitotane group (PZ0.05). As expected HC

was died in intensive care unit.

substitution as well as UFC levels were significant higher in the mitotane group

Conclusion

compared to the two other groups (PZ0.0014, PZ0.05 respectively). Median F

Several clinical data shown that the secretion and or proliferation of

levels were positively correlated with HC substitution (PZ0.027) (mitotane

adrenocortical tumors may have be affected by the hormonal context of

group was excluded).

pregnancy. Most of patients present with excess steroid hormone or abdominal

Conclusion

mass effects. In our patient, a mass was detected in the ultrasonography performed

Patients with NAI had statistically higher HC substitution as well as Hb1Ac and

with the cause of side pain. In pregnancy treatment procedure was not still

cholesterol levels in the follow up compared to AD group. Despite the small

standardized in ACC, but ACC was an aggressive malignant tumor, so our patient

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

was operated urgently. Because of her pregnancy chemotheraphy was planned

ACC size was 9 cm (P!0.05). In the ACC group, NLRO5 was found in 26.3%

after birth. But one week after delivery patient was died.

(5/19) patients which was higher compared to 9% (2/22) of the patients with

DOI: 10.1530/endoabs.49.EP69

NLRO5 in the adenoma group. PLRO190 was found in 36.8% (7/19) of ACC

patients compared to 18.2% (4/22) in the adenoma group. Mean NLRs in the ACC

and in the adenoma group were 3.6 and 3.1, respectively (PZ0.886) and mean

PLRs were 219.1 and 143.3, respectively (PZ0.026). Our results indicate that in

addition to tumor size, PLR might potentially serve as biomarker of malignant

tumor behavior.

DOI: 10.1530/endoabs.49.EP71

EP70

Abnormal aldosterone/renin ratio is common in patients of African

compared to European origin, is associated with hypokalaemia, and left

ventricular hypertrophy, but is rarely associated with abnormal

adrenal imaging characteristics

KS Ahmed, D Bogdanet, S Heshe, G Boran, LA Behan, M Sherlock &

J Gibney

EP72

Departments of Endocrinology, Cardiology and Chemical Pathology,

Adrenal involvement of Non-Hodgkin’s lymphoma: a case report

The Adelaide and Meath Hospital, Incorporating the National Children’s

Ozen Oz Gul, Soner Cander, Erdinc Erturk & Canan Ersoy

Hospital, Tallaght, Dublin 24, Dublin, Ireland.

Uludag University Medical School, Department of Endocrinology and

Metabolism, Bursa, Turkey.

Adrenal mineralocorticoid biochemistry differs between people of African and

European ancestry. The aldosterone/renin ratio (ARR) is the initial screening test

Introduction

for primary hyperaldosteronism (PHA), but little data exists regarding ethnic

The involvement of certain organs such as the adrenal gland is rare in non-

variations in this.

Hodgkin’s lymphoma (NHL). Although lymphomas can involve virtually all

Following clinical observation of a high prevalence of abnormal ARR in patients

extranodal organs, different organs show different frequency of involvement.

of African origin, we retrospectively reviewed all ARR measurements in a single

Adrenal gland involvement is usually bilateral. We report that a rare case of

centre over 10 years. Rates of hypokalaemia and intraventricular septal thickness

unilateral adrenal involvement of diffuse large B-cell lymphoma presenting with

(IVS, by echocardiography) were studied as end-points of PHA, and adrenal

abdominal pain.

imaging was reviewed. Data were analysed using Student’s t-test, c-square test

Case

and Mann-Whitney-Wilcoxon test as appropriate.

A 64-year-old-man presented with abdominal pain, weakness, weight loss.

ARR was available in 1,473 patients, and abnormal in 374 (25.4%). Abnormal

Abdominal computed tomography (CT) revealed 59!53 mm right adrenal mass,

ARR occurred in 305/1473 (20.7%) of European and 69/124 (55.6%) of African

40!25 mm paraaortic lymphadenopathy, multiple solid mass lesions in the

patients

(P!0.001). Among those with abnormal ARR, hypokalaemia

spleen and malignant infiltrating mass lesions in the perineal vascular structures.

(!3.5 mmol/l) was documented on at least one occasion in 171/305 (56.1%)

Surgical lymph node biopsy demonstrated a diffuse large B cell lymphoma. The

European and

43/69

(62.3%) African patients. Median

(range) IVS was

pathology specimens showed neoplastic infiltration of pleomorphic lymphoid

1.57(0.78-2.80) cm in African-origin and

1.2

(0.69-2.18) cm in European

cells with scanty cytoplasm, irregular nuclear contour, large nuclei, with one to

patients (P!0.002). Adrenal adenoma was identified in 2/69 (2.8%) African and

three peripherally positioned nucleoli. He was treated with rituximab, cyclopho-

41/305 (13.4%) of European patients (P!0.005).

sphamide, doxorubicin and vincristine (R-CHOP). The patient tolerated treatment

In summary, ARR was abnormal in 55.6% of African-origin patients screened at

well without significant side effects. After the six courses chemotherapy, the

an Irish hospital, but only 2.8% had demonstrable adrenal pathology. Rates of

patient’s systemic symptoms were improved.

hypokalaemia were similar between European-origin and African-origin patients,

Conclusion

while cardiac hypertrophy was more marked in African-origin patients. These

Extranodal organ involvement is more common in non-Hodgkin’s lymphoma

findings have implications for the use of current screening guidelines for ARR in

than in Hodgkin’s lymphoma. Systemic chemotherapy has been regarded as the

African-origin patients and also for the mechanistic role of aldosterone in

best therapeutic approach for NHL involving rare extranodal sites. Adrenal

hypertensive complications in African-origin patients.

involvement of systemic lymphoma should be considered when evaluated the

DOI: 10.1530/endoabs.49.EP70

adrenal masses.

DOI: 10.1530/endoabs.49.EP72

EP71

Neutrophil-lymphocyte and platelet-lymphocyte ratios as biomarkers in

distinguishing adrenocortical adenomas and carcinomas

EP73

Mirsala Solak¹, Ivana Kraljevic¹, Marko Kastelan¹, Luka Kakarigi¹,

Challenges in differential diagnosis of adrenal incidentaloma or clinical

Tina Dusek¹, Tanja Skoric Polovina¹, Annemarie Balasko¹,

case of multiple myeloma

Nikola Knezevic² & Darko Kastelan¹

Natalia Volkova¹, Maria Porksheyan¹, Ilya Davidenko¹, Kit Oleg² &

¹Department of Endocrinology, University Hospital Center Zagreb, Zagreb,

Dimitriadi Serguey²

Croatia;²Department of Urology, University Hospital Center Zagreb,

¹Rostov Sate Medical University, Rostov On Don, Russia;²Rostov Research

Zagreb, Croatia.

Institute of Oncology, Rostov On Don, Russia.

The role of systemic inflammation in promoting tumor progression has been a

Adrenal incidentaloma (AI) in patients with cancer poses diagnostic challenge for

topic of increasing interest. Neutrophil-lymphocyte ratio (NLR) O5 and platelet-

doctors. We present clinical case of generalised metastatic bone diseases and

lymphocyte ratio (PLR) O190 used as indicators of inflammation have been

adrenal mass.

reported to have prognostic value in numerous solid tumors. The aim of this

Male 59 years old asked the second opinion about incidental adrenal mass, which

retrospective study was to investigate NLR and PLR as biomarkers in

was suspected for adrenal cancer by urologist. His medical anamnesis began in

distinguishing between adrenocortical adenomas and adrenocortical carcinomas

April of 2015 with severe generalised bone pain. The whole body MRI/CT

(ACC). Nineteen patients with ACC (mean age 54 years, range 24-75; eight male,

detected multiple bone lesions, adrenal mass (57!45!56 mm, 37 HU) and

11 female) and 22 patients with adrenal adenomas (mean age 47 years, range 28-

prostate mass. Urologist studied PSA and carried out prostate biopsy, the results

71; six male, 16 female) were enrolled in the study. In the ACC group, only one

excluded prostate cancer. Basing on size and CT dencity of adrenal mass, the

patient presented with functional tumor (excess estradiol), whereas all the others

urologist suspected adrenal cancer and prepared to perform adrenal biopsy. First,

were discovered incidentally. Eleven out of 19 patients with ACC were operated

he decided to get an endocrinologist consultation to exclude pheochromocytoma

laparoscopically, while the open approach was used in eight of them. In the

and ask the second opinion about suspected adrenal cancer. There were excluded

adenoma group, the first presentation of the disease was hyperandrogenemia in

pheochromocytoma, subclinical Cushing and adrenal insuficiency. Taking into

one patient, and in the rest of the group, adenoma was discovered incidentally.

accout the fact that adrenal cancer metastasis affect liver and lung first, which

Open surgical approach was used in one patient with adenoma and the others were

were abcent in this case, lack of rapid growth of adrenal mass, the suspected

operated laparoscopically. The mean size of adenoma was 5.8 cm while the mean

diagnosis of adrenal cancer was hardly probable. The suggestion for adrenal

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

biopsy was refused because of hematologic disturbances and potential

study was to analyze differences in adipose tissue distribution in women with

hemorrhage. Also there was made an offer to perform the bone lesion biopsy,

Cushing’s disease and Cushing’s syndrome due to adrenal adenoma.

which is easier and safer to perform. The results were consistent with multiple

Method

myeloma. Patient was seen by hematologist, the appropriate treatment assigned.

We evaluated 12 women with Cushing’s syndrome, six with ACTH secreting

The interesting fact was that the hematologic, bony and urinary signs, which are

pituitary adenomas (Group A) and six with adrenal adenomas (Group B). In all

typical for myeloma, were abcent. Unfortunately, patient died after second cource

subjects BMI was calculated and body composition assessed by dual energy

of chemotherapy.

X-ray absorptiometry. Basal values of serum cortisol, ACTH and DHEA-S were

This case illustrates as diagnostic as administrative issues. First, the urologist did

determined at admission to the hospital.

not follow the diagnostic protocol for adrenal incidentalomas, which would have

Results

been fatal. Secondly, the management of AI in cancer or suspeceted cancer

Mean age was comparable between Group A and Group B (44.5C/K14.7 years

patients should be absolutely multidisciplinary. Thirdly, untypical signs of the

vs. 52.7C/K5.6 years, PZ0.23) while BMI was significantly higher in Group B

disease requires doctors to be more educated in edjacent specialities.

(32.7C/K5.5 kg/m² vs. 25.6C/K4.3 kg/m², PZ0.034). Group B had signi-

DOI: 10.1530/endoabs.49.EP73

ficantly higher percent of total body fat (45.4C/K4.3% vs. 34.5C/K8.4%,

PZ0.021) but borderline difference in trunk fat percentage (Group B 44.3C/K

6.8% vs. Group A 32.6C/K10.7%, PZ0.055). Main difference in adipose tissue

percentage was found on arms and legs, which was higher in Group B (arms

53.6C/K8.8% vs. 38.5C/K11.9%, PZ0.037; legs 47.6C/K4.4% vs. 39.0C/K

5.9%, PZ0.022). There was no significant difference in lean body mass or bone

mineral density between these two groups. As expected, ACTH was significantly

higher in group A (74.3C/K16.4 ng/l vs. 14.7C/K7.6 ng/l, PZ0.040), but with

EP74

no significant differences in morning cortisol concentrations (Group A 664.2C/K

Iatrogenic Cushing syndrome and suprarenal secondary insufficiency

210.4 nmol/l vs. Group B 432.8C/K146 nmol/l, PZ0.060), midnight cortisol

due to interaction between fluticasone and ritonavir

concentrations

(Group A 461.3C/K236.2 nmol/l vs. Group B

330.3C/K

Suarez Gutierrez Lorena¹, Veiguela Blanco Brenda², Dieguez

203.6 nmol/l, PZ0.410) or DHEA-S concentrations (4.9C/K5.4 nmol/l vs.

Felechosa Lorena², Manjon Miguelez Laura¹, Riestra Gonzalez Maria²,

2.8C/K3.8 nmol/l, PZ0.564) between groups.

Antun˜a García Nuria2, Diaz Fernandez Maria Jesus2 &

Conclusion

Casal Alvarez Florentino²

Our group of women with Cushing’s syndrome due to adrenal adenoma had

¹Hospital Universitario Central De Asturias, Oviedo, Spain;²Hospital De

higher BMI and increased total fat adiposity. It was not determined yet if the

Cabuen˜es, Gijon, Spain.

origin of hypercortisolism, or derangements in other related hormones or

metabolic pathways, could possibly influence body composition in those patients.

Introduction

DOI: 10.1530/endoabs.49.EP75

The interaction between corticosteroids and protease inhibitors (PIs) is a clearly

described drug interaction.

Case report

A 44-year-old woman diagnosed with HIV category B3 diagnosed in 1989; severe

lipodystrophy. In addition , HCV genotype IA. Bronchial asthma since 2000.

Treatment with fluticasone

1 inh/24 h, salbutamol on demand, darunavir

800 mg/day and ritonavir 100 mg/day. He had known lipodystrophy since 2001

and the abdominal perimeter was monitored, aiming to increase it. Likewise, it

EP76

presented progressive proximal weakness in lower limbs, with increased hair, hair

Clinical course of patients with adrenal incidentaloma: retrospective

fragility and alopecia reason why it is referred to Endocrinology. Moderate

analysis of a single center

hirsutism, muscular atrophy and in the analytical study: normal FSH and LH are

Ana Carolina Ruiz Serrano¹, Ana Megia Colet^1,2, Silvia Näf Cortes^1,2,

objectified. Testosterone

0.05 ng/ml

(0.1-0.9), ACTH

1.0 pg/ml

(7.2-63.3),

Joan Vendrell Ortega^1,2, Inmaculada Simon Muela^1,2, Esther Solano Fraile¹

Cortisol am 0.65 mg/dl (4.30-22.40) urinary free cortisol 3.74 mg/24 h (36-137).

& Theodora Michalopoulou Alevras¹

A Synacten test is performed: Basal 0.52; 30 min 2.33; 60 min 2.84 with ACTH 1

¹Endocrinology and Nutrition Service University Hospital of Tarragona

and was diagnosed as having an independent iatrogenic Cushing ACTH syndrome

Joan XXIII, Tarragona, Spain;²CIBERDEM, Tarragona, Spain.

associated with secondary adrenal insufficiency. With this diagnosis he is referred

to the pulmonology department for corticosteroid replacement. Inhaled and

substitution treatment was initiated with hydrocortisone and went home with a

In the adrenal incidentaloma (AI) it is fundamental to determine functionality and

new antiretroviral regimen (raltegravir, tenofovir and abacavir)

benignity. The aim of this study was to evaluated the clinical, radiological and

Discussion

hormonal evolution of AI and compare the frequency of autonomous cortisol

Fluticasone is a synthetic steroid that is cleared by the cytochrome P450 CYP3A4

secretion (ACS) between American and European Guidelines.

enzyme, which is inhibited or potentiated by a multitude of drugs, including

Methods

ritonavir. As it is not metabolized, an increase in circulating levels leads to a

Retrospective evaluation of patients with AI referred to our service in the last

decrease in the secretion of ACTH and therefore a suppression of the adrenal

5 years.

gland with insufficiency of the same and cushing syndrome.

Results

The options are the substitution of Fluticasone by a non-substrate of CYP3A4

140 patients were included, 50.9% were men. At diagnostic, the media of age was

such as beclomethasone and the substitution of ritonavir for another antiretroviral.

66G11.2 years and the median of size was 20 mm. CT detected the 95% of AI

Most cases resolve in about 9-12 months.

and 80% had an adenoma-like appearance (49.3% left). Hormonal evaluation

DOI: 10.1530/endoabs.49.EP74

revealed that

54.3% were nonfunctional (NF), 38.6% possible autonomous

cortisol secretion (PACS), 5.7% ACS, 5% Cushing’s syndrome (CS) and 1.4%

pheochromocytoma (PCC). Considering American guidelines: 87.9% were NF,

9.3% subclinical Cushing’s syndrome and 0.7% CS. The majority of patients

remained stable. None developed overt CS. The 13.6% showed growth, with a

median of 6 mm. Median follow-up: 30 months. There were significant statistical

differences (P!0.05) between the group of NF and PACS/CS in terms of size and

EP75

between NF and CS in terms of growth. No differences were observed in terms of

Body composition in women with Cushing’s syndrome of different

sex, age or cortisol-related comorbidities. Seven patients underwent surgery: one

etiology

PACS, three ACS, two PCC and one adrenal carcinoma. The 4.3% died due to

Dusan Ilic, Djuro Macut, Ivana Bozic Antic, Bojana Popovic,

unrelated adrenal disease.

Tamara Bogavac, Tatjana Isailovic, Valentina Elezovic, Sanja Ognjanovic

Conclusions

& Svetozar Damjanovic

The AI’s are predominantly small, benign, nonfunctioning; stable in time, tumor

Clinic of Endocrinology, Diabetes and Metabolic Diseases, Belgrade,

size and hormonal production. The use of the diagnostic criteria for ASC

Serbia.

according to European guidelines shows an increase in the frequency of

PACS/ACS, therefore, ACTH determination should be considered in the

diagnosis.

Introduction

Cortisol has important roles in the regulation of body composition and

DOI: 10.1530/endoabs.49.EP76

hypercortisolaemia have major impact on body fat distribution. The aim of this

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP77

In everyday PHA diagnostics practice there is still lack of “game changer”

bringing the final conclusion for diagnostic and profilactic strategies for the whole

Malignant androgen-secreting adrenocortical carcinoma with adrenal

hypertensive population.

insufficiency: a case report

Fatma Mnif, Mehdi Kalthoum, Mona Elleuch, Saafi Wajdi, Nadia Charfi,

DOI: 10.1530/endoabs.49.EP78

Mouna Ammar, Hamza Feki, Mona Mnif & Mohamed Abid

Endocrinology-diabetelogy Departement CHU Hedi Cheker, Sfax Tunisia,

Tunisia.

Adrenocortical carcinoma (ACC) is a rare malignancy, accounting for 0.02% of

all annual cancer. The majority of these tumors are benign, non-functioning

EP79

adenomas that are incidentally discovered on abdominal image studies. Others are

functional adenomas secreting cortisol, aldosterone, or less commonly androgens

Clinical, laboratorial and densitometric evaluation of adult women with

or estrogens. Pure androgen-secreting adrenal tumors are very rare.

congenital adrenal hyperplasia

Case report

Leilane Vensa˜o, Victoria Borba & Adriane Rodrigues

SEMPR, Curitiba, Paraná, Brazil.

A 34-year-old female patient presented with pain in the left upper abdomen. A

multiphasique CT scan abdomen was done, which revealed large adrenal mass

measuring 18!14!14 mm in dimension with central hemorrage. Patient gave

Introduction

history of amenorrhea since 6 months associated with increased hair growth of

There is paucity of data comparing bone densitometry and body composition in

chest, lower abdomen, and face. Moreover the patient declare recent weight loss

adult women with congenital adrenal hyperplasia

(CAH) treated with

(11 kg in 2 months) with asthenia, anorexia, and melanoderma.

glucocorticoids since childhood and the same parameters in healthy women of

On examination, heart rate was 84/min, blood pressure 120/70 mm of Hg.

the same age and BMI.

Hirsutism was evaluated based on Ferriman-Gallwey score

(result Z

13).

Methods

Biochemical screening showed a total testosteroneZ8 ng/ml (0.06-0.82), DHEA

20 women with classical CAH (35% simple virilizing, 65% salt losing), aged 16-

sulfate Z3.27 mg/ml

(0.4-2.17 mg/ml),

17-hydroxyprogesterone O20 ng/ml

45 years, had anthropometric, laboratorial and densitometry exam (DXA) for

(0.1-0.8 ng/ml), LHZ0.83 mUI/l and FSHZ0.1 mUI/l. The diagnosis of

bone mineral density (BMD) (L1-L4, total femur and femoral neck). Laboratory

Addison’s disease was confirmed by basal serum ACTHZ125.82 ng/l and

determinations during follow-up were recorded and expressed as average levels.

serum cortisolZ135 mg/l after ACTH test; serum aldosterone and 24 h urinary

18 control women of the same age and BMI as patients realized densitometric

VMA were normal. A diagnosis of androgen-secreting adrenocortical cancer with

evaluation for mineral density and body composition.

adrenal insufficiency was made.

Results

Patient underwent exploratory laparotomy with excision of large adrenal tumor

BMI ranged from16 to 41 kg/m² (average 26.3; 25% overweight and 30% obese),

without any complication. The histopathological examination described a mass

whereas height varied from136 to167 cm (average 151 cm). During follow-up,

21!18!12 mm with microscopique features of tumor cells sharing mild nuclear

35% patients were treated with prednisone as the sole glucocorticoid type, 50%

atypia and rare mitotic figures: histological and immunohistochmical aspect of

used prednisone and dexamethasone and 15% other combinations. Average daily

adrenocortical carcinoma (Weiss scoreZ3, Ki67Z10).

dose of prednisone was 7.5 mg (hydrocortisone equivalent dose 37 mg/day) and

On follow-up after 6 months, patient was comfortable, and no longer had

70% used fludrocortisone (average 0.1 mg/day). Combined oral contraceptives

amenorrhea or hursitism. Total testosterone was 0.03 ng/ml (0.06-0.82), DHEA-

were taken by 65% women. Half of women were not controlled based on average

sulfate was 0.174 mg/ml (0.4-2.17 mg/dl) and CT scan abdomen was normale.

testosterone and androstenedione levels, 40% presented altered glycemic status,

DOI: 10.1530/endoabs.49.EP77

26% elevated LDL cholesterol, 21% elevated triglycerides, 68% low HDL-

cholesterol levels. No patient presented low BMD according to Z-score and

compared to control group. Fat-free mass was considerably lower in patients than

controls (33.726 vs 40.637 kg) and it correlated positively with testosterone levels

(R 0.52, P 0.027). Women using fludrocortisone had lower body fat mass than

women who used only glucocorticoids (34.3C12.3% vs 44.9C3.8%).

Conclusion

Adult women treated for classical congenital adrenal hyperplasia had important

metabolic disturbances and alterations in body composition. Nevertheless bone

EP78

mass was preserved, possibly because hyperandrogenism was not controlled most

Hyperaldosteronism screening in Hypertensiologists experience -

of the time.

epidemiological review of over 800 cases

DOI: 10.1530/endoabs.49.EP79

Weronika Korzynska, Anna Jodkowska & Grzegorz Mazur

Department and Clinic of Internal and Occupational Diseases, Hypertension

and Clinical Oncology, Wrocław Medical University, Wroclaw, Poland.

Primary aldosteronism (PHA) is one of the most common cause of secondary

hypertension. It can possibly concern over 10% of hypertensive patients, but often

is being under-recognised. The basic tool of case PHA detection is aldosterone to

EP80

renin ratio (ARR). Appropriate cutoff value of ARR is still under discussion.

The effect of subclinical hypercortisolism on bone mineral density in

We review occurrence of CT/MRI detectable adrenal gland laesions according to

female patients with adrenal incidentalomas

assigned ARR cutoff value. Retrospective data from

833

consecutive

Sanja Ognjanovic, Djuro Macut, Milan Petakov, Valentina

hypertensive patients of average age 39.85 (S.D.:C/K15), 449 men and 384

Kovacevic Elezovic, Tatjana Isailovic, Ivana Bozic Antic, Dusan Ilic,

women was analized. ARRO20, 30, 40 concerned respectively: 12.7%, 7.6%,

Bojana Popovic, Tamara Bogavac, Jadranka Antic & Svetozar Damjanovic

4.7%. CT/MRI was performed respectively in patients with ARRO20, 30, 40 in

Clinic for Endocrinology, Diabetes and Metabolic Diseases, Belgrade,

55.7%, 66.7%, 69.2%. Laesions in adrenal glands in groups of ARRO20, 30, 40

Serbia.

concerned respectively: 47%, 52.4%, 56%. The most common CT/MRI findings

were adenomas: respectively: 37.3%, 42.9%, 44.4% in groups of ARRO20, 30

and 40. Less common was nodular hypertrophia: respectively: 10.2%, 9.5%,

To investigate the prevalence of SH and osteoporosis in female patients with

14.8% in groups O20, 30, and 40. The average potassium level in a group of

unilateral AIs (UAIs) and bilateral AIs (BAIs).

ARRO20 was 4.05 (mmol/l) (S.D.:C/K0.46), O30 3.94 (S.D.:C/K0.50), O40

We enrolled 106 female patients, 68 (64.2%) with UAIs and 47 (35.8%) with

3.93

(S.D.:C/K0.55).

BAIs. SH was diagnosed in the presence of serum cortisol levels after 2-day low-

Average concentration of urine aldosterone in a group O20 was 14.36 (mg/24 h)

dose dexamethasone suppression test (LDDST) O50 nmol/l with at least one of

(reference value 2.1-18.0 mg/24 h) (S.D.:C/K10.88), O30 15.72 (S.D.:C/K

the following parameter (midnight serum cortisol O208 nmol/L, 24-h urinary

12.33), O40 17.71 (S.D.:C/K14.08).

free cortisol O245 nmol/24 h, or ACTH !10 ng/l). BMD was measured with

Adrenal lesions in enlarged ARR group were notably more often than adrenal

dual-energy X-ray absorptiometry at lumbar spine (LS), femoral neck (FN), and

incidentalomas occurrence reported in population (47% vs 2-3%). Higher cutoff

total skeleton.

ARR value is more specific and allows to reduce costs of confirmative tests. If the

No difference was noted in age, BMI, percent of postmenopausal women and

ARR over O40 group we miss 16.95%, in ARR O30 group we miss 6.78% in

years since menopause. The overall prevalence of SH was 20.2%, and was more

compare to ARRO20. Can we afford missing them considering its’ increased

prevalent in BAIs than UAIs patients (36.1% vs 11.8%, respectively, PZ0.003).

cardiovascular risk?

The largest tumor diameter was similar in patients with UAI and BAI (PZ0.254).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

After adjustment for BMI, waist, and presence of BAIs, SH were associated with

Introduction

adrenal mass size (odds ratio (OR)Z1.101, 95% CI 1.041-1.166, PZ0.001) and

Adrenocortical carcinomas are rare neoplasms with an incidence of 0.7 to 1.5 per

age (ORZ1.086, 95% CI 1.021-1.155, PZ0.009). LS-BMD and total-BMD were

million/year. Diagnosis often requires a multidisciplinary approach. When the

lower in BAIs than in UAIs patients (0.94G0.13 vs 0.86G0.17, PZ0.015, and

disease is confined to the adrenal gland, absolute criteria defining malignancy,

1.08G0.18 vs 1.02G0.14, PZ0.029). There were no differences in FN-BMD.

do not exist, however a score of WeissO or Za 3 is considered diagnosis. The

Patients with BAIs had an increased frequency of osteoporosis (46.41% vs 23.5%,

prognosis is usually reserved and conventional chemotherapy is not curative.

respectively, PZ0.036). The presence of osteoporosis was associated with

Material and Methods

SH (ORZ5.775, 95%CI 1.423-23.426, PZ0.014) and lower BMI (ORZ1.226,

Retrospective analysis of the clinical and demographic characteristics, review of

95%CI 1.071-1.405, PZ0.003), after adjusting for age, menopause and

the anatomopathological and therapeutic criteria of patients with adrenocortical

vitamin-D.

carcinoma treated at our Institution between 1999 and 2015.

This study suggests significantly higher prevalence of SH in patients with BAIs

Results

than in patients with UAIs. Tumor mass could be of importance for the amount of

Twenty-two patients with a mean age of 56 years were evaluated, 50% of cases

autonomous cortisol production. The prevalence of osteoporosis was higher in

were male. The majority of patients (63.6%) were symptomatic and pain was the

patients with BAIs due to SH.

most frequent symptom (57.1%). All patients underwent surgical treatment.

DOI: 10.1530/endoabs.49.EP80

Multiorgan resection was performed in 5 cases (22.6%). The surgery was R0 in

72.7%. After histological examination,

72.7% presented Weiss scoreO

Adjuvant therapy was performed in 5 patients (22.6%). Considering the revision

of the Weiss score, TNM staging and margins status, 50% of the patients would

had indication for adjuvant treatments. In this series, the relapse rate (local or

distance) was 38.1% (8 cases) and the overall survival at 5 years was 62%; which

compares favorably with that described in the literature.

Conclusions

The rarity of this pathology makes diagnosis and therapeutic orientation difficult.

EP81

A rigorous and standardized histological evaluation is imperative to ensure the

most appropriate adjuvant treatment. The referral of this patients to centers of

Long term follow up of patients with adrenal incidentaloma and

expertise is essential, with the hope that new target therapies will lead to better

‘autonomous cortisol secretion’

results.

Ivana Kraljevic¹, Mirsala Solak¹, Tina Dusek^1,2, Tanja Skoric Polovina¹,

Annemarie Balasko¹ & Darko Kastelan^1,2

DOI: 10.1530/endoabs.49.EP82

¹University Hospital Center Zagreb, Zagreb, Croatia;²ZAgreb University

School of Medicine, Zagreb, Croatia.

The aim of this study was to compare the long-term co-morbidities and

biochemical data between patients with adrenal incidentaloma and ‘autonomous

cortisol secretion’ who were treated surgically and conservatively.

Methods

The research of the database of the patients with adrenal incidentaloma diagnosed

between

2007

and

2014

was performed. Among them,

patients with

‘autonomous cortisol secretion’ were identified and invited for a follow-up

EP83

visit. Diagnostic criteria for

‘autonomous cortisol secretion’ were: cortisol-

A near miss on blaming the heart: a rare case of Adrenocortical

O83 nmol/l after 1 mg dexamethasone suppression test plus one additional

carcinoma with thrombus extension into right atrium and

criteria (suppressed ACTH secretion or elevated urinary free cortisol). At follow-

Cushing syndrome

up visit the anthropometric as well as biochemical data were collected (blood

Hadeil Morsi¹, Mohamed Eisa³, Lynsey Goodwin², Peter Flegg² &

glucose, lipid panel test, HOMA index, cortisol after 1 mg dexamethasone,

Myint Aye²

urinary free cortisol, and ACTH). All patients were evaluated for hypertension,

¹North West Health Education England, Manchester, UK;²Blackpool

dyslipidemia, osteoporosis and diabetes mellitus/impaired glucose tolerance.

Victoria Hospital Foundation Trust, Blackpool, UK;³Wellstar Atlanta

Results

Medical Center, Atlanta, GA, USA.

Of the 43 invited patients, 26 patients performed follow up visit (4 males). Among

them, 17 patients were treated surgically and 9 were treated conservatively.

Median follow-up was 6 years (range 2-16), median age at follow-up was 62

A 39 year old female patient presented with one week history of Shortness of

years (range 41-76). There was no difference in BMI at baseline and at follow up

breathing. Over the last four months she noted bilateral leg swelling, which failed

in both groups. In the group of surgically treated patients, during follow-up period

to improve on diuretic. Examination revealed no other evidence of fluid overload

one patient was diagnosed with arterial hypertension, 4 with hyperlipidemia, and

or heart failure. An element of right heart strain rather than failure was raised on

one with diabetes mellitus. Nevertheless, nine out of

patients with

cardiologists review. Subsequently, an echo showed a friable mass extending

hypertension in the surgical group reported improvement/disappearance of

form inferior vena cava to right atrium into proximal left ventricle. The nature of

arterial hypertension at the follow-up visit. Among conservatively treated

which was revealed to be a tumor thombus extending from the upper pole of right

patients, six out of nine patients had no difference in co-morbidities, one was

kidney with resultant pulmonary emboli. To this end, an impression of invasive

newly diagnosed with osteoporosis, one with arterial hypertension and one with

renal carcinoma was made. Until endocrinology review for erratic hyperglycemia,

renal insufficiency. Conclusion: Patient who underwent surgery for ‘autonomous

when the patient reported irritability, 6 weeks amenorrhea, change in weight

cortisol secretion’ experienced improvement in the regulation of hypertension

distribution and facial hirsutism in addition to abdominal striae on examination.

after medium follow-up of 6 years. No other significant differences were found in

Hence,the diagnosis shifted to Adrenocortical carcinoma with Cushing. Tertiary

the prevalence of comorbidities between conservatively versus surgically treated

center was consulted. In the meantime, Mitotane was started gradually, alongside

patients.

Hydrocortison. It was a difficult time for the patient who preferred palliative

DOI: 10.1530/endoabs.49.EP81

support at home. Unfortunately, few days after discharge she was readmitted with

hypoglycemiia, metabolic acidosis and liver impairment. She was treated as

Addison crises, though cortisol levels came normal later. Liver involvement was

not confirmed to be Mitotane related toxicity or ischemic injury with progression

of malignancy.

Unfortunately, she did not survive his well-known aggressive tumor. ACC are

tumors are rare tumors and presentation with such vascular invasion is an

additional rarity. As clinician on medical take, there is tendency to overclaim

heart failure. Having high index of suspicion for patients with Cushing syndrome

EP82

is central, although not all tumors are functional. The definitive management of

ACC is surgical which is not always feasible, particularly with such vascular

Adrenocortical carcinoma - casuistic analysis

extension. Wider scale clinical studies pave the management of ACC and

Catia Ribeiro, Joao Lobo, Ana Mesquita, Pedro C Martins,

optimize Mitotatne therapy.

Mariana Peyroteo, Maria Joao Matos, Pedro Antunes, Cristina Sanches,

Augusto Moreira & Joaquim Abreu de Sousa

DOI: 10.1530/endoabs.49.EP83

IPO, Porto, Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP84

EP86

Congenital Adrenal Hyperplasia due to 11b-Hydroxilase Deficiency:

24 hour ambulatory blood pressure levels according to adrenal

clinical and molecular studies of two novel families with variable

adenoma size

phenotypes

Alp Atasoy¹, Evrim Cakir², Suleyman Ahbab¹, Derya Kayas¹,

Alessandra Pfeilsticker, Luciana Valadares, Selma Sousa, Sarah Cardoso,

Esra Ataoglu¹ & Mustafa Yenigun¹

Olivia Morais, Renata Santarem & Adriana Lofrano-Porto

¹Internal Medicine Department, Haseki Training and Research Hospital,

University of Brasilia, Molecular Pharmacology Lab, Brasilia DF, Brazil.

Istanbul, Turkey;²Endocrinology and Metabolic Diseases Department,

Haseki Training and Research Hospital, Istanbul, Turkey.

11b-hydroxylase deficiency is the second most frequent cause of congenital

adrenal hyperplasia (CAH), corresponding to approximately 5% of cases., and

Aim

caused by inactivating mutations in the CYP11B1 gene. We aimed to describe

The etiology and underlying pathology of non-functional adrenal adenoma has

four new cases from two different families with a clinical diagnosis of 11b-

not been clearly defined, yet. Blood pressure levels according to adrenal adenoma

hydroxylase deficiency. Family

1: Two siblings born from consanguineous

size has not been evaluated, yet. Therefore, we evaluated 24 hour ambulatory

parents. A 31-year-old (yo) woman presented at 5 yo with genital ambiguity

blood pressure levels in patients with non functional adrenal adenoma.

(Prader II), high blood pressure (HBP) and precocious pubarche (PP). She lost

Materials & Methods

follow and returned after 3 full term normal pregnancies while using prednisone.

We studied thirty newly diagnosed adrenal adenoma patients in a tertiary health-

4 years after last gestation, she remained normotensive without any treatment.

care center. They grouped in two categories according to adenoma size. Cut-off

Her 24 yo brother presented at age 7 yo with PP, hypokalemia and HBP, when

size was taken 23 mm. 24 hour ambulatory blood pressures were evaluated in all

glucocorticoids and anti-hypertensives were started. He had low treatment

participants. Delta blood pressure was found by calculating the difference

adherence and evolved with persistent hypertension and left ventricular

between maximum and minimum blood pressure values.

hypertrophy. Family 2: A 2.9 yo boy presented with PP and high BP, managed

Results

with hydrocortisone and anti-hypertensives. His sister presented at 21 days of life

There were 17 patients with lower adenomas size, which was smaller than 23 mm,

with genital ambiguity and salt wasting, managed with hydrocortisone and oral

the remaining 13 patient’s adenomas size was equal or higher than 23 mm.

sodium. A detailed steroid profile was performed in all subjects, which confirmed

Patients with higher adenomas size had statistically higher systolic delta levels

the diagnosis. The CYP11B1 coding region of the patients’ and their parents’ was

compared to lower size group

(70.84G34.9

51.29G18.0, PZ0.004).

automatically sequenced. In the two siblings from Family 1, a homozygous splice

Additionally; the maximume systolic

(165.6G28.7

152.0G23.1) and

site point mutation, IVS4 ds-1 GOA, was identified in exon 4 (g.3132GO A). In

maximum diastolic blood pressure (115.1G37.8 to 100.2G14.9) were higher

Family 2, both siblings harbored a nonsense mutation in exon 6 (c.1066 CO T),

and also minimum systolic (94.76G11.05 to 100.70G18.60) and minimum

which generates a truncated protein (p.Q356X). The mutations presented herein

diastolic blood pressure (60.69G9.01 to 62.41G12.62) were lower in this group.

were associated with a highly variable phenotype, from a mildly virilizing

However; the differences did not reach statistically significance.

phenotype to a high degree of virilization with hypertension and with salt wasting,

Conclusion

which is unexpected. Further studies of variants in other genes associated with

Delta systolic blood pressure has been found toe higher in higher adenomas size

hypertension, in compensatory pathways of steroid synthesis and metabolism, or

group. Further studies are necessary to better clarify the association between

the verification of chimeric CYP11B genes are needed to clarify the phenotypic

blood pressure and non functional adrenal adenoma.

heterogeneity.

DOI: 10.1530/endoabs.49.EP86

DOI: 10.1530/endoabs.49.EP84

EP85

Adrenal Medulla

‘Record-breaking hyponatraemia’ with Addison’s disease

EP87

Irfan Khan & Elizabeth Cheyne

Coexisting Graves’s disease and pheochromocytoma

Southmead Hospital, Bristol, UK.

Rim Belaid, Ibtissem Oueslati, Wafa Mimita, Karima Khiari &

Néjib Ben Abdallah

Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.

Addisons disease is a rare but potentially life threatening endocrine disorder. It is

well-known for disguising as a variety of presentations before diagnosis. Here

we present a case report of Addison’s disease presenting with very severe

Introduction

hyponatraemia. A 35 year old lady was admitted with lethargy, low mood, weight

Although Graves’ disease is often accompanied by other autoimmune diseases,

loss and feeling generally unwell for the last 3 months. Six weeks prior to her

only a few cases of Graves’ disease accompanied by pheochromocytoma have

admission, her GP arranged some routine investigations including U&E which

been described.

were normal with a Na of 137. He later prescribed her Mirtazapine for her low

Herein we report a rare case of coexisting Graves’ disease and pheochromocytoma.

mood and anxiety which she took for 4 days. This made her feel more unwell and

Observation

triggered the hospital admission. She looked tanned but there was no buccal or

A 50-year-old male patient was referred to our department for the evaluation of right

palmar pigmentation. She was alert with normal cognition.

adrenal incidentaloma of 80*66 mm. He had a history of coronary disease and he

Admission blood results showed a plasma Sodium of 94 mmol/l, K 5.7 and

presented with heat intolerance, diaphoresis, palpitations, intense headaches,

normal urea/creatinine. Further investigations showed: Serum Osmolality 252,

excessive nervousness, mood disturbances as well as a rapid weight loss of 30 kg

Urine osmolality 192, Urine Na 27, TSH 3.2 and random cortisol 290. She was

during the last one year.

monitored on ITU and was given normal saline and IV Hydrocortisone for a

On physical examination, he had a body weight of 53 kg, a body mass index of

presumed diagnosis of Addison’s disease. Her Sodium level slowly came up to

16.5 kg/m² and a blood pressure (BP) of 120/75 mm Hg in supine position and

114 and then to 118 over the next few days. The short synacthen test showed a flat

95/60 in standing position.

response with the following Cortisol values: 0 min 240, 30 min 242 and 60 min

However his blood profile showed paroxysmal hypertension with peaks of

260. She denied taking exogenous steroids in any form. Later her ACTH came

160/110 mm Hg. The pulse rate was 132 beats per minute (bpm). He had neither

back very high (O2000) with positive anti-adrenal antibodies confirming primary

goiter nor exophthalmos. Electrocardiogram

(ECG) showed a regular sinus

adrenal insufficiency. The Renin/Aldosterone results are still awaited. She

tachycardia at 138 bpm with signs of left ventricular hypertrophy.

transiently developed behavioral disturbance with strange affect raising the

Laboratory tests indicated diabetes mellitus with a fasting blood sugar of 2.86 g/l

suspicion of osmotic demyelination. Fortunately this resolved with reducing the

and a glycated hemoglobin of

7.9%, hyperthyroidism with a low TSH of

dose of Hydrocortisone suggesting ’steroid psychosis’ as cause of the behavioral

0.05 mIU/ml, an elevated free T4 of 1.96 ng/dl and urinary metanephrines and

symptoms. The sodium level stabilized in the low 120’s but increased further

normetanephrines were greater than

20 time normal values. TSH receptors

slowly with addition of Fludrocortisone.

antibodies were positive.

This case demonstrates the unusual presentation of Addisons disease with very

Thyroid scintigraphy showed homogeneous increased uptake involving the whole

severe hyponatraemia with surprisingly few neurological signs or symptoms. It

thyroid gland.

also highlights theproblem of antidepressants potentially exacerbating hypona-

The diagnosis of coexisting Graves’ disease and pheochromocytoma was

traemia in these patients.

established. Treatment with prazosin, benzylthiouracil and insulin was then

DOI: 10.1530/endoabs.49.EP85

initiated. Propranolol was added progressively. The patient was planned for right

adrenalectomy after achieving euthyroid state.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

Undiagnosed PHEO will put patients at unnecessary risk from having an

Pheochromocytoma and Graves’ disease are known by their similar clinical features

adrenergic crisis and even death. These cases highlight the importance of

making their differential diagnosis difficult. In our case, adrenal incidentaloma

considering routine biochemical screening for a catecholamine secreting tumour

evaluation had revealed the pheochromocytoma. Otherwise, a meticulous physical

in all patients with NF-1 to prevent the development of catastrophic events in the

examination and detailed laboratory investigations are needed in order to make a

future.

precise diagnosis.

DOI: 10.1530/endoabs.49.EP89

DOI: 10.1530/endoabs.49.EP87

EP90

EP88

Pheochromocytoma in pregnancy

Pheochromocytoma in neurofibromatosis type 1

Belgin Efe^1,2, Goknur Yorulmaz^1,2, Sevil Alaguney^1,2, Funda Canaz^1,3 &

Agustina Pia Marengo¹, Paula García-Sancho¹, Fernando Guerrero¹,

Bartu Badak^1,4

Inmaculada Peiró², Elisa Santacruz³, Andrés Ortiz³, Juan José Diez³,

¹Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey;

Pedro Iglesias³ & Carles Villabona¹

²Division of Endocrinology, Eskisehir Osmangazi University School of

¹Hospital Universitari Bellvitge, L’Hospitalet de Llobregat, Barcelona,

Medicine, Eskisehir, Turkey;³Pathology Department, Eskisehir Osmangazi

Spain;²Institut Català D’Oncologia, L’Hospitalet de Llobregat, Barcelona,

University School of Medicine, Eskisehir, Turkey;⁴Depertmant of General

Spain;³Hospital Ramón y Cajal, Madrid, Spain.

Surgery, Eskisehir Osmangazi University School of Medicine, Eskisehir,

Turkey.

Background

Individuals with neurofibromatosis type-1

(NF1) carry an increased risk of

Introductıon

pheochromocytoma (PHEO). Detection strategy is unknown but most experts

Pheochromocytoma is a tumor originating from the chromaffin cells. These

recommend screening if hypertension develops.

tumors secrete catecholamines which act on target organs and cause hypertensive

Objective

crises. They are rare during pregnancy, and a differential diagnosis must be

Report the characteristics of PHEO in patients with NF1 (NF1 group) and

carried out mainly with pregnancy-induced hypertension.

compare them with non-NF1-associated PHEO (non-NF1 group).

Case

Methods

A 27-year-old patient in week 17 of pregnancy admitted to our clinic with

Retrospective cohort study of patients undergoing PHEO resection in two Spanish

hypertension and 45!55 mm heterogeneous nodular lesion in left surrenal. The

tertiary hospitals, from 1980-2016.

hospitalized patient had tachycardia and hypertensive episodes despite the

Results

treatment. Urinary catecholamine and metanephrine collections revealed elevated

Of 78 patients undergoing PHEO resection, 5 (6.4%) had NF1. NF1 patients were

norepinephrine and normetanephrine. Magnetic resonance imaging identified a

younger than those with non-NF1 (mean age 41.8 vs 52.5 yr, PZ0.068). Males

adrenal adenoma. After subsequent pharmacological treatment with alpha and

comprised 60% versus 40% of the NF-1 group and non-NF1 group, respectively.

beta blockers, a left adrenalectomy was performed laparoscopically. The

PHEO was incidentally diagnosed in 3 of 5 (60%) from NF1 group and only in 29

histopathological report indicates pheochromocytoma (Pheochromocytoma of

of 73 (39.7%) from non-NF1 group (PZ0.395). Remaining NF1 cases were

the Adrenal gland Scaled Score: 6) and tumor weighing 70 g and measuring 6.5!

diagnosed by screening (hypertension, nZ1) and compatible adrenergic clinic

5.5!3.5 cm. After the surgery urinary catecholamine and metanephrine

(nZ1). Hypertension was present in 2 (40%) NF1 patients and in 33 (45%) non-

collections was normal. Postoperatively the patient with 24 weeks gestation

NF1 patients. Urinary and/or plasma catecholamines were elevated in all NF1

had no antihypertensive need.

patients and in 55 (88%) of non-NF-1 group. There was no significantly difference

Conclusion

(PZ0.207) in tumor size between both groups of patients (median 4.6 cm vs

Pheochromocytoma in pregnancy can cause the death of both the fetus and the

5.6 cm in NF1 and non-NF1 patients, respectively).

mother. This issue should be remembered in hypertensive pregnancies. The

Conclusion

approach to the biochemical diagnosis is the same as for the nonpregnant patient.

In our series, age at diagnosis and gender were similar in NF1 and non-NF1

MRI (without gadolinium enhancement) is the preferred imaging modality, and

PHEO patients. NF1-associated PHEO is diagnosed incidentally in more than half

¹²³I-MIBG is contraindicated. Adrenal pheochromocytomas should be removed

of the patients. Although all NF1-PHEO tumors were functioning, only two of five

promptly if diagnosed during the first or second trimester of pregnancy. In our

patients had hypertension. It is necessary to keep in mind the possibility of

case, its recognized with new onset hypertention and adrenal tumor was removed

developing PHEO in NF1 patients even in those non-hypertensive patients. On the

in the 2nd trimester.

contrary, in all patients with PHEO is advisable to search clinical criteria used to

DOI: 10.1530/endoabs.49.EP90

diagnose NF1, and thus confirming an often-delayed diagnosis.

DOI: 10.1530/endoabs.49.EP88

EP91

EP89

The role of p27 in pheochromocytoma development

Should all patients with Neurofibromatosis type 1 undergo biochemical

Andrea Kugler¹, Enzo Lalli², Juan Higareda Almaraz¹, Steffen Sass³ &

screening for Pheocromocytoma?

Natalia Pellegata¹

Ahmed Al-Sharefi, Suhel Ashraff, Ramesh Vanka & Satyajit Nag

¹Helmholtzzentrum Munchen, Institute of Diabetes and Cancer, Munich,

Department of Diabetes and Endocrinology, The James Cook Univeristy

Germany;²University Nice, Institute of Molecular and Cellular

Hospital, Middelsbrough, UK.

Pharmacology, Valbonne, France;³Helmholtzzentrum Munchen,

Institute of Computational Biology, Munich, Germany.

Pheocromocytomas (PHEO) are catecholamine secreting tumours which can

occur sporadically or as part of other hereditary/familial syndromes including

Defective p27 function predisposes mice and rats to pheochromocytomas (PCC),

Neurofibromotosis 1 (NF-1). Unlike the case with other genetic syndromes, the

and reduction of p27 repression is a feature of human PCCs. These findings

current neurofibromatosis guidelines do not recommend a routine hormonal

suggest that p27 plays a role in PCC tumorigenesis. Recently, it was reported that

screening strategy for PHEO in the absence of hypertension or other symptoms. In

p27 indirectly regulates gene transcription by associating with transcription

this paper we describe 2 asymptomatic and normotensive patients with NF-1

factors (TF) and inhibiting gene transcription at specific promoters.

where secretory PHEO were incidentally diagnosed. The first patient is 61- year

We hypothesized that defective p27 promotes tumor formation in adrenomedul-

old female with a history of NF-1 who received a diagnosis of takotsubo

lary cells because of aberrant gene expression. To address this hypothesis, we

cardiomyopathy and was found to have an incidental adrenal mass of 2.4 cm

used normal adrenomedullary tissue from wild-type rats or human individuals and

where subsequent investigations confirmed a diagnosis of secretory PHEO.The

performed chromatin immunoprecipitation-sequencing

(ChIP-Seq). DNA

second patient is a 44 - year old female with also a background of NF-1 who was

sequences bound by p27-contaning protein complexes were immunoprecipitated

found to have a 7.8 ! 7.0 ! 5.8 cm adrenal adenoma where further work up

from rat and human tissue extracts using an anti-p27 antibody coupled with

confirmed PHEO. Both patients underwent adrenalectomy and the histology

magnetic beads. DNA sequences were identified by quantitative next generation

confirmed the diagnosis and their catecholamines level normalised eventually.

sequencing (NGS).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

We successfully pulled down DNA sequences with the anti-p27 antibody,

Paragangliomas are rare neuroendocrine tumors derived from neural crest cells: if

indicating that p27, together with unknown transcription factors or co-factors

localized in the adrenal medulla they are called Pheocromocytomas (Pheo).The

binds the chromatin in adrenomedullary cells. DNA sequences bound by the p27-

30-40% of Pheo are mutated in one of the susceptibility genes among which there

containing complexes were mapped on the rat/human genome and analyzed using

are genes encoding for the four subunits of the succinate dehydrogenase (SDH).

both Genomatix and MEME suite software to identify the most enriched TFs and

Germ line mutations of SDHB are metastatic in about 80% of the cases. Surgery is

TF binding sites (Tcf19, Tcf4, Znf423, Runx1, Ascl2, Lhx4). The binding

the current therapy, but in presence of metastasis there is no effective treatment.

between p27 and these selected TFs is being verified by immunoprecipitation.

Using shRNA, we stably silenced for SDHB a Pheo murine cell line (MTT). The

The association of p27-containing complexes to specific promoters of these

proliferative growth of non-silenced cells (CN) was higher than that of the

identified genes is currently being validated. The p27-dependent regulation of the

silenced ones (B-). However, in co-culture with fibroblasts, the proliferation of

expression of selected target genes will be verified by modulating p27 levels in

B-was higher than that of the CN cultivated in the same conditions.

PCC cell lines. The significance of the p27-dependent gene expression will also

When cultured in fetal-bovine-serum (FBS), B- cells tended to aggregate more

be obtained by analyzing the expression of these target genes in normal adrenal

than the CN. When FBS was not present, both the cells lines lost this

medulla and PCC of MENX-affected rats (with loss of functional p27).

characteristic. When cultured in conditioned medium from activated murine

In conclusion, the observation that p27 may regulate gene transcription will give

fibroblasts (CAF), the aggregating effect disappeared, the cells assumed a longer

insight into the pathomechanisms associated with reduced p27

function

shape and started migrating.

specifically in adrenomedullary cells.

To understand whether this change corresponds to an epithelial to mesenchimal

DOI: 10.1530/endoabs.49.EP91

transition (EMT), we are evaluating the EMT markers and the expression of

metalloproteases either secreted in the medium or expressed on membranes. To

understand if the cross talk between fibroblasts and tumor cells was due to a signal

mediated by receptors, we evaluated the phosphorylation of mTOR, Akt and ERK

in B- and CN cells without detecting any difference.

These preliminary data suggest that the microenvironment, here represented by

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fibroblasts, affects the behaviour of cancer cells and studies on this interaction are

Role of microenvironment on metabolic control of murine

needed to identify new therapeutic targets in SDHB mutated tumors.

pheochromocytoma SDHB silenced cells

Vanessa D’Antongiovanni¹, Susan Richter^3,4, Serena Martinelli¹,

DOI: 10.1530/endoabs.49.EP93

Letizia Canu¹, Tonino Ercolino¹, Graeme Eisenhofer^3,4, Karel Pacak⁵,

Elena Rapizzi² & Massimo Mannelli¹

¹Department of Experimental and Clinical Biomedical Sciences, University

of Florence, Florence, Italy;²Department of Experimental and Clinical

Medicine, University of Florence, Florence, Italy;³Institute of Clinical

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Chemistry & Laboratory Medicine, Dresden, Germany;⁴Department of

Pheochromocytoma: a clinical and pathological study

Medicine III, Technische Universitat Dresden, Dresden, Germany;⁵Eunice

Elisa Santacruz¹, Agustina Pía Marengo³, Andrés Ortiz¹, Inma Peiró³,

Kennedy Shriver National Institute of Child Health and Human

Héctor Pián², Juan José Díez¹, Paula García-Sancho³, Carles Villabona³ &

Development, National Institutes of Health, Bethesda, MD, USA.

Pedro Iglesias¹

¹Department of Endocrinology, Hospital Universitario Ramón y Cajal,

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendo-

Madrid, Spain;²Department of Pathology, Hospital Universitario Ramón y

crine tumors. About 30-40% of Pheo/PGLs are due to a germ-line mutation in one

Cajal, Madrid, Spain;³Department of Endocrinology, Hospital de Bellvitge,

of the 13 main susceptibility genes which include the genes encoding the four

L’ Hospitalet de Llobregat, Barcelona, Spain.

subunits of the succinate dehydrogenase (SDH - mitochondrial complex II). In

PHEO/PGL due to SDHB mutations up to 80% of affected patients develop

Objective

metastatic disease and no successful cure is at present available. Tumor

To assess clinical features, diagnosis, treatment and outcome in patients with

microenvironment plays a pivotal role in modifying the metabolism and the

pheochromocytoma surgically treated in the past 3 decades in two tertiary referral

functional characteristics of tumor cells, becoming a potential therapeutic target.

hospitals.

To obtain an experimental model resembling the in vivo conditions of the SDHB-

Methods

mutated PHEO, we evaluated the effects of SDHB silencing and microenviron-

A retrospective study on clinical and pathological characteristics, treatment, and

ment on metabolism in the mouse tumor tissue-derived cell line (MTT), cultured

outcome in patients with pheochromocytoma followed up in specialized

alone or in association with mouse primary fibroblasts (here representing the

neuroendocrinology units who underwent surgery in the period 1981-2016 was

tumor microenvironment). SDHB silenced cells showed a significant increase of

performed.

both glucose and lactate uptake, and an increase of intracellular lactate compared

Results

with control. This increase was even more evident when SDHB silenced cells was

81 patients (45 women (56%); age 51G15 year (range, 13-76)) were studied. The

co-cultured with mouse primary fibroblasts. The expression levels of

tumor was sporadic in 68 patients (84%) and familial in 13 patients, more

monocarboxilase transporter 4 (MCT4), responsible for the transport of lactate

frequently in the context of a MEN type 2 (nZ6).10% of the pheochromocytoma

from the intracellular to the extracellular space, was found upregulated in

were bilateral. Most of the patients (66%) were symptomatic. The main complains

fibroblasts in co-culture with tumor cells. Consequently, in co-cultures, primary

were the classic triad

(27%), and hypertensive crisis

(27%).

40% of the

fibroblasts showed an increase of extracellular lactate. Surprisingly, SDHB

pheochromocytoma were incidentally discovered on imaging investigations. 47%

silenced cells in co-culture showed a reduction of ATP levels compared to SDHB

of patients were hypertense at diagnosis. 24-h urinary catecholamines excretion

cultured alone and control cells in co-cultures. Our data demonstrate that

was determined in 80% of patients, being elevated in 75% of cases. Fractionated

SDHB silencing strongly affects tumor metabolism, and these changes are more

urinary metanephrines were only determined in 23% of patients, and were

evident in co-cultures. The comprehension of the mechanisms driving these

elevated in 84%. Abdominal CT was the most used imaging technique (87%,

changes in tumor metabolism may suggest new therapeutic targets.

nZ68), followed by¹²³I-MIBG scintigraphy (54%, nZ42) which detected 88%

DOI: 10.1530/endoabs.49.EP92

of those tumors (nZ37). MRI was performed in 50% of the patients, 87% of those

tumors were hyperintense in T2. 89% (nZ65) patients had a preoperative alpha-

adrenergic blockage. 17 patients (22%) had a complication during surgery, being

hypertensive crisis the most common complication (12.5%, nZ10). Median

tumor diameter was 5.9G2.8 cm (range, 1.5-13). 15% of pheochromocytomas

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had vascular invasion, 15% had capsular invasion and 23% presented necrosis.

Only 6% presented ganglionar or distant metastasis. 68 patients were followed in

Role of microenvironment on proliferation and migration of an SDHB

our two centers, 55 patients (81%) were cured, 4 of them (6%) had persistent

silenced murine Pheochromocytoma cell line

disease and 9 (13%) had recurrence after surgery.

Serena Martinelli¹, Vanessa D’Antongiovanni¹, Susan Richter^3,4,

Conclusion

Letizia Canu¹, Tonino Ercolino¹, Graeme Eisenhofer^3,4, Karel Pacak⁵,

Pheochromocytoma in our series is generally a large, symptomatic and sporadic

Elena Rapizzi² & Massimo Mannelli¹

tumor. Incidentally discovered pheochromocytoma is common. Abdominal CT

¹Department of Experimental and Clinical Biomedical Sciences, University

is the preferred imaging technique for localization. Surgical complications are

of Florence, Florence, Italy;²Department of Experimental and Clinical

common. Despite the high rate of vascular invasion in the histopathological study,

Medicine, University of Florence, Florence, Italy;³Institute of Clinical

ganglionar and distant metastasis are rare. The presence of cases with persistent

Chemistry & Laboratory Medicine, Dresden, Germany;⁴Department of

and recurrent disease after surgery requires a long term follow-up. these tumors.

Medicine III, Technische Universitat Dresden, Dresden, Germany;⁵Eunice

Kennedy Shriver National Institute of Child Health and Human

DOI: 10.1530/endoabs.49.EP94

Development, National Institutes of Health, Bethesda, MD, USA.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

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Conclusion

We report a challenging situation, life-threatening without surgical treatment, but

Biochemical testing for pheochromocytoma

with a high surgical risk due to the severe comorbidities. A positive outcome was

Carolina Faria, David Barbosa, Ana Sofia Osório, Ema Nobre,

strongly dependent on the multidisciplinary collaboration of different

Joaquim Sampaio & Maria João Bugalho

departments.

Hospital de Santa Maria, Lisboa, Portugal.

DOI: 10.1530/endoabs.49.EP96

Introduction

Biochemical testing for Paraganglioma/Pheochromocytoma

(PGL/PHEO) is

recommended in patients with classical symptoms, in those harbouring an

adrenal incidentaloma and in patients who have a hereditary risk for developing

a PGL/PHEO. Measurements of plasma free metanephrines and/or urinary

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fractionated metanephrines provide a highly sensitive test for diagnosis but false-

positive results remain a problem.

Retrospective audit at a UK teaching hospital of phaeochromocytomas

Aim

and paragangliomas against the 2016 guidelines

Nawal Ibraheem & David Hughes

Comparative analysis of plasma and urinary metanephrines results in a group of

Derby Teaching Hospitals NHS Trust, Derby, UK.

individuals suspected of having PGL/PHEO.

Subjects and methods

Retrospective analysis of tests performed at a tertiary hospital during the year

Introduction

2015

(January 1st-December 31th) and correlation with imaging studies and

In this audit we explored the treatment and follow up of pre-2016 cases against the

clinical data.

2016 European Society of Endocrinology (ESE) guidelines on PPGL follow-up.

Results

686

measurements of urinary and/or plasma metanephrines, ordered by

Demographics of the patients revealed 50% were male with median age (45G5),

physicians of different medical specialties, were performed. From the analysis

82% of patients underwent surgery of which 73% were diagnosed with adrenal

of these results, we identified 124 patients with both measurements; they were 77

phaeochromocytomas & 27% with paragangliomas. Only 64% of surgical cases

women and 47 men with a mean age of 47.3 years (range 6-82). The main reason

were followed up in clinic in the last year. Of all surgical cases only 73% had

for testing was therapy-resistant or paroxismal hypertension (nZ68; 54.8%)

evidence of undergoing genetic testing. In the first year post surgery the following

followed by the presence of an adrenal incidentaloma (nZ13,10.4%). Abnormal

appropriate biochemistry screening was performed: Chromogranin AZ36.5%,

high values were observed in 56 patients: in 44 (45.2%) only abnormal urine

(27% unknown), Urinary MN or catecholaminesZ64%

(27% unknown),

values, in 6 (4.8%) both urine and plasma abnormal values and in 6 (4.8%) only

CalciumZ64% (27% unknown), PTHZ56%, (unknown in 27%), Calcito-

abnormal plasma values. 3/6 patients who presented elevation of urinary and

ninZ46% (27% unknown), CEAZ0% (27% unknown). In the first year post

plasma metanephrines had histologically proven disease (2 PHEO, 1 abdominal

surgery between 9% and 27% of patients underwent USS/CT/MRI/MIBG/PET

PGL). Among the patients with normal plasma metanephrines and high urinary

scan of neck or abdomen appropriately.

metanephrines only one (2.3%) had a bilateral pheochromocytoma in the context

Discussion

of a MEN2A syndrome. None of the

patients with normal urinary

The recommendations made in these guidelines have been implemented locally

metanephrines and increased plasma metanephrines had disease.

and a local registry of cases is in development to improve follow up of cases (see

Conclusion

poster for further details).

In the present series, all patients with a histologic diagnosis of PGL/PHEO had

DOI: 10.1530/endoabs.49.EP97

elevated urinary metanephrines regardless, in one case, normal plasma

metanephrines. On the other hand, the frequency of increased urinary

metanephrines without a positive imaging was very frequent.

DOI: 10.1530/endoabs.49.EP95

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Pheochromocytoma - surgical outcomes

Pedro Carvalho Martins, Cátia Ribeiro, Mariana Peyroteo, Helena Pereira &

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Abreu de Sousa

Paraganglioma and Fallot Tetralogy: case report

IPO-Porto, Porto, Portugal.

Ana Filipa Martins¹, João Martin Martins^1,2 & Sónia do Vale^1,2

¹Hospital de Santa Maria - CHLN, Lisboa, Portugal;²Faculdade de

Medicina de Lisboa, Lisboa, Portugal.

Objective

To retrospectively evaluate the results of the pheochromocytoma surgery in our

institution assessing the surgical complications, perioperative hemodynamic

Introduction

instability and oncologic outcomes.

Catecholamine secreting tumors are rare neoplasias. About

15% are para-

Methods

gangliomas. If untreated, they are almost invariably lethal. Surgery is the only

The medical records of patients admitted for pathologically confirmed

curative therapy.

pheochromocytoma between 2000

and

2015 were reviewed. Patients with

Case report

paragangliomas were excluded.

A female caucasian patient aged 32 was evaluated in the endocrine department.

Results

She had a dramatic medical history: Fallot’s Tetralogy was diagnosed soon after

We identified 40 patients with 43 resected pheochromocytomas. The mean age

birth but was not corrected. Only a Blalock-Taussing shunt was performed after

was 47 years with an equal distribution between genders. Twelve cases (30%) had

three isquemic strokes due to endocarditis, when patient was 22. She suffered

a syndrome known to have an increased incidence of pheochromocytoma. The

from sequelar right-side hemiparesis and epilepsy. She had also glucose-6-

mean tumor size was 7 cm (range of 1.5-17.2 cm). Most of the lesions were

phosphate desidrogenase deficiency. At 32 she was assisted at the emergency

functional (95%) and preoperative alpha-blockade has been instituted in 93% of

department because of recent vomiting, headache and arterial hypertension. She

the patients, with 48% having a beta blocker simultaneously. Fourteen cases

had a recent weight loss with a BMI of 16 kg/m². Examination revealed depressed

(30%) underwent a minimal invasive approach. The mean operative time was

mood, orthostatic hypotension, holosystolic aortic bruit and chronic hypoxia

150 min and the median of intraoperative blood loss was 150 ml. More than a half

signs. Several hypertensive paroxysms (maximum value: 240/140 mmHg) with

of the patients (54%) had a hypertensive crisis at some point during surgery,

diaphoresis were documented. Urinary normetanephrine and metanephrine were

almost always associated with manipulation of the lesion. Ten patients (25%)

very high (227 and 58 times higher than the upper limit of the reference range)

required vasopressor support after adrenal gland removal. Two patients (4.6%)

with a paradoxal increase in clonidine test. The CT scan revealed a solid

had CTCAE 3/4 complications. There were no cases of mortality and the median

hypervascular right paramedian retroperitoneal tumor with 49 mm of diameter at

length of stay was seven days. Two (5%) cases were defined as malignant: one

the level of the superior mesenteric artery with strong uptake in I¹²³-MIBG

secondary to metastatic disease to distant organs (recurrence at 30 months of

scintigraphy. Surgery was uneventful after careful pre-operatory preparation with

follow-up in the form of multiple lung metastasis) and other to lymph nodes who

a- and b-blockers and volume expansion. Five months later the patient recovered

is alive and disease-free. Three patients were diagnosed with contralateral

weight and was normotensive without antihypertensive drugs. Succinate

pheochromocytoma during the follow-up, admitted as a new primary lesion, in

dehydrogenase mutations (SDHA, SDHB and SDHC) were not found.

context of a known genetic syndrome.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

gene mutations in PC/PGL and are associated with younger ages at presentation,

The results of our retrospective study show that adrenalectomy is a safe, effective

higher rates of metastases and poorer prognosis. Although familial PGL

and a low morbidity procedure. However, the organization of surgical, anesthetic

syndromes were initially thought to predispose only for PCC and PGL, other

and medical teams experienced in this type of pathology is fundamental for

tumor types such as gastrointestinal stromal tumors

(GISTs), renal cell

perioperative management.

carcinomas (RCCs), and pituitary adenomas (PAs) have expanded the SDHx-

DOI: 10.1530/endoabs.49.EP98

associated tumor spectrum.

Case Report

A 34-year-old female patient, with a history of mild asthma, non-smoker, was

referred to the Endocrinology Department as an asymptomatic carrier of a

pathogenic heterozygous germline SDHB mutation

(c.1-?_72C?del). Her

paternal-uncle died from metastatic bladder paraganglioma by the age of .She

had also family history of breast cancer (paternal-aunt) and prostate cancer

(paternal-grandparent). Twenty-four-hour urinary excretion of fractionated

catecholamines and metanephrines were in the normal range. Screening

EP99

computed tomography (CT) scan showed a 3 cm mass in the lower lobe of the

Role of urinary fractionated metanephrines and catecholaminas in the

right lung. CT guided transthoracic lung biopsy revealed adenocarcinoma of

diagnosis of pheochromocytoma/paraganglioma

probable primary lung origin. Staging positron emission tomography with

Ma Luisa Martinez-Triguero, Ma Isabel del Olmo, Rosa Cámara del Olmo,

2-deoxy-2-[fluorine-18]fluoro-D-glucose

(¹⁸F-FDG PET/CT) showed, besides

Amparo Alba, Francis Fernández, Juan Francisco Merino & Begon˜a Laiz

malignant right lung involvement, moderate left paratracheal FDG uptake. She

Servicio de Análisis Clínicos, Servicio de Endocrinología, Hospital

underwent inferior right lobectomy with mediastinal lymph node ressection and

Universitario y Politécnico La Fe, Valencia, Spain.

histologic examine confirmed lung adenocarcinoma pT2a N0 M0 R0, stage I B.

The patient is under surveillance.

Discussion

Introduction

Questions still remain unresolved concerning non PCC/PGL tumors in patients

Paragangliomas/pheochromocytomas present frequently with vague symptoma-

with germline pathogenic SDHx mutations with regard to their pathogenesis,

tology which makes its diagnosis difficult and challenging. Cuantification of

clinicopathological phenotype, and possible causal relation to the aforementioned

fractionated metanephrines and fractionated catecholamines in 24 h urine sample

mutations.

are used for diagnosis. There are situationes that can produce false positive results

such as stress, drugs or smoking that must be taken into account.

DOI: 10.1530/endoabs.49.EP100

Patients and methods

Retrospective study on the requests made for the diagnosis of pheochromocy-

toma/paraganglioma to the laboratory with the determinations of fractionated

catecholamines and metanephrines during

10 months. Determinations were

analysed by HPLC with electrochemical detector (Teknochroma^w).

Results

During this period 260 determinatios (of 218 patients) were analysed. 10 of these

patients were diagnosed of pheochromocytoma, nine of extraadrenal para-

ganglioma and 199 patients did not present either of the pathologies. Patients with

paraganglioma were excluded (Table 1).

Table 1 Sensitivity and specificity of fractionated catecholamines and

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metanephrines.

Pheochromositoma in childhood

Olcay Evliyaoglu, Oya Ercan, Aydilek

¸ akır, Duhan Hopurcuog˘ lu &

Sensitivity CI 95%

Specificity

CI 95%

Betul C¸ ınar

Catecholamines

0.9

0.71-1.09

0.88

0.83-0.92

Istanbul University Cerrahpa¸a Medical School Pediatric Endocrinology

Metanephrines

0.9

0.71-1.09

0.89

0.85-0.93

Department, Istanbul, Turkey.

Of the patients who did not present pheochromocytoma (199), 35 had elevated

Introduction

catecholamines and/or fractionated metanephrines (18% false positive), 17 were

Feochromositoma is a rare neuroendocrine tumor derived from chrommaffin cells

due to antihypertensive or antidepressant drugs, 11 had other adrenal pathologies

of adrenal medulla. The most characteristic clinical symptoms are headache,

and seven others.

perspiration, palpitation, and paroxysismal hypertension. Childhood feochromo-

Conclusions

sitoma is generally genetic while it is mostly sporadic in adults. Here we report

1. Urinary fractionated metanephrines have a higher specificity than catechol-

three feochromositoma cases in whom two had von Hippel Lindau syndrome

amines. Both of them present the same sensitivity in our patients.

(VHLs).

2. The rate of false positive results surpasses those of true positive, especially

Case 1

those produced by drugs, as published in literature.

10 years old girl with admitted with fever. Her physical examination revealed

hyperthermia and hypertension. Urine VMA level was increased and ultrasound

DOI: 10.1530/endoabs.49.EP99

examination showed left adrenal mass, diagnosis of pheochromositoma was

confirmed after resection. In the second year of her follow-up GA-68 Octreotide

scintigraphy determined accumulations in right adrenal and pancreas, patho-

logical diagnosis were feochromositoma and neuroendocrine carcinom respect-

ively after resection. Two disoreders together suggested VHLs and heterozygous

p.L129P mutation in VHL gene was detected.

Case 2

11-years-old boy admitted with perspiration and palpitation in whom

hypertension was determined. Urine VMA level was increased, and bilateral

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adrenal mass was determined in ultrasonography. Diagnosis of pheochromosi-

toma was confirmed after resection. In his 5 years of follow-up he admitted with

Lung adenocarcinoma in a 34-year-old female SDHB asynptomatic

headache. Cranial MRI showed frontal, adrenal ultrasound showed right adrenal

mutation carrier - case report

masses, after resection hemangioblastoma and pheochromositoma were diag-

Maria João Matos, Claudia Costa, Ana Paula Santos, Manuel Teixeira,

nosed respectively. Associaton of two disorders suggested VHLs and

Carlos Franco, Joa˜o Bento, Isabel Azevedo, Susana Dias, Inês

heterozygous p.R161Q mutation in VHL gene was determined.

Lucena Sampaio, Ana Luísa Cunha & Isabel Torres

Case 3

Portuguese Oncology Institute of Porto, Porto, Portugal.

9-years-old boy admitted with perspiratation and palpitation in whom

hypertension was determined. His family history was significant with

Introduction

pheochromositoma in his father and grandmother. His urine VMA levels were

Patients with germline mutations in one of the succinate dehydrogenase (SDH)

high and adrenal ultrasound revealed bilateral adrenal masses. Diagnosis of

genes are at substantially increased risk of developing paragangliomas (PGL) and

pheochromositoma was confirmed after resection of both masses. No mutation in

pheochromocytomas (PCC). Mutations in SDHB are the most commonly found

VHL gene was detected.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

He had elevated 24-h urinary normetanephrines 6360 nmol/24 h and metane-

Although rare pheochromositoma should be thought in children with hyperten-

phrines 2530 nmol/24 h (normal !2129 and !1622 respectively), in keeping

sion. In children pheochromositoma is mostly genetic in which VHLs is most

with phaeochromocytoma. Subsequent meta-iodobenzylguanidine (MIBG) scan

frequent. Genetic tests should be performed in all children after diagnosis.

showed prominent activity in the region of the right adrenal gland. The patient

DOI: 10.1530/endoabs.49.EP101

was initially commenced on an alpha blocker doxazosin, and the dose was

incremented to the maximum of 16 mg BD. He was subsequently commenced on

beta blocker bisoprolol, and his blood pressure dropped from average of

150/100 mmHg (no history of hypertension) to around 110/70 mmHg.

This patient had a right adrenalectomy, made an uneventful recovery and was

discharged with no medication. His BP remained at around 130/85 mmHg at his

post-operative consultations. Phaeochromocytoma presents with various forms of

signs and symptoms. In our case, the history of episodes of intermittent

perspiration, back pain and severe aggression were uncommon symptoms

emphasising the importance of comprehensive history taking.

Since surgery the patient has no longer experienced any of the above, and he

EP102

describes himself to be calmer than ever.

A case of silent pheochromocytoma presenting with clinical and

DOI: 10.1530/endoabs.49.EP103

radiological findings suggesting metastatic adrenal lesion

Soner Cander¹, Ozen Oz Gul¹, Pinar Sisman² & Canan Ersoy¹

¹Uludag University Medical School, Bursa, Turkey;²Kars State Hospital,

Kars, Turkey.

Case

A 75-year-old male patient was treated for lung adenocarcinoma 12 years ago.

During the routine imaging studies of the patient who was followed without

treatment after curing, a suspicious, non-adenomatous lesion in the right adrenal

gland, 16!9 mm in size was detected by thoracic computed tomography. Serum

aldosterone/renin ratio and urine catecholamine tests were normal with no

EP104

complaints of suspicion for pheochromocytoma. F18FDG PET-CT showed an

Improvement of insulin secretion and oral glucose tolerance after

increase in metabolic activity

(SUVmax:4,8) in the right hilar region. The

pheochromocytoma removal: a case report

cytological examination was benign with bronchoscopy. Laparoscopic right

Zoran Erlic, Kathrin Roost, Oliver Tschopp & Christoph Schmid

adrenalectomy was performed because no other lesions were detected.

Division of Endocrinology and Diabetology, University Hospital Zurich,

Histopathologic examination revealed non-invasive pheochromocytoma showing

Zurich, Switzerland.

positive staining with synaptophysin and chromogranin.

Discussion

Introduction/case report

Pheochromocytoma is very rare in adrenal incidentalomas, however, can be

Diabetes mellitus is an important clinical manifestation of catecholamine excess

asymptomatic at rates up to 10%, as they can manifest with attack symptoms or

in patients with pheochromocytoma, and glucose control is usually better after

less with persistent hypertension. It is suggested that catecholamine synthesis is

tumour removal. Both impaired insulin secretion and increased insulin resistance

defective in these tumors. In some reports it is specified that, this phenomenon

have been implicated as underlying causes. We describe the case of a 38-year-old

may be seen in some mutations in the succinate dehydrogenase gene. In some

male patient diagnosed with left adrenal pheochromocytoma and personal history

reports, however, about 10-20% of silent pheochromocytomas were reported to

of diabetes mellitus diagnosed at age

36, under treatment with metformin,

be due to laboratory error. On the other hand, non-adenomatous lesions in the

saxagliptin and gliclazide, with a preoperative HbA1c of 7.2%. BMI of the patient

adrenal glands in a patient known as primer malignancy are generally considered

was 23 kg/m². After successful pheochromocytoma removal, the anti-diabetic

as metastases. In our case, the patient was referred to a similar presentation and it

medication was immediately stopped with remission of diabetes mellitus (HbA1c

was initially thought that the lesion may be a metastatic lesion. However, the fact

3-months-postoperative 5.7%).

that the primary malignancy has been in control for more than 10 years has been

Methods

questioned about metastasis. One of the methods that can be applied in such a case

is biopsy but pheochromocytoma should be firstly excluded. In this case report,

We performed oral glucose (75 g) tolerance tests and measured venous plasma

glucose and serum insulin levels at the time of diagnosis and three months after

we have demonstrated that; in non-adenomatous adrenal lesions, the absence of

successful surgery, to derive the insulinogenic index

(IGI) as proposed by

clinical signs and normal catecholamine levels do not exclude

Wareham, and whole body insulin sensitivity index (ISI) as proposed by Matsuda

pheochromocytoma.

and DeFronzo.

DOI: 10.1530/endoabs.49.EP102

Results

Plasma glucose and serum insulin levels are shown in the table 1.

Table 1

Time (min)

K15

120

Preop glucose (mmol/l)

9.8

9.5

10.9

12.7

15.8

16.1

Postop glucose (mmol/l)

5.3

8.0

10.7

10.9

7.0

Preop insulin (pmol/l)

104

161

248

181

EP103

Postop insulin (pmol/l)

316

461

613

354

The storm before the calm: a phaeochromocytoma

Yasmin Nikookam, Caoimhe Bonner, Edward Bettany,

Anthony Pittathankal, Ranjan Gunasekara, Edel Casey & Khash Nikookam

King George Hospital, London, UK.

Improved glucose levels were associated with increased insulin levels and an

increase in IGI, from a preoperative value of 5.7-33.6 pM/mM, while the ISI

remained unchanged.

We report a case of a male patient aged 45 years who presented with a history of

Conclusion/discussion

intermittent back discomfort over a year, but more persistent over the previous 2-

Remission of diabetes mellitus in our patient was associated with marked

3 months. His general practitioner (GP) referred him for an ultrasound of the spine

improvement of insulin secretion and oral glucose tolerance after removal of

for a possible encapsulated lipoma but the findings were unremarkable. He was

pheochromocytoma. Adrenergic alpha2A receptors on pancreatic beta cells play

then referred to a consultant gastroenterologist for further assessment. He had

an important role in mediating inhibitory effects of catecholamines on insulin

normal endoscopic examinations, however the MRI had shown a right adrenal

release, according to recent genetic association and pharmacological intervention

lesion which led to a referral to the endocrine team.

studies. In our case, impaired insulin secretion could be corrected by surgery.

On further history he reported episodes of perspiration and bursts of aggression,

for the past few years. Investigations revealed a normal cortisol response

DOI: 10.1530/endoabs.49.EP104

following overnight dexamethasone suppression and a normal renin aldosterone

ratio.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP105

palpitations, diaphoresis or tremors.¹²³I-MIBG scintigraphy revealed focus of

hyperactivity located on projection of the right adrenal gland suggesting the

Ephedrine/caffeine toxicity masquerading as phaeochromocytoma in a

presence of pheochromocytoma. We sent this patient to multidisciplinary expert

vigorexic male with paroxysmal hypertension and headache

team. Plasma-free metanephrines were measured with elevated results: 125 pg/ml

Manuel Nivelo-Rivadeneira¹, Agnieszka Kuzior¹, Sara Quintana-Arroyo¹,

(!65) and he will undergo unilateral adrenalectomy soon.

Carmen Acosta-Calero¹, Claudia Arnas-Leon¹, Ana Delia Santana-Suarez¹,

Discussion

Alba Lucia Tocino-Hernandez³ & Francisco Javier Martinez-Martin²

This case illustrates the possibility of false negative results in hormonal

¹Endocrinology Dpartment, Hospital Universitario de Gran Canaria Dr

evaluation of adrenal masses. These misleading results can happen, for example,

Negrin, Las Palmas de Gran Canaria, Spain;²Outpatient Hypertension

by an inadequate urine sampling. If we had not repeated the measurement of

Clinic, Hospital Universitario de Gran Canaria Dr Negrin, Las Palmas de

metanephrines, the diagnosis of pheochromocytoma had not be done at this time.

Gran Canaria, Spain;³Primary Care Center, Arucas, Las Palmas de Gran

Canaria, Spain.

DOI: 10.1530/endoabs.49.EP106

Clinical case

A 19-year-old male came to the Emergency Department complaining about

a holocraneal nonpulsatile headache growing in intensity for the last

3 h,

unresponsive to common analgesics. He had been suffering anxiety sleep

deprivation, nervousness, tremor and heart palpitations for the last week. Family

EP107

history was irrelevant, and the patient had no history of hypertension,

Unexplained resistant hypertension in a young male with recurrent

dyslipidaemia, diabetes or smoking or medication use; he reported moderate

transient ischemic attacks, resembling endocrine hypertension

alcohol, coffee and energy drink consumption but no cocaine nor amphetamines.

Ana Delia Santana Suárez¹, Manuel Nivelo-Rivadeneira¹,

He was on a high-protein diet with casein-based supplements, maintained a very

Agnieszka Kuzior¹, Sara Quintana Arroyo¹, Carmen Acosta Calero¹,

high level of physical exercise and lately had been consuming a ‘fat-burner’

Claudia Arnás León¹, Esperanza Perdomo Herrera² & Francisco Javier

obtained from a local gym, but ignored its composition. The patient was fully

Martínez Martín³

conscious and did not have chest pain, fever or dyspnoea. His BP was

¹Endocrinology Department, University Hospital Dr Negrin, Las Palmas,

219/126 mmHg and HR 129 bpm, with sinus tachycardia in the EKG. He was

Spain;²Primary Care Center of Escaleritas, Las Palmas, Spain;³Outpatient

treated with diazepam and diltiazem, discharged with BP 154/87 and HR 98 and

Hypertension Clinic, University Hospital Dr Negrin, Las Palmas, Spain.

referred to our Endocrinology Clinic for phaeochromocytoma screening. He

brought the ‘fat-burner’ pills containing ephedrine 50, ASA 100 and caffeine

150 mg; he had been taking 1-2 daily during the week before the hypertensive

A 27-year-old male without relevant familial or personal history had three TIAs in

episode. He was asymptomatic, with athletic constitution, weight 87 kg, height

the last year, lasting for about 20 min with partial right palsy and aphasia. By the

173 cm, BMI 29 kg/m², waist 88 cm, impedanciometry 19% fat mass, BP 119/76,

time he was cared for in the Emergency Department. he had already recovered;

HR 75. Physical exam was otherwise unremarkable. Lab tests including

his lab tests, chest X-ray and EKG were normal but his BP was high (PAS 170-

metanephrines, aldosterone, PRA, TSH and microalbuminuria; chest X-ray and

190 mmHg, PAD 105-120 mmHg). He had no chest pain, headache or

24 h. ABPM were normal.

neurovegetative symptoms. On discharge the patient was treated with manidipine

Diagnosis

and ASA and referred to the Neurology Clinic and to our Hypertension Clinic for

Paroxysmal hypertensive episode caused by ephedrine/caffeine toxicity, with

phaeochromocitoma/paraganglioma screening and diagnostic workup.

no target-organ damage. Vigorexia. Phaeochromocytoma/paraganglioma were

DOI: 10.1530/endoabs.49.EP107

ruled out.

Commentary

Ephedrine is a sympathomimetic amine with no legitimate medical indications at

present, but widely used as doping or to trim subcutaneous fat. Its use has been

linked with major cardiovascular and renal events, including ictus and sudden

death, and must be discouraged.

DOI: 10.1530/endoabs.49.EP105

Cardiovascular Endocrinology and Lipid Metabolism

EP108

Stress cardiomyopathy in pheochromocytoma

Cristina Alexandra Gheorghiu, Simona Jercalau & Corin Badiu

EP106

National Institute of Endocrinology ‘C.I. Parhon’, Bucharest, Romania.

Loss diagnosis of pheochromocytoma in the initial evaluation

Teresa Azevedo, Márcia Alves, Joana Guimara˜es, Rosa Dantas,

Introduction

Ana Margarida Balsa & Isabel Inácio

Rare cases of pheochromocytoma are associated with stress induced Takotsubo

Centro Hospitalar Baixo Vouga, Aveiro, Portugal.

cardiomyopathy explained by high catecholamine exposure causing micro-

vascular spasm and direct myocardial impact.

Case report

Introduction

A 49-year-old female with a history of poorly controlled hypertension, with

In most cases, adrenal masses are non-functioning adrenocortical adenomas. On

paroxysmal elevations in blood pressure and rare supraventricular extrasystoles,

‘Management of adrenal incidentalomas: European Society of Endocrinology

lipothymic events, was firstly assessed in the cardiologic department. She

Clinical Practice Guideline’ published in 2016, the experts ‘suggest against

presented with resistant hypertension, associated with acute pulmonary oedema

repeated hormonal work-up in patients with a normal hormonal work-up at initial

and cardiogenic shock. Echocardiography revealed new mid LV segment motion

evaluation unless new clinical signs of endocrine activity appear or there is

abnormality with apical ballooning, ECG - acute ST-segment elevation in the

worsening of comorbidities’.

anterior leads and a rise of cardiac biomarkers. The coronary angiography

Case report

excluded any coronary artery lesion. Thoraco-abdominal CT imaging revealed an

A 59-year-old male patient was referred to endocrinology with a right adrenal

86/85/68 mm left adrenal mass, suggestive for pheochromocytoma. Laboratory

mass of 17 mm compatible with adenoma, discovered in difficult-to-control

evaluation for

24-h urine and plasma catecholamine metabolites disclosed

hypertension study. The patient had no symptoms apart from hypertension, that

intermediary-low elevated values

(plasmatic MNZ10/11 pg/ml; plasmatic

was controlled with three classes of antihypertensive drugs. Initial hormonal

NMNZ59/41 pg/ml,

urinary

MNZ114/881 mg/24 h;

urinary

evaluation revealed normal urinary fractionated metanephrines, normal aldoster-

NMNZ632/1121 mg/24 h), despite high cardiac impact of the spells. She was

one/renin ratio (with interfering drugs suspension), intermediate hyperglycaemia

submitted to 12 days of alpha adrenergic blockade followed by beta blockers,

and subclinical hypercortisolism (1 mg overnight dexamethasone 2.1 mg/dl). One

during which control of blood pressure and spells was achieved. Improvement of

year later, adrenal mass was stable and hormonal study highlighted elevation of

systolic function (EKG and echocardiography) could be noticed. Laparoscopic

total and fractionated urinary metanephrines (total metanephrines 1921 mg/24 h

adrenalectomy was safely performed without hemodynamic events during

(329-1263), fractionated metanephrine 956 mg/24 h (64-302) and normetanephr-

surgery or immediately afterwards. Metanephrines and normetanephrines levels

ine 636 mg/24 h (162-527) with normal 3-methoxytyramine. The repetition of

normalised with good residual adrenal function. Long term systolic function as

metanephrines, with adequate preparation, confirmed these results: urinary total

well as high blood pressure returned to normal.

metanephrines

2005 mg/24 h

(329-1263), urinary fractionated metanephrine

Conclusions

1094 mg/24 h (64-302) and normetanephrine 545 mg/24 h (162-527) with normal

Takotsubo cardiomyopathy is associated with reversible LV-ballooning. In this

3-methoxytyramine. The patient kept lack of symptoms such as headache,

observation, we report a case of stress cardiomyopathy caused by

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

pheochromocytoma; a rare medical condition which is easily confused with acute

was applied and adrenal ganglioneuroma (mature type) was reported in the

coronary syndrome due to clinical and biochemical resemblance, especially in our

pathology examination.

case where plasma and urinary catecholamines were only slightly elevated.

Conclusion

DOI: 10.1530/endoabs.49.EP108

Ganglioneuroma is rarely seen in adults and diagnosis is difficult as it is

asymptomatic. As the masses are asymptomatic, they are not usually determined

before reaching large dimensions. With increased availability of high-resolution

tomography and MRI, an increase has been seen in the frequency of these types of

masses. In recent years, ganglioneuroma have been separated into two sub-types

as mature or maturing ganglioneuroma. In mature ganglioneuroma, the tumour is

Clinical Case Reports - Pituitary/Adrenal

completely formed of a ganglioneuromatous component. Diagnosis is made

EP109

histopathologically and it should be kept in mind as a rare tumour in adrenal

masses.

Prolonged zona glomerulosa insuffiency with hyperkalemia in primary

hyperaldosteronism after adrenalectomy

DOI: 10.1530/endoabs.49.EP110

Feyza Yener Ozturk, Esra Cil Sen, Rumeysa Selvinaz Erol, Emre

Sedar Saygili, Seda Erem Basmaz, Sezin Dogan Cakir, Adnan Batman &

Yuksel Altuntas

Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.

Introduction

EP111

Hyperkalemia due to zona glomerulosa (ZG) insufficiency is generally transient

Primary adrenal insufficiency and pregnancy - a case report

and mild for patients with aldosterone-producing adenoma

(APA) after

Slavica Savic¹, Mirjana Stojkovic^1,2, Biljana Nedeljkovic-Beleslin^1,2,

adrenalectomy. We report here a case with prolonged ZG insuffiency requiring

Tanja Nisic¹, Milos Stojanovic^1,2, Marija Miletic¹, Jasmina Ciric^1,2,

long-term mineralocorticoid replacement (MR) therapy.

Svetlana Spremovic-Radjenovic^2,3 & Milos Zarkovic^1,2

Case report

¹Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre

A 45-years-old female with hypertension and hypokalemia admitted to outpatient

of Serbia, Belgrade, Serbia;²School of Medicine, University of Belgrade,

clinic with incidentally detected right adrenal adenoma (3 cm) showing signal

Belgrade, Serbia;³Clinic for Gynecology and Obstetrics, Clinical Centre of

loss on opposed-phase images of MRI. Laboratory tests revealed high plasma

Serbia, Belgrade, Serbia.

aldosterone concentration (PAC) (72 ng/dl, N: 7-30 ng/dl), supressed plasma

direct renin concentrations

(DRC) (5.25 ng/l, N:

5.41-34.53 ng/l) and high

PAC/DRC ratio (13.71). PAC after saline infusion test was 30.7 ng/dl. After

Primary adrenal insufficiency (PAI) is uncommon in pregnancy. Women with

confirmation with adrenal venous sampling (AVS), right adrenalectomy was

PAI have reduced fertility and parity. If unrecognized or untreated during

performed laporoscopically. Serum urea, creatinine, sodium, PAC (19.6 ng/dl)

pregnancy PAI increases risk for maternal and foetal morbiditiy and mortality.

and DRC (13.6 ng/l) were in normal limits on postoperative 20th day; but serum

Majority of women diagnosed before conception and appropriately treated, have

potassium was markedly increased (5.9 mmol/l). The causes of pseudohyperka-

uneventful pregnancies, with increased risk of cesarean section (CS) and preterm

lemia and hyperkalemia were excluded. Because of low suppression index in the

delivery.

contralateral adrenal during AVS, hypoaldosteronism was thought to be the

We report a 38-year-old woman with PAI during first spontaneus pregnancy.

etiology as PAC did not increase while serum potassium level was higher than

The patient was diagnosed with Addison’s disease at the age of

17, and

5 mmol/l. Patient was followed-up with high-sodium, low-potassium diet on

hyperthyroidism 14 years later. Her family history revealed hyperthyroidism in

polystyrene sulfonate therapy. On the second month postoperatively, serum

mother. She had regular menstrual pattern and no pregnancy during 5 years of

potassium was still high

(5.6 mmol/l). MR therapy with fludrocortisone

marriage. Gynecological investigation was unremarkable, but she had addisonian

0.1 mg/day was started for persistent hyperkalemia. Treatment continued for

crisis during hysterosalpingography 6 months before conception. At that time she

eight months until PAC and DRC raised up to 23.27 and 20.8 ng/l, respectively.

was taking 30 mg hydrocortisone, 0.1 mg fludrocortisone and 50 mcg levothyr-

After then, serum potassium concentration remained at the upper limit of normal

oxine/daily. At 8 weeks of pregnancy she started to complain of fatigue, dizziness

range (5 mmol/l) with normal renal function tests, PAC (10.8 ng/dl) and DRC

and palpitations, with no nausea or vomiting. Physical examination was

(8.1 ng/l) without replacement.

unremarkable, BP

100/70 mmHg, with no orthostasis or discolouration of

Conclusion

skin/mucous membranes. Oral progesterone was started because of spotty vaginal

Suppression of contralateral ZG function by supressed plasma renin level in APA

bleeding and in 2 weeks she developed mild hyponatraemia. We recommended to

can lead to ZG insufficiency and hypoaldosteronism after adrenalectomy.

split hydrocortisone in four doses, and increased fludrocortisone to 0.125 mg.

Hypoaldosteronism cause impairment of renal potassium clearance and

During second trimester she was stable, plasma electrolytes and thyroid function

hyperkalemia. MR therapy may be essential in case of prolonged hyperkalemia.

test were normal, with no foetal or placental abnormalities on ultrasonography. In

DOI: 10.1530/endoabs.49.EP109

the middle of the third trimester hydrocortisone and fludrocortisone doses were

further ajusted to 35 mg and 0.15 mcg respectively. She underwent CS at the 39th

gestational week and a healthy baby girl weighing 3250 g was delivered. During

the 15-month follow-up period mother and baby were in good condition.

We presented a case of women with autoimmune polyglandular syndrome

(APS 2) and succesful pregnancy outcome. Women with PAI should be

EP110

monitored by a multidisciplinary team throughout pregnancy to ensure maternal

Mature ganglioneuroma of the adrenal gland

and foetal health.

Betul Aydin Buyruk¹, Medine Nur Kebapci¹, Goknur Yorulmaz¹,

DOI: 10.1530/endoabs.49.EP111

Evrim Yilmaz² & Enver Ihtiyar³

¹Department of Endocrinology, Eskisehir Osmangazi University Medical

Faculty, Eskisehir, Turkey;²Department of Pathology, Eskisehir Osmangazi

University Medical Faculty, Eskisehir, Turkey;³Department of General

Surgery, Eskisehir Osmangazi University Medical Faculty, Eskisehir,

Turkey.

EP112

Paraganglioma (PG) and cyanotic congenital heart disease (CCHD): the

Introduction

role of tisular hypoxia

Ganglioneuroma is an extremely rarely seen tumour in the adrenal gland, which

Amelia Oleaga, Fernando Gon˜i, Miguel Paja, Estibaliz Ugarte,

originates from neural crest cells. Clinically, they generally have a silent course

Cristina Moreno, Natalia Iglesias, Eider Etxeberria, Laura Calles,

and in laboratory tests, the hormone levels expressed from the adrenal gland are

Maddalen Dublang & Alba Zabalegui

within the normal range.

Basurto University Hospital, Bilbao, Vizcaya, Spain.

Case

A 46-year old male patient, for whom a mass in the adrenal gland was diagnosed

incidentally on abdominal ultrasonography and MRI. The physical examination,

Introduction

laboratory tests and hormonal tests were within normal limits. As the appearance

CCHD comprises a number of different congenital heart defects associated with

on dynamic adrenal CT was compatible with an adenomatous lesion, a biopsy was

elevated pulmonary artery pressure and pulmonary vascular resistance, resulting

applied to the left adrenal gland. In the histopathological examination, findings

in a reversed or bidirectional shunt (Eisenmenger syndrome). These entities

were determined of neuroblastic tumour and ganglioneuroma, so adrenalectomy

develop systemic hypoxia. Pheochromocytoma and paraganglioma (PHEO/PG)

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

are neuroendocrine tumours. Several inheritance genetic alterations have been

EP114

reported in PHEO/PG syndromes. A pathogenic association between these

Large adrenal adenoma presenting as a clinically inapparent Cushing

entities is proposed.

syndrome, a trap diagnosis

Case report

Denisa Petrescu¹, Cristina Alina Silaghi², Doina Crisan³, Daniel

A 41-year-old female diagnosed of a CCHD in the new-born period, on stable

Tudor Cosma⁴, Ionela Lungu¹, Carmen Emanuela Georgescu²,

medical treatment, as surgery was rejected. She presented with symptoms

Romeo Ioan Chira⁵ & Horatiu Silaghi⁶

suggesting exacerbation of heart failure. Catecholamine hypersecretion was

¹County of Emergency Hospital, Cluj-Napoca, Romania;²Department of

suspected; 24 hour urine metanephrine: 215 mg/24 h (NV!341) and normeta-

Endocrinology, ‘Iuliu Hatieganu’ University of Medicine and Pharmacy,

nephrine

(NM): 2491 mg/24 h (NV!444). Abdominal CT showed a retro-

Cluj-Napoca, Romania;³Discipline of Pathology, Department of Morpho-

peritoneal lesion consistent with a PG. Functional imaging with Iodine¹²³MIBG

logical Sciences, ‘Iuliu Hatieganu’ University of Medicine and Pharmacy,

showed a pathological uptake area at the same localization. No other pathological

Cluj-Napoca, Romania;⁴Diabetes, Nutrition and Metabolic Diseases

images were observed. Genetic testing was performed and no mutations in

Clinical Center, Cluj-Napoca, Romania;⁵Ist Internal Medicine Department,

SDHD, SDHC, SDHB, VHL, SDHAF2, MAX and TMEM127 genes were found.

‘Iuliu Hatieganu’ University of Medicine and Pharmacy, Cluj-Napoca,

She underwent surgery after alpha blockade. Pathological examination confirmed

Romania;⁶5th Department of Surgery, ‘Iuliu Hatieganu’ University of

the diagnosis of a PG. NM became normal after surgery and patient symptoms

Medicine and Pharmacy, Cluj-Napoca, Romania.

improved.

Discussion

Several hypoxemic phenomenon have been related to be implicated in the

Adrenal incidentalomas (prevalence between 0.4 and 7%) have become a very

pathogenesis of PHEO/PG, as it is known that some of the genetic alterations

common clinical problem, the major concern being the risk of malignancy and

(SDHx, VHL, HIF2) lead to enhanced production of hypoxia inducible factors,

hormone overproduction.

which induce an increase in angiogenic factors leading to the development of

A 57-year-old woman was admitted for asthenia and uncontrolled hypertension.

tumours. The patient had an evolved heart disease with significant cyanosis.

The only relevant clinical signs were abdominal obesity (BMIZ31.1 kg/m²) and

Chronic exposure to hypoxia in patients with CCHD could increase the risk for

hypertension. Abdominal ultrasonography showed a voluminous left adrenal

developing PHEO/PG. In addition, the noradrenergic biochemical phenotype

solid mass of 10/9 cm, with well-defined sharp borders, hypoechoic with necrotic

found agrees with that observed in some of the PHEO/PG syndromes. In patients

areas and hyperechogenic foci of scars and calcifications. The differential

with CCHD the diagnosis of PHEO/PG can be difficult to suspect because

diagnosis of an atypical adenoma and pheochromocytoma or adrenocarcinoma

symptoms may be confounding, nevertheless catecholamine excess may be

was difficult.

dangerous. Therefore we consider that the existence of a PHEO/PG should be

Laboratory assays revealed hypercortisolism, indicated by the loss of the

ruled out in patients with CCHD and aggravation of the previous heart function.

circadian rhythm of cortisol secretion: cortisol value at 8 a.m. of 7.84 mg/dl and at

DOI: 10.1530/endoabs.49.EP112

midnight of 11.2 mg/dl, elevated free 24 h urinary cortisol of 731.4 mg/24 h

(normal range: 50-190 mg/24 h), no suppression at overnight dexamethasone

suppression test (cortisol of 5.46 mg/dl), low ACTH level of ! 1 pg/ml and

decreased cortisol level !50% at the high dose dexamethasone test. Plasmatic

metanephrines, normetanephrines, renine and aldosterone were normal. Abdomi-

nal CT scan indicated a tumoral left adrenal mass of 10/8.5/8.5 cm, well defined,

inhomogeneous, with microcalcifications, !10 HU, induced caudal displacement

of the left kidney, no lymphadenopathy or other visceral involvement. She

underwent left laparoscopic adrenalectomy. The histopathological evaluation

EP113

indicated Ki67!1% and chromogranin, synaptophysin, calretin, protein S100,

inhibin were isolated low positive; PanCK, EMA were negative; CD31 showed

Von Hippel Lindau disease in two Turkish families with different

the capillary network, without emboli; vimentin was positive; suggesting an

mutations

atypical adenoma and excluding an adrenocarcinoma, a kidney and liver tumor,

Mine Ada¸, İlkim Deniz Toprak & Recep Yılmaz Bayraktarli

but also a pheochromocytoma. Two weeks after surgery, a large ischemic

Istanbul Okmeydani Education and Research Hospital, Istanbul, S¸ i¸li,

vascular attack occurred, with poor prognosis. We should keep in mind that

Turkey.

voluminous cortisol-producing adrenal adenomas could have clinically inappar-

ent features, but with hidden vascular damages and increased cardiovascular risk.

Von Hippel-Lindau (VHL) disease is an inherited, autosomal dominant syndrome

DOI: 10.1530/endoabs.49.EP114

manifested by a variety of benign and malignant tumors. Herein we describe, two

families who had VHL. A 21-year-old man (index case 1) presented with bilateral

adrenal mass, serendipitously discovered by radiologic examination. He had

newly diagnosed arterial hypertension. His family history was significant for his

mother who had operated for pheochromocytoma, his two uncles who had

experienced cerebral tumors and his mother’s cousin who had bilateral

pheochromocytoma. After the diagnosis of bilateral pheochromocytoma, bilateral

EP115

adrenalectomy was performed. Histopathological data correlated with pheochro-

NK/T lymphoma adrenal presenting as adrenal insufficiency and

mocytoma. A genetic test was carried out. A germline mutation p.R167Q

cranial nerves neuropathies-a case report

(c.500GOA) was detected in the patient confirming VHL. A further genetic test

Shalini Sree Dharan, Norazizah Aziz, Shueh Lin Lim &

was prescribed in other family members. His mother had a history of cystic

Pavitratha Puspanathan

astrocytoma, meningioma, hemangioblastoma and right adrenalectomy for

Penang General Hospital, Penang, Malaysia.

pheochromocytoma. A germline mutation p.R167Q (c.500GOA) was detected,

too. Index case 1’s brother had a history of arterial hypertension and the germline

mutation p.R167Q (c.500GOA) was detected, too. Index case 1’s mother’s

Adrenal Lymphoma is extremely rare with fewer than 200 cases reported. The

cousin had a

24-year history of hypertension. He had experienced right

most common subtype is the diffuse large B cell lymphoma. Malignant lymphoma

adrenalectomy

24 years ago and left adrenalectomy

4 years ago with the

arising in the endocrine glands represents only 3% of extranodal malignant

diagnosis of pheochromocytoma. The germline mutation p.R167Q (c.500GOA)

lymphomas and is usually confined to the thyroid gland. NK/T-cell lymphoma

was detected, too. A 43-year-old woman (index case 2) was referred from the

presents primarily in the nasopharynx and sinuses. Although involvement of the

cardiology department to our outpatient clinic to examine the etiology of

adrenal glands can be seen in disseminated disease, primary presentation with

endocrine-induced arterial hypertension (150/90 mmhg). After the diagnosis of

adrenal masses and adrenal insufficiency is extremely rare. We report a case of 34

pheochromocytoma, the right adrenalectomy was performed. 5 years after the

years old gentleman presenting with prolonged fever, constitutional symptoms

operation she had operated for the pancreatic neuroendocrine tumor and 15 years

and symptoms and signs of adrenal insufficiency. He was treated as adrenal crisis

after the operation she was diagnosed as hemangioblastoma. A genetic test was

in the district hospital with hypotension, hyponatremia, and hyperkalemia. He

carried out. A germline mutation p.L118R was detected in the patient. A genetic

appeared cachexic, with no hyperpigmentation or palpable lymph nodes. His

test was prescribed to the other members of the family. Her two boy’s genetic tests

lactate dehydrogenase enzymes (LDH) was elevated. Cortisol taken during this

were detected the same mutation. All patients with pheochromocytomas should

stressful period was deemed too low. This was confirmed by an inadequate

be screened for the genetic syndromes for example MEN 2 and VHL. It is

response to the Synacthen test. CT Adrenal was performed and reported as

important for averting the further morbidity and mortality in the patients and their

bilateral enlarged adrenal, likely hyperplasia. He developed multiple cranial

families. Family screening is crucial in patients who are diagnosed with the

nerves neuropathies that progressively worsened. CT Brain was normal. Lumbar

disease.

puncture revealed high opening pressure and CSF biochemistry revealed no cells

DOI: 10.1530/endoabs.49.EP113

and negative for tuberculosis. With the possibility of disseminated tuberculosis,

empirical anti-tuberculosis medications were started but failed to abate his

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

symptoms. Laparoscopic left adrenal excision biopsy was performed and

Results

histology features are in keeping with high grade NK/T cell lymphoma. His

A 61-year woman was admitted for a right adrenal and a thyroid incidentaloma

condition deteriorated fast and he succumbed to his illness. This case illustrates

after left UN for renal cancer with clear cells, Fuhrman Nuclear Grade of 2

the need to include Primary Adrenal Lymphoma in the differential diagnosis of

(pT3N0Mx). Post-operatory endocrine panel of investigations were consistent for

adrenal masses especially when adrenal contour is preserved on imaging,

non-secretor low risk lesion. A fine needle aspiration biopsy at thyroid excluded a

hypoadrenalism and high LDH.

second malignancy. A 56-year old female had left UN 14 years ago for a benign

DOI: 10.1530/endoabs.49.EP115

condition. One year after surgery a right adrenal tumour of 1.2 cm was discovered

at CT

(computer tomography) scan. After

years, the subject became

hypertensive and experienced hot flushes in association with secondary

amenorrhea so an endocrine evaluation was considered. Non-secretor adrenal

profile and high Follicle Stimulant Hormone consistent for physiological

menopause was associated with stationary CT aspects for right adrenal tumor

EP116

but also a left adrenal tumor of 1.3 cm was identified. Nevertheless, abdominal

Primary hyperparathyroidism and primary hyperaldosteronism -

CT scan performed 1 year later showed similar aspects. Further serial imaging

cause or coincidence in arterial hypertension - case report

was recommended.

Tijana Icin^1,2, Ivana Bajkin^1,2, Dusan Tomic¹, Jovanka Novakovic-Paro^1,2,

Discussion

Bojan Vukovic^1,2, Jovana Prodanovic¹ & Milica Medic-Stojanoska^1,2

Adrenal incidentaloma discovered in menopausal patients with UN requires a

¹Clinic of Endocrinology, Diabetes and Metabolic Disorders, Clinical

complex differential diagnosis including the fact that they need to be

Center of Vojvodina, Novi Sad, Serbia;²Department of Internal Medicine,

differentiated from metastases arising from kidney cancer. Also, serial imaging

Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.

assessments after kidney removal may lead to the discovery of different solid

masses as thyroid incidentaloma or nodules.

Introduction

DOI: 10.1530/endoabs.49.EP117

30% of the adult population has high blood pressure. About

6% of the

hypertension may be caused by primary aldosteronism and very rare by primary

hyperparathyroidism. The combination of these two causes is very rare.

Case report

Our patient is women (age 50) with a 21 year long history of uncontrolled

hypertension. Treatment of hypertension consist of a beta-blocker, calcium

EP118

channel blockers, angiotensin converting enzyme inhibitor, loop diuretics and

Case with metastatic lung cancer who developed adrenal insufficiency

thiazide diuretics. Laboratory tests confirmed the presence of hypercalcemia

Buket Yilmaz Bulbul¹, Ece Celik², Mehmet Celik¹, Semra Ayturk¹,

(ionized calcium 1.42 mmol/l), and hypokalemia (3.4 mmol/l). After correction

Funda Ustun³ & Sibel Guldiken¹

of medical therapy results shows elevated levels of parathyroid hormone

¹Department of Endocrinology and Metabolism, Medical Faculty, Trakya

(221.7 pg/ml) and aldosterone/renin ratio (A/RO30), normal value of metane-

University, Edirne, Turkey;²Department of Chest Diseases, Edirne Sultan 1.

phrines and normetanefrine, normal ACTH and cortisol levels and diurnal rithm

Murat State Hospital, Edirne, Turkey;³Department of Nuclear Medicine,

of secretion. CT of the abdomen showed adenoma like enlargement of left adrenal

Medical Faculty, Trakya University, Edirne, Turkey.

gland of

2 cm. Scintigraphy and ultrasound confirmed the presence of

hyperplasia/adenoma of the lower left parathyroid gland. Bone mineral density

indicates osteoporosis and ultrasound of abdomen described nephrolithiasis in the

Adrenal metastasis is common (35%) among the patients with lung cancer, while

left kidney. Due to hypercalcemia, first we have decided to operate the

less than

3% of the patients develop bilateral adrenal metastasis. Adrenal

parathyroid glands. Surgery leads to normalization of calcium. The pressure is

metastases are generally small and clinically asymptomatic. Adrenal insufficiency

regulated without both the diuretics at a reduced dose of a calcium channel

is rare despite the presence of adrenal metastasis. Lam et al. reported this ratio as

blockers. After recovering from surgery, in a hospital setting we discontinued

0.7%. We aimed to present a case with lung cancer and bilateral adrenal

therapy and dynamic testing was conducted (volume loading test and postural

metastasis who developed adrenal insufficiency.

stimulation test) that indicate adrenal hyperplasia as a cause of primary

A 63-year old male patient was presented with cough. Chest X-ray revealed a mass

hyperaldosteronism. Patient started with spironolactone therapy that even in

lesion in the upper zone of left lung. PET/CT examination was performed and

small doses leads to normalization of potassium and reduce the need for other

demonstrated increased FDG uptake in upper lobe mass lesion of left lung,

antihypertensive agents.

mediastinal lymph nodes, bilateral surrenal glands (9 mm at the right and 5.5!

Conclusion

2 cm at the left),liver and bones. Following bronchoscopy, the patient was

More endocrine disorders can simultaneously affect arterial hypertension.

diagnosed with non-small cell lung cancer. Pathologic examination of surrenal

Treatment of hyperparathyroidism may lead to better control of hypertension.

biopsy material revealed surrenal metastasis. The patient had no signs of adrenal

Despite the existence of left adrenal enlargement that looks like an adenoma,

insufficiency and electrolyte imbalance at the time of diagnosis. He was scheduled

adrenal hyperplasia is a possible cause of primary hyperaldosteronism.

for cisplatinCgemcitabine chemotherapy. Although lung and adrenal gland

DOI: 10.1530/endoabs.49.EP116

lesions were stable within

6 months after treatment, the patient developed

hypoglycemia, hypovolemia, hyponatremia and hyperkalemia. Laboratory

examination revelaed ACTH:1250 pg/ml (normal: 0-46), and cortisol 4.43 mg/dl

(n:5-29). The patient was given prednisolone and fludrocortisone treatment with

the diagnosis of adrenal insufficiency. Symptoms of the patient were subsided after

treatment. Post-treatment laboratory examination revealed Na:138 mEq/l

EP117

(normal:135-145), K: 4 mEq/L/normal:3.5-5.5) and ACTH:37 pg/ml.

Endocrine masses displayed as incidentalomas in patients with

It should be considered that patients with lung cancer and adrenal metastasis may

unilateral nephrectomy

later develop adrenal insufficiency despite the absence of adrenal insufficiency at

Adina Ghemigian¹, Eugenia Petrova², Nicoleta Dumitru², Andra Buruiana²,

the time of diagnosis. Although fatigue, nausea, hypotension and hyponatremia

Mara Carsote¹ & Ana Valea³

may also be seen in the patients with cancer, these may also be the signs of adrenal

¹C.Davila UMPh & I.Parhon National Institute of Endocrinology,

insufficiency.

Bucharest, Romania;²Parhon National Institute of Endocrinology,

DOI: 10.1530/endoabs.49.EP118

Bucharest, Romania;³I.Hatieganu UMPh & Clinical County Hospital,

Cluj-Napoca, Romania.

Introduction

Menopausal adrenal tumours may be elements of a complex panel of

co-morbidities. Some of these are represented by the presence of a second

EP119

pathology requiring surgery at the kidney level.

Adrenal haemorrhage: from Urology to Endocrinology

Aim

Catarina Silvestre, Ana Gomes, Raquel Carvalho & Maria João Bugalho

We aim to introduce a series of two cases involving menopausal women who were

Santa Maria Hospital, Lisbon, Portugal.

referred for specific endocrine assays after they had a unilateral nephrectomy

(UN).

Method

Background

This is a cases series observational study. The patients gave their consent. They

Bilateral adrenal haemorrhage (Waterhouse-Friderichsen syndrome) is a rare

were followed in different medical and surgical centres from Romania.

consequence of sepsis (usually a result of meningococcal infection), with an

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

estimated 15% mortality. Despite the predominant association with meningo-

EP121

coccal infection, there are other recognised aetiologies: sepsis resulting from

A rare case: adrenal lymphangioma

other organisms, and non-infectious causes, such as anticoagulant treatment,

Yusuf Durmus¹, Mehmet Celik², Buket Yilmaz Bulbul², Semra Ayturk²,

trauma and postoperative adrenal haemorrhage.

Nuray Can³, Ebru Tastekin³ & Sibel Guldiken²

Case report

¹Department of Internal Medicine, Medical Faculty, Trakya University,

A 53-year-old man was admitted in the Urology department, to undergo a

Edirne, Turkey;²Department of Endocrinology and Metabolism, Medical

retropubic radical prostatectomy

(prostatic adenocarcinoma). Other medical

Faculty, Trakya University, Edirne, Turkey;³Department of Pathology,

history: thromboangiitis obliterans, managed with warfarin and acetylsalicylic

Medical Faculty, Trakya University, Edirne, Turkey.

acid. No complications on the postoperative period; prophylactic antibiotherapy

was started with ceftriaxone. On the 7^th postoperative-day, the patient had a

lipothymia episode, with a decrease of consciousness level

(Glasgow

9),

Adrenal lymphangioma is a rare benign tumors of the adrenal gland. Because of

hypotensive and subfebrile condition. Blood evaluation consistent with sepsis:

the increased use of imaging methods in recent times, the diagnosis is usually

leukopenia, thrombocytopenia, raised transaminases, C-protein reactive and

made incidentally. It is usually due to malformation between the lymphatic and

troponin, and severe hyposmolar hyponatremia

(113 mEq/l). No anomalies

the venous system. Those with small indiameters are generally asymptomatic

detected on neurologic evaluation or cranial computerized-tomography (CT).

and can be evacuated by needlea spiration. However, surgery is recommended

Antibiotherapy was changed to Piperacillin-Tazobactam. A random ACTH,

for cysts over 6 cm in diameter due to risk of infection, bleeding, compression of

cortisol and TSH were performed as workup for hyponatremia: ACTH 141 pg/ml

neighboring organs, and perforation. A 45-year-old male patient was admitted

(0-46), cortisol 2.5 ug/dl (4.3-23), normal TSH. Abdominal CT scanning was

due to left abdominal pain and swelling for 2 months. There was no chronic

performed: grossly abnormal adrenal glands bilaterally, with masses compatible

disease or drug use in hisstory. Blood pressure: 130/80 mm/hg, pulse rate was

with hematomas. On the 8^th day he began intravenous hydrocortisone in high

94/min. Ultrasonography revealed a grade II hepatosteatosis in the liver and a

doses, with recovery of natremia and consciousness level. Blood and urine

70 mm multilocular cystic lesion in the left suprarenal region. A mass lesion

cultures results were negative (probably “decapitated”). When discharged, the

with multilocule cystic components was observed in the abdominal MRI was T₁

patient was asymptomatic, with normal blood evaluation, and taking long-term

hypointense, T₂ hyperintense in the left adrenal gland and 75 mm in diameter.

hydrocortisone and fludrocortisone. So far, the patient has been asymptomatic and

There were no blood pressure attacks, flushing and palpitations. In laboratory

is being monitored by the Endocrinology department.

tests: sodium 138 mmol/l (n:135-145), potassium 4.3 mmol/l (n:3.5-5.5), ACTH

Conclusions

27.4 pg/ml (n:0-46), basal cortisol 15.83 mg/dl (n:5-29), 1 mg dexamethasone

This case highlights the importance of awareness for symptoms/signs and

supression test

0.83 mg/dl (!1.8) was detected. Plasma aldosterone-to-renin

electrolyte variation when assessing surgical patients post-operatively. The early

ratio was!10, metanephrine and normetanephrine were normal in 24 hour

recognition of this disease allowed immediate treatment, avoiding a worse

urine.

outcome and leading to a quick recovery. There are risk factors, as antic-

Laparoscopic left surrenalectomy was performed for the hormone inactive mass.

oagulation therapy, predisposing the development of this rare, but serious,

Pathologic examination revealed D2.40 positive, CD34 positive, MelanA on

disease.

cystwall as local positive lymphangioma. The patient was asymptomatic for

DOI: 10.1530/endoabs.49.EP119

8 months. We aimed to present the rare case of adrenal lymphangioma in

ourcase.

DOI: 10.1530/endoabs.49.EP121

EP120

EP122

Hemangioma a rare adrenal tumors: report of two cases

A rare case of a patient with MEN 4 phenotype and associated

Aribi Yamina, Bensaleh Meriem, Brakni Lila, Iabassen Malek &

pheochromocytoma

Ould Kablia Samia

Alexandra Mirica¹, Rodica Petris¹, Radu Mirica³, Sorin Paun^2,4 &

Central Hospital of the Army, Algiers, Algeria.

Diana Loreta Paun^1,2

¹C.I.Parhon National Institute of Endocrinology, Bucharest, Romania;

Introduction

²Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;

Dramatically with increased use of computed tomography (CT) and magnetic

³Saint John Emergency Hospital, Bucharest, Romania;⁴Floreasca

resonance imaging (MRI), more and more uncommon adrenal masses have been

Emergency Hospital, Bucharest, Romania.

detected at abdominal examinations. Adrenal cavernous hemangiomas (ACH) are

rare vascular tumor. The first case report was published in 195 by Johnson and

Introduction

Jeppesen. Approximately less than 70 cases were reported in the literature to date.

MEN4 syndrome is a recently described form of MEN in patients with parathyroid

ACH are nonfunctioning benign tumors that is often discovered incidentally.

and anterior pituitary tumors, which may also develop bronchial, gastric and

They are more frequent in women in the 5th or 7^th decade. Their differential

pancreatic neuroendocrine tumors. In general, the patients present with clinical

diagnosis preoperatively is rather challenging.

signs of primary hyperparathyroidism and simptoms caused by pituitary hormones

These tumors are unilateral lesions in general large and most usually cavernous.

hypersecretion or due to the tumor mass. However, clinical cases with the

All cases reported were treated with surgery.

coexistence of pituitary tumors and pheochromocytoma are very rare described.

Case report

Case presentation

We describe two cases of ACH in a 66 years old woman and a 36 years old men.

We present a young male patient of 44 years old, who presented in our department

In the first case ACH was discovered as incidentaloma and in the second it was

for endocrinological pre-operative assessment of a pituitary macroadenoma. The

revealed by flank pain.

brain MRI indicated a macroadenoma (31/30/21 mm) with supra- and para-sellar

The diagnostic was performed on ultrasonography. Because of the impossibility

extension, compressing the optic chiasm, optic tract and the 3^rd cranial nerve on the

of ruling out the presence of malignancy (CT, MRI), surgical adrenalectomy was

right side. The patient accused acute right blindness starting 2 weeks ago, denying

performed. The patients did well postoperatively. Pathological examination

other simptoms. On clinical examination, the patient was obese (BMIZ36 kg/m²)

revealed that the adrenal masse corresponded to an ACH.

and hypertensive (BP Z170/100 mmHg). In addition, personal and family medical

Discussion

history were not significant, excepting personal arterial hypertension debut at 36

ACH is an uncommon benign vascular tumor. These rare tumors usually localized

years old. Endocrinological evaluations showed normal levels of pituitary, thyroid,

in the liver and the skin. Adrenal site is extremely rare occurring only in 0.01% of

mineralocorticoid and glucocorticoid hormones. However, there were detected

cases and accounts for 63 reported cases in the literature.

elevated values of parathyroid hormone

(110 pg/ml), plasmatic and urinary

ACH are often discovered as incidentalomas either by imaging studies or

normetanephrines (250 pg/ml and 900 ug/24 h) and plasmatic chromogranin A

histologic examination.

(230 ng/ml). Furthermore, abdominal computed tomography have identified a left

The indications for resection of this neoplasm particularly in tumours more than

adrenal nodule of 1.02/1.14 cm with no other lesions. Thus, in the first instance, the

3 cm in diameter are to relieve the mass-effect-type symptoms, to exclude

patient underwent laparoscopic left adrenalectomy and afterwards transsphenoidal

malignancy, and to treat complications such as haemorrhage, necrosis and

pituitary surgery, after which he regained visual acuity of the right eye and also it

thrombosis.

was obtained normalized blood pressure values. Adrenal histopathology confirmed

DOI: 10.1530/endoabs.49.EP120

the presence of pheochromocytoma. Blood samples were collected for genetic

testing.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

EP125

We present the case of a young patient with pituitary non-functioning

Incidentaloma as a first manifestation of lymphoma

macroadenoma and hyperparathyroidism (MEN4syndrome), also associating

Pamela R. Chávez Díaz, Cristina Álvarez Escola, Miriam Zapatero Larrauri,

left pheochromocytoma.

José Tomás Castell Gómez, Alfredo Aguilera Bazán & Lucrecia Herranz de

Keywords: MEN 4 phenotype; pheochromocytoma.

la Morena

DOI: 10.1530/endoabs.49.EP122

Hospital U. La Paz, Madrid, Spain.

Introduction

Incidentally discovered adrenal masses (incidentalomas) are common and in

some cases differential diagnosis could be a challenge.

EP123

Case report

The difficulty in predicting aggressive tumour behaviour of

A 55-years old woman presented with an incidental left adrenal mass of 36mm

phaeochromocytomas

discovered on an abdominal ultrasound. As sole background she underwent

Edouard Mills, Ali Naqvi, Roberto Dina, Fausto Palazzo & Florian Wernig

resective surgery of an ovarian serous cyst. She denied symptoms like flushing,

Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust,

headache, diaphoresis or palpitations. Physical examination was irrelevant. BP:

London, UK.

130/76 mmHg; CF:78 bpm.

Fractionated metanephrines and catecholamines in a 24-hour urine specimen,

sodium and potassium levels, 24-hour urinary free cortisol, adrenocorticotropic

Phaeochromocytoma and paragangliomas

(PH/PG) are rare neuroendocrine

hormone, aldosterone/plasma renin plasma ratio and dehydroepiandrosterone

tumours. Prediction of aggressive tumour behaviour remains a major challenge.

sulfate were normal.

The Phaeochromocytoma of the Adrenal gland Scaled Score (PASS) is used to

Abdominal computed tomography showed an heterogeneous left adrenal gland

separate benign from malignant lesions with a score O 4 showing potential for

and multiple nodes in locations such as subdiaphragmatic region, celiac trunk,

biologically aggressive behaviour. Pre-operatively, MIBG together with CT/MRI

gastrohepatic ligament, splenic hilum and retroperitoneal area, most of them with

remain the diagnostic radiological gold standard.

the presence of central necrosis.

We report a 68-year-old female who was found to have a locally arising colonic

Additionally axillary and paratracheal nodes were found, and also lungs nodules

adenocarcinoma on biopsies. Staging also identified a 10.7 cm right adrenal lesion

less than 5mm in diameter were described. PET F-18 FDG scan identified an

and work-up revealed markedly raised urinary metanephrines and positive MIBG

hypodense centrum area suggestive of necrosis into the left adrenal. A

imaging. The MDT decision was to first remove the colonic cancer with

tomography guided biopsy only detected necrotic cells. Finally a left

appropriate alpha blockade. It was felt that a combined laparoscopic approach

adrenalectomy was performed and histopathological study revealed a diffuse

would not be appropriate given the adrenal lesion size, which might require an

large B-Cell non-Hodgkin’s lymphoma. The patient was started on chemotherapy

open procedure. Histology confirmed a stage III Duke’s C tumour and adjuvant

with a successful response.

chemotherapy commenced. Although adrenal surgery had been planned once she

Conclusion

completed chemotherapy, she did not tolerate chemotherapy and it had to be

Biopsy could be necessary in the differential diagnosis of necrotic adrenal masses

discontinued. An open adrenalectomy was undertaken. Histology was consistent

even when lymph nodes are present.

with a phaeochromocytoma with a PASS score of eight. 2 months after adrenal

DOI: 10.1530/endoabs.49.EP125

surgery, she reported intermittent tingling and numbness in the left arm with

thoracic back pain. An MRI confirmed a soft tissue mass at T₂ extending into the

spinal cord. Urinary metanephrines confirmed persistently elevated normeta-

drenaline levels. She underwent bilateral laminectomy under alpha-blockade.

Histology confirmed a metastatic phaeochromocytoma. She is currently awaiting

Ga⁶⁸-DOTATATE PET-CT imaging to guide further management.

Ga⁶⁸-DOTATATE PET-CT has been shown to be the most sensitive imaging

modality for detection of metastatic PH/PG and would potentially have identified

metastatic lesion(s) not seen on MIBG scanning. We therefore propose that Ga⁶⁸-

EP126

DOTATATE PET-CT - where available - should be used for initial staging and

Clinical case of aldosterone-producing adrenocortical carcinoma

MIBG should be reserved for those patients only for whom MIBG therapy is

Alexey Krivosheev¹, Iya Voronkova^1,2, A Platonova¹ & Timur Britvin¹

being considered.

¹Moscow Regional Research and Clinical Institute, Moscow, Russia;

DOI: 10.1530/endoabs.49.EP123

²Endocrinology Research Centre, Moscow, Russia.

Aldosterone-secreting adrenocortical carcinoma (ACC) is rare neoplasm, which

detected in 2.5% of active ACCs.

EP124

Clinical case

A 58 years old female, was admitted to our clinic with complaints of high blood

An unusual cause of unilateral adrenal haemorrhage

pressure, back pain, weakness, convulsions. Biochemical evaluation confirmed

Jayamalee Jayaweera¹, Emily Symington² & John Clark¹

primary hyperaldosteronism

(serum aldosterone

1012 pg\ml, serum renin

¹West Suffolk Hospital, Suffolk, UK;²Addenbrookes Hospital-Cambridge

concentration

0.5 mkME\ml, aldosterone-renin ratio

202.4, hypokalemia

University Hospitals, Cambridge, UK.

1.2 mmol\l). There was no evidence of cortisol co-secretion on standart low-

dose dexamethasone test. The level of metanephrine and normetanephrine in

A 24 year old man was admitted by the Surgeons with left sided abdominal pain. He

urine were in normal range. A CT scan with contrast-enhanced identified right

was febrile and tachycardic and found to have raised inflammatory markers.

adrenal tumor 8*6*9 cm with heterogeneous structure. Native density of tumor

Abdominal CT scan revealed a 6 cm left adrenal haemorrhage with no evidence of

was 38 Hounsfield units (HU). In arterial and venous phase tumor density was 70

an underlying lesion. Initial endocrine investigations were unremarkable for

HU, delayed - 55 HU. Dynamics of growth was C5 cm in 6 months. Surgical

Cushings, Conn’s and adrenal insufficiency. Norepinephrine levels were high but

treatment was performed: in the right retroperitoneal there was tumor about 15 cm

settled subsequently. He had a coagulopathy and evidence of reactivation of EB virus.

in diameter, comressed the inferior vena cava, right renal artery, and renal veins.

He had a past history of Multiple sclerosis treated eighteen months previously with

Adrenalectomy with a tumor and lymph node dissection was performed.

Alemtuzumab.

Histological examination revealed adrenocortical cancer. Ki-67

expression

He remained febrile and developed acute kidney injury. His symptoms and signs

was up to 75% in ‘hot spots’. Number of Weiss score - 6. A 1.5 month follow-

fitted the criteria for haemophagocytic lymphohistiocytosis (HLH), confirmed on

up CT-scan was no evidence of local reccurence. Serum aldosterone level was in

bone marrow biopsy. His coagulopathy was due to antibodies to factor VIII (acquired

normal range.

haemophilia) and he developed autoimmune thyroiditis requiring Thyroxine

Although rare, this case demonstrates the ability of this pathology, and therefore

replacement. His HLH was successfully treated with steroids and Rituximab.

requires caution against the ACC at the small size of the tumor. As a method of

We think Alemtuzumab treatment had induced the autoimmune disorders (his

follow-up screening can be a controlling level of aldosterone and potassium in the

coagulopathy and thyroid disease), as well as reactivating EB virus. The combination

blood and monitoring blood pressure. To improve the results of treatment these

of coagulopathy and EB viral infection may have caused his adrenal haemorrhage.

patients it is necessary to conduct studies with larger numbers of patients, as well

Endocrinologists should be aware of the wide spectrum of autoimmune disorders that

as development of new diagnostic and prognostic criteria allowing to improving

can be precipitated by monoclonal antibody treatment.

diagnosis ACC before and after surgery.

DOI: 10.1530/endoabs.49.EP124

DOI: 10.1530/endoabs.49.EP126

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP127

tumours with supressed renin but inappropriate low aldosterone, not suggesting

PA. Early diagnosis can be very important because malignancy is the rule in this

The case of adrenal incidentaloma due to unrecognized nonclassic

peculiar pathology.

congenital adrenal hyperplasia

Milina Tancic-Gajic, Miomira Ivovic, Ljiljana Marina, Zorana Arizanovic,

DOI: 10.1530/endoabs.49.EP128

Zorana Stojanovic, Aleksandra Kendereski & Svetlana Vujovic

Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic

Diseases, Clinical Center of Serbia, University of Belgrade, Belgrade,

Serbia.

EP129

Introduction

Aldosterone-producing adrenocortical carcinoma and alteration of

A rare cause of adrenal incidentaloma is congenital adrenal hyperplasia (CAH).

secretion pattern on recurrence: a case report

Nonclassic CAH is one of the most frequent autosomal recessive disorders. Most

Joana Lima Ferreira, Ana Paula Marques, Carlos Sottomayor &

cases of nonclassic CAH are never diagnosed due to very mild symptoms.

Vitor Valente

Case report

Hospital Pedro Hispano, ULS Matosinhos, Portugal.

A 62-year-old woman admitted at our Department for right adrenal incidentaloma

sized 39!34!38 mm confirmed by MRI. She was asymptomatic. Her past

Introduction

medical history included stabile hypertension, euthyroid Hashimoto thyroiditis,

Adrenocortical carcinoma (ACC) is a rare neoplasm with a variable but overall

uterine leiomyoma, varicose vein surgery and pulmonary embolism. Menarche

poor prognosis. The presentation is heterogeneous usually with mass effect and

occured at the age of 18, and the monthly menstrual cycle continued until the

less often with evidence of hormonal secretion. About half of cases the tumors are

menopause at the age of 51. She had a miscarriage and three failed in vitro

hormonally active most commonly with cortisol secretion followed by sexual

fertilisation attempts. Upon physical examination clitoromegaly was present.

hormones production, being rare the aldosterone secretion.

Endocrine assessment for excess of cortisol, catecholamine and aldosterone

Case report

concluded that the adrenal mass was hormonally non-functioning. ACTH level

A 41-year-old male presented with hypertensive crisis and marked hypokalemia.

was normal. 17- hydroxyprogesterone, total testosterone, androstenedione and

A primary hyperaldosteronism was diagnosed and Computed Tomography (CT)

progesterone were elevated:

26 nmol/l,

3.4 nmol/l,

8.5 ng/ml,

16.2 nmol/l,

showed a 9 cm suspicious adrenal mass. The patient started on spironolactone and

respectively. A

0.25-mg intravenous ACTH-stimulation level of cortisol

underwent open adrenalectomy. A total resection was done (R0) and it was a

(341/347/402) and

17- hydroxyprogesterone

(29/51) showed partial cortisol

10 cm adrenal carcinoma, Weiss score 5, Ki67 30% and stage II ENSAT. There

insufficiency and nonclasssic CAH. After informed consent molecular genetic

was clinical and biochemical normalization and at 9 months CT didn’t show any

study for CAH was conducted. Our patient was found to be a heterozygote with

recurrence. Due to high risk carcinoma therapy with mitotane was proposed,

two mutations in the CYP21A2 gene: p.P30L i I2G, that verified the diagnosis of

however the patient refused and left follow-up. 30 months after surgery, he was

CAH. In order to prevent adrenal insufficiency Hydrocortisone was advised in a

admitted to the Emergency Department for adrenal carcinoma relapse and

case of surgical procedures or illness. During the 2 year follow-ups there were

disseminated metastatic disease with simultaneous secretion of aldosterone and

changes in either clinical and biochemical presentations or in repeated abdominal

cortisol. He started on chemotherapy with EDP-M (etoposide, doxorubicin,

MRI examinations.

cisplatin and mitotane). Despite initial favorable course, the patient got worse

Conclusion

with disease progression, culminating in death 44 months after the diagnosis.

Undiagnosed nonclassic CAH is the cause of miscarriage, infertility and adrenal

Discussion

incidentaloma in our patient. 17- hydroxyprogesterone would be determined in all

The management of ACC is challenging. Surgery is crucial for treatment and

patients with infertility or adrenal incidentaloma.

mitotane is important as an adjuvant therapy, as a chemotherapeutic agent and

DOI: 10.1530/endoabs.49.EP127

also to control the hormonal secretion. We report a case of an aldosterone-

producing ACC, an extremely rare cause of primary hyperaldosteronism. Even

rarer was the change on secretion profile throughout disease evolution with

multiple steroid production. The hormonal profile should be carefully

investigated in an ACC and the possibility of multiple combined hormonal

secretion or the shift of the profile secretion should be considered.

DOI: 10.1530/endoabs.49.EP129

EP128

DOC secreting adrenal adenoma, a rare cause of hypertension

Miguel Paja, Maddalen Dublang, Alba Zabalegui, Cristina Arrizabalaga,

Amaia Expósito & Javier Espiga

Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain.

EP130

Congenital adrenal hyperplasia: hazards of non-compliance with

treatment!

Secondary endocrine hypertension affects around

10% of all hypertensive

Mazhar Dalvi¹ & Faisal Dalvi²

population, most frequently primary aldosteronism (PA). Less frequent forms

¹Al Noor Hospital, Abu Dhabi, United Arab Emirates;²Aster Medical

of adrenal hypertension include pheochromocytomas and other causes of

Centre, Dubai, United Arab Emirates.

mineralocorticoid excess than PA, featuring suppressed renin without excess of

aldosterone. Featuring. We present a 29-year-old woman with difficult to control

hypertension diagnosed two years before and poor response to ACEI and ARA II

treatment. She was referred for study and treatment. She had a normal appearance,

A 30-year-old male presented to emergency with history of palpitations for

without Cushing’s stigmata, overweight nor clinical suspect of pheochromocy-

6 months. At birth he was diagnosed with salt-losing congenital adrenal

tomas. She had not noticed hirsutism and maintained regular menstrual cycles.

hyperplasia

(female pseudohermaphrodite) and commenced on steroid

Biochemical study was normal except for slightly lower potassium (3.48 mmol/l).

therapy. He also underwent corrective surgery. He needed both fludrocorti-

Hormonal study showed suppressed renin activity (!0.2 ng/ml per h), with

sone and hydrocortisone. At age 17, he visited urology because of bilateral

normal to low aldosterone (7.3 ng/dl), normal urinary metanephrines and normal

testicular enlargement. On examination he had normal secondary sexual

plasma ACTH (34.5 pg/ml). Abdominal CT revealed a well-defined hetero-

features, but his testicles felt hard and four times the normal size. His serum

geneous and much vascularized right adrenal mass of

6 cm in diameter.

testosterone level was

50.4 nmol/l

(10-38 nmol/l),

17-OH-progesterone

Deoxycorticosterone

(DOC) measured in previous stored sample was

142 nmol/l (!13 nmol/l) and ACTH (corticotrophin) of 139 ng/l (0-50 ng/l),

237.9 ng/dl (normal ! 15 ng/dl) with normal deoxycortisol (4.5 ng/ml; NV ! 7.2),

clearly indicating non-compliance. He had bilateral orchidectomy. Upon

testosterone, DHEAs and plasmatic and urinary cortisol. Open right adrena-

pathologic review, these lesions were most consistent with testicular tumors

lectomy was performed due to the size and suspicion of malignancy. On light

of the adrenogenital syndrome. Patient continued to default at clinic

microscopic examination, the tumour was an adenoma of

6.5 cm not

appointments. At age 26, he presented to the surgeon with increasing

encapsulated, composed of cells with clear and eosinophilic cytoplasm and

abdominal girth and abdominal pain. CT of the abdomen demonstrated very

large nuclei without mitosis nor necrosis. Weiss’s criteria classified it as

low-density adrenal masses (18!11 cm on the left side and 8!4.5 cm on

adrenocortical adenoma. Postoperatively, DOC level fell to 7.1 ng/dl and blood

the right side). Blood work up showed high 17-OH- progesterone indicating

pressure and potassium normalized.

inadequate suppression with glucorticoids partly due to non-compliance. As

Conclusion

these adenomas was new onset and there was a possibility of adrenocortical

DOCA-producing adrenal neoplasm are exceptionally reported, and they are

cancer the patient underwent laparoscopic bilateral adrenelectomy. The final

usually malignant tumours. They should be suspected in the presence of adrenal

histology to be consistent with adrenal myelolipomas. Hydrocortisone dose

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

was doubled and fludrocortisone 100 mcg/day was started. Now at age 30,

134/92 mmHg (sleep).

24-hour urinary levels of catecholamine and

he presented with history of palpitations and dizziness. He had sinus

metabolites were significantly higher than normal ranges; noradrenaline

tachycardia In ECG

(HR120/min). Blood work up: Na

130 mmol/l

was 787.99 mg/24 h, dopamine 3635.43 mg/24 h, normetanephrine 1605.31

(135-145 mmol/l) K

5.33 mmol/l

(3.5-5.1 mmol/l) Plasma renin

mg/24 h. MR imaging revelaed a heterogeneous lesion (49!37 mm) in the

100 mIU/ml (!40 mIU/ml). This indicated under replacement. He was clearly

left adrenal gland. Because of the early stage of pregnancy laparoscopic

tachycardic because of volume depletion. His compliance was enforced.

surrenalectomy was performed. Histopathologic examination revealed a

Within 6 weeks his heart rate normalised with normalisation of renin levels.

tumor consistent with pheochromocytoma. In the follow-up, there was no

Persons with CAH are at increased risk of developing adrenal myelolipomas,

maternal problem except hypotensive state but unfortunately, because of

testicular adrenal rest tumours particularly if their CAH is poorly controlled.

anhydramnios and intrauterine growth retardation, medical abortion was

DOI: 10.1530/endoabs.49.EP130

applied at the 27th gestational-week. Pheochromocytoma is a very rare

cause of hypertension in pregnancy however, early detection are crucial

because of the increased risk of maternal-fetal mortality. Therefore, in cases

of high blood pressure which can not be explained by gestational

hypertension, it is necessary to carefully evaluate other secondary causes

such as pheochromocytoma. The most suitable period for the operation is the

second-trimester. Surgical approach was used and no complication related to

the operation occurred in our case. However, it was thought that the outcome

EP131

of fetal loss due to developmental delay was related to the adverse effects of

Adrenal insufficiency due to both hemorrhage and thrombosis related

circulatory factors due to long-term illness in the patient. The fact that the

with primary antiphospholipid syndrome

patient could not be examined in the pre-pregnancy period and probably the

Buket Bicer¹, Pinar Sisman², Soner Cander³, Ozen Oz Gul³ & Canan Ersoy³

prolongation of the duration of the illness resulted in a negative result.

¹Uludag University Medical School, Department of Internal Medicine,

Especially in women of childbearing age, the importance of hypertension in

Bursa, Turkey;²Harakani State Hospital, Endocrinology and Metabolism

terms of maternal and fetal outcomes is emphasized by this case report.

Clinic, Kars, Turkey;³Uludag University Medical School, Department of

DOI: 10.1530/endoabs.49.EP132

Endocrinology and Metabolism, Bursa, Turkey.

Background

Antiphospholipid syndrome

(APS) is characterized by venous or arterial

thrombosis and/or an adverse pregnancy outcome in the presence of persistent

laboratory evidence of antiphospholipid antibodies. Loss of adrenal function due

to bilateral adrenal vein thrombosis, resulting in hemorrhagic infarction, may

occur in association with APS.

EP133

Case presentation

POEMS: a rare cause of adrenal insufficiency in a young male

We present the case of a 45-year-old woman with APS diagnosis since she was

Joanna Prokop¹, João Estorninho¹, Sara Marote², Teresa Sabino¹,

37, with history of multiple thrombotic events (deep vein thrombosis, sigmoid

Aida Botelho de Sousa³, Eduardo Silva² & Ana Agapito¹

sinus thrombosis, spontaneous abortion, adrenal hematoma and pulmonary

¹Endocrinology Department, Centro Hospitalar de Lisboa Central, Lisbon,

embolism). She was hospitalized for adrenal hematoma under anticoagulant

Portugal;²Internal Medicine Department, Centro Hospitalar Lisboa Central,

therapy with warfarin. The basal adrenal function tests revealed morning serum

Lisbon, Portugal;³Hemato-Oncology Department, Centro Hospitalar Lisboa

cortisol

0.7 mg/dl

(reference range

3.7-19.4) and ACTH 345 pg/ml (5-46).

Central, Lisbon, Portugal.

Abdominal CT showed nodular lesion with

HU density (29!27 mm)

suggestive of adrenal hematoma in the left adrenal gland; right gland is

thickenned. Adrenal insufficiency was associated with both hematoma in the left

adrenal gland and thrombosis in the right gland. The patient was discharged under

POEMS syndrome characterized by polyneuropathy, organomegaly,

corticosteroid treatment and low molecule weight heparin (LMWH). After being

endocrinopathy, monoclonal gammopathy and skin changes is a rare disease

discharged, warfarin was started again and she was admitted in the emergency

that usually presents in the 6th decade. We report a case of a young male in

department with dyspnea and pleuritic chest pain. Initial analytical study revealed

whom the presenting manifestations were mandibular mass, adrenal

INR (2.26), hypoxemia (PO2:64 mm/Hg) and hypocapnia (32 mm/Hg). She was

insufficiency and peripheral polyneuropathy. Clinical case: A thirty-three

restarted on therapy with LMWH. Further study showed deep vein thrombosis in

year old man from Guinea-Bissau was admitted to our hospital with

right lower extremity. The patient was discharged after vena cava filter

asthenia, weight loss, decreased tactile sensibility with pain and muscle

replacement.

weakness in upper and lower limbs. Bedridden for 2 years, after surgery of

Discussion

mandibular mass with nondiagnostic histological examination. Physical

The recurrence rate of thrombotic events among patients with APS is highly

examination revealed mandibular deformity, unilateral gynecomastia,

variable among studies, with an annual recurrent thrombosis risk ranging from

bilateral axillary lymphadenopathy, sensorial motor peripherial polyneuro-

5 to 12%. However adrenal involvement has been reported in 13% of cases of

pathy, edema of lower limbs. Lab. evaluation: normochromic, normocytic

catastrophic APS. In patients with antiphospholipid antibody syndrome, adrenal

anemia, thrombocytosis, hyperkalemia, normal renal/liver function and

insufficiency is often seen with bilateral adrenal thrombosis, although rarely in

protein electrophoresis, immunofixation: monoclonal protein negative,

some patients an adrenal gland hemorrhage may occur with other adrenal gland

urine: increased kappa/lambda chains, Bence Jones protein neg., morning

hematomas.

cortisol 8.3 ug/dl, ACTH 129 pg/ml. Laboratory workup confirmed adrenal

DOI: 10.1530/endoabs.49.EP131

insufficiency, subclinical primary hypothyroidism and primary hypogonad-

ism. Thoracic-abdominal CT: hepatosplenomegaly, multiple sclerotic

lesions in thoracic vertebras and ribs. Gluco- mineralocorticoid substitution

and levothyroxine therapy were started with clinical improvement. Bone

marrow biopsy revealed plasma cell dyscrasia and confirmed POEMS

syndrome. Axillary lymphadenopathy biopsy: Castleman disease. The

patient had several community-acquired, nosocomial pneumonias and an

EP132

episode of pulmonary edema. Autologous hematopoietic cell transplantation

(HCT) was planned, cyclophosphamide induction started. Meanwhile he

In spite of long-term symptoms, a pheochromocytoma diagnosed in

suffered two ischemic strokes which resulted in motor aphasia and

pregnancy results in fetal loss despite proper approach

hemiparesis. Cerebral angiography revealed vascular lesions compatible

Soner Cander, Ozen Oz Gul, Erdinc Erturk & Canan Ersoy

with vasculitis and stenosis of two cerebral arteries. Comments: In this case,

Uludag University Medical School, Bursa, Turkey.

although serum immunofixation was negative for monoclonal protein, bone

marrow biopsy confirmed POEMS syndrome. There is no standard therapy,

however patients with disseminated bone marrow involvement are treated

A 27-year-old woman with had sweating flushing attacks for three years

with chemotherapy with or without HCT. In this patient despite the young

prior to pregnancy, but did not follow with any medical examination. At

age, the disease was already advanced and resulted in severe complications,

12th gestational week, hypertension was detected and alpha-methyldopa

which led to resignation from chemotherapy and HCT complications, which

was started, no abnormal findings were found in the routine examinations,

led to resignation from chemotherapy and HCT.

in the 24-h holter study, blood pressure values (using alpha-methyldopa)

DOI: 10.1530/endoabs.49.EP133

were found to be higher than 144/99 (general),

147/101 (awake) and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP134

¹Endocrinologist, Sparti, Greece;²Endocrinologist, Athens, Greece;

Recurrent phaeochromocytoma - Iatrogenic

³Department of Rheumatology, St. Paul’s Hospital, Thessaloniki, Greece;

Samantha Anandappa, Jeya Navaratnam, David Fish, Brendon Conry,

⁴Department of Endocrinology, Red Cross Hospital, Athens, Greece.

Sithara Perera & Jesse Kumar

Maidstone and Tunbridge Wells NHS Trust, Kent, UK.

Adrenocortical tumorigenesis has been observed in mice. It is speculated to

be gonadotropin dependent. In particular LH receptors appear to be found

Phaeochromocytoma is a common endocrinological diagnosis with an

within such adrenal tumors in high density and elevated LH levels may be

incidence of 1-2 per 10 000 people. Prompt evaluation and treatment leads

related to adrenal tumorigenesis. The aim was to describe the case of a

patient who after ovariectomy developed a large malignant adrenal tumor.

to an excellent prognosis. Recurrence has been documented rarely (with

A patient, female, aged 42 presented with uterine leiomyomas. She was

literature reporting possibility of up to

8 years delay) and causes are

treated by surgical excision of the uterus along with ovariectomy.

generally attributed to inherited mutations, seeding during surgery or

Subsequently, she refused to be treated with estrogens, developing however

malignancy. Malignancy rates have been variable from 10% depending on

severe postmenopausal symptoms. At the age of 50 she presented with

site and mutations. In addition, the definition of malignant pheochromocy-

musculoskeletal symptoms affecting the spine, both knees and the left

toma/paraganglioma is not always clear as there is no combination of

shoulder. A CT scan of the abdomen was performed showing a large mass

clinical, histopathologic, or biochemical features to reliably predict biologic

originating from the left adrenal gland. An MRI was performed and the

behaviour. In general; pathologic evaluations provide little prognostic

patient was treated by left adrenalectomy. The adrenal tumor was malignant,

insight to predict risk of recurrences or metastases reliably. We present a

measuring

6!6!5 cm, androgen receptor positive and progesterone

case that demonstrates relapse as a result of possible seeding from original

receptor positive in some areas. The patient recovered. On follow up 6

laparoscopic adrenalectomy as one of the factors. Thus, pre-operative

months later she was free of any malignant disease. She developed

features that potentially make the tumour a high risk for recurrence should

Hashimoto’s thyroiditis, antithyroglobulin antibodies being

425 IU/ml

be identified and aid in creating an individualised management plan. Aspects

(normal values

!115 IU/ml) and antimicrosomal antibodies being

that have been recognised to be directly related to outcome such as the size

213 IU/ml (normal values !34 IU/ml), while TSH was 3.9 IU/L (0.3-

of tumour, underlying conditions such as MEN 2A/B and neurofibromatosis,

4.2 IU/L). In conclusion, the case of a patient is presented who developed a

the site of the tumour and anatomical ease of surgical intervention. This case

large adrenal tumor following ovariectomy. Adrenal tumorigenesis has been

highlights the importance of the recognition of such factors & multi-

observed in mice following ovariectomy. It is believed to be related to LH

disciplinary team input, to prevent recurrences which have a significant

stimulation by elevated LH levels, LH receptors having been observed

effect on long-term cure and prognosis.

within the adrenal tumors. In mice tumorigenesis may be prevented by the

DOI: 10.1530/endoabs.49.EP134

administration of agents lowering gonadotropin levels

(Rahman et al,

Reprod Biol 2001). It may be that in such cases of premature ovarian failure

following surgical ovariectomy, thought should be given to possible

treatment aiming at low gonadotropin levels.

DOI: 10.1530/endoabs.49.EP136

EP135

An association of adrenal ganglioneuroma, Addison’s disease and

Mediterranean fever: a case report

EP137

Nabila Rkik, Houcem Mrabet, Mouna Elleuch, Mouna Ammar,

Faten Haj Kacem & Mohammed Abid

ACTH-independent Cushing syndrome with concomitant parathyroid

Department of Endocrinology, Hedi Cheker University Hospital, Sfax,

carcinoma

Tunisia.

Georgiana Alexandra Smarandoiu¹, Raluca Trifanescu^1,2,

Andra Caragheorgheopol¹, Anda Dumitrascu¹, Sorina Schipor¹ &

1,2

Catalina Poiana

Introduction

¹C.I. Parhon National Institute of Endocrinology, Bucharest, Romania;

Ganglioneuroma is a rare benign tumour arising from neural crest sympathogonia.

²Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

It is usually asymptomatic and non functional. An association between

ganglioeneuroma and genetic or autoimmune diseases such as Addison’s disease

or Mediterranean fever has never been described.

Introduction

Case description

The incidence of parathyroid carcinoma in primary hyperparathyroidism is less

We report the case of a

24-year-old woman presenting with paroxysmal

than 1% and the association with ACTH-independent Cushing syndrome is very

abdominal pain with loss of weight and no fever. Physical examination along with

rare.

biological and hormonal explorations were normal. CT scan showed a solid

Case report

tumour of the right adrenal gland, measuring 50!31 mm, with no sign of

A 40-year-old female was admitted for weight gain and reddish-purple striae. One

malignancy and a moderate ascites, so the patient underwent adrenalectomy.

month earlier she had a³⁴ parathyroidectomy for primary hyperparathyroidism

Anatomopathological examination of the adrenal gland confirmed the presence of

with histopathological examination showing a parathyroid carcinoma and two

a ganglioneuroma, and the patient presented an adrenal insufficiency 4 days after

parathyroid adenomas. She also had a history of deep vein thrombosis. She had no

the surgery. Addison’s disease was confirmed with positive anti- adrenal

family history of endocrinopathies. The physical exam revealed a positive

antibodies, with anti-21-hydroxylase at 2866.9 U/ml and she received corticos-

Chvostek sign, facio-troncular obesity, reddish-purple striae and grade I

teroid replacement therapy. The patient continued to have recurrent abdominal

hypertension. Biochemical assessment revealed hypocalcaemia

(5.75 mg/dl)

pain, fever and ascites. A Mediterranean fever was suspected, and she was put on

and diabetes mellitus. Hormonal assessment revealed hypoparathyroidism

colchicine 1 mg per day, with improvement of paroxysmal abdominal pain.

(PTHZ12.45 pg/ml), no catecholamine excess, normal prolactin level. High

Genetic confirmation is underway.

levels of urine free cortisol

(415.91 mg/dl) and positive long low dose

Conclusion

DST(2mg/day!2 days) (12.29 mg/dl) confirmed the clinical suspicion of Cushing

We report for the first time an association between ganglioneuroma, Addison’s

syndrome. ACTH levels were suppressed. Chromogranin A levels were normal.

disease and Mediterranean fever whose clinical features can be confused.

We performed a pituitary MRI and a CT of the neck, thorax and abdomen that

A possible underlying genetic mechanism can be suspected rather than just a

showed bilateral adrenal macronodular hyperplasia with no other suspicious

random association.

masses including pituitary adenomas. DXA evaluation showed osteoporosis for

which she later received bisphosphonate therapy. A bilateral adrenalectomy was

DOI: 10.1530/endoabs.49.EP135

performed and subsequent mineralocorticoid and glucocorticoid replacement

therapy was initiated. Genetic test for MEN1

syndrome is pending. The

hyperparathyroidism relapsed 18 months after the parathyroidectomy. Calcium

levels remained in the high normal range during monitoring with normal renal

function and the last scintigraphy and CT scan showed an adenoma of the

EP136

remaining parathyroid with no sign of local recurrence of the parathyroid

Adrenal carcinoma after ovariectomy. Report of a case

carcinoma. Periodic follow-up also revealed a pituitary microadenoma with

Eleni Xanthakou¹, Panagiotis Spyropoulos², Panagiotis Athanassiou³

minimally raised prolactin and a thymic lesion that were stationary over the last

& Ifigenia Kostoglou-Athanassiou⁴

7 years of monitoring.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

carcinoma, the images were suggestive of malignancy. Although there

In patients with primary hyperparathyroidism special attention should be given

were no signs of metastasis in toraco-abdomino-pelvic-CT, a PET-scan

to signs of other endocrinopathies as hyperparathyroidism could be the first

is arranged to exclude some other lesions. Gynecomastia in adult males is

manifestation of a MEN syndrome.

usually related with drugs and systemic or endocrine diseases. However, it is

DOI: 10.1530/endoabs.49.EP137

less often related with rare conditions, such as the testicular tumor of Leydig

cells and the rarest adrenal feminizing tumor. Surgery is the main option for

EPAGT, nevertheless the prognosis is very poor.

DOI: 10.1530/endoabs.49.EP139

EP138

Incidental adrenal cyst: a case report

Aribi Yamina, Bensaleh Meriem, Brakni Lila, Khaldi Hassiba, Sellal Zoubir

& Ould Kablia Samia

EP140

Central Hospital of the Army, Algiers, Algeria.

Virilization - a non-negligible manifestation of an adrenal tumor

Daniela Magalhães^1,2, Eduardo Vinha¹, João Sérgio Neves^1,2,

Pedro Souteiro^1,2, Celestino Neves^1,2, Paula Freitas^1,2, José Costa Maia³,

Introduction

Elisabete Rios⁴, Ana Catarina Fernandes⁵, Elisabete Rodrigues^1,6 &

Cystic adrenal lesions (CAL) are a rare diseases representing 5.4-6.0% of all

Davide Carvalho^1,2

pathological changes affecting adrenal glands. In about one-third of the cases,

¹Department of Endocrinology, Diabetes and Metabolism of Centro

lesions are detected incidentally; in the remaining two-thirds cysts lesions are

Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, Porto,

symptomatic, which is typically related to their large size or rapid growth.

Portugal;³Department of General Surgery of Centro Hospitalar de São João,

Although CAL are usually benign, since malignancy is reported in up to 7% of all

Porto, Portugal;⁴Department of Pathological Anatomy of Centro Hospitalar

CAL. Management algorithms for CAL vary and are controversial because of the

de São Joa˜o, Porto, Portugal;5Department of Oncology of Centro Hospitalar

overall rarity of such lesions.

de Sa˜o João, Porto, Portugal;6Endocrine and Cervical Pathology Multi-

Case report

disciplinary Group of Centro Hospitalar de São João, Porto, Portugal.

We describe a case of a 29-year-old man who presented with abdominal pain. The

computed tomography of the upper abdomen revealing the presence of a 4-cm

simple cyst originating from the left adrenal. All serological and hormonal

Introduction

secretion tests were negative. So the final diagnosis was a simple left adrenal cyst;

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy

8 months later, abdominal ultrasound follow-up revealed adequate cyst shrinkage

with a poor prognosis. Hormone-secreting ACC appear with manifestations of

down to 2.8!6.9 cm. The patient remains symptom free to date.

virilization, feminization or Cushing syndrome.

Discussion

Case Report

Surgical excision of adrenal cysts is indicated by the presence of symptoms,

A 63-year-old woman with no pathological history of relief was referred to

suspicion of malignancy, or the detection of a functioning adrenal cyst. Cysts

Endocrinology evaluation with an history of deepening of the voice since 1-year

may coexist with primary and metastatic adrenal tumours. Malignancy of the cyst

ago, as well as hair loss and facial and abdominal hirsutism with 6-month

is found in

7% of all affected patients. Adrenocortical and adrenomedullar

evolution. The analytical study revealed the following results: total testosterone

hyperfunction is accompanied by adrenal cysts in ca. 15% of cases. What is more,

6.03

(Normal Range (NR) 0.06-0.82) ng/ml, delta-4 androstenedione O10.00

adrenal cysts accompany approximately 7% of primary and metastatic cancerous

(NR 0.30-2.99) ng/ml, DHEA-S 545.8 (NR 18.9-205) mg/dl, 17-OH-Proges-

processes, and in 0.5% of cases they are of parasitic origin and their clinical

terone 6.32 ng/ml, SHBG 71.4 (NR 14.1-68.9) nmol/l, FSH 7.96 ng/ml, LH

management remains controversial. However, surgical intervention is not

5.96 ng/ml Estradiol 123.8 pg/ml; normal urinary catecholamines and metane-

recommended for asymptomatic patients with incidental cysts, for the fact that

phrines; normal renin and aldosterone values; ACTH 2.1 ng/l (NR !63.3),

the pathological data of our series revealed no malignant cases. Patients after

urinary free cortisol 353.6 (NR 36-137) mg/day, late-night salivary cortisol 0.499

surgical resection should be followed up closely especially in functional cysts and

(NR !0.32) mg/dl and plasma cortisol after 1-mg overnight dexamethasone

when histopathology showed cystic tumor.

suppression test 13.3 mg/dl (NR!1.8). She performed an abdominal MRI with

DOI: 10.1530/endoabs.49.EP138

documentation of a massive solid tumor lesion with heterogeneous contrast

uptake, well delimited and measuring about 13.4 cm in diameter, which was

admitted to be dependent on the left adrenal gland. Were identified several hepatic

and lung nodularities suggestive of secondary lesions. In a multidisciplinary

evaluation, it was decided to perform left adrenalectomy by laparotomy. No

ascites or signs of peritoneal carcinomatosis were present. The anatomopatho-

logical examination revealed an ACC ENSAT stage IV, pT2NxMx, with a

modified Weiss score of five and a classic Weiss score of seven. The patient is

EP139

now proposed for adjuvant chemotherapy with mitotane.

Gynecomastia in men: A rare case of adrenal feminizing tumors

Conclusions

Vitória Duarte, David Veríssimo, Dolores Passos, Filipa Serra, João Silva,

We report a case of an ACC combining hyperandrogenism with Cushing’s

Luís Lopes, J.J. Castro & Mafalda Marcelino

syndrome. Hormonal hypersecretion, particularly hypercortisolism, is associated

Hospital das Forc¸as Armadas, Lisbon, Portugal.

with a worst outcome. Complete tumor removal remains the only potentially

curative treatment.

DOI: 10.1530/endoabs.49.EP140

Estrogen-producing adrenal gland tumors (EPAGT) are extremely rare,

accounting for only 1-2% of all adrenal tumors. They are most commonly

observed in men or in children, and are unusual in women. They are almost

always malignant even if they seem benign at presentation, and most of them

have a poor prognosis. We present a case of a 71-year-old man with painful

bilateral gynecomastia, without galactorrhea, over

4 months. Markedly

elevated plasma estradiol levels were found (161.7 ng/l; normal 15.5-63.3)

with low LH and FSH values. All other parameters were within normal

Clinical Case Reports - Thyroid/Others

range (b-HCG, PRL, TSH, FT4, total testosterone, SHBG, cortisol, ACTH,

EP141

DHEA SO4, delta-4-androstenedione,

17OHPRG, fractionated metane-

The ovarian origin of hiperandrogenism in the postmenopausal woman

phrines, cromogranine-A). Echographic images and mammography showed

with the adrenal adenoma - a case report

bilateral mammary gland hypertrophy excluding any nodules. CT abdo-

Marta Kialka¹, Tomasz Milewicz¹, Katarzyna Doroszewska¹,

minal scan indicated a large retroperitoneal mass measuring 14!8 cm with

Sandra Mrozinska² & Robert Jach¹

posterior and inferior deviation of the left kidney, with heterogeneus

¹Department of Gynecological Endocrinology, Jagiellonian University,

contrast uptake. It appeared to be a retroperitoneal tumor independent of any

Medical College, Cracow, Poland;²Department of Metabolic Diseases,

other retroperitoneal organ. To clarify its etiology, a biopsy was performed.

Jagiellonian University, Medical College, Cracow, Poland.

The histology suggested an adrenal cortex tumor. It displayed cell

proliferation with abnormal nuclei. Immunohystochemistry was positive

for melan A, HMB45, INHA and focal AE1/AE3. The Ki-67 was around

Hyperandrogenism is a clinical condition characterized by excessive secretion of

15%. While it was impossible to distinguish between adenoma and

male sex hormones. An excess amount of androgens in women is manifested by

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

symptoms of defeminization and masculinization. Hormonally active adrenal and

microprolactinoma, primary hyperparathyroidism). He was first referred to our

ovarian tumors and non-tumor causes must be considered in the differential

Clinic in

2007 after being incidendally diagnosed with well differentiated

diagnosis. The authors describe the case of a 77-year-old patient who had

pancreatic neuroendocrine tumor (CT-scan performed for nephrolithiasis and

hirsutism and reduction of the timbre of the voice. At the beginning she was

repeated renal colic revealed a pancreatic mass that was surgically removed).

suspected to have adrenal hyperandrogenism because of the tumor in the adrenal

2009 the patient was diagnosed with primary hyperparathyroidism and

gland. Then adrenalectomy was conducted but it did not lead to alleviate

multinodular goiter for which subtotal parathyroidectomy and total thyroid-

symptoms. A MRI of the pelvis revealed a change of appendages projection and

ectomy were performed. He also presented MEN1 associated tumors such as non-

the patient underwent the total hysterectomy. The normalization of testosterone

functioning left adrenal adenoma, bilateral asymmetric lipomastia and multiple

levels as well as reduction of the symptoms was observed after the operation.

subcutaneous lipomas and conditions associated with calcium disorders:

Finally, the ovary etiology of hyperandrogenism was confirmed. This case report

nephrolithiasis, nephrocalcinosis, secondary osteoporosis. Regarding these

is an example of difficulties in recognition the etiology of hyperandrogenism.

findings, the patient was diagnosed with MEN1 syndrome and started undergoing

DOI: 10.1530/endoabs.49.EP141

periodical follow-up. Between 2009 and 2016, at the anual reevaluation, no

clinical or paraclinical evidence of tumor recurrence was found. In October 2016

he presented a mild elevation of calcium and PTH levels and the sestamibi

parathyroid scan revealed the presence of parathyroid adenoma. The CT-scan

showed two pancreatic masses, immunohistochemistry tests from the biopsy

supported the diagnosis of neuroendocrine tumor NET G1 and the patient started

treatment with somatostatin analogues. Further assessment of the possibility of

tumor resection and parathyroidectomy is considered.

Conclusion

Considering the high risk of tumor recurrence in MEN1 patients, regular follow-

EP142

up is crucial in detecting and treating the relapses. Our patient developed both

Secondary autonomic neuropathy in patient with polyglandular

recurrence of neuroendocrine tumor and hyperparathyroidism.

autoimmune syndrome III and type 1 gastric neuroendocrine tumor:

DOI: 10.1530/endoabs.49.EP143

a case report

Jekaterina Nagaiceva¹, Natalija Fokina², Karina Levina¹, Janis Mednieks²,

Kristine Bernarde² & Valdis Pirags^1,2

¹Latvian University, Riga, Latvia;²Paul Stradins Clinical University

Hospital, Riga, Latvia.

The polyglandular autoimmune syndromes (PAS) are rare disorders characterized

as multiple autoimmune-mediated organ failure. PAS III includes chronic

autoimmune thyroiditis with type 1 diabetes mellitus or pernicious anemia and/or

EP144

vitiligo or alopecia and many other organ-specific autoimmune diseases, but

Insulinoma- from diagnosis to full recovery. Case study

never involves adrenal cortex. Several patients with PAS III and associated type 1

Marcin Lewicki^1,2, Magdalena Urbanczuk^2,3, Agnieszka Zwolak^2,4,

gastric neuroendocrine tumor (NET) have already been reported. We report

Marta Dudzinska^2,4, Monika Lenart-Lipinska^2,5 & Jerzy S. Tarach²

probably the first case of PAS III, type 1 gastric NET and concomitant secondary

¹Chair and Department of Epidemiology and Clinical Research Method-

autonomic failure as the main clinical manifestation. A 65-years-old woman with

ology of Medical University of Lublin, Lublin, Poland;²Department and

severe postural and postprandial orthostatic hypotension admitted to the hospital.

Clinic of Endocrinology of Medical University of Lublin, Lublin, Poland;

The orthostasis has been debilitating and gradually has worsened in the past year.

³Chair and Department of Clinical Pathomorphology of Medical University

She has lost about 25 kg due to postprandial sickness and consequent dietary

of Lublin, Lublin, Poland;⁴Department of Internal Medicine and Internal

restrictions. The patient has a history of mild type 2 diabetes mellitus. She has

Medicine in Nursing, Medical University of Lublin, Lublin, Poland;

been treated with metformin and her HbA1c has been ! 6% during the last

⁵Department of Laboratory Diagnostics of Medical University of Lublin,

8 years. Diabetes has resolved due to weight loss and the patient has had a good

Lublin, Poland.

glycemic control without any treatment for the past year. The patient has a history

of primary hypothyroidism due to chronic autoimmune thyroiditis. Besides that

she has suffered from hair loss with global alopecia over the last decades of life.

Introduction

Initial B12

vitamin deficiency without anemia has been detected. Upper

Insulinoma is a rare form of a functional neuroendocrine tumor with an estimated

endoscopy was performed, showing multiple gastric polyps. Histological

incidence at

1-2 new cases per million persons per year. This infrequent

examination revealed chronic atrophic gastritis, hyperplasia of endocrine cells

endocrinopathy, frequently escaping standard disease course, constitutes a

and gastric NET G1, Ki-67Z1%. Numerous gastric polyps have been removed

diagnostic challenge for every endocrinologist. Successful surgical resection of

during endoscopy. The patient has been treated with intramuscular B12 vitamin

the lesion is the only available method that ensures patient’s full recovery.

injections with a gradual positive effect on the autonomic dysfunction. Annual

Case study

endoscopic follow-up and lanreotide injections are recommended to prevent

53 years old patient with complaints about recurring episodes of hypoglycemia,

progression and dissemination of the gastric NET.

without accompanying adrenergic symptoms though, was admitted to Department

DOI: 10.1530/endoabs.49.EP142

and Clinic of Endocrinology, Medical University of Lublin. During diagnostic

procedures: low glucose levels

(ranging from

1.94-3.56 mmol/l) with

corresponding inadequately high insulin levels were observed in a prolonged

glucose tolerance test, where glucose and insulin concentrations measurements

had been carried out every hour. Afterwards supervised 72-h fast was introduced,

only to be terminated after just

24 h, due to symptomatic hypoglycemia

(2.28 mmol/l). Insulin levels at the end of fasting remained disproportionately

elevated (10.7 mU/l). Based on follow up diagnostic tests we were able to exclude

EP143

other potential causes of hypoglycemia in the form of adrenal insufficiency and

hypothyroidism. Abdomen CT scan didn’t reveal any lesions in pancreas whereas

MEN 1 Syndrome- a case with recurrence of neuroendocrine tumor and

abdomen MRI unveiled presence of the tumor, 2 cm in diameter, located in the

hyperparathyroidism after 9 years of follow up

tail of pancreas. On the

1st of September 2016 patient underwent surgical

Bianca Maria Leca¹, Iustina Gherasim¹, Elisabeta Sava², Sorina Martin^1,2,

resection of the pancreas mass. Histologic evaluation confirmed the diagnosis of

Suzana Florea¹ & Simona Fica^1,2

insulinoma

(pNET: G2 insulinoma). Octreoscan and abdomen MRI didn’t

¹Elias University Clinical Hospital, Bucharest, Romania;²Carol Davila

indicate a diffuse process. Currently all of the symptoms subsided, the patient

University of Medicine and Pharmacy, Bucharest, Romania.

doesn’t require any additional treatment.

Conclusions

Introduction

Insulinomas are neuroendocrine tumors of rare occurrence. The readily available

Life expectancy is decreased in MEN1 patients due to multiple tumors that may

imaging methods rarely allow for a location confirmed diagnosis because of

be larger, more aggressive, resistant to treatment and with a higher risk of

borderline small size of lesions. Persistent hypoglycemia being the most

recurrence.

characteristic symptom facilitates the diagnosis and introduction of proper

Case report

treatment.

We report a 59-year-old male patient with family history of endocrine tumors

DOI: 10.1530/endoabs.49.EP144

(father- pituitary adenoma, son- primary hyperparathyroidism, daughter-

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP145

study designed to evaluate the MetS prevalence in the general population, pair-

matched by age, gender and place of birth. Hyperinsulinemia and IR were defined

Insulinoma masquerading as neurologic disease

according to Mattews’s classification. WD DNETs were classified according to

Catarina Machado, Patrícia Tavares, Sara Monteiro, Gustavo Rocha

primary tumour localization, hormonal secretion, TNM stage and WHO grading.

& Maria João Oliveira

Results

Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE, Vila Nova de Gaia,

MetS was present in 45.8% of WD DNETs. According to grading, 66.7% were G1

Portugal.

and 27.1% were G2 tumours. The disease was localized in 31.3%, locoregional in

16.7% and disseminated in 43.8%. Both patients and controls had high mean body

Introduction

weight (26.9 vs 27.2 kg/m², PZ0.645). No significant differences were found

Insulinomas are the most frequent cause of hypoglycemia and the most common

between the two groups for waist circumference, Fasting Plasma Insulin (FPI) and

functional endocrine pancreatic tumors. Whipple triad is often present and should

HOMA-IR (PZ0.236; PZ0.372 and PZ0.274, respectively). Median Fasting

alert to the diagnosis.

Plasma Glucose (FPG) and Impaired Fasting Glucose (IFG) frequency were

Case report

higher in WD DNETs (P!0.001 and PZ0.013, respectively). FPGR100 mg/dl

A 36-year-old male was admitted in the emergency room with loss of

and HOMA-RIR5 were associated with a higher risk for WD DNETs (OR 4.3

consciousness, diaphoresis and blurred vision, and hypoglycemia (50 mg/dl).

(95%CI 2.3-8.2, P!0.001); OR 4.1 (95%CI 1.2-13.5, PZ0.014), respectively).

The patient recalled recurrent symptoms of diaphoresis, tremors and palpitations,

When anthropometric and metabolic parameters are compared, there was no

sometimes with loss of consciousness and incontinence of urinary sphincters, for

difference between somatostatin analogues users and no-users.

the past 4 months, having been diagnosed with epilepsy and medicated with

Conclusion

anticonvulsive drugs. This symptoms were associated with weight gain, occurred

Association of glucose metabolism abnormalities and IR with WD DNETs

before meals and were relieved with eating carbon hydrates. He had no family

confirmation can open new perspectives for prevention and treatment, through

history of endocrine disease. Prolonged supervised fasting test was applied and

modifying lifestyle and insulin sensitizers use.

led to symptomatic hypoglycemia with hyperinsulinemia

(blood glucose

DOI: 10.1530/endoabs.49.EP146

40 mg/dl, plasma insulin 68.7 mIU/ml and C-peptide 7.07 ng/ml). Other hormonal

studies were normal, rejecting the diagnosis of multiple endocrine neoplasia. He

maintained severe hypoglycemia despite glucose fluid administration and

nutritional adequate plan, and medical treatment was necessary with octreotide

300 mg/day and diaxozide

900 mg/day. Abdominal magnetic resonance

demonstrated a well-defined enhanced lesion in the tail of the pancreas measuring

14 mm. Nodule enucleation was performed by laparoscopy and pathological

examination revealed an encapsulated pancreatic mass measuring 17!14!

15 mm. Mitotic index was !2 per 10 CGA and proliferation index ki-67 was

estimated !2%. Immunohistochemically, tumor cells showed a positive staining

for insulin, synaptophysin and cromogranine. Shortly after surgical treatment,

EP147

glucose level increased to normal range. The patient was discharged without any

Clinical and hormonal characteristics of adrenal incidentalomas

hypoglycemic symptoms after 7 days.

Rym Belaid, Ibtissem Oueslati, Wafa Mimita, Karima Khiari,

Conclusion

Nadia Mchirgui & Néjib Ben Abdallah

The diagnosis of insulinoma may be challenging due to its rarity and variable

Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.

presentation. Other diseases, such as neurologic, may be considered first, but it’s

important to contemplate the diagnosis since chronic and severe hypoglycemia

can be fatal and the surgery is usually curative.

Introduction

DOI: 10.1530/endoabs.49.EP145

Widespread use of abdominal imaging has led to the identification of an

increasing number of adrenal incidentalomas (AI) in the last decades. Causes of

these adrenal masses are multiple.

Aim

The aim of this study was to investigate the clinical and hormonal characteristics

of AI.

Materials and methods

The study was a retrospective monocentric analysis of 44 patients with AI who

underwent radiographic and endocrine evaluations.

Results

The mean age was 59.25G10.3 years and the sex ratio (F/M) was 1.3. Arterial

hypertension was diagnosed in 27 patients (61.4%), obesity or overweight in 84%,

Endocrine Tumours and Neoplasia

diabetes in 18 patients (40.9%), dyslipidemia in 7 patients (15.9%). Five patients

EP146

had an extra-adrenal tumor (11.4%). First diagnostic procedure was computed

Glucose metabolism abnormalities and insulin resistance are frequent

tomography (CT) in 63.6%, abdominal ultrasonography in 31.8% and magnetic

in well diferentiated digestive NETs

resonance imaging in 4.5%. Regarding the location of the masses: 36.4% were in

Ana P Santos^1,6, Ana C Santos^2,5, Clara Castro^1,2, Luís Raposo²,

right side,

34.1% were in left side and 29.5% were bilateral. The Cause of

Isabel Torres¹, Rui Henrique^6,7, Mariana P Monteiro³ &

radiologic imaging was kidney problems in 50%, liver disorders in 20.4%,

M Helena Cardoso^3,4

epigastralgia in 13.6%, thorax pathology in 6.8%, rheumatologic causes in 6.8%

¹IPO Porto, Porto, Portugal;²ISPUP/EPI Unit - UP, Porto, Portugal;

and an inflammatory syndrome in 2.3% of cases. The average diameter of tumors

³UMIB/ICBAS - UP, Porto, Portugal;⁴CHP, Porto, Portugal;⁵FMUP - UP,

was 26.6G15.9 mm. The mass was single in 65.9%, well limited in 95.5% and

Porto, Portugal;⁶IPO Porto, Research Unit, Porto, Portugal;⁷EPOP, Porto,

homogeneous in 81.8%. Patients with functioning tumors had larger tumor

Portugal.

diameters than those with non-functioning tumors (P!0.05). Final diagnosis

was: non-functioning adenomas in

68.2%, pheochromocytoma in

6.8%,

Cushing’s syndrome in

6.8%, primary aldosteronism in

4.5%, subclinical

Introduction

Cushing’s syndrome associated to phéochromocytoma in 2.3%, hematoma in

Incidence of Digestive NETs (DNETs) has increased in the last 40 years. Visceral

2.3%, tuberculosis in 2.3% and metastasis in 6.8%. Patients with functioning

obesity, metabolic syndrome

(MetS) and insulin resistance

(IR) have been

tumors had larger tumor diameters than those with non-functioning tumors

associated with several types of cancer.

(P!0.05). Two patients were diagnosed with adrenal insufficiency.

Aim

Conclusion

To evaluate possible associations of obesity, hyperinsulinemia and IR with well-

Our study showed that AI occurred more frequently in overweight or obese

differentiated (WD) DNETs through a case control study.

women with diabetes and hypertension. Its most common diagnostic procedure

Materials and methods

was CT and etiologies were dominated by nonfunctioning adenomas.

Ninety-six patients with gastrointestinal (75.0%) and pNET (22.9%) WD DNETs

were recruited from Endocrine Tumours Clinic of IPO Porto and cross-matched

DOI: 10.1530/endoabs.49.EP147

with a control group (nZ96) from PORMETS, a nationwide epidemiological

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP148

Conclusion

The hypersecretion of Gh induces an organomegaly, and the development of

Pituitary insufficiency, the beginning of a diagnostic journey

multinodular goiter is very frequent but discovery of thyroid carcinoma is rare, the

Amalia Ioana Arhire¹, Lumnita Cima^1,2, Simona Petrescu^1,2,

prevalence of this association remains to be determined.

Miron Adrian^1,2, Florin Andrei¹ & Carmen Gabriela Barbu^1,2

¹Elias Hospital, Bucharest, Romania;²“Carol Davila” University of

DOI: 10.1530/endoabs.49.EP149

Medicine and Pharmacy, Bucharest, Romania.

Introduction

We report a case of a pituitary insufficiency apparently resistant to treatment.

Case report

A 74 year old patient was admitted through the ER in our department for a

EP150

recently discovered pituitary macroadenoma. His general condition was poor in

spite of the initiation of corticotherapy. Evaluation: Smoker, with no significant

Small pancreatic neuroendocrine incidentalomas: an observational

medical history, the BP: 100/60 mmHg, no orthostatic hypotension, disoriented,

prospective study

C Villabona¹, J Busquets², L San Martín¹, A Planas¹, N Peláez², J Fabregat²,

confused, with moderately altered general state and no visual deficit.

A Teulé³ & I Peiró⁴

Biologically: normal ionogram, TSH: 0.076 mcIU/ml, fT₄: 0.767 ng/dl, total

¹Department of Endocrinology, Hospital Universitari de Bellvitge (HUB),

T₃ !40 ng/dl, prolactin: 21.5 ng/dl, IGF1: 84.8 ng/ (low). He had leukocytosis,

l’Hospitalet de Llobregat, Spain;²Department of Surgery, HUB,

high neutrophils, but normal markers of inflammation. No causes of infection

l’Hospitalet de Llobregat, Spain;³Department of Oncology, Institut Català

were found, but the clinical condition worsened in the next 2 days despite an i.v.

d’Oncologia (ICO), l’Hospitalet de Llobregat, Spain;⁴Clinical Nutrition

with Hydrocortisone and oral Levothyroxine. Additional imaging studies showed

Unit, ICO, l’Hospitalet de Llobregat, Spain.

an adenoma of 3.4/2.8/3.8 cm, with a mass effect on the optic chiasm, multiple

secondary lesions in the upper and infratentorial regions at the cerebral MRI.

During the neck ultrasound we found a multinodular goiter with a large nodule

Background

of 1.53/1.33 cm with multiple large pathological laterocervical adenopathies.

Diagnosis of small pancreatic neuroendocrine incidentalomas

(PNETs-I) is

The thoraco-abdomino-pelvic CT found a large pulmonary mass of 45/49 mm in

increasing during last years and often their management remains unclear.

the left lung, some osteholytic lesions in the right ribs and body of L5, a large

Objective

cephalic pancreatic lesion of 35/24 mm and bilateral adrenal metastatic lesions.

To describe our experience with patients with PNETs-I in our institution.

At that moment we thought that the pituitary macroadenoma was highly probable

Methods

to be a metastatic lesion with multiple options regarding the origin of the primary

Since March 2000, patients with non functioning PNETs-I %30 mm were

neoplasia. The biopsy of an excised cervical adenopathy showed an aggressive

evaluated in our center, prospectively. A descriptive analysis of all patients and

neuroendocrine tumour as the probable cause, diagnosis which was unfortunately

a comparative study between observational group (OG) vs resection group (RG)

sustained by the lethal outcome of the patient.

was made.

Conclusion

Results

The pituitary insufficiency in normally a benign condition which responds to

Forty-six patients were evaluated: 36 in OG and 10 in RG. Median follow up

treatment and has a favourable outcome; if this is not the case we must search for

(months) was 35.9 in OG and 76.6 in RG. Most of patients (69.9%) were

additional causes of poor responders.

diagnosed in the last 6 years. Mean age (years): 69.5 in OG and 57 in RG

DOI: 10.1530/endoabs.49.EP148

(P!0.003). Gender: 56.5% women. Mean tumor size (mm) was 12.5 (11 in OG

vs 18.7in RG P!0.005). PNETs-I were multiple in 17.4% cases. At diagnosis, all

PNETs-I’s size were%20 mm in OG, without metastases. In RG, 8 patients (80%)

had surgery complications, mostly mild to moderate without deaths. Diagnosis

was made by imaging procedures in 91.6% of OG. In our series, 82% had a CgA

assessment at diagnosis. Median CgA value was 179 mg/l (72-304). At the end of

follow up, 88% in OG of patients had no change in tumor size, the rest had tumor

growth !20%; In OG no PNETs-I resection were needed, and none of the

patients metastasized or died because of PNETs-I in this group.

Conclusions

EP149

Non functioning PNETs-I is increasing in incidence in our center. After almost

Thyroid carcinoma in multiple endocrine neoplasia type 1

36 months of follow up, no patients had significant growth, developed metastases

Khelil Nour El Houda^1,2, Loudjedi Lotfi², Meghelli Sidi Med^1,2

and neither of them died from PNETs-I. In OG, active surveillance is safe in

& Berber Necib^1,2

selected PNETs-I patients. We need prospective multicentric studies to confirm

¹Abou Bekr Belkaid University, Tlemcen, Algeria;²University Hospital of

our results.

Tlemcen, Tlemcen, Algeria.

DOI: 10.1530/endoabs.49.EP150

Introduction

Multiple endocrine neoplasia type 1 (MEN1) is a cancer syndrome characterized

by the development of neuroendocrine tumors of the pituitary gland, parathyroid

and pancreas, and other neoplasms such as adrenocortical tumors and carcinoid.

Observation

We report the case of a 70-year-old women with acromegaly that diagnosed 15

EP151

years ago, in relation with pituitary macroadenoma (30!25 mm) invading the

Potential inhibitory effect of progesterone on breast cancer metastasis

left cavernous sinus and in contact with the third ventricle without endocrine or

via the regulation on protein expression of apoptosis- and EMT-related

ophthalmological repercussions. The impact of acromegaly is diabetes mellitus

genes

treated with insulin complicated by retinopathy. The visceral assessment revealed

Gyu-Sik Kim, So-Ye Jeon & Kyung-Chul Choi

a hypertension with cardiomegaly and a multinodular goiter diagnosed 2 years

Laboratory of Biochemistry and Immunology, Veterinary Medical Center

after the discovery of the acromegaly. Refusing pituitary surgery and radio-

and College of Veterinary Medicine, Chungbuk National University,

therapy, the patient remains uncontrolled with maximal dose of somatostatin

Cheongju, Chungbuk, Republic of Korea.

analogues and dopaminergic agonists, the Gh level is 70 and IGF1 is 638 ng/ml.

Exploration of the goiter finds 3 nodules (20 to 30 mm of diameter) benign in fine

needle aspiration biopsy, operated 10 years later and the pathological examination

Breast cancers that are estrogen receptor

(ER)/progesterone receptor

(PR)-

finds papillary carcinoma of the thyroid, patient is treated by iodine 131 under

positive are more likely to respond to hormone-related treatments than tumors

recombinant TSH, It is currently in remission, her thyroglobulin level is under

that are ER/PR-negative. The present study investigated the effect of progesterone

0.20 ng/ml. During evolution, the patient presents bilateral renal lithiasis

(P4) on

17b-estradiol

(E2)-induced cell proliferation, apoptosis, EMT, and

repeatedly, the balance allowed the discovery of a primary hyperparathyroidism

migratory and invasive features of MCF-7 clonal varient (CV) breast cancer cells

with high serum calcium and PTH around 150 pg/ml due to a right inferior

that are ER/PR-positive. Preferentially, E2 was verified to induce breast cancer

parathyroid adenoma, complicated with osteoporosis for which the patient

progression by stimulating cell proliferation, EMT, and migration of MCF-7 CV

refused surgery. In this clinical context, the genetic studies to search presence of

breast cancer cells. On the other hand, P4 reduced E2-induced MCF-7 CV cell

mutation in MEN1 gene encoding the menin protein was performed and confirm

proliferation by down-regulating the protein expression of cyclin D1 and E1 and

multiple endocrine neoplasia type1.

induced apoptosis of MCF-7 CV cells by up-regulating Bax and p53 and by

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

down-regulating Bcl-2. Also, P4 appeared to inhibit E2-induced EMT process by

decades. Primary hepatic neuroendocrine tumors (PHNETs) are rare neoplasms.

increasing mRNA and protein expression of E-cadherin, a crucial epithelial

Despite increased incidence of PHNETs over time, these tumors remain a rarity.

marker, as well as by reducing the expression of mesenchymal markers such as

According to the previously reported cases, primary neuroendocrine carcinoma of

N-cadherin and vimentin and EMT-associated transcription factors such as snail

the liver is usually multicentric, often mimicking liver metastases. The

and slug. Eventually, E2-induced migration and invasion ability of MCF-7 CV

demonstration of the hepatic origin of a neuroendocrine carcinoma is often

cells and the protein expression of proteolytic enzymes such as MMP-9 and

arduous.

cathepsin B were reduced by P4 treatment. Co-treatment of RU486, a PR

Case presentation

inhibitor, restored the inhibited cellular migration and invasion and the reduced

A 59-year-old woman underwent ultrasound examination 3 years ago, that

expression of proteases by P4 to the control levels, suggesting the involvement of

revealed two liver nodular tumors (the largest having approximately 4 cm), with a

PR in P4-induced inhibition on migration and invasion of MCF-7 CV cells. Taken

complex structure. Abdominal IRM images confirmed multiple liver nodular

together, P4 treatment may be suggested as an effective tool for suppression of

tumors with intense vascularization, suggesting liver metastases. The patient was

human breast cancer progression and metastasis. (This work was supported by a

asymptomatic. In order to determinate the primary site of the tumor, the patient

grant from the Next-Generation BioGreen 21 Program (no. PJ011355-2015),

underwent multiple imagistic investigations and endoscopies. Among the blood

Rural Development Administration, Republic of Korea.)

tests (5-hydroxy indole acetic acid, carcinoembryonic antigen, chromogranin A,

Keywords: Progesterone; breast cancer cells; epithelial-mesenchymal transition;

serotonin), only chromogranin A presented significantly high values. Further, a

metastasis; migration.

liver aspiration biopsy was performed. The histopathological examination result

DOI: 10.1530/endoabs.49.EP151

completed with the immunohistochemistry techniques suggested a well

differentiated neuroendocrine carcinoma of an intermediary stage, with a

proliferation marker ki67 of 4%, most likely a metastasis. For a full diagnosis,

Octreoscan (11In-pantreotide scintigraphy) was performed. The whole body

scintigraphy at 10 minutes completed with the SPECT/CT at 4 hours established a

primary liver site with secondary spleen metastases, along with liver and renal

adenopathies. Treatment with somatostatin analogues (SANDOSTATIN LAR

30 mg/month), was commenced, with favourable outcome. After 18 months of

EP152

treatment, serum chromogranin values are still normal, while the volume of the

Incidental paraganglioma, diagnosis and follow-up - case report

tumors decreased significantly (by repeated MRI).

Alice Violante¹, Roberto Lemme¹, Sarah Galva˜o1 & Erika Naliato2

Conclusion

¹Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;²Ricardo A T

Despite that the liver represents the common site for metastases from other

Catilho Center of Studies Teresopolis Medical Association, Teresopolis,

gastrointestinal neuroendocrine carcinomas or other tumors, primary hepatic

Brazil.

neuroendocrine tumors are rare, but can occur. The diagnosis of primary

neuroendocrine tumors of the liver is difficult, as radiological appearances on

ultrasound, CT scan and MRI can mimic other pathologies.

Paragangliomas and Pheochromocytomas are tumors originated from chromaffin

Keywords: Neuroendocrine tumors; liver metastases.

cells

(Pheochromocytomas (PHEO): adrenal glands; Paragangliomas (PGL):

paravertebral thoracic, abdominal, and/or pelvic sympathetic ganglia, and

DOI: 10.1530/endoabs.49.EP153

glossopharyngeal and vagal neck and skull base parasympathetic ganglia).

Catecholamine hypersecretion predominates in PHEO, while PGL are

oligosymptomatic with compression-related symptoms. The authors report the

case of a 33-year-old male with an incidental retroperitoneal PGL, detected

during an investigation for urinary lithiasis

(abdominal pain that shifted to

different location, varying in intensity), without clinical evidence of catechol-

amine hypersecretion. The abdominal ultrasound identified a well-defined

5.0!4.5 cm hypoechoic nodular area at the right retroperitoneal region, above

the renal pelvis, dislocating the renal vein anteriorly. The image was confirmed by

CT (a 5.6!4.5!4.1 cm nodular area anterior to the right adrenal gland without a

EP154

cleavage line with the inferior cava vein), MRA (a 5.4!3.5!4.6 cm nodular area

anterior to the right adrenal gland), and PET/TC with FDG (a right retroperitoneal

Development of an everolimus-resistant BON1 cell line with altered cell

5.2!3.8 cm mass that dislocated the inferior cava vein at the confluence of the

cycle and c-Met activity

renal veins; SUVmax Z29.7).¹²³I-MIBG scintigraphy showed a discrete tumoral

Elke Tatjana Aristizabal Prada, Julian Maurer, Gerald Spottl,

uptake. Ultrasound-guided biopsy: the patient presented a hypertensive peak

Christoph Auernhammer & Svenja Nolting

during this procedure and was successfully medicated. He did not present arterial

Klinikum der Universitat Munchen, Munich, Germany.

hypertension during the follow-up. Histopathology: suggestive of paraganglioma

and neuroendocrine tumor.chemical investigation for catecholamines and

Introduction

plasmatic metanephrines hypersecretion: negative. Surgery: anterior laparotomy

Pancreatic neuroendocrine tumors (panNETs) are often inoperable at diagnosis.

(without pharmacological preparation, since the tumor was non-secreting)

The mTORC1 inhibitor everolimus is approved for the treatment of advanced

without complications. Histopathology: paraganglioma/neuroendocrine tumor.

NETs. Unfortunately, the development of resistance against everolimus limits its

Post-op follow-up: normal levels of metanephrines/catecholamines. I¹²³ MIBG

clinical efficacy.

scintigraphy without evidence of the previously described lesion in the right

Aim

lumbar region. No recurrence or clinical evidence of disease after a 5-year period.

Our aim was to establish an everolimus-resistant panNET cell line to find

Conclusion

common mechanisms of resistance.

Despite the tumour dimensions, there were no symptomatology previously to the

Methods

diagnosis and no recurrence at a 5-year follow-up.

Pancreatic neuroendocrine tumor cells (BON1) were treated for 24 weeks with

DOI: 10.1530/endoabs.49.EP152

10 nM everolimus (Novartis). Medium supplemented with 10 nM everolimus was

changed every 3 days. Two independent everolimus resistant BON1 cell lines

were established (RR1 and RR2). Resistance was defined with an at least 2-fold

higher IC₅₀, compared to the parental/control cell line.

Results

After 24 weeks of permanent exposure to everolimus both cell lines (RR1 and

EP153

RR2) showed morphologic changes when compared to the control cell line. The

Primary hepatic neuroendocrine tumor with multiple liver metastases

control cell line showed sensitivity to everolimus with cellular survival declining

treated with somatostatin analogues: case report

to 54.70% (IC₅₀Z34 nM) at 144 h treatment, whereas RR1 and RR2 showed

Ioana Golu¹, Melania Balas¹, Daniela Amzar¹, Marioara Cornianu² &

resistance with cellular survival rates of 96.70% (IC₅₀Z5200 nM) and 92.30%

Mihaela Vlad¹

(IC₅₀Z2500 nM), respectively. Western blot analysis showed different adaptive

¹Department of Endocrinology, University of Medicine and Pharmacy

changes of the protein expression level in RR1 and RR2, but two prominent

“Victor Babes”, Timisoara, Romania;²Department of Morphopatology,

mutual features: The cell cycle component CDK1 (cdc2), which orchestrates the

University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania.

G1-S and G2-M progression was remarkably downregulated and the tyrosine

kinase c-Met responsible for tumor cell motility, invasion and metastasis

Introduction

formation was upregulated. Consequently, flow cytometric analysis showed a

Somatostatin analogues (SSA) have been used as first line treatment to control the

significant cell cycle shift to G1 phase in RR1 and RR2 cells as well as a higher

symtoms in hormonally active neuroendocrine tumors (NET), for over three

migration potential than control cells after everolimus treatment.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

Methods

Everolimus resistance might be acquired by permanently altering the cell cycle

Cases coded as D35.0; D44.1; C74.1; C74.9; E26.0; E27,8; E24,8 according to

and the migration potential. Combinatory treatment approaches to overcome

ICD-10 classification were retrieved from database. Electronic data capture

resistance will be subject of further studies.

system was used to extract CT scans and biochemical testing data retrospectively.

DOI: 10.1530/endoabs.49.EP154

Results

There were 714 subjects assessed for adrenal masses from 2010 to 2016 at

VUHSK. At least one FU and non-functioning adrenal masses with obvious

benign features on CT scan had 216 subjects and thus were included into further

analysis. They were 61.6G11.2 years of age (184 female) with tumour size at

baseline of 22.8G12.8 mm. Average FU time was 4.1G1.4 years (from 2 to 7),

during which tumour size increased in 84 (39%), decreased in 48 (22%), did not

change in 84 (39%) cases. Significant increase (by O 20% in addition to at least

EP155

5 mm increase in maximum diameter) was observed in 19 (8.8%) cases. Average

False positive findings on 6-[18F]fluor-L-3,4-dihydroxyphenylalanine

size of

19 significantly enlarged tumours changed from 19.37G7.60 mm to

Positron Emission Tomography (¹⁸F-FDOPA-PET) performed for

30.58G13.68 mm in 2.7G1.4 years. All these tumours were associated with

imaging of neuroendocrine tumors

female gender. Despite tumour size enlargement, none of them became

MA Berends¹, JW Bolt¹, MN Kerstens¹, TP Links¹, E Korpershoek²,

functioning during observation time.

RR de Krijger^2,3, AME Walenkamp¹, W Noordzij¹, B van Etten¹,

Conclusions

G Kats-Urgurlu¹, AH Brouwers¹ & ANA van der Horst-Schrivers¹

Our study showed, that the significant enlargement of non-secreting initially

¹University Medical Center Groningen, Groningen, The Netherlands;

benign adrenal masses during follow up of about 2.7 years occurred in 8.8% of

²Erasmus University Medical Center, Rotterdam, The Netherlands;³Reinier

cases and was associated with female gender. Further larger studies with longer

de Graaf Hospital, Delft, The Netherlands.

follow up are needed to suggest time-frame for imaging follow up in order not to

miss the enlargement of the adrenal masses that could require surgery and also to

Background/Aim

estimate possible enlargement prediction factors.

Neuroendocrine tumors (NETs) are rare tumors arising from neuroendocrine cells

DOI: 10.1530/endoabs.49.EP156

throughout the body. Positron Emission Tomography (PET) scanning with 6-

[18F]fluor-L-3,4-dihydroxyphenylalanine (¹⁸F-FDOPA) has been shown to be a

valuable technique for the imaging of NETs. While the sensitivity has been

assessed numerously, studies systematically describing false positive results,

other than physiological variants, are lacking. Our aim was to systematically

examine, in a large series of¹⁸F-FDOPA PET scans, false-positive results and

determine which other tumor types have the potential of¹⁸F-FDOPA uptake.

Patients and methods

EP157

A single-center study was conducted among patients, aged 18 years or older, who

Medullary thyroid carcinoma and pheochromocytoma in multiple

underwent a¹⁸F-FDOPA-PET scan for the clinical suspicion or follow-up of a

endocrine neoplasia type 2A - a reversed order diagnosis

NET between January 2004 and December 2014. Clinical data were retrieved

Ana Coelho Gomes, Catarina Silvestre, José Marçalo,

from medical charts. We compared the original¹⁸F-FDOPA PET scan report

Maria Raquel Carvalho & Maria João Bugalho

with the pathology report of the¹⁸F-FDOPA PET-positive lesion. In case this

Endocrinology, Diabetes and Metabolism Department, Santa Maria

was inconsistent with the diagnosis of a NET, both the scan and the pathology

Hospital, Lisbon, Portugal.

slides were reassessed. Non- NET tissues were immunohistochemically stained

for aromatic-L-aminoacid decarboxylase

(AADC), Chromogranin A and

Synaptophysin.

Introduction

Results

RET germline mutation in codon 634 of exon 11 is one of the most frequent

1070¹⁸F-FDOPA PET scans from 705 patients were evaluated. Focal or multiple

mutations of classical multiple endocrine neoplasia type 2A (MEN2A). Virtually

¹⁸F-FDOPA avid lesions were described in 709¹⁸F-FDOPA PET scans (66%).

all patients with classical MEN2A develop medullary thyroid carcinoma (MTC),

Histology of these¹⁸F-FDOPA PET positive lesions was present for 508 (72%)

which is often the first manifestation of the disease and usually occurs early in

scans. In eight cases the original pathology report and revision was not compatible

life. Pheochromocytomas (PHEOs) tend to be diagnosed several years later or

with a NET but showed a squamous cell carcinoma of the cervix and larynx, a

simultaneously with the MTC.

multiple myeloma (in two cases), a hepatocellular carcinoma, a schwannoma, an

Case report

adrenocortical carcinoma and a skeletal myxoid chondrosarcoma, with positive

The patient, a 45 year-old man, was referred to the Endocrinology outpatient

immunohistochemical staining for AADC in four out of the seven stained tumor

department following a bilateral adrenalectomy, performed 2 months before,

tissues.

(Pheochromocytoma of the Adrenal gland Scaled Score: left Z0, right Z4) and

Conclusions

the finding of a thyroid micro nodule in a neck ultrasonography. There was no

Pathological uptake of¹⁸F-FDOPA does not always indicate the presence of a

familiar history of MEN2 neither of its components. The physical examination

NET. The possibilty of¹⁸F-FDOPA uptake by tumor types other than NETs

did not disclose particular signs namely skin alterations in the interscapular

should be considered.

region. Laboratory tests revealed elevated calcitonin (63.47 pg/ml, n !2). CEA,

DOI: 10.1530/endoabs.49.EP155

calcium, phosphorus, parathyroid hormone and plasmatic metanephrines were

within the normal range. Thyroid, ultrasound guided, fine needle aspiration

cytology of a 7 mm nodule in the left lobe was negative. Genetic testing of the

RET proto-oncogene identified the heterozigous pathogenic variant c.1901GOA

(p.Cys634Tyr) in the exon 11. The patient was submitted to total thyroidectomy

with bilateral central neck dissection. The histology revealed multifocal and

bilateral MTC (biggest diameter - 10 mm).

EP156

Discussion

Although less common the PHEO can be the first manifestation of MEN2A.

Imaging follow-up of non-functioning adrenal masses at Vilnius

Moreover, MTC is not always the most aggressive component of the syndrome.

University Hospital Santariskiu Klinikos: 2010-2016

Kristina Svaikeviciene^1,2, Milda Girdziute³ & Zydrune Visockiene^1,2

DOI: 10.1530/endoabs.49.EP157

¹Vilnius University Faculty of Medicine, Vilnius, Lithuania;²Vilnius

University Hospital Santariskiu Klinikos, Vilnius, Lithuania;³Antakalnis

Clinic, Vilnius, Lithuania.

Background

EP158

Current guidelines suggest against further imaging follow-up (FU) of patients

Bilateral pheochromocytomas, asyptomatic medullary thyroid

with non-functioning adrenal masses with clear benign features on imaging

carcinoma associated with left side thyroid hemiagenesis in a patient

studies.

with MEN2A: diagnostic correlations

Aim

Ionela Lungu¹, Carmen Emanuela Georgescu^1,2, Anca Ciurea³,

To analyse the data of patients with non-functioning adrenal masses who had FU

Carmen Georgiu⁴, Denisa Petrescu¹, Daniel Tudor Cosma⁵, Horatiu Silaghi⁶

at Vilnius University Hospital Santariskiu Klinikos (VUHSK) from 2010 to 2016.

& Cristina Alina Silaghi^1,2

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Endocrinology Clinic, County Emergency Hospital, Cluj-Napoca,

with unilateral AI there was a significant growth (28.85G15.63 mm), so they

Romania;²Department of Endocrinology, Iuliu Hatieganu University of

underwent surgery to remove them. None of them were malignant.

Medicine and Pharmacy, Cluj-Napoca, Romania;³Department of

Conclusions

Radiology, Iuliu Hatieganu University of Medicine and Pharmacy,

There wasn’t any patient with new cathecolamine production in the follow-up. In

Cluj-Napoca, Romania;⁴Department of Pathology, Iuliu Hatieganu

10.20% of patients we discovered a subclinical Cushing. Our findings agree with

University of Medicine and Pharmacy, Cluj-Napoca, Romania;⁵Diabet,

previously published studies. There was a significant AI growth in 5% of the

Nutrition and Metabolic Diseases Clinical Center, Cluj-Napoca, Romania;

patients so they were operated upon. Pathological diagnosis didn’t show

⁶5th Department of Surgery, Iuliu Hatieganu University of Medicine and

malignancy in any case, which is consistent with the available scientific evidence.

Pharmacy, Cluj-Napoca, Romania.

DOI: 10.1530/endoabs.49.EP159

Multiple endocrine neoplasia 2A (MEN2A), an autosomal dominant genetic

syndrome caused by germline mutation in RET proto-oncogene, associates

medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and primary

hyperparathyroidism (HPT). Thyroid hemiagenesis (TH), the absence of one lobe,

is a rare congenital abnormality (300 cases are reported in literature). Most cases

of TH are diagnosed when patients present a lesion in the functioning lobe. TH

was observed among members of the same family and genetic causes have been

evoked. The present case is a 35 year-old-female patient with family history of

MEN2A (the pedigree was studied). Genetic testing of the patient’s cousin and

EP160

nephew indicated heterozygosity for the same mutation at codon 634. Plasma

A case of silent pancreatic neuroendocrine tumour of carcinoid variety

metanephrines, normethanephrines, parathormone (PTH) and calcitonin (CT)

masquerading as an insulinoma

levels were increased. Serum ionized calcium was normal. Abdominal computed

Tarik Elhadd¹, Noor Suleiman¹, Mohamed Bashir¹, Emad Naem¹,

tomography provided the bilateral heterogeneous adrenal masses measuring 30!

Khalid Mohamed², Ahmed Elaffandi² & Abdul Badie Abou Samra¹

21 mm on the right and 20!16 mm on the left with an intense enhancement after

¹Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar;

contrast infusion. Neck ultrasound examination described

hypo-echoic,

²Section of Hepato-biliary Surgery, Hamad Medical Corporation, Doha,

heterogeneous thyroid micro-nodules in the right thyroid lobe, with micro-

Qatar.

calcifications inside, which measure 78!58, respectively 45!47 mm. In the left

side, hemiagenesis of the thyroid lobe was observed. No parathyroid adenoma or

lymphadenopathy were found. The patient had underwent a bilateral laparoscopic

Objective

adrenalectomy for PHEO followed by total right thyroidectomy. Microscopic

To highlight an unusual cause of hyperinsulinaemic hypoglycemia

examinations established the diagnosis of multicentric PHEO and synchronicity

Methods: Case Report

of C-cell hyperplasia with medullary thyroid microcarcinoma. Although the

Results or Case Presentation

identified RET mutation has hight risk, suggesting a possible aggressive

A previously healthy and fit 52 year old gentleman of Asian descent presented

evolution, in this case the CMT development was gentle, with a good prognosis

with recurrent severe neuroglycopenic hyperinsulinemic hypoglycemic symp-

(lesion

! 1 cm diameter, without distant metastases, preoperative basal

toms, suggestive of insulinoma. On several occasions he was confirmed to have

calcitonin ! 150 pg/ml). In conclusion our patient is a rare case of association

severe hypoglcaemia with venous blood glucose values ranging between 1.5 and

of an anatomic thyroid abnormality and MTC in the context of a complex genetic

2.7 mmol/l with inappropriate high level of insulin and C-peptide of 32 mc/unit

disease.

per ml (N. 2-23) & 4.5 ng/ml (N. 0.78-5.19) respectively. Other hormonal

assessment including pituitary hormones, chromogranin A, urinary 5-HIAA, and

DOI: 10.1530/endoabs.49.EP158

cortisol were all normal. CT imaging picked up a 4!4 cm well circumscribed

lesion in the tail of the pancreas, with no lesion elsewhere. Endoscopic

ultrasonography confirmed the mass to be avascular and within the pancreas. He

underwent laparoscopic distal pancreatectomy uneventfully in February 2016.

Histology of the tumour showed a well differentiated neuroendocrine tumour of a

carcinoid variety, grade

2, with positive staining for chromogranin A, and

Synaptophysin CK. Following surgery, the patient had no further hypoglycemia

and remained symptom free up to 9 month of follow up. Postoperative PET scan

and CT scanning of chest, abdomen and pelvis showed no recurrence of the

tumour, and no lesion elsewhere.

Discussion

EP159

Non-islet cell tumours induced hypoglycemia is generally caused by big IGF-II

Follow-up of adrenal incidentalomas after the initial approach

molecules secretion. Rarely carcinoid tumours were reported to secrete insulin but

Ángel Rebollo-Román, Paloma Moreno-Moreno,

this is usually in the context of carcinoid syndrome and has been reported to arise

Inmaculada Prior-Sánchez, Aura-Dulcinea Herrera-Martínez,

from tumours in the lungs, appendix and the liver. For a silent pancreatic

Ana Barrera-Martín & María-Ángeles Gálvez-Moreno

carcinoid tumour to cause hyperinsulinaemic hypoglycemia is rather unusual.

Endocrinology Service, Hospital Universitario Reina Sofía, Córdoba, Spain.

Plausible mechanisms include processing and secretion of insulin from tumour

cells. Alternatively secretion of insulin from adjacent islet cells may have been

Aim

caused by paracrine effects. The exact mechanism in our case, however, only

To describe the follow-up of adrenal incidentalomas (AI) classified as non-

remains speculative.

functioning and no suspicious for malignancy in the first approach.

Conclusion

Patients and methods

Tumours of the pancreas causing hypoglcemia may not necessarily be

Observational retrospective study of a cohort of patients who consulted in the

insulinoma. Silent neuroendocrine tumour of the carcinoid

(Argantafinoma)

Endocrinology service between 2005 and 2015 because of an AI. Statistical

variety may be the culprit.

analysis performed with SPSS 19th version.

DOI: 10.1530/endoabs.49.EP160

Results

Two hundred and one patients with IA were firstly evaluated. Thirty two of them

(15.92%) underwent surgery after the initial evaluation. One hundred and twenty

four patients out of the 169 who didn’t undergo surgery (73.37%) were followed:

97 unilateral AI and 27 bilateral AI. Age: 58.48G11.84 years. Size: 26.36G

14.14 mm. 57.3% Women. Repeated measurement of plasma metanephrines in

26 patients (20.97%): 21 unilateral AI (21.65%) and five bilateral AI (18.52%).

No catecholamine production in any AI. Median follow-up: 4.12G3.44 years.

Ninety eight patients (79.03%) underwent a 1 mg dexamethasone suppression test

to screen the cortisol autonomous production: 76 unilateral AI (78.35%) and 22

EP161

(81.48%) bilateral AI. Follow-up:

2.83G2.67 years.

10 patients

(10.20%)

CYP2W1*6 polymorphism as a potential predictive marker of

diagnosed with subclinical Cushing not present in the first evaluation. The rest of

sensitivity to mitotane treatment in adrenocortical carcinoma.

them showed no autonomous cortisol production. A follow-up imaging study was

Barbara Altieri^1,2, Sabine Herterich³, Silviu Sbiera¹, Marco Volante⁴,

performed in 103 patients (83.06%): 80 with unilateral AI (82.47%) and 23 with

Matthias Kroiss¹, Silvia Della Casa², Alfredo Pontecorvi²,

bilateral AI (85.19%). Median follow-up: 2.77G2.70 years. In four patients (5%)

Massimo Terzolo⁵, Martin Fassnacht¹ & Cristina L. Ronchi¹

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Division of Endocrinology and Diabetes, Department of Internal Medicine

Results

I, University Hospital of Wuerzburg, Wuerzburg, Germany;²Division of

Of the 31 patients, 65% (20/31) were women and 35% (11/31) men. Median

Endocrinology and Metabolic Diseases, Catholic University of the Sacred

follow-up was 23 months (0-217). Median age at diagnosis was 62 years (21-78),

Heart, Rome, Italy;³Central Laboratory, University Hospital of Wuerzburg,

with peak incidences in age groups 30-39 and 60-69 years. Most patients

Wuerzburg, Germany;⁴Department of Oncology, San Luigi Hospital,

presented with hypokalemia (87%), muscle weakness (77%), ankle edema (74%),

University of Turin, Turin, Italy;⁵Division of Internal Medicine I, San Luigi

hypertension

(71%), psychiatric manifestations

(58%), changes in body fat

Hospital, University of Turin, Turin, Italy.

distribution (58%), and bruises (51%). Median (range) cortisol, ACTH and 24 h

urinary free cortisol were

1467 nmol/l

(121-4380),

155 ng/l

(16-4700),

8221 nmol/l

(568-69038), and median

(range) cortisol after

1 mg DST

Mitotane is the only approved drug for the treatment of advanced adrenocortical

1103 nmol/l (74-3390), respectively. Thirteen (42%) underwent CRH-testing,

carcinoma (ACC) and we recently demonstrated that a high expression of

which was accurate (! 50% increase in ACTH and ! 20% in cortisol) in 9/13

cytochrome P450 2W1 (CYP2W1) correlated with response to mitotane. The

(69%) patients. Underlying tumours: pancreatic NET (nZ6), pulmonary NET

association between CYP2W1 alleles and a generally increased cancer risk is

(nZ6), pulmonary small cell carcinoma (nZ6), unknown primary (nZ4; no

under debate. Aim of the study was to evaluate the frequency of CYP2W1

tumour detected nZ2, disseminated disease nZ2), medullary thyroid carcinoma

polymorphisms and its correlation with the response to mitotane treatment in

(nZ3), thymic NET (nZ2), and, ileum NET, prostate carcinoma, poorly

ACC patients.

differentiated pulmonary NEC, poorly differentiated pulmonary LCC (nZ1 for

Methods

each). Median overall survival was 23 month (0-217). At the end of follow-up,

DNA was isolated from whole blood of 108 Caucasian ACC patients (F/MZ

12/31 (39%) patients were alive. Four patients initially cured recurred at 2, 6, 6

68/40) treated with mitotane monotherapy in adjuvant (nsZ66) or palliative

and 10, and 12 years, respectively. Surgery of the primary tumour was possible in

(nZ42) setting. Three CYP2W1 polymorphisms were genotyped by PCR and

10/31 (32%) patients, nine (90%) of whom were alive at the end of follow-up.

sequenced: CYP2W1*2 (p.A181T), CYP2W1*5 (p.Q482H) and CYP2W1*6

Bilateral adrenalectomy was performed in 10/31 (32%) patients, three (30%) of

(p.P448L). The response to therapy was evaluated by time to progression (TTP).

whom were alive at the end of follow-up. Outcome was best in thymic and

Results

pulmonary NETs.

The allele frequencies for CYP2W1*2 and CYP2W1*6 were 8 and 18%,

Conclusion

respectively, and are comparable to those found in the European population (1000

EAS affects women in 65% of cases. Incidence peaks in age groups 30-39 and

Genomes Project Phase 3 allele frequencies, ENSEMBLE, 5% for CYP2W1*2

60-69 years. Recurrences are possible O 10 years later. Overall survival is poor.

and

17% for CYP2W1*6). For CYP2W1*6

there were slightly more

DOI: 10.1530/endoabs.49.EP163

homozygotes than expected (PZ0.1). Both variant alleles were in the Hardy-

Weinberg equilibrium. CYP2W1*5, which is only reported in non-Causasian

population, was not found. We did not find any correlation between CYP2W1*2

allele and clinical outcomes. Whereas, we observed that patients with advanced

disease who have CYP2W1*6 allele have a worse response to therapy (median

TTP 3.0 vs 5.5 months, PZ0.03, HR 1.83). Among these patients, 86% who have

CYP2W1*6 allele did not reach the therapeutic range of mitotane plasma level

(14-20 mg/l) in comparison to 61% of those without CYP2W1*6 allele (PZ0.09,

chi-squaredZ2.7). No relevant impact of CYP2W1*6 was observed in patients

treated with adjuvant mitotane.

EP164

Conclusion

Ectopic Cushing’s syndrome caused by a pulmonary

This study further suggests that CYP2W1

might be involved on mitotane

adrenocorticotropic hormone secreting tumour: a case report

metabolism and that CYP2W1*6 allele might correlate with a worse sensitivity

Renata Pauliukiene¹, Edita Prakapiene^1,2, Rasa Koreiviene^1,2,

to mitotane palliative treatment.

Raimonda Klimaite^1,2, Lina Barsiene¹ & Valdas Sarauskas³

DOI: 10.1530/endoabs.49.EP161

¹Hospital of Lithuanian University of Health Sciences, Kauno Klinikos,

Endocrinology Department, Kaunas, Lithuania;²Lithuanian University of

Health Sciences, Kaunas, Lithuania;³Hospital of Lithuanian University of

Health Sciences, Kauno Klinikos, Pathological Anatomy Department,

Kaunas, Lithuania.

Introduction

Ectopic adrenocorticotropic hormone (ACTH) production by the pulmonary

EP162

neuroendocrine tumour (p-NET) is rare, and is considered an aggressive variant

of carcinoid tumours with poor prognosis.

Case presentation

Abstract unavailable.

59-year-old male with fast progressing generalized fatigue, abdominal

discomfort, and diarrhea was hospitalized in gastroenterology unit of Hospital

of Lithuanian University of Health Sciences, Kauno klinikos (HLUHS KK).

Digestive tract diseases were ruled out. Persistent hypokalaemia

(up to

2.2 mmol/l) was observed and endocrine pathology changes were considered.

Examinations revealed markedly elevated plasma ACTH

(44.4 pmol/l) and

cortisol (O1665 nmol/l) levels, diabetes, osteoporosis. No suppression of serum

cortisol level with high-dose dexamethasone test was found, confirming ACTH

dependent Cushing syndrome. The treatment with Metirapone was started.

Pituitary and abdominal magnetic resonance imaging

(MRI), abdominal

computer tomography (CT) scans were normal. Thoracic CT scan showed

nodules in the S2, S3, S6 of the left lung. No cytologic changes were found in

repetitive bronchial leachates through endoscopic bronchoscopy. There were two

episodes of pneumonia (Pseudomonas aeruginosa) and two episodes of sepsis

EP163

(Staphylococcus aureus and Enterococcus faecium). Suspected fungal infection,

Ectopic ACTH-syndrome - 31 consecutive patients from the Helsinki

intended antifungal treatment. Single nodule in S3 of the left lung with no changes

University Hospital

in size was found in repeated chest CT.^99MTc-tectrotyd SPECT-CT showed left

Sanna Toivanen¹, Helena Leijon², Timo Sane¹ & Camilla Schalin-Jantti¹

lung S3 neuroendocrine tumour. The radical surgery (bilobectomia superior

¹Endocrinology, Abdominal Center, University of Helsinki and Helsinki

sinistri) was performed. Histological result was well-differentiated p-NET (pT1a

University Hospital, Helsinki, Finland;²Department of Pathology,

N0 R0 G1). No radiochemotherapy was suggested. On the follow up visit after

University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

three months normal glycaemia, potassium and cortisol were found.

Conclusion

Background

We present ectopic ACTH secreting neuroendocrine lung carcinoma with likely

Ectopic ACTH syndrome (EAS) is rare and published series are scarce.

good prognosis. No clearly defined guidelines of follow up exist.

Aim

DOI: 10.1530/endoabs.49.EP164

To increase the understanding of EAS we describe 31 consecutive cases in years

1997-2016.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP165

mostly distributed in abdomen (60%), head and neck (26.2%), rarely in spine

(9.2%) and chest (4.6%). Hereditary form of disease was present in 22.5% of

Could alcohol ablation become the standard of care for benign

patients. The most common mutation was in SDHB gene (10/16), hereafter in

insulinomas?

VHL gene (3/16); two patients had mutation in SDHD gene and one in SDHC.

Isabel Mazarico¹, David Subías¹, Fèlix Junquera², Carme Vilardell³,

Multiple PGLs were identified in six patients. Hormonally secreting tumors were

Ignasi Saigí⁴, Albert Cano¹, Laia Casamitjana¹, Olga Giménez-Palop¹,

present in 28%; 16/30 patients had positive finding on I-123 MIBG scintigraphy.

Lara Albert¹, Ismael Capel¹, Assumpta Caixàs¹ & Mercedes Rigla¹

Surgical resection was performed in 79% of patients, tumor embolization in 11%.

¹Endocrinology and Nutrition Department, Parc Taulí Hospital Universitari,

At 22 patients the median proliferation index Ki67 was 1.8% (0.1-18%) and

Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma

median PASS score 3(1-6). Metastatic disease was present in 18.8% of patient at

de Barcelona, Sabadell, Spain;²Department of Gastroenterology, Parc Taulí

the time of diagnosis and five patients had acquired metastasis. These patients

Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT,

were treated with PRRT (6/14), chemotherapy (3/14) and sutent (3/14). Median

Universitat Autònoma de Barcelona, Sabadell, Spain;³Endocrinology and

overall survival (OS) was 284 months (95%CI 251-318) with 10-year OS 88%.

Nutrition Department, Althaia Fundation, Manresa, Spain;⁴Internal

Mean disease free survival was estimated 20 months (95%CI 8-31). We presented

Medicine Department, Consorci Hospitalari de Vic, Vic, Spain.

clinical characteristics, genetic profile, treatment options and survival of our

patients with PGLs, our experience as single tertiary center.

Introduction

DOI: 10.1530/endoabs.49.EP166

Surgical resection is currently considered the standard treatment for symptomatic

insulinomas; however, its morbidity is high (O10%) and it is restricted to suitable

candidates. In recent years, alternative minimally invasive therapies, such as

endoscopic ultrasound (EUS)-guided ethanol ablation (EA), have emerged as new

therapeutic options, especially for small lesions or poor surgical candidates. We

report two cases of insulinoma ablated with EA.

Cases report

We report two cases of recurrent hypoglycaemia due to benign insulinoma: a

75-year- old man, with a 9 mm hypoechoic lesion in the neck of the pancreas,

unfit for surgery because of comorbidities (case 1); and a 71-year- old man with

a 19!14 mm hypoechoic lesion in the pancreas head, who refused surgery

treatment

(case

2). EUS fine needle aspiration

(EUS-FNA) confirmed

EP167

neuroendocrine tumor with a Ki67 !5% in both of them. They were admitted

Corticotroph deficiency in patients with insulinoma

to our department for EA. Insulinomas were punctured under EUS guidance with

Faten Hadj Kacem¹, Mouna Ammar¹, Mouna Elleuch¹, Dorra ghorbel¹,

a 22 G needle. A total volume of 0.8 ml (case 1) and 13 ml (case 2) ethanol 98%

Rihab Ben Abdallah², Nadia Charfi¹, Wajdi Sefi¹, Mouna Mnif¹ &

was injected. After each injection a whitish halo was observed inside the lesion,

Mohamed Abid¹

and no extravasation of alcohol was detected. There were no perioperative or

postoperative complications. In case 1, hypoglycaemia was not reported along the

¹Department of Endocrinology and Diabetes Hedi Chaker, Sfax, Tunisia;

two years follow-up period. Case 2 presented occasional mild hypoglycaemia

²Faculty of sciences, Sfax, Tunisia.

1 year after treatment, so we considered repeating EA, but the patient refused it.

Conclusion

Introduction

EUS-guided ethanol ablation of a single small insulinoma is an effective,

The metabolic stressor, hypoglycemia, elicits integrated counterregulatory

minimally invasive, and safe therapeutic modality. Currently, it is considered

responses, including activation of the hypothalamic-pituitary-adrenal axis.

when surgery cannot be an option. However, this new technique should be applied

However, it is suggested that recurring insulin-induced hypoglycemia can impair

to a wider range of potential candidates. A multicentric study seems necessary to

this counter-regulation. Here we report three cases of patients with isulinoma and

establish the indications of EA in insulinomas.

corticotroph deficiency.

DOI: 10.1530/endoabs.49.EP165

Case reports

The first case, 38-year-old man was referred because of recurrent episodes of

hypoglycemia. Hormonal investigations were in favour of dissociated anterior

pituitary failure, with growth hormone and corticotroph deficiency. The

hypothalamic-pituitary MRI was normal. The fasting test argued in favour of a

hyperinsulinemic hypoglycemia. The abdominal scan and the endoscopic

ultrasound showed a mass within the tail of the pancreas. Distal pancreatectomy

was performed. Histology disclosed an insulinoma. On follow up, no

hypoglycemic episodes recurred and cortisol and GH response to induced

hypoglycemia was normal. The second case, 68 years old man referred for

investigation of hypoglycemic episodes. He was diagnosed with corticotroph

EP166

deficiency and hypergonadotropic hypogonadism with negative investigations.

Clinical characteristics and survival of patients with paraganglioma:

The hypothalamic-pituitary MRI was normal. After treatment with glucocorti-

a single center experience

coids, hypoglycemic episodes were significantly improved. After 6 years, he

Valentina Elezovic, Djuro Macut, Sanja Ognjanovic, Tatjana Isailovic,

presented severe hypoglycemia and investigations revealed a 1.5 cm tumor in the

Bojana Popovic, Ivana Bozic-Antic, Tamara Bogavac, Dusan Ilic,

head of the pancreas with hepatic and pulmonary metastases. The third case,

Jovana Bankovic & Svetozar Damjanovic

38 years old woman with a history of primary hypothyroidism for 6 years,

Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center

presented with symptomatic hypoglycemia and a history of weight gain.

of Serbia, Belgrade, Serbia.

Laboratory investigations argued in favour of a hyperinsulinemic hypoglycemia

and the abdominal scan showed a mass within the tail of the pancreas.

Furthermore, she was diagnosed with corticotroph deficiency. The hypothalamic-

Paragangliomas (PGLs) and pheochromocytomas (PCCs) are rare neuroendocrine

pituitary MRI was normal.

tumors that derived from pluripotent neural crest stem cells. PCCs are derived

Conclusions

from the adrenal medulla, while PGLs are histologically identical tumors derived

Our clinical cases show that hyperinsulinemia and hypoglycemia in patients with

from ganglia outside the adrenal gland. Even though the majority of tumors are

insulinoma can give rise to functional corticotrophin deficiency. The pathophy-

benign, they are associated with high morbidity rates caused by excessive

siological mechanism of this defective counter-regulation remains to be clarified;

catecholamine secretion. We retrospectively analyzed 71 patients (36 female and

some studies suggest it could be related to hyperinsulinemia-induced decreased in

35 males) with PGLs between January 2002 and December 2016. Twenty three

CRF secretion.

patients were lost to follow up. Kaplan-Meier curve was used as the univariate

DOI: 10.1530/endoabs.49.EP167

version of survival analysis. The median age at diagnosis was 47.0 years (11-75)

and the mean tumor size was 53 mm (26-170 mm). PGLs in our group were

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP168

EP170

Hyperinsulinemic hypoglycemia in a 71-year-old patient with a

A rare cause of secondary endocrine hypertension in a young woman

suspected case of b-cells hyperplasia of pancreatic body and

with hypokaliemia and recurrent transient ischemic attacks

tail- case report

Francisco Javier Martinez-Martin³, Sara Quintana-Arroyo¹,

Jelena Malinovic Pancic^1,2, Bojana Caric^1,2 & Bojana Popovic³

Carmen Acosta-Calero¹, Claudia Arnas-Leon¹, Ana Delia Santana-Suarez¹,

¹University Clinical Center of Republic of Srpska, Banja Luka, Bosnia and

Manuel Nivelo-Rivadeneira¹, Agnieszka Kuzior¹ & Elisa Gonzalez-

Herzegovina;²Medical Faculty Banja Luka, Banja Luka, Bosnia and

Rodriguez²

Herzegovina;³Clinical Center of Serbia, Belgrade, Serbia.

¹Endocrinology Department, Hospital Universitario de Gran Canaria Dr.

Negrin, Las Palmas de Gran Ganaria, Spain;²Endocrinology Department,

Hospital Vithas Santa Catalina, Las Palmas de Gran Ganaria, Spain;

B-pancreatic cells are programmed to react to plasma glucose level with insulin

³Outpatient Hypertension Clinic, Hospital Universitario de Gran Canaria

secretion. Insulin secretion is precisely regulated and in the physiological

Dr. Negrin, Las Palmas de Gran Ganaria, Spain.

conditions fasting glucose levels are maintained in the range 3.5-5.5 mmol/l. In

hyperinsulinemic hypoglycemia, a disorder of the regulation of insulin secretion,

insulin secretion continues at low concentrations of plasma glucose. In adults

Clinical Case

hyperinsulinemic hypoglycemia is the cause of 0.5 to 5.0% of hypoglicaemias and

A 39-year-old woman was referred to our Hypertension Clinic for workup after

are result of eather b-cell tumor

(insulinoma), or b-cell hyperplasia. Rapid

three episodes of TIA with SBP O180 mmHg in the last 6 months. Diagnosed and

diagnosis and treatment is essential in the prevention of acute and chronic

treated of hypertension and hypokaliemia since she was

15 years old, no

complications of hypoglycaemia, especially in central nervous system.

secondary cause had been searched. She was treated with Telmisartan/Amlodi-

We are presenting the 71-year-old patient who had been previously diagnostic

pine/Hydrochlorothiazide

80/10/25 mg plus Carvedilol

12.5 mg BID and

evaluated at the primary health care level due to frequent episodes of

potassium supplements. She had no history of diabetes or dyslipidemia and did

unconsciousness and weakness periodically in period of

3 years prior to

not smoke. Height was 168 cm, weight 63 kg, IMC 22.3 kg/m², office BP

admission. After established refractory hypoglycemia patient was sent to our

142/88 mmHg, HR 72 bpm. The physical exam was otherwise normal.

department where endogenous hyperinsulinism after 72-hour test of hunger was

Treatment was changed to Diltiazem/Doxazosin for 3 weeks. Lab: normal

found. After endoscopic ultrasound showed probable b-cells hyperplasia of the

including TSH and metanephrines, except venous pH 7.51, Cr 1.23 mg/dl, CKD-

body and tail of the pancreas. I-131

ocreotid scintigraphy of somatostatin

EPI eGFR 57 ml/min/1.73 m², albuminuria 139 mg/g Cr, aldosterone 792 ng/ml,

receptors was negative. Calcium artery stimulation of the pancreas with insulin

PRA 58 ng/ml per h, normal ratio (13.7).

sampling from vein lienalis showed a clear gradient of insulin and distal

Funduscopy: stage 2 hypertensive retinopathy, brain RMN: scattered white matter

pancreatectomy was suggested which patient refused. inhibitor of potassium

microinfarctions, heart US: normal function, mild LVH (LVMI 92 g/m²). Chest

channels-diazoxide was introduced in the therapy which led to reduction in

X-ray and abdominal US: normal.

subjective symptoms and no registered hypoglycaemas.

AngioCT excluded renal artery sclerosis, but showed a 12 mm subcapsular mass

DOI: 10.1530/endoabs.49.EP168

in the right kidney. The adrenals were normal.

Renal venous sampling for renin: Peripheral 628 U/l (normal ! 42), Left renal

vein 645 right renal vein 3120 U/l; right/left ratio 4.8. Laparoscopic nodulectomy

was performed; a encapsulated 14 mm adenoma with clean margins was obtained.

It tested positive for renin.

EP169

Diagnosis

Respiratory symtoms lead to a diagnosis of pheochromocytoma:

Secondary aldosteronism due to reninoma, resistant hypertension and target-

An unusual presentation

organ damage (retinopathy, brain microinfarctions and TIAs, stage IIA CKD with

Luís Teles^1,2, João Sérgio Neves², Pedro Souteiro², Sofia Castro Oliveira²,

microalbuminuria, LVH). Two months after surgery the patient is normotensive

Celestino Neves², Paula Freitas² & Davide Carvalho²

with manidipine 10mg/day: aldosterone, ARP, K^C, venous pH and albuminuria

¹Internal Medicine Department Centro Hospitalar Entre Douro e Vouga,

are normal.

Santa Maria da Feira, Portugal;²Endrocrinology Department Centro

Commentary

Hospitalar São João, Porto, Portugal.

Reninoma is rare but probably infradiagnosed, and a long diagnostic delay is not

unusual. Even with well-controlled BP, it may cause severe organ damage due to

hyperaldosteronism. Thus, it should be included in the workup of secondary

Introduction

hypertension.

Pheochromocytoma is one of the major secondary causes of hypertension. The

DOI: 10.1530/endoabs.49.EP170

classic triad of pheochromocytoma symptoms of headache, sweating and

tachycardia is not present in a high percentage of patients and is sometimes

diagnosed as incidentaloma or atypical presentations.

Case report

The authors present a 56-year-old man, with no known diseases, referred to

Endocrinology evaluation by incidentaloma of the right adrenal gland, from the

Pneumology appoitment, where he was followed by persistent cough, after an

episode of bronchospasm. From the complementary study, a 32 mm nodule in the

right adrenal gland was observed on thoracic computed tomography and

EP171

confirmed by MRI. Bronchofibroscopy with bronchoalveolar lavage and

Atypical symptoms of hypoglycemia, hiding a diagnosis of insulinoma:

functional respiratory tests were also performed, which were normal. Patient

a case report

didn’t refer any symtoms, however, he maintained a sustained hypertension in the

Agne Petrenaite^1,2, Greta Jagucianskaite^1,2, Rasa Juskiene², Rasa Ziukaite²

ambulatory monitorization. Analytically, there was a significant increase in the

& Zydrune Visockiene^1,2

urinary normetanephrines (2585 ug/24 h for a reference value !390) and urinary

¹Faculty of Medicine, Vilnius University, Vilnius, Lithuania;²Vilnius

metanephrines (1551 ug/24 h, for a reference value !320), as well as plasma

University Hospital Santariskiu Klinikos, Vilnius, Lithuania.

noradrenaline (1107 pg/ml for a reference value !750) and plasma adrenaline

(137 pg/ml, for a reference value

!110). Remaining study was without

alterations, namely renin-angiotensin-aldosterone axis, thyroid function and

Introduction

urinary free cortisol. Patient started alpha-adrenergic blockade with phenox-

Insulinoma is a rare pancreatic tumor, typically sporadic, solitary and benign.

ybenzamine and laparoscopic adrenalectomy was performed 3 weeks later.

However, nonspecific symptoms of hypoglycemia, negative laboratory investi-

Pathological anatomy confirmed diagnosis of pheochromocytoma.

gations and small size of these tumors can retard the diagnosis, and symptoms

Conclusion

may be misattributed to psychiatric, cardiac, neurological disorders.

Authors present a case of atypical presentation of pheochromocytoma. The

Case presentation

respiratory airways are sensitive to the effects of catecholamines. Although they

A 35-year-old male had history of night time seizures with hallucinations,

have mainly beta-adrenergic receptors, there are also alpha receptors that may

delirium and spasms, lasting from 10 minutes to 1.5 hours for about 2 years. These

explain the patient’s clinical condition (bronchospasm).

seizures were always resolving spontaneously. Due to recurrent seizures he was

Given the existence of multiple presentations, detection of a pheochromocytoma

consulted by phychiatrist and diagnosed with depression and conversion disorder

might be difficult but is mandatory, not only for the potential cure of the

and treated with psychotropic medications. As the spasms remained, he was

hypertension but also to avoid the potentially lethal effects of the unrecognized

referred to neurologists. During examination early in the morning while

tumor.

performing electroencephalography typical dyscognitive seizures occured.

DOI: 10.1530/endoabs.49.EP169

Plasma glucose analysis was performed for the first time and hypoglycemia of

1.4 mmol/l was found. Symptoms disappeared after intravenous glucose infusion.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Management and outcome

Relation of dehydroepiandrosterone sulphate

(DHEAS) concentration and

The patient was hospitalized due to suspected insulinoma and supervised 72-hour

adrenal tumors (AT) has never been investigated systematically. After promising

fast test was performed. Plasma glucose was

3.5 mmol/l, plasma insulin

Terzolo group (1995, 1996, 2000) investigations, there was made a recommen-

49.3 pmol/l (43-210 pmol/l) and C-peptide - 780 pmol/l (260-1730 pmol/l) at the

dation in the last clinical guidelines for adrenal incidentaloma (2016) to assess

baseline. The test was ended after 16 hours with plasma glucose of 1.7 mmol/l,

concentration of DHEAS in special clinical situations. Here we present the first

plasma insulin - 29.7 pmol/l, C-peptide - 521 pmol/l. These results confirmed the

systemic study of DHEAS in adrenal tumors.

diagnosis of insulinoma. Abdominal computed tomography scan with contrast

The aim was to analyse the clinical and laboratory characteristics (including

demonstrated a well-defined hypervascular lesion involving the head of pancreas

DHEAS) of 109 males and 54 females with AT.

measuring 10!15 mm in diameter, typical of neuroendocrine tumor. The patient

Methods

underwent laparoscopic extirpation of the pancreatic mass. Histopathological

During 2014-2016 years concentration of DHEAS was determined in 5133

evaluation revealed a pancreatic well-differentiated (G1) neuroendocrine tumor -

patients. Out of those case records of 590 females and 450 males were randomly

benign insulinoma. The patient gradually discontinued all psychotropic

selected for a detailed retrospective analysis. The relation between presence or

medications following the operation. Currently he is feeling well, without any

absence of AT and DHEAS was established. Age and gender adjusted maximal

seizures and normal plasma glucose for about 1.5 years.

values (R max) and minimal values (R min) of DHEAS concentration were used

Conclusion

to express the results.

We recommend to check plasma glucose for all patients with seizures of unknown

Results

origin, although they are not typical to hypoglycemia.

AT were detected in 109 males and in 54 females. R max %0.4 was found in

DOI: 10.1530/endoabs.49.EP171

64.81% of females starting from 45 years-old and in 67% of males starting from

60 years-old. R max value O1 was found in 11 cases of females (20.4%) and only

in one case of males (0.92%). R min !1 value was detected in 13 cases of males

(11.92%) and in two cases (3.7%) of females.

Conclusions

Out of all 163 cases of adrenal tumors, high level of DHEAS was found more

frequently in females (7.36%), otherwise, low level of DHEAS was found more

EP172

frequently in males (7.97%).

A nomogram consisted of routine biochemical tests may increase the

DOI: 10.1530/endoabs.49.EP173

diagnostic accuracy of chromogranin A in detecting patients with

neuroendocrine tumors

Ivan Vurnek¹, Ivan Kruljac², Miroslav

´ a

´i

´², Bo

ˇidar Peri

´²,

Maja Filipovi

´-Grči

´², Gorana Miroševic´2, Davor Kust2 & Milan Vrkljan1,2

¹School of Medicine, University of Zagreb, Zagreb, Croatia;²University

Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia.

EP174

Introduction

Falsely elevated serum chromogranin A (CgA) is associated with the use of

Jejunum/ ileum Neuroendocrine Tumours: results of a multicentric

proton pump inhibitors, the presence of renal impairment and systemic

retrospective study

inflammation. We aimed to investigate which laboratory parameters are

Ana Paula Marques¹, Ana Paula Santos², Isabel Claro³, Ana

independently associated with increased CgA and to develop a nomogram, in

Cristina Sanches², Isabel Fernandes⁵, José Manuel Lopes⁶, John Preto⁶,

order to improve the diagnostic accuracy of CgA in detecting patients with

Fernando Rodrigues⁷, Ana Luisa Catarino⁸, Juan Mellidez⁹,

neuroendocrine tumors (NET).

Bernardo Pereira¹⁰, Gustavo Rocha¹¹, Maria Joa˜o Bugalho5 & Grupo

Methods

Estudos Tumores Neuroendócrinos¹²

Our retrospective study included 155 subjects (controls) and 55 treatment naïve

¹Hospital Pedro Hispano, Matosinhos, Portugal;²Instituto Português

patients with NET, with available data on CgA, other laboratory tests, medical

Oncologia, Porto, Portugal;³Instituto Português Oncologia, Lisboa,

history and antropomethric parameters. Nomogram was developed in a form of

Portugal;⁴Instituto Português Oncologia, Porto, Portugal;⁵CHLN, Lisboa,

scoring system, based on z-score obtained from receiver operating curve analysis

Portugal;⁶CHSJ/IPATIMUP, Porto, Portugal;⁷Instituto Português Onco-

for each parameter that was independently associated with CgA.

logia, Coimbra, Portugal;⁸HBA, Loures, Portugal;⁹HSP, Aveiro, Portugal;

Results

¹⁰HGO, Almada, Portugal;¹¹CHVNG, Vila Nova de Gaia, Portugal;

CgA was positively associated with erythrocyte sedimentation rate, red cell

¹²Portugal, Portugal, Portugal.

distribution width, serum creatinin, glucose, urine leukocyte casts and the use of

proton pump inhibitors. The combination of all these parameters was associated

Introduction

with increased CgA with an area under the curve of 0.771 (P!0.001). Overall,

The Neuroendocrine Tumors Study Group of the Portuguese Endocrine Society

CgA level of 189 had a sensitivity of 56.4% (42.3-69.7) and a specificity of 76.8%

(SPEDM) performed the first observational study between November 2012 and

(69.3-83.2) in detecting patients with NET

(area under the curve

0.656,

July

2014 too assess the profile of Gastroenteropancreatic Neuroendocrine

P!0.001). In subjects with a score of !6, CgA level of 150 ng/ml had a

Tumours (GEP-NET) patients (pts) followed at the main Portuguese hospitals.

sensitivity of 68.2% (45.1-86.1) and specificity of 89.4% (80.8-95.0), (AUC

Several demographic and clinical data were collected

0.767, P!0.001). In subjects with a scoreR6, AUC decreased to

0.534

Objective

(PZ0.538).

Characterize the clinicopathological features and treatment of patients with NET

Conclusion

originating in the jejunum and ileum.

CgA should not be used as a biomarker for NET in patients with laboratory signs

Material and methods

of inflammation and renal impairment. Our study suggests the possibility to adjust

Included 71 pts with R18 years and a confirmed diagnosis of jejunum /ileum

CgA in these patients in order to increase its diagnostic accuracy.

NET based on histopathology/cytology findings.

DOI: 10.1530/endoabs.49.EP172

Results

Mean age was 57.2 (32-83) years, 61% (nZ43) males. Most tumors 89% (nZ63)

were located at the ileum; two were multifocal. Ki67 was available in 86% of pts,

64% G1. At diagnosis 91% (51/56) had lymph node metastases and 70% (43/61)

distant metastases.

The most common symptom, available in 59 pts, was abdominal pain in 49%

(29/59). Serum Chromogranin A (Crg A) was available in 65% (46/71) and was

EP173

2!R upper limit of normal in 61%(28/46). Urinary 5HIAA checked in 61%

Concentration of dehydroepiandrosterone sulphate in 109 males and

(43/71) was elevated in 56%(24/43), 86% of these with distant metastases. CT

54 females with adrenal tumors

scan was the preferred radiologic procedure in 87% of pts. Nuclear medicine

Ilona Banisauskaite¹, Paulina Simaityte¹, Milda Sarkinaite¹,

imaging, either octreotide scan or⁶⁸ Ga-DOTA-NOC Pet Scan was used in

Viktorija Bakstyte¹, Juste Baksanskaite¹, Rasa Steponaviciute²,

75%(53/71) of pts Tumor size known in 58 pts was 24G14.7 mm. Primary tumor

Astra Vitkauskiene², Vaidotas Urbanavicius³ & Valentinas Matulevicius¹

surgery was performed in 90 and 32% did surgery of hepatic metastases. 62% of

¹Institute of Endocrinology, Lithuanian University of Health Sciences,

the pts received somatostatin analogues(SA), two were treated with SA and

Kaunas, Lithuania;²Department of Clinical Laboratory, Hospital of

interferon and two with systemic chemotherapy. 11 cases were submitted to

Lithuanian University of Health Sciences, Kaunas, Lithuania;³Faculty of

hepatic transarterial embolization. Peptide Receptor Radionuclide Therapy with

Medicine, Vilnius University, Kaunas, Lithuania.

¹⁷⁷Lu was done in 9%.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

Methods

This paper reveals important information regarding clinical practice. Most of our

Fifty-nine (45 females) patients with GNEN1 were retrospectively studied. All

pts presented with well differentiated tumors but in an advanced stage. Regarding

patients included in the study had positive parietal-cell antibodies. All patients

therapy there was an extensive use of surgery and systemic treatment mainly

underwent a gastroscopy with multiple biopsies. Chromogranin A, gastrin,

with SA.

vitamin B12, folate and ferritin levels were also assessed.

DOI: 10.1530/endoabs.49.EP174

Results

The mean age and follow up were 54.14G13.62 years and 67.66G48.9 months,

respectively. At diagnosis, chromogranin A, gastrin, vitamin B12, folate and

ferritin levels were:

277.54G173.54 ng/ml

(!98),

896.18G818.98 pg/ml

(!110),

395.43G488.18 pg/ml

(300-960),

12G11.36 ng/ml

(2-20) and

58.02G75.08 ng/ml (20-350), respectively. Intestinal metaplasia appeared in

48 patients (81.35%) with GNEN1; 41 (85.5%) had large IM, 1 (2%) had small

and 6 (12.5%) had both small and large IM. In univariate regression analysis, only

EP175

mean follow-up from the parameters studied

(age at diagnosis, gender,

Follow-up in neuroendocrine tumors: is chromogranin A the

biochemical markers) predicted the presence of intestinal metaplasia

(OR:

confounder?

0.979; 95%CI: 0.961-0.997, PZ0.021).

Diana Martins¹, Carla Baptista¹, Ana Velez², Fernando Macário³ &

Conclusion

Francisco Carrilho¹

Our study showed a high prevalence of large IM in GNEN1. Mean follow up

¹Endocrinology, Diabetes and Metabolism Department of Coimbra Hospital

predicted IM presence. Further clinical studies are required to determine which

and Universitary Centre, Coimbra, Portugal;²General Surgery Department

parameters predict the presence of IM in patients with GNEN1.

of Coimbra Hospital and Universitary Centre, Coimbra, Portugal;

DOI: 10.1530/endoabs.49.EP176

³Nephrology Department of Coimbra Hospital and University Centre,

Coimbra, Portugal.

Introduction

Chromogranin A continues to be one of the most valuable markers for

neuroendocrine tumors (NETs) however, it has several limitations, including

its reduced specificity.

EP177

Methods

Pancreatic neuroendocrine tumors (PNETs) in patients with MEN1

The authors present the case of a patient diagnosed with a midgut NET, during

syndrome

follow-up.

Tatjana Isailovic¹, Djuro Macut¹, Sanja Ognjanovic¹, Milan Petakov¹,

Results

Valentina Elezovic¹, Ivana Milicevic², Bojana Popovic¹, Ivana

Male patient, 61 years old, with chronic renal disease (CRD), underwent right

Bozic Antic¹, Tamara Bogavac¹, Dusan Ilic¹ & Svetozar Damjanovic¹

hemicolectomy owing to ileo-cecal valve lesion; histological result consistent

¹Clinic for Endocrinology, Department for Endocrine Tumors and Heritable

with NET. Pre-operatory staging: without metastatic disease on thoracic-

Cancer Syndromes, Belgrade, Serbia;²Clinic for Endocrinology, Genetic

abdominal CT; octreoscan with elevated expression of somatostatin receptors

Laboratory, Belgrade, Serbia.

on ileo-cecal valve topography; CgA 32 nmol/l (!6.0), NSE 14 ng/ml (!15.0).

Anatomopathological examination of surgical specimen: well-differentiated G1

NET; mesenteric infiltration and metastization in 1 of 20 lymph nodes (T3N1Mx;

PNETs represent the leading cause of mortality in MEN1 patients. Yet, their

AJCC-IIB; R0). After 3 years of stable disease, the patient presented CgA of

characteristics, behaviour, and therefore management, are still uncertain.

1173.8 ng/ml (!85), with impaired CRD (Cr 4.42 mg/dl), on dyalisis. 3 months

The aim of this study was to describe the main clinical characteristics of NETs in

later: CgA

1619.0 pg/ml and Calcitonin

26 pg/ml

(!10). In additional

MEN1, and to compare them with sporadic NETs.

investigation, cervical-thoracic-abdominal CT and 68 Ga-PET rated negative

We investigated 164 patients with PNETs retrospectively, treated in one centre

for relapse. Total colonoscopy, including evaluation of ileocolonic anastomosis,

from 2004-2016. We identified 15 (9.1%) patients with MEN1. All patients had

didn’t demonstrate alterations. The patient maintained follow-up with clinical

germline mutations in MEN1 gene, except one who had sporadic MEN1. There

stability, showing in the last evaluation CgA 272.3 ng/ml, Calcitonin 38 pg/ml,

was no gender difference among the groups. No difference in age at onset between

NSE 12 ng/ml (!15) and Cr 6.88 mg/dl.

the groups was noted (48G16.1 in MEN1 vs 53.8G13.5 years in sporadic,

Conclusions

PO0.05). According to WHO classification, well-differentiated tumors were the

Evaluation of CgA in end stage renal disease is not reliable. Although it’s

most frequent in MEN1, in contrast to sporadic PNETs where well-differentiated

postulated that higher the degree of renal failure, higher the CgA concentration, it

carcinomas prevailed (P!0,01). Functioning PNETs were more frequent in

wasn’t verified such correlation. In NET patients, renal function should be

MEN1 group (60 vs 30%, P!0.05). Among functioning tumors, insulinoma and

carefully evaluated and ruled out the potential impact on the concentration of

gastrinoma were the most frequent in both groups (PO0.05). MEN1 patients had

CgA.

multiple tumors more frequently (33.3 vs 5%, P!0.05). Metastatic disease as

DOI: 10.1530/endoabs.49.EP175

initial presentation had 17% of MEN1, and 26% of sporadic patients (PO0.05).

Surgery was performed in 70% of MEN1, and 92% of sporadic patients. Tumor

size did not correlate with the presence of metastases at surgery in any of the

groups. Median OS was 149 months (95%CI 71-226) with no difference between

the groups (X²Z2.049, PO0.05). Mean time to tumor progression (TTP) was

estimated to 41 months (95%CI 10-75). However, no difference was found

regarding the MEN1 status (X²Z0.22, PO0.05). TTP negatively correlated to

Ki-67, local invasiveness and stage of the disease in all patients, but not to size or

functionality. These data suggest that MEN1

PNETs share similar clinical

EP176

behaviour as sporadic PNETs. Therefore, close tumor surveillance and early

Large intestinal metaplasia is a precancerous lesion present in patients

surgery are advocated, irrespective of the tumor size or functionality.

with gastric neuroendocrine neoplasms type 1

DOI: 10.1530/endoabs.49.EP177

Georgios Boutzios¹, Krystallenia Alexandraki¹, Vassiliki Mavroeidi¹,

Eleni Koukoulioti², Ioannis Papanikolaou² & Gregory Kaltsas¹

¹Endocrine Unit, Department of Pathophysiology, Medical School, National

and Kapodistrian University, Laikon University General Hospital, Athens,

Greece;²Hepatogastroenterology Unit, Second Department of Internal

Medicine - Propaedeutic, Research Institute and Diabetes Center, Medical

School, National and Kapodistrian University, Attikon University Gen,

EP178

Athens, Greece.

Dysregulation of the components of the splicing machinery in

neuroendocrine tumors and its association with malignancy and

Background

aggressiveness

Intestinal metaplasia

(IM) of the gastric mucosa is a relatively frequent

Sergio Pedraza-Arévalo¹, Emilia Alors-Pérez¹, Aura D. Herrera-Martínez²,

precancerous lesion. The aim of the study was to assess the prevalence and the

Mercedes del Río-Moreno¹, Rafael Sánchez-Sánchez³, Rosa Ortega-Salas³,

kind of IM and also to find parameters that could predict the presence of IM in

Raquel Serrano-Blanch⁴, María A. Gálvez-Moreno², Manuel D. Gahete¹,

gastric neuroendocrine neoplasms type 1 (GNEN1).

Raúl M. Luque¹ & Justo P. Casta

˜o¹

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Department of Cell Biology, Physiology and Immunology, Maimonides

mutated vs WT patients. Quantification of serum succinate levels after treatment

Institute of Biomedical Research of Cordoba (IMIBIC), Reina Sofia

is in progress and aims to evaluate succinate as a biomarker of response in SDH-x

University Hospital (HURS), University of Cordoba (UCO), CIBER Physi,

MPP patients.

Cordoba, Spain;²Service of Endocrinology and Nutrition, HURS/IMIBIC,

DOI: 10.1530/endoabs.49.EP179

Cordoba, Spain;³Service of Anatomical Pathology, HURS/IMIBIC,

Cordoba, Spain;⁴Service of Medical Oncology, HURS/IMIBIC, Cordoba,

Spain.

Dysregulation of the splicing machinery is emerging as a novel cancer hallmark

due to its association with multiple dysfunctions in tumor cells. An inappropriate

function of the components of this machinery (spliceosome) could be primarily

EP180

linked with the generation of tumor-associated aberrant splicing variants. In line

Survival analysis of patients with gastroenteropancreatic

with this, we have previously reported that overexpression of aberrantly spliced

neuroendocrine tumors

variants of somatostatin receptor 5 (sst5TMD4) and ghrelin (In1-ghrelin) is

Miguel Sampedro-Nún˜ ez1,2, Angeles Maillo-Nieto1,

directly associated to malignancy features in gastroenteropancreatic neuroendo-

Ana María Ramos-Leví^1,2, Isabel Huguet^1,2, Sandra Campos^1,2,

crine tumors (GEP-NETs). Therefore, in this study we aimed to characterize, for

Elena Fernandez¹, Nerea Aguirre¹, Jose Luis Mun˜oz de Nova3,

the first time, the pattern of expression of a selected set of components of the

Elena Martín³ & Mónica Marazuela^1,2

splicing machinery in GEP-NETs samples, compared to adjacent non-tumoral

¹Department of Endocrinology, Hospital Universitario de La Princesa,

control-tissues, and to determine its relationship with the aggressiveness of these

Madrid, Spain;²Instituto de Investigación Princesa, Madrid, Spain;

tumors. Accordingly, we designed a PCR-based array to determine the expression

³Department of Surgery, Hospital Universitario de La Princesa, Madrid,

levels of components of the major (nZ13) and minor spliceosome (nZ4) and

Spain.

associated splicing factors

(nZ28) using a microfluidic technology in

pancreatic NET-samples (47% G1, 47% G2 and 6% G3) and control-tissues. The

Introduction

results showed that the expression of several splicing factors and spliceosome

One of the main difficulties in the study of gastroenteropancreatic neuroendocrine

components was altered in tumor tissues compared to non-tumoral adjacent

tumors (GEP-NETs) is their wide heterogeneity and variable outcome. Several

tissues. Remarkably, important splicing factors (e.g. CELF4, NOVA1, SNW1,

potential influencing factors on patient survival have been recently identified.

and RAVER1) and components of spliceosome

(e.g. PRP8) were clearly

These factors could help predict patients’ prognosis.

overexpressed in NET-samples, wherein they were correlated with some

Objectives

malignancy features. Furthermore, in vitro assays using NETs cellular models

Analysis of long-term survival of our GEP-NETs cohort according to the presence

(i.e. BON-I/QGP-I-cells) demonstrated that CELF4 and NOVA1 overexpression

of metastatic disease, tumor grade, age, sex, tumor functionality and tumor origin.

induced an increase on cell-proliferation, while their silencing (using specific

Materials and methods

siRNAs) caused a marked decrease on cell-proliferation, suggesting a role in the

Ambispective study of patients with GEP-NETs in Hospital Universitario La

aggressiveness of these tumors and their putative suitability as therapeutic targets

Princesa (Madrid, Spain) from 1995 to the present. Survival analysis and factors

in pancreatic NETs. Hence, our results demonstrate an alteration of splicing

involved were assessed by Kaplan-Meier method and Cox regression analysis

machinery in pancreatic NETs and unveil its putative relevance in NETs

using STATA v12.0.

development/progression, where it could provide novel diagnostic biomarkers

Results

and therapeutic tools for this pathology.

One hundred and four patients were evaluated (55 women, age 61G16 years).

DOI: 10.1530/endoabs.49.EP178

Primary origin was pancreatic in 39, intestinal in 69 and unknown in 6 cases.

Histological tumor grade was G1 in 51%, G2 in 39% and G3 in 10% of cases. 68%

patients had metastatic disease and 33 died during follow-up. Median survival

time was 5261 days (CI 3247 to not reached). Grade G3 multiplied the risk of

mortality by 26 (CI 6 - 112); metastatic disease doubled the risk (CI 1.3 - 5.1);

every 10-year increase in age multiplied the risk by 1.6 (CI 1.2 - 2.2); and if the

tumor had unknown primary origin, the risk was multiplied by 2.5 (IC 0.9 - 7.4).

Sex and tumor functionality did not significantly affect survival.

Conclusions

EP179

Several factors influence the heterogeneity and clinical outcome of patients with

NETs. Median survival is reduced in patients with G3, metastasis, and primary

Serum succinate: investigation of its putative role as a new biomarker in

tumors of unknown origin. Knowing these factors guides the therapeutic approach

malignant SDH-x mutated pheochromocytoma-paraganglioma

of this rare disease.

patients?

DOI: 10.1530/endoabs.49.EP180

Constance Lamy¹, Julien Hadoux¹, Lionel Mercier¹, Dorian Bailleux¹,

Ségolène Hescot¹, Angelo Paci^1,2, Eric Baudin¹ & Sophie Broutin¹

¹Gustave Roussy, Villejuif, France;²Université Paris-Sud,

Châtenay-Malabry, France.

Introduction

Malignant paraganglioma/pheochromocytoma (MPP) are very rare neuroendo-

EP181

crine tumors with heterogeneous prognostic and no gold-standard treatment. MPP

Insulinoma - clinical features and outcome of patients diagnosed at a

can be associated with germline mutations at SDH-x genes which encode for the

central hospital

succinate dehydrogenase that catalyzes the oxidation of succinate to fumarate.

Joanna Prokop, Ana Cláudia Martins, Carolina Neves, Teresa Sabino,

SDH-x mutations lead to inactivation of the enzyme and thus accumulation of

Paula Bogalho, José Silva Nunes, Fernando Fonseca & Ana Agapito

succinate.

Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,

Aim

Portugal.

This project aims to evaluate succinate as a potential early serum biomarker in

SDH-x MPP patients.

Material & Methods

A fully validated LC-MS/MS method has been developed to quantify succinate

Insulinoma, a rare neuroendocrine tumor (NET), is benign in more than 90%

serum levels. A prospective collection of MPP patients ‘serum has been initiated.

of cases. We present a review of patients diagnosed with insulinoma at our

Results

Department.

Succinate has been quantified in 108 serum samples collected from 47 MPP

Methods

patients. Among them 25 presented a SDH-B mutation, 4 a SDH-D mutation and

Retrospective review of clinical records of patients diagnosed with insulinoma

15 were SDH wild-type (WT). Succinate levels were statistically higher in the

between 2011 and 2016.

SDH-B group (mean Z25 mM, min-max: w3-106 mM) compared to the WT

Results

group (mean Z7 mM, min-max: 4-11 mM) (PZ0.01).

Six female patients were diagnosed with insulinoma (age at presentation 30-66,

Conclusion

follow-up:

0.25-3.25

years). Episodes of sweating, palpitations, tremor,

These results suggest a role of succinate as serum biomarker in SDH-x patients.

confusion, visual disturbances and weight gain were present in five patients

TNM adjustment is ongoing to determine cut-off value that may differentiate

from 2 months to 5 years before diagnosis. There was no familial history or

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

clinical findings of hereditary tumor syndromes. The 72-h fast test confirmed

EP183

endogenous hyperinsulinism at 4-12 h of fast. Abdominal CT: pancreatic lesion

Treatment with (177Lu)-DOTATATE in patients with advanced

in four patients

(14-25 mm). Endoscopic ultrasound done in four patients

metastatic somatostatin receptor-positive tumors

revealed pancreatic nodule; three performed cytology/biopsy compatible with

Antonio Ballesteros Martín-Portugués, María Isabel Del Olmo García, Pilar

pancreatic neuroendocrine tumor (pNET). Five patients underwent surgery: two

Bello Arqués, Ángel Segura Huerta, Rosa Cámara Gómez & Juan Francisco

tumor enucleation, three central and distal pancreatectomy with left hepatectomy

Merino Torres

and splenectomy in 1 of these. Histopathology: well differentiated pNET G1(two

Hospital la Fe, Valencia, Comunidad Valenciana, Spain.

patients) and G2 (three patients). Two patients had lymph node involvement and

one of them liver metastases. Among five surgically treated patients: four did not

have recurrence of hypoglycemia and the one with liver metastases was treated

Introduction

with octreotide and deceased 2 years after diagnosis. The sixth patient had

The NETTER 1 trial resulted in markedly longer progression-free survival (PFS),

undergone central and distal pancreatectomy with splenectomy 5 years earlier due

with preliminary evidence of an overall survival benefit. We report the results of

to pNET without diagnosis of insulinoma at that time and presented us with large

PFS and safety of (177Lu)-DOTATATE in patients treated in our hospital

hepatic metastases and hypoglycemia. Octreotide and peptide receptor radio-

between 2014 and 2016.

nucleide therapy (DOTA-TATE) were started due to hepatic hyperfixation in

Methods

PET-68Ga-DOTANOC.

Transversal and descriptive study of seven patients with advanced, progressive,

Discussion

somatostatin receptor-positive tumors who had received previous treatments. All

In this group there was a high prevalence of malignancy, which is unusual. Time

of them were treated in progressive disease with (177Lu)-DOTATATE. Results

elapsed from onset of symptoms to diagnosis was highly variable. The natural

are expressed in average (S.D.) or percentage(%). SPSS version 2.2 was used for

history of malignant insulinoma is difficult to predict, however uncontrolled

statistical analysis.

hypoglycemia, liver tumor burden exceeding 30% of liver volume, morphologic

Results

progression and Ki67 O10-20% are factors of poor prognosis.

71.4% (5) were women, with an average age of 46.4 (16.2). Histological

DOI: 10.1530/endoabs.49.EP181

classification was: 4 (57%) well-moderate differentiated neuroendocrine tumors

(three pancreatic, one ileal), 2 (28.6%) paragangliomas and 1 (14.3%) follicular

thyroid carcinoma. At the time of administration of (177Lu)-DOTATATE, all

tumors were in metastatic stage. The localization of the metastasis was: bone

85.7% (6), liver 57.1% (4), lymph nodes 42.8% (3) and lungs 14.3% (1). All

patients had received previous treatments: two underwent surgery exclusively,

five of them several systemic therapies: one with somatostatin analogues (SA) and

surgery, two only SA, one surgery, SA, temsirolimus and sunitinib, and one

patient with diagnosis of metastatic follicular thyroid carcinoma, received:

surgery, radioiodine, sorafenib, sunitinib, everolimus, adryamicine, and SA.

EP182

177Lu-DOTATE was infused every eight weeks in four doses, except in two

Effects of ketoconazole on ACTH-producing and non ACTH-producing

patients who have received only three. At the data-cutoff date PFS was of 20.29

neuroendocrine tumor cells

(7.13) months. Two patients had adverse events related to the treatment: one

Aura D Herrera-Martínez^2,3, Richard Feelders¹, Justo Castan˜o2,4,

hematologic events (mild-moderate thrombocytopenia and anemia), and one self-

Fadime Dogan¹, Peter van Koetsveld¹ & Leo Hofland¹

limited nausea and vomiting. Death occurred in one patient after 15 months of

¹Department of Internal Medicine, Division of Endocrinology Erasmus

stable disease.

University Medical Center, Rotterdam, The Netherlands;²Maimonides

Conclusions

Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain;

In real world practice treatment with (177Lu)-DOTATATE not only shows

³Endocrinology and Nutrition Service, Reina Sofia University Hospital,

benefit in advanced intestinal NETS but also in other patients with metastatic

Córdoba, Spain;⁴Department of Cell Biology, Physiology, and Immu-

disease, previous treatments, and positive somatostatin-receptor expression it

nology, University of Córdoba, Córdoba, Spain.

seems to have favorable results attending to PFS and safety.

DOI: 10.1530/endoabs.49.EP183

Prolonged spontaneous remission of hypercortisolemia in ectopic ACTH

syndrome after long-term treatment with steroidogenesis inhibitors has been

described. Direct drug effect on the adrenal glands, effects on tumoral

ACTH secretion and/or POMC gene expression have been suggested.

Medical treatment could be used for symptoms, but also for disease control.

Materials and methods

In human BON-1 and DMS-79 cells, we have evaluated the effects of

ketoconazole on cell growth, apoptosis, cell cycle, LDH production, POMC/-

EP184

chromogranin-A mRNA expression and ACTH/serotonin secretion.

Results

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) followed

In the BON-1 cells, ketoconazole significantly suppressed cell growth in a dose

in the endocrinology and nutrition service’s monographic outpatient

and time-dependent manner. Maximal inhibitory effects by 10 mM ketoconazole

clinics of neuroendocrine tumors in hospital clínico san carlos (HCSC).

were 41 and 95% after 3 and 7 days (P!0.0001); the ratio LDH/DNA after 3 days

Description of its characteristics and evolution

was increased. The IC₅₀ value of growth inhibition was 7.8 mM after 7 days of

Ines Jimenez-Varas¹, Angela Amengual¹, Rona Penso¹, Anna Ortolá²,

treatment. Ketoconazole also induced a significant G1-phase arrest accompanied

Ane Azkutia¹, Lorea Herraiz¹, Paz de Miguel¹ & Jose Angel Díaz¹

by a decrease in S-phase and G2-phase, as well as a significant increase in early

¹Hospital Clinico San Carlos, Madrid, Spain;²Hospital Clinico Universi-

and late apoptosis (P!0,01), confirmed using an ELISA method. Ketoconazole

tario, Valladolid, Spain.

(up to 10 mM) did not significantly affect the chromogranin-A expression or

serotonin secretion (corrected for cell number). DMS-79 cells are less sensitive to

Introduction

ketoconazole, with maximally inhibitory effects by 50 mM ketoconazole of 44 and

The multidisciplinary approach of the patients with GEP-NETs is very important,

94% after 3 and 7 days of treatment (P!0.0001). The IC₅₀ value of the growth

having a fundamental role the participation of the endocrinologist.

inhibitory effect was 15 mM after 7 days of treatment. The highest ketoconazole

Methods

concentration (50 mM) tested induced a significant G1-phase arrest (P!0.001),

Description of cases of GEP-NETs followed in the Service of Endocrinology of

increased number of dead cells (P!0,001) without significant effect on early/late

the SCCH from 1990 to 2016.

apoptosis, increased total apoptosis

(ELISA; P!0.0001), as well as the

Results

LDH/DNA (P!0.001). Ketoconazole up to 10 mM suppressed ACTH secretion

95 patients were included, 53.7% were males, age 61.2 years (IR: 50.5-73.5). The

(P!0.01). POMC expression did not show significant changes.

diagnosis was incidental in 53.8%. 27.6% presented clinical secretion, from them

Conclusions

the most frequent was carcinoid (13.8%). The median primary tumor size was

These results suggest a potential direct effect of ketoconazole on cell

3 cm (IR: 2-4). The most frequent location was pancreas (43.2%) followed by

proliferation, apoptosis and cell cycle in ACTH- and non-ACTH producing

small intestine (20%). The initial stage was 49.5% I and 39.6% IV (72% hepatic

NET cells. Additional studies are required to confirm and extend these results.

metastases). Clinic as a cause of diagnosis was significantly associated with

DOI: 10.1530/endoabs.49.EP182

staging (Cramer’s V (V) 0.72, P!0.05). Chromogranin A (CrA) was high in 30%

and 5-Hydroxyindolacetic in 18.7% (only 73.7 and 58.4%, respectively) were

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

studied.

9.4% of the patients had history of familiar syndrome. Degree of

Introduction

differentiation (DD) 1 and 2 (63 and 30.3%) predominated. The follow-up was

In recent years, it is thought that cardiovascular risk is increased in patients with

6.63 years (IR: 4.6-9.3). During that period, 30.2% of the cases were lost, with

nonfunctional adrenal insidentaloma (NFAI). There are not enough studies in the

mortality rate of 17.9% of the remaining group, due to progression in 83.3% of the

literature that evaluating this condition in patients with NFAI who don’t have

patients. The most frequently used treatment was surgery (39.1%). From stage IV

traditional cardiovascular risk factors. The aim of our study is to determine

patients 20.8% received only somatostatin analogues and 45% received more than

peripheral and central blood pressures and arterial stiffness in patients with NFAI

one treatment

(surgery, chemotherapy, antiangiogenic drugs, somatostatin

who don’t have traditional risk factors and autonomous cortisol release with pulse

analogues or everolimus) There was significant association between mortality

wave analysis (PWA) measurement.

and stage (V 0.42, P 0.04), CrA (V 0.38, P 0.012), presence of symptoms at

Material and methods

diagnosis (V 0.32, P 0.017) and DD (V 0.41, P 0.02).

In our cross-sectional study, we evaluated 70 participants (35 patients with NFAI

Conclusion

and 35 healthy volunteers) without traditional cardiovascular risk factors. All

Patients followed in the endocrinology outpatients clinic are more frequently

participants were similar in terms of gender, age and body mass index.

stages I and DD1 and DD2 that have been incidentally diagnosed. More than 50%

Measurements of peripheral and central blood pressures and PWA were made

of the cases were treated only with surgery or somatostatin analogues. One third

with Mobil-O-Graph PWA/ABPM device (I.E.M. GmBH, Stolberg, Germany).

of the patients had secretion.

Radiological and biochemical data were obtained retrospectively in the NFAI

DOI: 10.1530/endoabs.49.EP184

group.

Results

In the NFAI group, systolic blood pressure (SBP), diastolic blood pressure (DBP),

mean arterial pressure (MAP), central SBP, central DBP, peripheral vascular

resistance, augmentation pressure (AP), augmentation index that corrected based

on pulse rate of

75 bpm (Aix@75) and pulse wave velocity (PWV) were

significantly higher than control group. We also found that PWA measurements

are affected by age and the time from diagnosis to PWA measurement. There was

no significant correlations between biochemical parameters and central blood

pressures and arterial stiffness parameters in NFAI group.

EP185

Conclusion

Descriptive and survival study of 142 cases of gastroenteropancreatic

In patients without traditional cardiovascular risk factors who have NFAI that

neuroendocrine tumor (GEP-NETs) diagnosed at the Hospital Clínico

known as cardiometabolically innocent, both peripheral and central blood

San Carlos (HCSC)

pressures and arterial stiffness parameters are affected negatively. These patients

Rona Penso¹, Inés Jiménez-Varas¹, Angela Amengual¹, Lorea Herraiz¹,

are at risk for cardiovascular diseases.

Ane Azkutia¹, Anna Ortolá², Paz de Miguel¹ & José Angel Díaz¹

DOI: 10.1530/endoabs.49.EP186

¹Hospital Clinico San Carlos, Madrid, Spain;²Hospital Clinico

Universitario, Valladolid, Spain.

Introduction

Neuroendocrine tumors (NETs) constitute a very heterogeneous group of rare

neoplasms, although their incidence has increased in recent years. We describe its

evolution and survival.

Methods

Retrospective study. All patients with histopathological diagnosis of GEP-NETs

performed at the HCSC between 2000 and 2016 were selected, data from the

EP187

medical history were included. Statistical analysis were done with SPSS.

Landscape of sporadic adrenal tumours from surgical unit -

Results

histopathological audit of 101 cases from a single centre in Poland

One hundred and forty-two patients, 54.9% male, mean age 60.2 years (S.D. 19.7).

Anna Jodkowska¹, Maciej Sroczynski², Monika Sepek²,

The median follow-up time was 3.3 years (IR: 0.78-6.33). The most frequent

Krzysztof Tupikowski³ & Grzegorz Mazur¹

locations were pancreatic (28.2%) and rectal (16.2%). The tumor stage was: I

¹Department and Clinic of Internal and Occupational Diseases, Hyperten-

47.2%, II 4.9%, III 13.4%, IV 34.5%. The initial stage (IS) presented positive

sion and Clinical Oncology, Wroclaw Medical University, Wroclaw,

correlation with the degree of differentiation (DD) (Cramer’s V 0.46, P !0.05)

Poland;²Department of Minimally Invasive Surgery and Proctology,

and with levels of Chromogranin A (Cramer’s V 0.37, P !0.05). 12% had

Wroclaw Medical University, Wroclaw, Poland;³Department of Urologic

progression and 64% died during follow-up (72% due to tumor). Overall survival

Oncology, Lowersilesan Oncology Centre, Wroclaw, Poland.

at 5 years was 69 and 53% at 10 years. There were significant differences in

survival according to location, with gallbladder and colon being the lowest (0 and

38% at 5 years, respectively). DD, IS and sex were also associated with survival

(at 10 years: G1 95% vs G3 14.3% P!0.01, stage I 91% vs IV 28% P!0.01,

Laparoscopic surgery of adrenal tumours is widely used because of its high

median males 7.5 years vs 16.9 in females P 0.018). These differences were

effectiveness, patients safety and relatively low cost. Current indications to

maintained after multivariate analysis in the case of DD and IS.

adrenalectomy of oncological and endocrinological origin are highly

In stage IV survival was modified according to surgical treatment (operated

accepted. However there is still lack of perfect clinical tool identifying

median 5.9 years vs non-operated 0.64 years, P!0.01).

malignant lesions. In everyday practice clinicians rely on low specific

Conclusion

features, especially considering larger nonsecretory lesions to surgery.

In our sample the overall mortality was high, despite having a low rate of

To show the landscape of sporadic adrenal tumours we analysed

progression. DD and IS were determinants of survival. In advanced stages

retrospectively histopathological findings from 101 consecutive adrenalec-

surgical treatment improves survival significantly.

tomies performed in our centre in 71 women and 30 men of average age 57.7

DOI: 10.1530/endoabs.49.EP185

years (S.D. 13.5), between 2009 and 2016 years.

There were 53 (52.47%) adenomas found; 7 (6.93%) of them secreting: 4

(3.96%)-cortisol,

(2.97%)-aldosterone. Pheochromocytoma occurrence

was notably often-14 cases (13,86%). Adrenal cancer was found in two

cases (1.98%), metastatic lesions from lung, kidney and urinary bladder in

three cases (2.97%); and 1(0.99%) malignant peripherial nerve seath tumor

(MPNST) derived from ganglioneuroma of adrenal gland was found.

Thirteen cases (12.87%) of adrenal hyperplasia were found. In 16 cases

(15.84%) the histopathological findings were classified as “various” in detail

EP186

consisting of: 3 myelolipomas, 1 angiomyolipoma, 2 cysts, 6 pseudocysts or

Nonfunctional adrenal incidentaloma affects central blood pressures

secondary posthaemorrhagic/inflammatory lesions, 1 normal adrenal tissue,

and arterial stiffness parameters

1 fatty tissue, 1 mesenteric cyst and 1 teratoma. In two cases benign adrenal

Tolga Akkan¹, Mustafa Altay², Yasemin Aydogan Unsal¹,

lesions coincided with unilateral kidney cancer. Seventeen patients

Murat Dagdeviren² & Esin Beyan¹

(16,83%) had previous oncological anamnesis positive, while patients

¹Internal Medicine, Kecioren Education and Research Hospital, Ankara,

with adrenal cancer had negative previous oncological anamnesis.

Turkey;²Endocrinology and Metabolism, Kecioren Education and Research

We observe that adrenalectomy of oncological indications is prevalent:

Hospital, Ankara, Turkey.

adrenal lesions with positive previous cancer history; lesions suspected of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

malignancy because of the CT morphological features. In the audit almost

Introduction

half of them occur benign incydentalomas. Are we overtreating, then?

Neuroendocrine tumors may develop in almost any organ. These types of tumors

We conclude there is a great need of new specific clinical tools to identify

may present with giant and asymptomatic mass. We describe a case of a large non

malignancy in adrenal glands in everyday practice.

functional neuroendocrine tumor reported in the department of endocrinology and

diabetology of Hedi Chaker hospital in Sfax-Tunisia in 2016.

DOI: 10.1530/endoabs.49.EP187

Presentation of case

A 28 years old male presented with asthenia, gastric heaviness and epigastric

pain. Further computerized tomography, a large mass (20 cm) near the stomach in

the coeliomesenteric region has been demonstrated. Magnetic Resonance

Imaging has showed the presence of a voluminous encapsulated mass with

abundant vascularization and central necroses, measuring

18.5 cm!14.5 cm

compressing the vascular structures. The dosage of methoxylated plasma

derivatives was negative. The dosage of NSE was returned positive at

30.5 ng/l. The biopsy of the mass showed a histological and immunohistochem-

EP188

ical aspect of a neuroendocrine tumor. The therapeutic decision was to start with

An elevated chromogranin A: is it always a tumor progression?-case

exploratory laparotomy and tumor excision if possible. Because of the

report

vascularized character and significant bleeding during the intervention, a surgical

Anamaria Bursuc¹, Alina Daniela Belceanu¹, Ioana Armasu¹,

abstention was decided. The patient had two chemoembolization sessions with

Mirela Tirnovan¹, Adina Manolachie¹, Felicia Crumpei², Delia Ciobanu³,

good tumor response. It is being evaluated for possible re-intervention.

Letitia Leustean¹ & Carmen Vulpoi¹

Conclusion

¹Department of Endocrinology, ‘Gr. T. Popa’ University of Medicine and

The incidence of neuroendocrine tumors has been increasing during the last

Pharmacy, Iasi, Romania;²Department of Radiology, ‘Gr. T. Popa’

decade, underscoring the need to improve our understanding of their biology and

University of Medicine and Pharmacy, Iasi, Romania;³Department of

behavior especially.

Pathology, ‘Gr. T. Popa’ University of Medicine and Pharmacy, Iasi,

DOI: 10.1530/endoabs.49.EP189

Romania.

Introduction

Pancreatic neuroendocrine tumors

(PNET) are rare, with an incidence of

1/100,000/year. Chromogranin A (CgA) is the most valuable marker in the

diagnosis and monitoring of PNET. One of the disadvantages is its low specificity

and the existence of a number of processes leading to an increase in its

concentration, which often results in confusion and diagnostic difficulties.

Case report

EP190

We present a 44-years-old female patient with a history of PNET-pT3NxMx-G3

A challenging case of metastatic paraganglioma and metastatic

surgically excised in 2007, chemotreated with 6 cycles of Gemcitabine and

melanoma and prolactinoma

Capecitabine. In 2009, a left thoracotomy for lung metastasis was performed,

Rehmat Karim¹, Kamrudeen Mohammed¹, Najeeb Zaheer Shah¹ &

followed by 10 cycles of chemotherapy and in 2015 the patient was diagnosed

Muhammad Fahad Arshad²

with a recurrence of PNET which required atypical pancreatectomy. Immuno-

¹Hull Royal Infirmary, Kingston Upon Hull, East Yorkshire, UK;

histochemistry revealed intense positive markers: NSE, chromogranin, synapto-

²Doncaster Royal Infirmary, Doncaster, South Yorkshire, UK.

physin CD56

and ki67Z3%. The subsequent evaluations showed normal

biological

(CgA, serotonin,

5HIAA) and morphological (thoraco-abdominal

CT) parameters until 2016, when CgA level was 7-fold higher that the upper

Background

normal value (545 ng/ml vs 76 ng/ml) but with normal thorax and abdomino-

Paragangliomas are extremely rare endocrine tumours and can cause diagnostic

pelvic CT. As the patient took moderate doses (40 mg/day) of Omeprazole 6

difficulty, especially with a coexistent metastatic malignancy.

months for gastroesophageal reflux disease, iatrogenic elevation of CgA was

Case

suspected. After cessation of proton pump inhibitors (PPIs) therapy for 1 week,

A 78-year-old man with diagnosed metastatic melanoma underwent a PET scan for

serum CgA level rapidly decreased to 66 mg/l (N!100 mg/l).

staging of the malignancy. It showed a left upper quadrant mass with multiple

Conclusions

skeletal deposits and a lesion in the pituitary all with intense focal uptake. The mass

In this case, the elevated CgA raised the suspicion of a new recurrence which

was unusual for a metastatic lesion from melanoma although other lesions,

required further investigations. PPIs may cause serious differential diagnostic

including pituitary could be explained by metastatic melanoma. A biopsy of the

problems with elevation of serum CgA especially in suspected neuroendocrine

abdominal mass showed histological features of a paraganglioma; 24-h urinary

tumors. An interesting phenomenon highlighted by this case is the report of rapid

catecholamines showed raised noradrenaline 1474 nmol/24 h (70-550 nmol/24 h),

normalization of CgA after withdrawal of PPI. Giving particular attention to the

dopamine 6277 nmol/24 h (400-3000 nmol/24 h) and a normal adrenaline

use of PPIs as a possible cause for elevated CgA levels might help to prevent the

!21 nmol/24 h (0-190 nmol/24 h) confirming a functional paraganglioma. The

need for further diagnostic procedures.

diagnosis of the skeletal lesions was unclear, and a 123-MIBG scan showed

increased activity at the skeletal lesions but no avidity at pituitary confirming

DOI: 10.1530/endoabs.49.EP188

skeletal metastases from the paraganglioma with no definite explanation for the

pituitary lesion. An MRI pituitary showed diffuse enlargement of pituitary gland

with fossa expansion indicating chronicity and suggestive of prolactinoma rather

than metastasis as his prolactin was 9400 mU/l and rest of his pituitary function was

normal. He had no symptoms of diabetes insipidus. Resection of the paraganglioma

was performed after preoperative alpha and beta blockade. His post-operative

catecholamines normalised and post operative PET scan has shown stable

appearance of skeletal lesions. He was started on Cabergoline for his prolactinoma

and referred for chemotherapy for the metastatic skeletal lesions.

EP189

Conclusion

An unknown giant neuroendocrine tumor

Metastatic paragangliomas in patients with a separate existing metastatic

Nabila Rekik, Dorra Ghorbel, Fatma Mnif, Mahdi Kalthoum,

malignancy provides a diagnostic and management challenge. With a structured

Houcem Mrabet, Nadia Charfi, Hamza Elfekih, Mouna Mnif &

approach to investigation and management the clinical picture can be clarified,

Mohamed Abid

which then facilitates appropriate intervention.

The Department of Endocrinology and Diabetology of Hedi Chaker

DOI: 10.1530/endoabs.49.EP190

Hospital in Sfax, Sfax, Tunisia.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP191

Accurate identification of disease site, cell type and associated hormone

Biology and differential diagnosis of calcitonin secreting

secretion is paramount in delivering optimal clinical care - evidence based

neuroendocrine tumors

guidelines are available for most neuro/endocrine tumours - but consideration

Bojana Popovic, Djuro Macut, Valentina Elezovic Kovacevic,

should also be given to meeting the psychosocial and informational needs of

Tatjana Isailovic, Ivana Bozic Antic, Tamara Bogavac, Dusan Ilic,

the individual diagnosed with one of these rare cancers.

Sanja Ognjanovic, Gordana Rodic, Milan Petakov & Svetozar Damjanovic

1. http://www.endocrinecancer.eu/en/pages/statement.

Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center

2. http://www.ese-hormones.org/guidelines/index.aspx.

of Serbia, Belgrade, Serbia.

3. http://www.enets.org/current_guidelines.html

DOI: 10.1530/endoabs.49.EP192

Introduction

Calcitonin secreting neuroendocrine tumors

(NET) are rare and not well

recognized. Due to many similarities, it is sometimes difficult to differentiate

them from medullary thyroid carcinoma (MTC), which can hamper choice of

proper therapy. We investigated our group of patients with this type of NET in

terms of diagnosis and biology.

EP193

Patients and Methods

We analyzed 38 patients with calcitonin secreting NET (5% of all our patients

Short-term contralateral recurrence of a Litynski-Conn adenoma

with NET). In addition to standard work up, calcium-stimulation test for

Agnieszka Kuzior¹, Manuel Nivelo-Rivadeneira¹, Ana Delia Santana-

calcitonin was performed in 15 of them, and results compared to 34 patients with

Suarez¹, Claudia Arnas-Leon¹, Carmen Acosta-Calero¹, Sara Quintana-

MTC, and 21 control subjects with elevated calcitonin level and thyroid

Arroyo¹, Marta Martin-Perez² & Francisco Javier Martinez-Martin¹

pathology other than MTC. Statistical analysis was done with SPSS software.

¹Division of Endocrinology and Nutrition, Doctor Negrin University

Results

Hospital of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria,

Primary localization of NET was lung (16), pancreas (12), unknown primary (8)

Spain;²Primary Care Center of Guia, Doctor Negrin University Hospital of

and intestine (2), with majority (54.1%) being grade G3, and high majority being

Gran Canaria, Las Palmas de Gran Canaria, Spain.

metastatic (94.7%). Majority (55.6%) had goiter and 26.3% concomitant TPOAb,

while 28.9% co-secreted another hormone (ADH, insulin, serotonin, PTHrP).

Clinical Case

Patients with NET had significantly higher basal calcitonin levels compared to

A hypertensive 60-year-old woman with nephroangiosclerotic stage IV chronic

controls (P(0.01), but with no significant difference compared to patients with

renal failure (eGFR 23.44 ml/min/1.73 m²) was referred to our hypertension clinic

MTC (PZ0.427). Unlike this, patients with NET achieved significantly lower

after the CT finding of a 26-mm left adrenal mass with adenoma density during

calcitonin levels after calcium stimulation compared to patients with MTC

hypertension workup, with normal right adrenal. Physical exam was unremark-

(P(0.01), but no different compared to controls

(PZ0.102). There was no

able except for BP 167/98 mmHg. Plasma aldosterone was 353 ng/ml, PRA

significant correlation between basal calcitonin level and presence of TPOAb

1.3 ng/ml/h, ratio 90.2, K^C3.1 mEq/l, and metanephrines were normal. Primary

(PZ0.816) or goiter (PZ0.670) in these patients. Their median overall survival

aldosteronism was confirmed by standard captopril test. Adrenal vein sampling

was 24.0 months (95% CI 10.9-37.1).

showed full left lateralization of aldosterone secretion. The patient underwent

Conclusion

laparoscopic adrenectomy, and a 21-g left adrenal -including a 4-cm adenoma

Patients with calcitonin secreting NET can secrete very high calcitonin levels, but

with clean margins- was removed. One month after surgery, K^C, aldosterone and

can be differentiated from patients with MTC by absence of significant response

ARP were normal, and BP was controlled with manidipine 20 mg.

to stimulation with calcium. Survival of these patients is poor, but influence of

One year later, BP and plasma K^C were still controlled but the patient showed

calcitonin on survival is yet to be determined.

again a pattern of primary aldosteronism with aldosterone

747 ng/ml, PRA

DOI: 10.1530/endoabs.49.EP191

0.9 ng/ml/h, ratio 83.0. A new CT showed absent left adrenal, and a 17!11 mm

mass in the right adrenal, with adenoma density. Low-dose

(12.5 mg)

spironolactone was added to the treatment, but surgery was deferred.

Diagnosis

Primary aldosteronism caused by aldosterone-producing adenoma (Litynski-

Conn syndrome), with contralateral recurrence after one year. Secondary

hypertension with nephroangiosclerotic stage IV chronic renal failure.

EP192

Commentary

Cancerous neuroendocrine vs endocrine tumours: broad commonalities

Contralateral recurrence of an aldosterone-producing adenoma in a previously

and differences

normal adrenal after a complete surgical removal is exceedingly rare, particularly

Nicola Jervis & Catherine Bouvier

after such a short follow-up. The differential diagnosis would include familial

NET Patient Foundation, Leamington Spa, UK.

type II aldosteronism (as types I and III usually cause severe hypertension in the

pediatric age and associate normal or bilaterally hyperplastic adrenals but not

adenomas, while type II may associate adenomas in adult patients) but as there is

no known genetic marker for this condition, confirmation is not possible at this

Endocrine cancers are defined, by European Taskforce on Endocrine Cancer,

point.

as malignant tumours arising from endocrine organs including thyroid,

adrenal, parathyroid, pituitary, as well as neuroendocrine tumours in general.

DOI: 10.1530/endoabs.49.EP193

Cancerous neuroendocrine tumours arise from neuroendocrine cells which

can be found within the endocrine system: in the pituitary, pineal, parathyroid

and (medulla of the) adrenal gland, or more scantily within the thyroid,

pancreas, ovaries and testicles, or more diffusely throughout the body, being

present in respiratory, urinary and digestive tracts, as well as breast, skin,

prostate and gynaecological structures.

Neuroendocrine and most endocrine cancers are considered both rare and

EP194

complex.

Acinic cell adenocarcinoma of the parotid gland associated with

Commonalities exist in terms of gross classification, that is, designation by

paraneoplastic Cushing’s syndrome - a rare clinical case

site, cell type and whether they are associated with excess hormone/peptide

Sofia Castro Oliveira^1,2, Joa˜o Sérgio Neves1,2, Pedro Souteiro1,2,

secretion - differences are revealed as this broad definition narrows.

Sandra Belo^1,2, Ana Isabel Oliveira^1,2, Celestino Neves^1,2, Paula Freitas^1,2 &

For example: within the adrenal gland:

Davide Carvalho^1,3

Endocrine - adrenocorticol carcinoma (ACC) arises within the cortex, and

¹Department of Endocrinology, Diabetes and Metabolism of Sa˜o João

may be associated with excess secretion of steroidal hormones. TNM staging.

Hospital Center, Porto, Portugal;²Faculty of Medicine, University of Porto,

Neuroendocrine - pheochromocytoma arises within the medulla, and may be

Porto, Portugal;³Instituto de Investigação e Inovação em Saúde, University

associated with the overproduction of catecholamines. No standardised

of Porto, Porto, Portugal.

staging and malignancy designation may be withheld in the absence of

metastatic disease, though presentation, family history and proliferation rate

will influence treatment planning and follow-up.

Introduction

Both may be associated with inherited disorders such as multiple endocrine

Primary acinic cell carcinoma (ACC) is an uncommon salivary gland (SG) tumor,

neoplasia, therefore careful history taking and consideration of genetic

making up 1-3% of all SG neoplasms, more frequent in women, at 40-60 year

counselling (Table & diagram of sites, cell type and associated hormone).

old. The cause is still unknown and the only well-established risk factor is

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

ionizing radiation. ACC metastasize in 10-15% of the cases, 35% tends to recur

Conclusion

and the rate of disease-associated death is about 16%. Surgical resection is the

Malignant pheochromocytomas present clinicians with three major challenges:

mainstay treatment, but radiation therapy may be used in some cases and, more

scarcity, complexity of characterization, and heterogeneous behavior and

rarely, chemotherapy in advanced ACC.

prognosis.

Case Report

DOI: 10.1530/endoabs.49.EP195

We describe a case of a 46-year-old man referred by paresthesias, general malaise

and hypokalemia of 2.5 mEq/l. The patient had a history of pericentimetric nodule

in the left submandibular gland diagnosed 1 year before, hypertension and

dyslipidemia diagnosed 4 months before and also new-onset diabetes mellitus

(DM) diagnosed in the previous month. Ambulatory analysis showed endogenous

hypercortisolism, and he was admitted to the endocrinology department for

further investigation. Hormonal study revealed: ACTH 206.8 (!63.3) ng/l,

Neuroendocrinology

cortisol 30.1(6.2-19.4) mg/dl; cortisoluria, 24-hour salivary cortisol and low-dose

EP196

dexamethasone suppression test confirmed Cushing’s syndrome(CS); high-dose

Identification of molecular targets of Sunitinib in pancreatic

dexamethasone suppression test was compatible with ectopic CS. Initial imaging

neuroendocrine tumours

study found several hepatic nodular lesions, suggestive of secondary lesions by

Giulia Bresciani¹, Teresa Gagliano¹, Leo J Hofland², Erica Gentilin¹,

neoplastic process. Investigation was continued, with imaging and cytological

Simona Falletta¹, Eleonora Riva¹ & Maria Chiara Zatelli^1,3

documentation of probable primary parotid malignancy with hepatic metastasis.

¹Section of Endocrinology, Department of Medical Sciences, University of

Octreoscan revealed increased uptake in the parotid gland and mild expression

Ferrara, 44121 Ferrara, Italy;²Department of Internal Medicine, Erasmus

in hepatic metastasis. No uptake was observed in PET-Gallium. The patient

Medical Center, Rotterdam, The Netherlands;³Laboratorio in Rete del

underwent right parotidectomy, with the histological diagnosis of ACC,

Tecnopolo Tecnologie delle Terapie Avanzate (LTTA), University of

pT3NxR1, with no neuroendocrine differentiation, Ki67

70%. Imaging

Ferrara, 44121 Ferrara, Italy.

reevaluation revealed disease progression, with pulmonary and bone metastasis,

and the patient started chemotherapy. Meanwhile, hypercortisolism was

controlled with metyrapone (3 g/day), ketoconazole (400 mg/day) and lanreotide

(120 mg/month).

Pancreatic neuroendocrine tumours (pNETs) are rare neoplasms arising from the

Conclusion

endocrine pancreas. The fist line treatment is surgery that is often not curative in

The authors present a very rare case of ACC, with paraneoplastic CS and

the presence of metastatic disease. Therefore, there is an increasing need for

aggressive behavior, presenting significant diagnostic and management

medical therapy. Sunitinib is a multi-target receptor tyrosine-kinase

(RTK)

challenges.

inhibitor, described as having as main target VEGF receptor, with antitumor and

DOI: 10.1530/endoabs.49.EP194

antiangiogenic effects, approved for pNETs medical treatment. This study is

aimed at evaluating Sunitinib effects in the human pNET cell line, BON1, in order

to identify tissue-specific molecular targets that might predict the efficacy of the

treatment. We tested BON1

cell viability and proliferation by means of

Proliferation Assay and Luminescent Cell Viability Assay after treatment with

Sunitinib

(0.25-7.5 mM) and found an IC50Z5 mM. Western blot analysis

confirmed that BON1 cells express VEGF, IGF1 and EGF receptors, therefore we

tested the effects of VEGF 50 ng/ml, IGF1 100 nM and EGF 15 nM alone or each

in combination with Sunitinib 5 mM. We found that BON1 cell viability is not

affected by VEGF and EGF, while it is significantly enhanced by IGF1 (C20%;

EP195

P!0.05), that was capable of blocking the antiproliferative action of Sunitinib,

Malignant pheochromocytoma - a challenging diagnosis with

suggesting that the main target of this drug is IGF1 receptor. Therefore, we tested

nonconsensual management

Linsitinib, a specific IGF1 receptor inhibitor, and found that it significantly

Sofia Castro Oliveira^1,2, João Sérgio Neves^1,2, Pedro Souteiro^1,2, Eva Lau^1,2,

reduces BON1 cell viability (K25%; P!0.05) and blocks the proliferative effects

Ana Isabel Oliveira^1,2, Celestino Neves^1,2, Paula Freitas^1,2 &

of IGF-1. These data indicate that IGF1 receptor represents the main molecular

Davide Carvalho^1,3

target of Sunitinib in BON1 cells and that it may play a crucial role in pNET cell

¹Department of Endocrinology, Diabetes and Metabolism of São Jo

˜o

proliferation control, suggesting that Linsitinib might be an effective medical

Hospital Center, Porto, Portugal;²Faculty of Medicine, University of Porto,

treatment.

Porto, Portugal;³Instituto de Investiga

˜o e Inova

¸a˜o em Saúde,

DOI: 10.1530/endoabs.49.EP196

University of Porto, Porto, Portugal.

Introduction

Pheochromocytomas and extra-adrenal paragangliomas are rare neuroendocrine

tumors, with a peak incidence between the 3rd-5th decades of life and about 10%

are malignant. Although they have the same radiographic and histologic

EP197

characteristics of their benign counterpart, malignant pheochromocytomas are

Study of different in vitro systems for the evalutation of Sunitinib effects

diagnosed by the presence of local invasion or metastatic tumor in the non-

in pancreatic neuroendocrine tumour cells

chromaffin tissues, and offer a poorer prognosis. Treatment is typically extirpative

Giulia Bresciani¹, Teresa Gagliano¹, Leo J Hofland², Erica Gentilin¹,

surgery, although MIBG-radiotherapy and chemotherapy have been offered in

Simona Falletta¹, Eleonora Riva¹ & Maria Chiara Zatelli^1,3

nonsurgical cases.

¹Section of Endocrinology, Department of Medical Sciences, University of

Case Report

Ferrara, 44121 Ferrara, Italy;²Department of Internal Medicine, Erasmus

An 83-year-old man with history of diabetes mellitus and hypertension presented

Medical Center, Rotterdam, The Netherlands;³Laboratorio in Rete del

abdominal pain, anorexia and weight loss. An abdominal CT revealed a large,

Tecnopolo Tecnologie delle Terapie Avanzate (LTTA), University of

hypocaptant and heterogenous neoformative lesion of left adrenal gland, 48!

Ferrara, 44121 Ferrara, Italy.

58 mm, and adjacent metastatic adenomegaly with 18 mm. He was then referred

to our Endocrine Department. Imaging study was repeated and revealed an

additionally left renal mass, on the posterior face, exophytic, with 40!13!

38 mm, suspected for metastasis. Biochemical diagnosis of pheochromocytoma

Finding new preclinical models to study the effects of anticancer drugs is

was established by a marked increase of urinary catecholamines and fractionated

one of the aims of biomedical research. Indeed, testing different in vitro

metanephrines: norepinephrine 1222 (!97) mg/24 h, epinephrine 106 (!27)

systems can lead to a better understanding of the molecular pathways

mg/24 h and dopamine 1166 (!500) mg/24 h; normetanephrines 3711 (!390)

regulating tumor development and growth, and help to find new therapeutic

mg/24 h and metanephrines 1226 (!320) mg/24 h; vanillylmandelic acid (VMA)

approaches. This is crucial especially in the settings of pancreatic

was

29.3

(1.4-6.5) mg/24 h.

¹²³I-MIBG scintigraphy was performed and

neuroendocrine tumours (pNET), where one of the main drugs approved

evidenced left adrenal gland lesion compatible with pheochromocytoma, without

for medical treatment is Sunitinib, a multi-targeted receptor kinase inhibitor.

uptake on left renal mass. The patient started alpha-adrenergic blockade with

Clarifying the effects of this drug may be important to develop more

phenoxybenzamine (10C10 mg/day) and 6 weeks later underwent exploratory

effective medical treatment, therefore we tested Sunitinib on the human

laparotomy surgery, with left adrenalectomy and nefrectomy. Histological

pNET cell line, BON1, grown in two different in vitro systems, monolayer

examination confirmed malignant pheochromocytoma diagnosis and the patient

and spheroid, in order to understand the different effects of the drug in 2D

maintains close surveillance.

and 3D settings.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

BON1 cells were grown in monolayer and treated with Sunitinib at increasing

¹Department of Endocrinology, Asaf Harofe Medical Center, Zeriffin,

concentrations

(0.25-5 mM). Cell Proliferation Assay and Luminescent

Israel;²Department of Oncology, Asaf Harofe Medical Center, Zeriffin,

Cell Viability Assay were employed to test Sunitinib antiproliferative effects.

Israel;³Department of Gastroenterology, Asaf Harofe Medical Center,

We found that Sunitinib 5 mM significantly reduced BON1 cell viability by

Zeriffin, Israel;⁴Department of Surgery, Asaf Harofe Medical Center,

30% (P!0.01 vs control) after

days. Similarly, Sunitinib

5 mM

Zeriffin, Israel;⁵Department of Pathology, Asaf Harofe Medical Center,

significantly reduced BON1 cell proliferation by 50% (P!0.05 vs control)

Zeriffin, Israel;⁶Sackler School of Medicine, Tel Aviv University,

after 3 days and by 90% (P!0.05 vs control) after 7 days.

Tel Aviv, Israel.

Then, BON1 cells were grown in spheroids with Sunitinib at increasing

concentrations

(0.25-5 mM). Spheroids size was analyzed with ImageJ

Introduction

software after 3 and 7 days. We found that Sunitinib does not affect spheroid

GEP-NETs incidence increased markedly over the past decades probably due to

size, but induces spheroid disgregation after 7 days of treatment at 5 mM.

increased imaging. GEP-NETs are generally indolent but often have unpredict-

These results indicate that measuring spheroid diameter in a 3D system is not

able biological behavior and aggressive clinical course.

the optimal system to assess the antiproliferative effects of Sunitinib on

Aims

BON1 cells. On the other hand, the differences observed between the

To collect information regarding demographics, presentation, pathology

employed models could reflect the variations in drug response depending on

characteristics, treatment and outcome of GEP-NETs.

cell aggregation state.

Methods

DOI: 10.1530/endoabs.49.EP197

Following approval of our institutional ethical board, pathology and clinical

records of all GEP-NETs patients diagnosed and treated at our institution during

2005-2015 were reviewed.

Results

We identified 110 patients with GEP-NETs distributed by site as pancreatic 32

EP198

(FZ45.1%, age 61.2G6.8), gastric 19 (FZ50%, age 66.2G11), duodenum 9

(FZ33.3%, age 66.3G12), small bowel 13 (FZ25%, age 60G12), appendix 34

Von Hippel-Lindau syndrome: in vivo portrait with 68Ga-DOTANOC

(FZ55.8%, age 36G19) and colorectal 3. The pNETs presented with abdominal

PET-CT

pain

(45.1%) incidentally

(25.8%) or syndromatic

(21.8%); including two

Ana Paula Moreira^1,2, Gracinda Costa^1,3 & João Pedroso de Lima^1,2

insulinomas, one gastrinoma and four MEN1 patients. Mean size was 31G23 mm

¹Centro Hospitalar e Universitário de Coimbra (Nuclear Medicine

Department), Coimbra, Portugal;²Instituto de Ciências Nucleares Aplicadas

and grading was G1 39.2, G2 42.8, G3 17.8%. Distant metastases (DM) were seen

à Saúde - Universidade de Coimbra (ICNAS-UC), Coimbra, Portugal;

in five patients (M1Z3). Surgery was performed in 61.3%, additional treatment

³Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.

given to 32.2% (re-op, somatostatin analogue, TKI, chemotherapy). The gNETs

presented mostly during work-up for anemia or GI bleeding (70.6%). Mean size

was 15 mm and the majority (82.3%) were GCT1 and there were no DM. The

Introduction

dNETs presented with anemia (43%), abdominal pain (43%) or incidentally.

Von Hippel-Lindau syndrome (VHL) is an autosomal dominantly inherited

None was syndromatic. Mean size was 11.2 mm, 50% were G1, and 2 had DM at

neoplastic disorder with marked phenotypic variability, characterized by a broad

presentation. Surgery was performed in 33.3% patients. The sbNETs presented

spectrum of clinical manifestations in central nervous system (CNS) and viscera.

with bowel obstruction (27%), abdominal pain (36%) or incidentally. None were

Specific gene mutation can be demonstrated; however imaging plays an important

syndromatic. Only 15% were G1, 6 had DM (M1Z5), and 77% had surgery.

role in diagnosis. 68Ga-labelled somatostatin analog (68Ga-DOTANOC) PET-

Excluding aNETs, the overall mortality at last visit was 23.7% (7.9% disease

CT is routinely employed for somatostatin receptor (SSTR) imaging, mainly for

related) at mean follow-up of 34.5 months.

neuroendocrine tumors evaluation, but could be an optimal whole body imaging

Conclusion

method for screening and follow-up VHL patients.

GEP-NETs are associated with significant morbidity and mortality. The primary

Purpose

site of the tumor has clinical implication for disease management.

To present 68Ga-DOTANOC-PET-CT findings in three VHL female patients (58,

DOI: 10.1530/endoabs.49.EP199

58 and 65 years old), demonstrating both CNS and visceral tumors.

Material and Methods

68Ga-DOTANOC-PET/CT scan was acquired 45 min after intravenous admin-

istration of 100-200MBq 68Ga-DOTANOC in three patients with VHL referred

for pancreatic neuroendocrine tumor (PNET) evaluation. Abnormal findings were

correlated with histopathology or other imaging modalities

(CT, MR,

ophthalmoscopy).

Results

68Ga-DOTANOC-PET/CT showed, in all patients, other lesions than PNET,

EP200

which proved to be related to VHL. Retinal and spinal cord hemangioblastomas

Insulinoma: diagnostic features and treatment management

were detected in two patients. Endolymphatic sac tumor was demonstrated in one.

Liana Khacimova¹, Tatiana Karonova^1,2, Uliana Tsoy¹, Liubov Ianevskaia¹

Lung hemangioblastoma was suspected in one. Liver and lymph node metastasis

& Elena Grineva^1,2

were present in one patient. Two patients had a pheocromocytoma previously

¹Federal Almazov North-West Medical Research Centre, Saint-Petersburg,

removed by surgery.

Russia;²Pavlov First Saint Petersburg State Medical University,

Discussion

Saint-Petersburg, Russia.

In VHL diagnosis a multidisciplinary approach is mandatory. Although genetic

testing is available, imaging plays a key role in the identification of abnormalities,

Backgraund

their follow-up and in the screening of asymptomatic gene carriers. Several

Insulinoma is the most common functional pancreatic neuroendocrine tumor

analytic and imaging modalities are needed for diagnosis and follow-up.

originating from b-cells, with unregulated insulin production and rarely

Screening is essential because the lesions in VHL disease are treatable. Early

associated with MEN-I syndrome. Diagnosis and treatment of insulinoma are a

detection enables more conservative therapy and may enhance the patient’s length

challenge in the practice of endocrinologist.

and quality of life. In these three VHL patients, 68Ga-DOTANOC-PET-CT has

Aim

demonstrated to be a promising whole-body screening high-resolution imaging

To determine on the basis of retrospective analysis the optimal approaches to the

method for evaluation of the entire picture of this disease.

management of patients with organic hyperinsulinism.

DOI: 10.1530/endoabs.49.EP198

Materials and methods

Medical records of 72 patients admitted with suspected organic hyperinsulinism

had been screened and medical histories of patients with a confirmed diagnosis of

organic hyperinsulinism were included into the analysis. Anamnesis, results of

objective, laboratory and instrumental examinations, methods and results of the

EP199

treatment were analyzed.

Results

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs):

The diagnosis of insulinoma was confirmed in thirty two cases. Hypoglycemia

clinico-pathological characteristics and disease outcome of 110 patients

treated at single referral medical center

was achieved within the first 48 h after the start of the 72-h fasting test in 100% of

Shlomit Koren¹, Karen Or¹, Miri Steinschneider¹, Esther Kummer¹,

cases. Study results showed that in 50% of cases the size of the pancreatic

Nirit Yarom^2,6, Haim Shirin^3,6, Ron Lavy⁴, Gratiana Gratiana^5,6 &

neoplasm was more than 1.4 cm. Inverse correlation between tumor size and

Carlos Benbassat^1,6

plasma glucose concentration at the time of hypoglycemia was found (rZK0.45,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

PZ0.02). Surgical treatment was carried out in thirty out of 32 patients. Surgical

Case report

enucleation of insulinoma was performed in 12 (40%) cases, distal pancrea-

A 59-year-old woman presented with a 3-month history of episodic hypotension,

tectomy - in 18(60%). Insulinoma was confirmed in 27 cases, while in three

tachycardia and face and upper trunk flushes. She had a history of cecum tumor

patients diagnosis of non-insulinoma pancreatogenous hypoglycemia (‘nesidio-

resection 18 years ago. It was a poorly differentiated mixed adenoneuroendocrine

blastosis’) was established according to histological findings. Positive clinical

carcinoma. The tumor extended in the pericolic adipose tissue with perineural and

result was achieved after all surgeries. In postoperative period patients were

lymphonodular invasion. It was TNM stage IIIB (T3N1M0). Postoperatively, she

discharged within 11-30 days. Patients without post-operative complications

received interferon and 5-fluoracil chemotherapy for 6 months.

were discharged 13.0G1.4 days after surgery. Twelve (40%) patients developed

The patient was asymptomatic for 18 years until symptoms of carcinoid syndrome

post-operative complications. The duration of hospital stay in these cases was

(CS) appeared. Serum chromogranin A and 24-h urine 5-hydroxy-indole-acetic-

significantly longer 20.1G1.9 (P!0.01).

acid (5-HIAA) were abnormally high. An abdominal magnetic resonance imaging

Conclusions

revealed multiple metastatic liver lesions confirmed by biopsy. In111-

Obtained data confirmed that comprehensive approach including 72-h fasting test,

pentetreotide scintigraphy detected the lesions in the liver and others in the left

use of modern imaging techniques and application of high-tech treatment

shoulder and the right sternum-clavicle joint. Bone lesions were also

methods, is crucial for successful diagnosis and treatment of insulinoma.

demonstrated by Tc-99m DTP scan. Octreotide LAR 30 mg per month was

DOI: 10.1530/endoabs.49.EP200

initiated and resulted in amelioration of symptoms. Chromogranin A and 5-HIAA

decreased but remained above normal range. The symptoms of CS reappeared

after 2 years and the patient received 9 cycles of targeted radiotherapy (177Lu-

Dotatate), which finally resulted in clinical and imaging improvement.

Conclusion

We report a rare case of a patient with a mixed adenoneuroendocrine carcinoma

of the cecum who presented with metastatic disease and carcinoid syndrome 18

years postoperatively. Due to the rarity of these tumours and the unknown natural

EP201

history, lifelong follow up is required.

A rare case: non-islet cell tumor hypoglycemia with adrenal

DOI: 10.1530/endoabs.49.EP202

insufficiency

Veysi Asoglu¹, Mehmet Celik², Buket Yilmaz Bulbul², Semra Ayturk²,

Funda Ustun³ & Sibel Guldiken²

¹Department of Internal Medicine, Medical Faculty, Trakya University,

Edirne, Turkey;²Department of Endocrinology and Metabolism, Medical

Faculty, Trakya University, Edirne, Turkey;³Department of Nuclear

Medicine, Medical Faculty, Trakya University, Edirne, Turkey.

Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome

and is the second most common cause of tumor-related hypoglycemia following

EP203

insulinoma. Its prevalence is not known and is likely that many cases would go

undiagnosed. In here, we describe a patient with PNET who presented with severe

Quality of life in patients with neuroendocrine tumors treated with

hypoglycemia.

177Lu-[DOTA⁰,Tyr³]-octreotate: a Single Tertiary Care Portuguese

A 37-year-old male with known metastatic Pancreatic neuroendocrine tumors

Center Experience

(PNET) presented with weight loss, sweating, and tremor, episodic altered

Adriana Lages, Helder Moreira, Gracinda Costa, Patrícia Oliveira,

sensorium. He had documented blood glucose values below 35 mg/dl during

Diana Oliveira, Diana Martins, Mara Ventura, Nelson Cunha &

those episodes. He received two cycles of lutetium therapy and was referred to our

Francisco Carrilho

institute. At blood glucose of 33 mg/dl, he had undetectable plasma insulin

Coimbra Hospital and University Center, Coimbra, Portugal.

(%0.19 mU/l), low C-peptide 0.159 ng/ml (normal: 0.8-4), cortisol: 5.6 mg/dl

(n:5-29), GH: !0.05 ng/ml and low IGF1 !25 ng/ml (normal: 109-284 ng/ml).

Introduction and purpose

ACTH: 60 pg/ml (normal:

0-46), Na:

136 mmol/l

(normal:

132-146), K:

177Lu-[DOTA⁰,Tyr³]octreotate (177Lu-DOTA-TATE) is a radiopharmaceutical

4.2 mmol/l (normal:3.5-5.5), TSH 1.274 uIU/ml (n: 0.35-4.94), FT₄: 1.47 ng/dl

frequently used in peptide receptor radionuclide therapy (PRRT), which is a

(n:0.7-1.48), FT₃: 2.6 pg/ml (n: 1.71-3.81), prolactin: 8.28 ng/ml (n:2.1-17.7),

promising treatment modality in patients with metastasized neuroendocrine

LH: 5.08 IU/l (1.5-9.3), FSH: 10.22 IU/l (n:1.4-18.1), testosterone: 405.78 ng/dl

tumors (NETs). We purpose to evaluate the quality of life (QoL) in patients with

(n:241-2270). Magnetic resonance imaging of pituitary gland was normal. We

somatostatin receptor positive inoperable or metastatic NETs throughout the three

were started prednisolone 30 mg/day with which his symptoms abated. After

cycle’s (with three months intervals) protocol used in our hospital.

prednisolone treatment, there was no recurrence of hypoglycemia on follow-up.

Patients and methods

In NICTH patients, the serum levels of insulin, C-peptide, and IGF1 are usually

We included 24 patients, 16 men and 8 women (age: meanZ67 years; rangeZ

decreased or undetectable; however, the circulating level of total IGF2

29-81). The majority (13/24 cases; 54.2%) were gastroenteropancreatic NETs.

determined by conventional immunometric or receptor assays may be increased,

Patients were treated with a mean cumulative 177Lu-DOTA-TATE activity of

decreased, or normal. In the absence of IGF2 assays, low serum insulin in

614 mCi (range: 303-1177 mCi).

combination with low IGF1 levels at the time of hypoglycemia is a strong

Patients were invited to self-report QoL during PRRT cycles. We analyzed the

biochemical evidence of NICTH. High-dose glucocorticoid therapy has

overall QoL and specific domains of QoL according to the Organization for the

immediate beneficial effect on symptomatic hypoglycemia.

Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC

DOI: 10.1530/endoabs.49.EP201

QLQ-C30) scoring manual.

Results

From 24 patients, 15 completed at least 2 copies of the EORTC QLQ-C30 at

different time-points (during the 1st or 2nd cycle and during the 3rd). Twelve

patients had progressive disease, eleven had stable disease and one had notable

lesions regression during PRRT.

Regardless the treatment outcome, Global Health Status/QoL (GHS/QoL) and all

EP202

the functional scales (except social status) improved significantly in all group

Late manifestation of a mixed adenoneuroendocrine carcinoma of the

(P!0.05). On GHS/QoL, we found an improvement on scores superior to 10

cecum

points before vs after therapy (DC10.56; PZ0.003).

Paraskevi Kazakou, Xakousti Tzamali, Alexis Travlos, Evangelia Vogiatzi,

Besides GHS and functional scales, we observed also a favorable impact on

Georgia Ntali, Vasiliki Sarantopoulou & Antonis Polymeris

disease-related symptoms as fatigue

(PZ0.00003), insomnia

(PZ0.0003),

Department of Endocrinology, Alexandra General Hospital, Athens, Greece.

appetite loss (PZ0.0003), constipation (PZ0.033) and diarrhea (PZ0.014).

Conclusions

Introduction

A better health-related QoL in cancer patients with incurable disease is an

Mixed adenoneuroendocrine carcinoma

(MANEC) is a rare tumor of the

important outcome of cancer therapy, especially when survival is prolonged.

gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendo-

Therapy with 177Lu-DOTA-TATE significantly improved QoL regarding to

crine differentiation. The clinical behavior seems to be influenced by the

several functions and had favorable impact on global health status even on those

neuroendocrine component. We report a patient with mixed adenoneuroendocrine

with progressive disease.

carcinoma of cecum who presented 18 years after her initial diagnosis and

DOI: 10.1530/endoabs.49.EP202

treatment.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP204

whereas the frequency of heterozygous (DN) was 0 in patients and 0.15 in

controls. The frequency of allele D was 0 in patients and 0.075 in controls. The

Triple tumors in a patient with insulinoma

frequency of allele N was 1 and 0.925 in patients and controls respectively.

Urska Ksela & Mitja Krajnc

UKC Maribor, Maribor, Slovenia.

DOI: 10.1530/endoabs.49.EP205

Introduction

Hypoglycemia is a rare clinical problem in patients not being treated for diabetes

mellitus and requires further evaluation and management if Whipple’s triad is

present. Insulinoma commonly presents with fasting hypoglycemia. Insulinoma is

rarely associated with type 1 multiple endocrine neoplasia, when tumors are

usually multiple and more frequently malignant. The diagnosis of insulinoma is

established by demonstrating inappropriately high serum insulin concentrations

during a spontaneous or induced episode of hypoglycemia, e.g. 72-h fast.

EP206

Patient

Congenital adrenal hyperplasia: impact of therapy on growth and

46-years old female was referred to our department for evaluation of spontaneous

sexual maturation - a 5-year retrospective study of a Tertiary Pediatric

fasting hypoglycemia. She had multiple episodes of temporary probably

Endocrinology Center

neurohypoglycemic symptoms (confusion, unusual behaviour) and gained a lot

Camelia Procopiuc, Madalina Vintila, Iuliana Gherlan, Amel Cirla,

of weight in 2016 (C20 kg). Before the beginning of 72-h fast her serum glucose

Andreea Brehar, Andra Caragheorgheopol, Suzana Vladoiu Oana Popa &

was

1.8 mmol/l, insulin concentration

20.6 mcU/ml, C-peptide

1.2 nmol/l.

Cristina Dumitrescu

Testing was stopped after 6 h due to very low glucose levels (1.5 mmol/l) but

CI Parhon National Institute of Endocrinology, Bucharest, Romania.

without any obvious symptoms of hypoglycemia, insulin was high. After

glucagone 1 mg i.v. glucose increased for 1.5 mmol/l. Her serum calcium, iPTH,

prolactin and IGF-1 were normal. CT showed 1.8 cm lesion in the pancreatic neck

Objective

and also unusual lesion in proximal jejunum that appeared to be a neuroendocrine

To evaluate the comparative effects of different glucocorticoid treatments on

tumor. There was also typical teratoma in left ovary (maximal size 6.6 cm), also

growth and sexual maturation in patients with congenital adrenal hyperplasia.

seen on US. The patient underwent operation - partial pancreatectomy, proximal

Patients and methods

jejunal resection with anastomosis and left ovariectomy. Based on patohistology

We conducted a retrospective observational cohort study in 78 patients (60 girls,

and imaging results benign insulinoma was confirmed, in jejunum there was

18 boys) diagnosed with congenital adrenal hyperplasia (CAH), followed-up for a

ectopic pancreatic tissue, and there was mature teratoma of left ovary. We have

period of 5 years. The majority had 21-hydroxylase deficiency (75 patients), 2 had

not performed genetic testing for MEN1 since we thought it was unlikely. After

11-b hydroxylase deficiency and 1 patient had 3-b hydroxysteroid dehydrogenase

operation, the patient was asymptomatic and normoglycemic.

deficiency. Patients received either Prednisone (PDN), Hydrocortisone (HC) or

Conclusions

Hydrocortisone plus Dexamethasone (DEX). Data on growth, bone maturation,

We found three different tumors, including insulinoma, in a single patient. This

puberty onset, predicted adult height, and parental height were collected. Height

combination has not yet been described to coincide and is not due to multiple

gain was calculated as the difference between parentally determined target height

endocrine neoplasia.

and final or predicted height at the last evaluation.

Results

DOI: 10.1530/endoabs.49.EP204

Height gain with therapy was 0.42 S.D. over the initial estimated height deficit.

Height gain correlated with the clinical form of CAH, with better outcome in non-

classical vs classic forms (P!0.01). There were no significantly differences

between groups in regard to type of therapy (PZ0.164). There was no difference

in change of body mass index regarding the type of treatment (PZ0.99). Girls

Paediatric Endocrinology

over 12 years of age treated with HC had higher rates of spontaneous menarche

versus PDN treated girls (PZ0.006). Twelve children developed precocious

EP205

puberty, which correlated with older age at treatment initiation (PZ0.048).

An analysis of R356W and Q318X mutations and 8 bp deletion in

Conclusions

21-hydroxylase gene CYP21A2 in causing pseudo-precocious puberty in

The type of therapy did not influenced height gain. HC facilitated spontaneous

patients with congenital adrenal hyperplasia in Pakistani children

menarche onset in normal age range. Late diagnosis and therapy led to higher

Nadiaj Parveen¹, Samar Minallah¹, Muhammad Ismail², Qaiser Mansoor²,

rates of precocious puberty in children with CAH.

Maleeha Akram¹, Zubaria Iqbal¹, Sarwat Jahan³, Kiran Afshan³,

DOI: 10.1530/endoabs.49.EP206

Gulbin Shahid⁴, Faheem Tahir⁵, Afzaal Ahmed Naseem¹, Mazhar Qayyum¹

& Syed Shakeel Raza Rizvi¹

¹Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University

Rawalpindi, Rawalpindi, Punjab, Pakistan;²Institute of Biomedical and

Genetic Engineering (IBGE), Islamabad, Pakistan;³Department of Animal

Sciences, Quaid-e-Azam University, Islamabad, Pakistan;⁴The Children’s

Hospital, Pakistan Institute of Medical Sciences (PIMS), Islamabad,

Pakistan;⁵Reproductive Physiology, Public Health Laboratories Division,

National Institute of Health, Islamabad, Pakistan.

Pituitary - Clinical

The first signs of puberty are visible around the age of 8 years in girls and 9 years

EP207

in boys. If signs of puberty appear before the designated ages in girls and boys,

The risk of hypotension, evaluated by ambulatory blood pressure

puberty is viewed as precocious. In peripheral precocious puberty, androgens

monitoring, during fasting and outside fasting in patients with adrenal

concentrations increase due to testicular tumours or congenital adrenal

insufficiency

hyperplasia (CAH). Two mutations, R356W and Q318X, and one 8 bp deletion

Melika Chihaoui¹, Wafa Grira¹, Meriem Yazidi¹, Ons Rejeb¹,

in CYP21A2 gene, causing CAH type of precocious puberty were examined.

Fatma Chaker¹, Ibtissem Oueslati¹, Jihane Bettaieb² & Hedia Slimane¹

Blood samples were obtained from 42 CAH patients (30 boys and 12 girls)

¹Department of Endocrinology, Faculty of Medicine of Tunis, La Rabta

exhibiting higher 17-OH progesterone concentrations and 42 normal healthy

Hospital, University of Tunis El Manar, Tunis, Tunisia;²Department of

controls. DNA was extracted, primers of exons of CYP21A2 splice sites were

Medical Epidemiology, Faculty of Medicine of Tunis, Pasteur Institute of

designed and PCR-RFLP method was employed. The PCR product of CYP21A2

Tunis, University of Tunis El Manar, Tunis, Tunisia.

digested by enzyme Fnu4HI for R356W mutation gave bands of AA (w106, 110,

229 and 37 bp). The frequency of this genotype was 100% in both groups

indicating absence of R356W mutation in both groups. For Q318X, the restriction

The risk of hypotension during Ramadan fasting in patients with adrenal

enzyme, PstI gave bands of 3 different genotypes, GG (161 and 329 bp segments)

insufficiency is unknown. The aim of our study was to evaluate objectively this

18 patients, GC (490, 329 and 161 bp segments) in 21 patients and CC

risk.

(segment of 490 bp) in 3 patients (2 boys and 1 girl). For 8 bp deletion, PCR

Methods

amplification with allele specific primers yielded a segment of w710 bp; 8 bp

It is a prospective case-crossover study on 28 patients with known and treated AI.

deletion was not found in any patient but 3 control subjects were heterozygous for

Patients had no hypertension and were regular fasters. All patients underwent a

it. The frequency of homozygous wild type (NN) was 1 in patients and 0.85 in

clinical examination and a 24-hours blood pressure monitoring during Ramadan

controls; the frequency of homozygous mutants (DD) was 0 in both groups,

fasting then outside fasting.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

This clearly demonstrates the key role of

11b-hydroxylase being the most

There were 23 women. The mean age was 37G14 years. It was a central adrenal

influenced enzyme by the adrenocortical axis suppression.

insufficiency in 26 patients. The mean duration of the disease was 9G8 years. The

DOI: 10.1530/endoabs.49.EP208

mean daily dose of hydrocortisone was

19G3 mg. Systolic hypotension

(!90 mmHg) did not occur during fasting and occurred in two cases outside

fasting. Diastolic hypotension (!60 mmHg) occurred in 12 cases during fasting

and in 13 cases outside fasting without a significant difference. All cases of

hypotension were asymptomatic. The levels of systolic and diastolic blood

pressure during the 24 h and during the fasting period (from pre dawn to sunset)

did not significantly differ between the fasting day and the non-fasting day.

Thyroid Cancer

Conclusion

EP209

Blood pressure levels during fasting were comparable to those outside fasting and

there was not an increased risk of hypotension during fasting.

Clinical relevance of RET proto-oncogene variants L769L and S836S

(exon 11, 13, 14, and 15) in patients with sporadic medullary thyroid

DOI: 10.1530/endoabs.49.EP207

carcinoma

Darko Katalinic¹, Miljenko Solter² & Nora Nikolac²

Department of Internal Medicine, Faculty of Medicine, J.J. Strossmayer

University of Osijek, Osijek, Croatia;²Faculty of Medicine, UHC Sisters of

Charity, University of Zagreb, Zagreb, Croatia.

Steroid Metabolism C Action

Background

Medullary thyroid cancer (MTC) makes up to 5-10% of all cases of thyroid

EP208

malignancies. The clinical course of MTC varies from an extremely indolent

Steroid metabolome changes in the 1 mg dexamethasone

tumour to an aggressive variant that is associated with a high mortality rate. RET

suppression test

proto-oncogene germline mutations are crucial for the onset and the progression

Václav Hána jr¹, Mikuláš Kosák¹, Václav Hána¹ & Martin Hill²

of MTC. The aim of this study was to evaluate the L769L (subgroup L) and S836S

¹3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles

(subgroup S) allele frequencies in patients with sporadic MTC (group A, nZ89)

University and General Teaching Hospital, Prague, Czech Republic;

compared to healthy subjects

(group B, nZ83) and to determine if these

²Institute of Endocrinology, Prague, Czech Republic.

polymorphisms have influence the clinical presentation and the course of MTC.

Methods

A non-isotopic polymerase chain reaction based single strand confirmation

Introduction

polymorphism analysis and heteroduplex gel electrophoresis method was used

Dexamethasone induced negative feedback on CRH, ACTH and cortisol secretion

to screen tumour DNA extracted from 89 formaldehyde fixed and paraffin

is one of the key principles in the diagnostic workup of hypercortisolism. Cortisol

embedded MTC specimens. We also analysed relevant clinical data in the group

secretion has been studied extensively, but changes of other steroids remained

of patients with MTC. The study was conducted according to the Declaration of

apart. Our aim was to establish steroid profile changes in 1 mg dexamethasone

Helsinki, the protocol was reviewed and approved by the institutional

test.

independent ethics committee. All patients were provided with written informed

Methods

consent.

The Steroid profile consisting of 103 steroids and their metabolites from the

Results

serum of 9 male and 8 healthy female controls was measured before and in the

Mean age was 51.6G9.2 years for the patients with MTC (range, 42.4-60.8) vs

morning at 0800 hours after 1 mg dexamethasone administered at 1100 hours.

45.4G7.1 (range

38.3-52.5) for the group of healthy subjects. The allele

Samples were analyzed using GCMS/MS for the measurement of most of the

frequencies showed a similar level of the L769L and S836S variants in both

steroids. Only a few were measured by RIA.

subgroups of examinees (group L, 52.5% vs group S, 47.5%; PO0.001). Lymph

Results

node metastases were found in all patients with MTC (subgroup L, nZ42 vs

Dexamethasone administration suppressed the most the levels of corticosterone

subgroup S, nZ47; PO0.001), and distant metastases in nine patients (subgroup

(29!), cortisol (20!), 11-OH-androstenedione (12!), 11b-Hydroxy-androster-

L, nZ5 vs subgroup S, nZ4; PO0.001). Postoperatively, 52% of patients in

one (13!), 11b-Hydroxy-etiocholanolone (13!), 11b-Hydroxy-epiandrosterone

subgroup L vs 55% of patients in subgroup S were biochemically cure (PO0.001).

(6!),

17-Hydroxypregnenolone

(5!). Other steroids like DHEA

(3!),

In the subgroup L, pT-category was: T0, nZ23; T1, nZ14; and T2, nZ5. In the

Androstenedione (2!), Pregnenolone (2!) were suppressed at much lower

subgroup S, pT-category was: T0, nZ21; T1, nZ16; and T2, nZ10.

rate than their 11b-hydroxylated metabolites. As expected, none of the measured

Conclusion

steroids increased after dexamethasone.

We did not find any statistically significant difference in representation of the

Conclusions

L769L and S836S gene variants. The RET L769L and S836S (exon 11, 13, 14,

Inhibition of ACTH secretion leads to a strong suppression of the whole adrenal

and 15) gene variants are not contributing factor in the development of sporadic

steroidogenesis including androgen production.

MTC and are not promoting factor for development of metastatic MTC.

The most prominent changes were observed in corticosterone, cortisol, and

interestingly 11-OH-androstenedione and their 5-b/a-reduced metabolites, which

DOI: 10.1530/endoabs.49.EP209

all decrease more than 10 times in comparison with the basal levels.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Bone & Osteoporosis

(Orx C CT; 100 IU/kg b.w.) every second day for 6 weeks. The rats from SO and

second Orx group received the same volume of vehicle alone by the same

EP210

schedule. The peroxidase-antiperoxidase method was applied for localization of

CT in C-cells. CT-immunopositive thyroid C-cells, thyroid follicular epithelium,

interstitium and colloid were evaluated morphometrically. An ImageJ public

Abstract withdrawn.

domain image processing program was used to measure bone histomorphometric

parameters of the proximal tibial specimens. Blood serum samples were analyzed

for CT, osteocalcin (OC) and thyroxine (T₄), and urine samples fot calcium

(Ca^2C) concentration. We found a significant decrease in the Vc and Vv of

thyroid C-cells after CT treatment compared to both SO and Orx. The Vv of the

colloid was higher, while V_V of the follicular epithelium was lower after CT

treatment compared to Orx. Analysis of trabecular microarchitecture showed that

salmon CT administration significantly increases of cancellous bone area (B.Ar),

trabecular thickness (Tb.Th), and trabecular number (Tb.N) whereas trabecular

separation (Tb.Sp) was significantly decreased. CT treatment markedly elevated

serum CT, but serum OC, T₄ and urinary Ca^2C concentrations were lower than in

the Orx group. These findings indicate that administration of salmon CT inhibited

EP211

calcitonin-producing thyroid C-cells and changes the structure of the thyroid

gland indicating hypoactivity.

Bisphosphonate related osteonecrosis of the jaw: risk factors: a case

report

DOI: 10.1530/endoabs.49.EP212

Pablo Young, Natalia Elias, Noelia Rella, Marcela Moran & Marina Curria

British Hospital, Buenos Aires, Argentina.

Introduction

Bisphosphonates

(BP) have been employed for many years and have

demonstrated an excellent safety profile. Nevertheless, severe osteonecrosis of

the jaw (ONJ) have been described in patients with bone metastases that were

treated with BP for many years.

EP213

Case

Primary hyperparathyroidism: hormonal profile and risk of

A 72 year old female with breast cancer and bone metastases treated with

complications

quadrantectomy, axillary lymph node dissection, radiotherapy, tamoxifen and

Alina-Andreea Gatu¹, Cristian Velicescu^1,2, Cristina Preda^1,2,

pamidronate 90 mg/month. Two years later, the patient suffered from pain in the

Voichita Mogos^1,2, Carmen Vulpoi^1,2, Simona Mogos^1,2, Valentin Zaharia²,

right body of the jaw one month after the extraction of low dental pieces. She had

Adrian Aancute² & Dumitru Branisteanu^1,2

an extended intraoral ulcer, which leaved exposed part of the body of the jaw and

¹Gr. T Popa University of Medicine and Pharmacy, Iasi, Romania;

loss of dental pieces. The patient had not received radiotherapy in the jaw. X ray

²St. Spiridon Emergency Hospital, Iasi, Romania.

revealed osteolysis and CT scan showed lesions in bone and soft parts of the jaw.

Biopsy confirmed necrosis. Irrigation with chlorhexidine gluconate 0,12% and

extraction of dental pieces were performed. In spite of the conservative treatment,

Background

she presented severe pain and suppuration. The right side of the jaw was removed.

Vitamin D deficiency is frequently associated with primary hyperparathyroidism,

Pamidronate treatment was discontinued. The patient had cancer progression and

but the impact of this association on disease evolution and complications is ill

died some months later.

defined. Aims: to assess the role of vitamin D status on the metabolic profile and

Conclusion

spectrum of complications at patients with primary hyperparathyroidism.

The aim of this presentation is to emphasize the importance of taking into account

Materials and methods

the risk factors of ONJ at the moment of performing an invasive procedure. The

Transversal study involving

patients with primary hyperparathyroidism

estimated incidence of ONJ in patients with malignancy who receive BP seems to

submitted to parathyroidectomy. We evaluated serum calcium, phosphate, serum

range between 1 and 10%. The risk factors of ONJ are related to BP, local,

PTH and 25OHD3, bone mineral density by DXA (Hologic) and anamnestic

systemic and demographic factors. The use of less traumatic techniques available

episodes of bone fractures and kidney lithiasis. Fifteen patients had episodes of

and adequate antibiotic treatment is mandatory in the presence of risk factors of

kidney lithiasis, whereas 27 patients did not develop this complication. Twenty

ONJ. BP treatment should be interrupted after surgery until the wound is fully

patients were diagnosed with osteoporosis whereas 22 patients had bone mass in

healed.

the range of normal or osteopenia. Data between groups were compared using the

DOI: 10.1530/endoabs.49.EP211

t test and were considered significant at P values ! 0.05.

Results

Twenty-nine of the 42 patients had 25OHD3 in the range of deficiency (lower

than 20 ng/ml) and 20 had severe 25OHD3 deficiency (lower than 10 ng/ml).

Serum calcium and phosphate were similar irrespective of the presence or absence

of complications. No differences were found between mean PTH and 25OHD3

levels of patients with or without osteoporosis. Patients with kidney lithiasis had,

however, higher PTH (390C/K 90 pg/ml vs 209C/K 64 pg/ml, P!0.001) and

lower 25OHD3 levels (12.8C/K 6 ng/ml vs 19.2C/K 7.8 ng/ml, P!0.05) than

patients without kidney lithiasis.

EP212

Conclusions

D hypovitaminosis accompanies frequently primary hyperparathyroidism.

Salmon calcitonin affects thyroid endocrine cells and trabecular bone in

Patients with higher risk of kidney lithiasis seem to have higher PTH and lower

a rat model of male osteoporosis

25OHD3 levels.

Branko Filipović¹, Branka

ˇ oši

´-Jurjevi

´¹, Jasmina

ˇivanović1,

Milica Manojlovi

´-Stojanoski¹, Nataša Nestorovi

´¹, Svetlana Trifunovi

´¹,

DOI: 10.1530/endoabs.49.EP213

Ivana Jarić¹, Gordana Ušćebrka² & Verica Miloševi

´¹

¹Institute for Biological Research “Siniša Stankovic´”, University of

Belgrade, Belgrade, Serbia;²Faculty of Agriculture, University of Novi Sad,

Novi Sad, Serbia.

Calcitonin (CT) is a hypocalcemic hormone produced by thyroid C-cells that acts

as an bone antiresorptive agent. The other endocrine cell population in thyroid,

called follicular cells produce thyroid hormones (TH) which also affect bone

EP214

turnover. In this study, we evaluated the effects of salmon CT administration on

structure and function of both CT and TH producing thyroid cells as well as

Efficacy and safety of bisphosphonate discontinuation in

trabecular bone microarchitecture in orchidectomized (Orx) middle-aged rats.

postmenopausal osteoporosis: a systematic review

Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One

Panagiotis Anagnostis¹, Stavroula Paschou¹, Gesthimani Mintziori¹,

group of Orx animals were injected subcutaneously with synthetic salmon CT

Irene Lambrinoudaki² & Dimitrios Goulis¹

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Unit of Reproductive Endocrinology, First Department of Obstetrics and

but not indicated in osteopetrosis. Our approach was to treat her with activ vit.D

Gynecology, Medical School, Aristotle University of Thessaloniki,

products since her actual fracture risk was not cinsidered increased.

Thessaloniki, Greece;²Second Department of Obstetrics and Gynecology,

DOI: 10.1530/endoabs.49.EP215

National and Kapodistrian University of Athens, Athens, Greece.

Introduction

The maximum period of bisphosphonate use has not been determined, as their

long-term appliance has been associated with adverse effects, such as

osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF).

The aim of this study was to systematically present existent data regarding the effect

of bisphosphonate discontinuation on fracture risk and bone mineral density (BMD).

Methods/design

MEDLINE, Scopus, EMBASE and Cochrane databases were searched (up to

December 2016) for randomized placebo-controlled trials.

EP216

Results

Osteonecrosis of the jaw and bilateral atypical femoral fracture both

Regarding alendronate, five studies fulfilled eligibility criteria (“drug holiday”:

occurring during treatment of osteoporosis

two-five years). Extending alendronate

(5-10 mg/d) use to five years, after

Edelissa Payumo, Thelma Crisostomo & Ivan Cudal

continuous treatment for five years, reduced clinical vertebral fracture risk by 55%,

Makati Medical Center, Makati, The Philippines.

without difference in morphometric vertebral or non-vertebral fractures (one study).

Lumbar BMD remained higher than pre-treatment levels in the discontinuation

Background

group, although lower compared with the extension group. Hip BMD decreased or

Osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF) are rare

remained unchanged.

potential adverse effects of bisphosphonates and RANK-L inhibitor, occurring in

Regarding zoledronic acid, two studies fulfilled eligibility criteria. After three

1 and 2 per 100,000 person-years, respectively. The pathogenic mechanisms of

annual infusions (5 mg/y), extending treatment to six years reduced risk of new

both conditions are known to be independent of each other. Here, we report both

morphometric vertebral fractures by 49%, without benefit in clinical vertebral or

conditions sequentially occurring in the same patient.

other types of fractures. Lumbar BMD remained above pre-treatment values in the

Clinical case

discontinuation group, but reduced in hip sites. Extending treatment to nine years

An 81-year old, obese, diabetic, female was admitted due to hypertensive urgency

provided no additional benefit.

and persistent jaw pain after tooth extraction. The patient has postmenopausal

Regarding risedronate, one study fulfilled eligibility criteria. Discontinuation for

osteoporosis for fourteen years and was on intermittent unsupervised treatment

one year (after 5 mg/d for three years) did not increase non-vertebral fracture risk,

with alendronate, denosumab and ibandronate. She had suffered sequential

but continued to confer a reduced risk in vertebral fractures (46%). Lumbar BMD

fracture of both femurs during the eighth and eleventh year of treatment. Both

remained higher, whereas femoral neck BMD decreased, compared with

fractures were transverse, non-comminuted, at the proximal femoral shaft, which

pretreatment levels. No increased risk of ONJ or AFF was shown in these studies.

occurred after a minor trauma, and were managed with open reduction and

Conclusions

internal fixation.

A “bisphosphonate holiday” may be considered after five years of treatment with

Upon presentation, the patient was noted with tenderness intraorally of tooth

alendronate, three with risedronate and three with zoledronic acid for up to five, one

number 35 periapical region, no pus, no mandibular swelling. There was

and three years, respectively. However, this decision should be individualized.

peripheral leukocytosis, elevated erythrocyte sedimentation rate, C-reactive

DOI: 10.1530/endoabs.49.EP214

protein. Panoramic with periapical view radiograph showed presence of bony

sclerosis which represent a sequestrum compatible to chronic osteomyelitis in the

molar area of the left hemi-mandible. Antibiotic infusion and excision and

debridement of left posterior mandible were done. Necrotic bone with

histopathologic finding of acute and chronic osteomyelitis with bacterial colonies

was removed consistent with a diagnosis of osteonecrosis of the jaw. The patient

was discharged on the fourth post-operative day and was placed on drug holiday.

Conclusion

ONJ and AFF can occur both in the same patient during prolonged treatment with

bisphosphonates and RANK-L inhibitor and may suggest a common pathogenic

mechanism. This case further emphasized that to avoid these grave consequences,

EP215

bisphosphonates should be given in a limited period—five years, as recommended

Osteopetrosis vs Osteogenesis Imperfecta-is that so hard to distinquish?

by experts.

Case report

DOI: 10.1530/endoabs.49.EP216

Theodor-Eugen Oprea, Mirela Bonea, Suzana Florea & Carmen Barbu

Elias University Emergency Hospital, Endocrinology Clinic, Bucharest,

Romania.

Osteopetrosis and O.I. are both bone metabolic disorders with opposite features in

terms of the metabolic turnover: while osteopetrozis has a low turnover and

increased BMD due to the failure of osteoclasts to resorb bone, O.I. is well known

as a high turnover disease with low BMD caused bt mutations in the COL1A1 and

EP217

col COL1A2 genes that encode type 1 procollagen; yet, both condition, in spite of

Clinical manifestations and treatment approach in osteogenesis

different mechanism, end up with increased ftracure prevalence. We report the

imperfecta

case of a 46 year old women who presented for clinical and biological evaluation

Dimitra Tampouratzi¹, Styliani Kalaitzidou¹, Aggeliki Sapera¹,

with a prior diagnisis of osteopetrosis. The anamnesis revealed that the diagnosis

Michalis Kotis¹, Fotini Kanouta¹, Eleni Triantafillou¹, Taxiarchis Kyrimis¹,

of osteopetrozis was set when the patient was 2 year old based on radiologycal

Georgios Papadakis², Anna Drakopoulou¹, Victoria Kaltzidou¹ &

features and multiple nontraumatic fractures suffered in childwhood; last fracture

Athanasia Tertipi¹

she recalls was at

20 year old and. Also she claims a familial history of

¹Endocrinology Department, Metaxa Anticancer Hospital, Piraeus, Athens,

osteogenesis imperfecta

(maternal grandfather). The clinical examination

Greece;²STEPS Stoffwechselzentrum, Biel/Bienne, Switzerland.

revealed: Hight-125 cm; Weight-50 kg; BMI-32 kg/sm; blue sclerae, left leg

orthosis, with unequal inferior limbs accompanied by difuze joint pain. Lab tests

highlighted mild hypercholesterolemia,

25OHVitD insufficiency, low beta-

Objectives

crosslaps level, normal PTH, normal TSH and fT4. Near normal BMD. Dorsal

Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affects

and lombar spine X-ray:rarefaction of trabecular bone structure, suggesting a

the bones. The underlying mechanism is usually a disorder of connective tissue

medium grade of demineralization.

due to lack of type I collagen. Usually, the disease is due to mutations in the

Our O.I. final diagnosis proved to be quite difficult, taking into account the prior

COL1A1 or COL1A2 genes. The disease is inherited in an autosomal dominant

one of osteopetrosis, the history of pubertal fractures, familial history of O.I.,

manner or occurs via a de novo mutation. There are eight types of the disease.

growth impairment, lack of decreased BMD and increased bone turnover, mild

Type I is the most common and the least sever type and is due to mutation in

VitD insufficiency. However, the importance of establishing the diagnosis, in our

COL1A1 gene. We evaluated the clinical, laboratory and radiological profile of a

case, consists in choosing the optimal treatment; bisphosfonates are used in O.I.

woman with OI Type I who was treated over a 3-years period in our clinic.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

Introduction

A 61-year old female patient with family history of OI (son and sister) was treated

The improvement of the survival of diabetics is accompanied by the emergence of

in our clinic. She had history of multiple repeated fractures since 18 years old,

bone fragility which can directly affect, at various levels, the various components

short stature (138 cm), discoloration of the sclera, dental abnormalities, poor

of the bone tissue leading to quantitative and qualitative anomalies. The effects of

muscle tone in arms and legs, triangular face and skeletal deformities such as

type 2 diabetes on bone are complex because they are associated with the

osteoporosis, spinal canal stenosis and kyphoscoliosis. Bone densitometry found

sometimes associated disorders of nutrition, weight and age. Densitometric

severe osteoporosis. Treatment included zoledronic acid IV, vitamin D and

studies in this context are quite contradictory. We proposed to study the bone

calcium carbonate per os.

status of type 2 diabetics.

Results

Patients and methods

After treatment with zoledronic acid the patient reported reduced bone pain and

We carried out a cross-sectional study of 290 type 2 diabetics. These patients

had stable bone mass (0.547 g/cm² before treatment and 0.535 g/cm² (femoral

benefited from a measurement of bone mineral density (BMD) associated with

neck) after treatment) and increased T-score (femoral neck) (K3.3 SD before

PTH, vitamin D and calcemia.

treatment and K2.88 SD after treatment, 3 years later).

The results

Conclusion

The average age of our population was 62.5 years. 38% of our patients were

Osteogenesis imperfecta is a heterogeneous disease and may have an indolent

treated with insulin with a predominantly mixed regimen (basal insulin combined

course. The diagnosis may be brought forward late in adulthood. The

with oral treatments), with an average HBA1C of 7.05% for an average duration

management includes the replacement of a calcium and vitamin D deficit and

of diabetes of 8 years. Mean calcium in the general population was 2.33 mmol/l,

biphosphonates. Bisphosphonates remain effective and can increase bone mass,

with 2.36 mmol/l in males and 2.27 mmol/l in females, with no significant

reduce bone pain and fractures.

relationship between the two sexes (PZ0.1370).

DOI: 10.1530/endoabs.49.EP217

5 patients had secondary hyperparathyroidism (O 65 pg/ml), the mean PTH in the

study population was 46.82 ng/ml, higher in women than in men. 75.6% of

patients had normal BMD, 23.3% had osteopenia, 24.3% were women, and 21%

were men. The mean concentration of vitamin D is 13.93 ng/ml, with a maximum

of 35 ng/ml and a minimum of 3 ng/ml. The mean concentration in males was 15,

14 ng/ml, significantly higher than that of females in the order of 11.91 ng/ml

(P!0.1ZPZ0.0018). A negative and significant correlation was found between

the serum levels of 25OHD3 and those of PTH. This correlation persisted after

adjusting for age and BMI. Our study did not find any significant relationship

between PTH levels and BMD scores with (PZ0.6091).

EP218

Conclusion

Special features of body composition and bone mineral metabolism in

According to data from the literature and despite normal BMD in patients with

children with primary nephrotic syndrome

type 2 diabetes, it should be borne in mind that BMD alone is insufficient to assess

Natalia Volkova¹ & Angelika Soltsava²

bone status, management of other factors such as Diet rich in vitamin D and

¹2th City Children’s Hospital, Minsk, Belarus;²Belarusian State Medical

sufficient calcium intake is required.

University, Minsk, Belarus.

DOI: 10.1530/endoabs.49.EP219

Objective

To learn characteristics of biochemical markers of bone metabolism, parameters

of bone mineral density (BMD) and fat component of body composition for early

diagnosis of bone disorders in children with primary nephrotic syndrome (NS).

Material and methods

We compared data of laboratory investigations (phosphorus (P), total calcium

(Ca), parathyroid hormone (PTH), and alkaline phosphatase (ALP)), protocols of

dual-energy X-ray absorbtiometry of the axial skeleton and total body of 27

children with NS (group 1 - G1, age 9.71G4.23 yrs) and 13 children of control

group (G2, age 10.84G3.84 yrs, PZ0.48). Group 1 was divided in subgroups G1a

EP220

(relapse of NS, nZ12) and G1b (remission of NS, nZ15). Results were processed

using SPSS17.

Effects of acromegaly on bone tissue mRNA levels relevant to bone

metabolism

Results

Tatiana Grebennikova¹, Zhanna Belaya¹, Galina Melnichenko¹,

G1 showed significantly lower age-matched z-score of BMD of lumbal spine (L1-

Olga Brovkina², Alexey Nikitin², Ludmila Astaf’eva³, Andrej Grigoriev¹ &

(K0.71G0.96) compared with G2 (0.08G1.13, PZ0.036). One child of G1

Ivan Dedov¹

had low bone density of lumbal spine with z-score K2.9. Total BMD was similar

¹Federal State Institution “The National Research Center for Endo-

in the groups

(0.88C/K0.12 g/cm²

in G1

0.91C/K0.19 g/cm²

in G2,

crinology”, Moscow, Russia;²Federal Research and Clinical Center FMBA,

PZ0.39). Fat component of body composition was increased in G1 (38.33G

Moscow, Russia;³N.N. Burdenko Neurosurgery Institute, Moscow, Russia.

11.30%) compared with G2 (27.52G6.59%, PZ0.0001). Android/gynoid fat

ratio was higher in G1 (0.90G0.18) than in G2 (0.70C/K0.20, PZ0.013).

Children of G1a showed lower level of Ca than control (2.24G0.18 mmol/l vs

Molecular basis of the bone disorders in patients with acromegaly are largely

2.37G0.07 mmol/l, PZ0.009). Concentration of Ca in G1b was similar to G2

unknown.

(2.37G0.07C/K 0.13

2.44G0.15 mmol/l, PZ0.71) We didn’t reveal

Objective

significant difference in of PTH, P and ALP levels in the groups (PO0.05).

To investigate gene expression profiles that regulate bone metabolism in bone

Conclusions

tissue samples from patients with acromegaly.

Most children with NS showed normal BMD of lumbal spine, though it was lower

Materials and Methods

than in healthy controls. Patients with NS had higher fat component of body

Patients with clinically evident and biochemically proven active acromegaly and

composition with increased android type of its distribution.

patients with hormonally inactive pituitary adenoma matched by age, sex and

DOI: 10.1530/endoabs.49.EP218

BMI were invited to participate. Bone samples were taken during transsphenoidal

adenomectomy from the base of the sella-turcica, immediately placed in lysis

buffer (QIAzol) and subjected to homogenization. Insulin-like growth factor 1

(IGF-1) was measured by an electrochemiluminescence assay on a Liaison. Total

RNA isolation from bone tissue with on-cjlumn digestion of the genomic DNA

was carried out with miRNeasy Mini Kit on the automatic station ‘QIAcube’.

Reverse transcription was carried out using a High-Capacity RNA-to-cDNA Kit.

Gene expression analysis was performed by Real-Time PCR on StepOnePlus

instrument with Custom TaqMan Array 48 Plus plates, TaqMan Advanced

EP219

miRNA Assays.

Results

Bone densitometry of type 2 diabetics (about 290 patients)

We enrolled 21 subjects (12 patients with acromegaly and 9 with hormonally

Samir Ait Abderrahmane, Zahra Kemali, Sihem Hatri, Elmahdi Haffaf,

inactive pituitary adenomas); 13 females and 8 males, the mean age was 38 years

Nacer Sobhi, Lila Brakni & Brahim Oudjit

(confident interval (CI) 95% 33-43) mean BMI - 28 (CI95% 25-31) kg/m². There

HCA, Kouba, Algeria.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

were no significant difference within the groups. Mean IGF-1 in subjects with

drug treatment for osteoporosis have raised the hypothesis that osteoporosis may

acromegaly - 785 (CI95% 527-1042) ng/ml. The expression of SOST 5,7 (CI95%

be not only a treatable but moreover a curable disease.

1,01-10,44, PZ0.022), DKK1 7,97 (CI95% 4,4-11,54, P!0.001), BGLAP 1,51

The aim was to describe the case of a patient with osteoporosis who after

(CI95% 0.82-2,19, P!0.001) was increased in subjects with acromegaly as

treatment with alendronate for 6 years had osteopenia and remains in the state of

compared to inactive pituitary adenoma. miRNA 199a-5p 0,37 (CI95% 0.06-

osteopenia for a long period after drug cessation.

0,68, PZ0.023) was suppressed.

A patient, female, aged 65 years, postmenopausal, presented with osteoporosis, T

Conclusion

score in the spine being K3.2. Alendronate 70 mg once weekly was administered

In spite of increased expression of Wnt signaling antagonist, bone formation is not

along with calcium and vitamin D. The patient also had hypothyroidism on

suppressed in subjects with acromegaly. The suppression of miRNA might

treatment with L-thyroxine, TSH levels being within the normal range.

explain the predominant differentiation to the cartilage tissue.

Bone mineral density measurement was performed yearly while the patient was

Disclosures

on treatment with alendronate, calcium and vitamin D. Six years later bone

This study was supported by the Russian Science Foundation (grant # 15-1530032).

mineral density measurement in both the spine and the hip revealed osteopenia, T

DOI: 10.1530/endoabs.49.EP220

score being K1.3 and K1.1 in the spine and the hip, respectively. Alendronate

was discontinued, while calcium and vitamin D were administered to the patient.

The patient is being followed for her osteopenia yearly, T score in the hip being

K1.1 five years after treatment cessation.

In the case presented alendronate appears to have had a long lasting beneficial

effect on the bone in a patient with osteoporosis. The state of osteopenia appears

to be stable in the presented patient. This case of persistent improvement of

osteoporosis after long lasting treatment with alendronate raises the question of

whether osteoporosis may be a curable disease, not being merely a manifestation

of aging. This case raises the hopeful hypothesis that osteoporosis with the

emergence of novel effective forms of therapy may be cured.

DOI: 10.1530/endoabs.49.EP222

EP221

Osteoporosis and fractures in the real world setting

Eleni Pantazi¹, Alexios Travlos¹, Evaggelia Vogiatzi¹ &

Ifigenia Kostoglou-Athanassiou²

¹Department of Endocrinology, Alexandra Hospital, Athens, Greece;

²Department of Endocrinology, Red Cross Hospital, Athens, Greece.

Osteoporosis is a bone disease predisposing to bone fragility. Nowadays, the

population is screened for osteoporosis and measures are taken for fracture

prevention. Additionally, people are urged to have a diet rich in calcium, are

EP223

given calcium supplements and are being treated for vitamin D deficiency.

Fractures at post-partum and lactation: common presentation of

Moreover, osteoporosis treatment is administered. Therefore, the relationship

different clinical entities

between osteoporosis and fractures in the real world setting is very interesting.

Zoe Efstathiadou, Albana Sykja, Athanasios Panagiotou & Marina Kita

The aim was to study the prevalence of fragility fractures in a cohort of patients

“Hippokration” General Hospital of Thessaloniki, Thessaloniki, Greece.

being followed up and treated for osteoporosis in a center of excellence for the

management of osteoporosis in Athens.

A cohort of 91 patients, 82 female and 9 male, aged 69.71G1.09 years, who were

Introduction

followed up and treated as needed for osteoporosis in a center of excellence was

Osteoporosis of pregnancy and postpartum is a rare clinical entity, which usually

studied. Bone mineral density was measured in the spine and the hip. The number

presents with back pain, due to spine fractures. We aimed to describe four

of fractures having occurred in the cohort studied was recorded.

different cases presenting with back pain and fractures post-partum, in who, with

Bone mineral density in the spine as assessed by T score was K1.9G0.11 (meanG

diverse underlying pathophysiology, recovery time and treatments used.

SEM) and in the left hip K2.6G0.11. In the cohort of patients studied 19 patients

Case 1

(20.88%), 15 female and 4 male, suffered a fracture. The fractures recorded were 8

A 32-year-old patient presented with intense back pain and difficulty in standing

vertebral, 7 distal radius, 2 tarsal joint, 2 rib fractures and 1 fracture of the calcaneus.

and walking, 2 weeks after delivery. She had hypercalcaemia, hyperphosphatemia

Within the cohort studied 2 patients had suffered two fractures, a distal radius and a

and multiple vertebral fractures. Breast examination and mammography were

vertebral and a rib and a vertebral fracture, respectively.

inconclusive due to lactation. The diagnosis of metastatic breast cancer was made

It appears that in the modern real world setting despite the measures taken for

after a bone lesion biopsy. The patient received zolendronic acid and was referred

osteoporosis prevention and management in a cohort of patients being followed up

to an oncologist.

within a center of excellence in Athens, fractures tend to occur especially in the

Case 2

female population. However, interestingly, within the cohort studied many patients

A 35 year-old patient, several weeks after a singleton pregnancy, presented with

with osteoporosis remained free of fracture at the point of time of the study.

acute back pain. Imaging studies revealed an L2

fracture and laboratory

assessment showed increased bone turnover markers and vitamin D deficiency.

DOI: 10.1530/endoabs.49.EP221

She received zolendronic acid and was started on vitamin D3 substitution. Her

clinical course was uneventful.

Case 3

A 41 year-old lady was diagnosed with T12 and L3 vertebral fractures, while still

breast-feeding. No secondary causes of osteoporosis were found. She received an

18-month course of teriparatide and Vitamin D3 supplementation. Six months

after teriparatide discontinuation she presented with urinary tract lithiasis

complicated by upper urinary tract infection.

Case 4

A 32-year-old patient presented with lumbar spine bone mineral density Z-score

of K2.8, but no fractures, after her first pregnancy. She was treated with

EP222

intranasal calcitonin and VitD3

supplementation. An improved BMD

(Z-

Is osteoporosis a curable disease?

scoreZK2.1) was measured after 2 years. Her second pregnancy was uneventful.

Ifigenia Kostoglou-Athanassiou¹, Eleni Pantazi² & Panagiotis Athanassiou³

Conclusions

¹Department of Endocrinology, Red Cross Hospital, Athens, Greece;

Post-partum osteoporosis is a rare cause of bone pain during the puerperium.

²Department of Endocrinology, Alexandra Hospital, Athens, Greece;

Fractures should be diagnosed early in order to avoid permanent incapacity. It is

³Department of Rheumatology, St. Paul’s Hospital, Thessaloniki, Greece.

mandatory to look for and exclude secondary causes of osteoporosis including

breast cancer and vitamin D deficiency.

DOI: 10.1530/endoabs.49.EP223

Osteoporosis may be a disease of unknown etiology, or a degenerative disorder in

the context of aging. Nowadays, the availability of multiple forms of effective

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP224

Spontaneous BMD increase (LS Z-score K2.4) was observed already 2 months

after surgery. Except for calcium and vitamin D supplementation, no bispho-

A multidisciplinary clinic for bone metabolism diseases; descriptive

sphonate therapy was prescribed, given this impressive increase of BMD and

analysis of our experience in quiron salud malaga hospital

because she was still premenopausal. X-Rays did not show any new vertebral

Araceli Mu

˜ oz-Garach¹, Maria Carmen Ordo

˜ ez-Can˜ izares2,

fracture. BMD continued to increase. 24 months after surgery, densitometry

Ana Nieto-Gonzalez², Pablo Manzano Fernández-Amigo² &

showed 40% absolute increase in LS BMD and 16% in FN BMD, vs baseline. She

Jose Manuel García-Almeida¹

reached normal BMD values at all sites 3 years following surgery.

¹Endocrinology and Nutrition Department. Quiron Salud Hospital, Málaga,

After a 9-years follow-up (DXA and BTMs, yearly), complete spontaneous BMD

Spain;²Rheumatology Department. Quiron Salud Hospital, Málaga, Spain.

recovery was confirmed (LS T-score C1.2 and FN T-score K0.3) with normal

and stable BTMs.

Introduction

Our case suggests no need for any antiresorptive therapy in severe osteoporosis

A multidisciplinary clinic has been developed to optimize the diagnosis and

due to cortisol-secreting adrenal adenoma after successful surgery, at least in

treatment of bone metabolism diseases. Initiated in March 2013, it is carried out

premenopausal women.

simultaneously, once a week by an Endocrinologist and a Rheumatologist.

DOI: 10.1530/endoabs.49.EP225

Objective

To describe the experience of this unit in the last 12 months.

Material and methods

Cross-sectional observational study. 235 patients were attended from December

2015 to December 2016. In the first visit, we carried out a medical record using a

checklist form and impedancemetry. We requested a blood test with bone

remodeling markers (CTX-I and P1NP), vitamin D, PTH, sex hormones and

24-hour urine with calciuria and phosphaturia, densitometry and dorsum-lumbar

spine x-rays. In the following visit the results were evaluated and the team formed

by both specialists agreed the protocol of action. Subsequently we studied

treatment tolerance and analytical, radiographic and densitometric changes.

EP226

Results

Cinacalcet for control of primary hyperparathyroidism: a single centre

97% were women with a mean age of 60G9.7 years. Weight 66.3G12.7 kg,

experience

height 158.2G5.8 cm, BMI 26.6G4.9 kg/m². Impedancemetry showed mean

Tiago Nunes da Silva, Ana Gonc¸alves Ferreira, Maria Carlos Cordeiro,

lean mass was 43.0G5.9 kg and mean fat mass 23.3G10.1 kg. 36.2% and 20% of

Ana Catarina Matos & Jorge Portugal

the patients had a personal and family history of fracture, respectively. 15.2%

Endocrinology Department Hospital Garcia de Orta, Almada, Portugal.

patients had taken previous corticoid treatment; 9.5% had more than 2 falls in the

Although primary hyperparathyroidism (PHPT) is usually cured by surgery, some

last year. 5.7% were active smokers. 87.4% had menopause; early menopause in

individuals are unable to undergo parathyroidectomy and are refractory to

13.4% and surgical menopause in 10.7%. 60% practiced more than 3 days of

standard calcium lowering medical therapy. In such cases, targeted therapy with

physical activity per week, 78.8% sunbathed more than 10 minutes a day and

cinacalcet may be useful.

36.2% took adequate dairy milk consumption. Among the digestive antecedents,

The aim of this study was to access the short-term efficacy of cinacalcet in

39% had gastroesophageal reflux and 16.2% hiatus hernia. 17.5% have had a

lowering calcium

(Ca^2C) levels in patients with PHPT unable to undergo

vertebral fracture. In the densitometric data according to T-score they had

parathyroidectomy and refractory to standard medical therapy.

osteoporosis 55.06%; Osteopenia 42.76% and normal 2.24%. The FRAX index

Methods

was 4.3% for major fracture and 0.9% for hip fracture. Among the treatments

Patients with PHPT refractory to standard medical treatment were treated with

received prior to the first consultation,

29.5% took bisphosphonates,

9.5%

cinacalcet. Statistical analysis was carried out using the Wilcoxon test.

denosumab, 2.9% PTH. 37.5% calcium plus vitamin D.

Results

Conclusions

Five patients (all female) with a median age of 76 years were included. The

A high percentage of patients received treatment before coming to the clinic. The

known duration of the PHPT was 60 months. The median follow-up of cinacalcet

most used was bisphosphonates. The aggregate management by two specialists in

treatment was 12 months. Hypercalcemia related comorbidities were mental

the multidisciplinary clinic is beneficial and improves the quality of care in our

changes in 4, osteoporosis in 3 and kidney stones in 2 patients. Before medical

patients.

treatment, baseline median (quartile 1 (Q1), Q3) serum PTH was 252 (159, 614)

DOI: 10.1530/endoabs.49.EP224

pg/ml (reference range 15-65) and serum Ca^2C was 11.7 (11.6, 12.65) mg/dl

(reference range 8.1-10.2). After standard medical treatment, baseline median

(quartile 1 (Q1), Q3) serum PTH was 222 (149, 304) pg/ml and serum Ca^2C was

11.9

(11.2, 12.6) mg/dl (PO0.05). After the last stable dose of cinacalcet, median

(quartile 1 (Q1), Q3) serum PTH was 190 (139, 361) pg/ml and serum Ca^2C was

10.1

(9.7, 12) mg/dl (PZ0,005). Serum Ca^2C normalized in 60% of patients. The

median decrease of Ca^2C was 15.1% (PZ0,005) and of PTH was 14.4%

(PZ0,174). Only one patient developed side effects (muscle spasms) without the

need to stop cinacalcet.

Conclusions

EP225

These results demonstrate the efficacy and safety of cinacalcet in controlling

Spontaneous recovery of BMD after surgical cure of Cushing’s

hypercalcemia refractory to standard medical therapy.

syndrome due to an adrenocortical adenoma: a 9-years follow-up

DOI: 10.1530/endoabs.49.EP226

F. Baleanu, L. Iconaru, R. Karmali & J.J. Body

Centre Hospitalier Universitaire Brugmann, Université Libre de Bruxelles,

Brussels, Belgium.

A 33-year-old Belgian woman was referred in June 2006 to our Metabolic Bone

Diseases Clinic for recent vertebral fractures. X-Rays showed a 3-level severe

compression fractures with collapse of the superior endplates of D11, D12 and L1.

DXA showed significantly decreased lumbar spine (LS) and femoral neck (FN)

Z-scores, at K3.1 and K2.5, respectively.

She was complaining of severe back pain, muscle weakness, cognitive

dysfunction, anxiety and irritability. Physical examination revealed moon-shaped

face, ecchymosis, purple stretch marks on the breasts, arms, abdomen and thighs.

EP227

Morning cortisol was normal but ACTH level was suppressed. Urinary free

Bone remodeling markers predict bone loss in premenopausal women

cortisol was elevated. A late-night salivary cortisol also elevated. Standard 2-day

Gala Gutierrez Buey¹, Sonsoles Botella¹, Patricia Restituto², Macarena

2-mg dexamethasone suppression test showed no cortisol suppression. A loss of

Rodriguez Fraile³, Amparo Calleja¹, María Llavero¹, Javier Gargallo¹,

diurnal variation in ACTH and cortisol levels was also demonstrated. Cushing’s

Carolina Perdomo¹, Patricia Andrada¹, Nerea Varo² & Juan C Galofré¹

syndrome was confirmed. Abdominal MRI showed a 3 cm left adrenal mass.

¹Department of Endocrinology, University of Navarra, Pamplona, Spain;

Osteoporosis was considered secondary to this endogenous hypercortisolism.

²Department of Clinical Chemistry, University of Navarra, Pamplona,

Bone turnover markers (BTMs) and 24h urinary calcium excretion were elevated.

Spain;³Department of Nuclear Medicine. University of Navarra, Pamplona,

Successful laparoscopic left adrenalectomy was performed in October 2006.

Spain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Aim

EP229

Bone turnover markers (BTMs) predict more rapid rates of bone loss. However,

Association between bone mineral density and muscle strength in

most of these studies have been carried out in postmenopausal women. Few

patients with Turner syndrome, after consideration of selected

prospective studies have examined the degradation marker C-terminal telopeptide

hormonal and metabolic parameters

of type I collagen

(CTX) and the bone formation marker N-aminoterminal

Elzbieta Sowinska-Przepiera, Monika Koziolek, Lilianna Osowicz-

propeptide of type I collagen (P1NP) measured during the menopausal transition

Korolonek, Jakub Poblocki, Martyna Patalong-Nowak & Anhelli Syrenicz

to predict the subsequent bone loss.

Pomeranian Medical University, Szczecin, Poland.

Methods

We performed a prospective cohort study including 72 healthy premenopausal

women from de Endocrinology service at the Clinica Universidad de Navarra. Six

Turner syndrome (TS), resulting from complete or partial loss of X chromosome,

women were lost in the follow-up and two were excluded because of treatment

occurs in 1 per 2000-2500 liveborn female neonates. Most patients with TS,

that affects bone. We measure demographic variables, CTX, P1NP and bone

especially those untreated with growth hormone, present with osteoporosis or

mineral density at baseline and five years later. SPSS 20.0 was used for statistical

osteopenia, and are at increased risk of bone fractures. Available evidence suggests

analysis. Differences between study groups were evaluated by Student’s t test for

that depletion of bone mass may be associated with inadequate level of physical

normally and Mann-Whitney-U test for non-normally distributed variables.

activity, and consequently, with too low muscle mass and strength. The aim of the

Results

study was to analyse an association between muscle strength and bone mineral

Mean age at baseline was 49.2G0.3. After 5 years, there were no significant

density in patients with TS, after consideration of selected hormonal and metabolic

changes in baseline demographic characteristics (percentage of smokers, coffee

factors. The study included 52 subjects (age 28-45 years), among them 32 women

intake, sun exposure and physical activity) although there was a significant

with TS (45,X karyotype; Group A) and 20 controls (Group K). The list of analysed

increase in BMI (PZ0.027).

variables included body height, body weight, BMI, bone mineral density (BMD

Five years later, 69% became menopausal, 48.4% (31) had normal bone, and

L1-4 and BMD Total), total body fat (BF) and visceral adipose tissue (VAT)

51.6% (33) had pathological bone (below the expected range for age and/or

volumes determined by means of DXA, hand grip strength measured with a manual

osteoporosis). There was a significant decrease in BMD at 5 years of follow-up

dynamometer, and laboratory parameters: TSH, FT4, FSH, oestradiol, testoster-

compared to baseline (femoral neck 0.92G0.1vs 0.87G0.1 (PZ0.000), lumbar

one, DHEA-SO4, ACTH, cortisol, PTH, vitamin D3 concentrations, lipidogram,

spine 1.17G0.19 vs 1.08G0.1 (PZ0.000) and a significant increase in BTMs

levels of glucose and insulin during OGTT. Patients from Group A presented with

P1NP (ng/ml) 37.22G10 vs 52.23G21 (PZ0.000) and CTX (ng/ml) 0.245G

significantly lower left (PZ0.001) and right handgrip strength (P!0.000), lower

0.125 vs 0.441G0.233 (PZ0.000). Increased levels of P1NP and s-CTX in the

BMD (P!0.000), lower concentrations of testosterone (P!0.000) and DHEA-

premenopausal group at baseline associated with pathological bone five years

SO4 (PZ0.006), larger VAT volumes (PZ0.005), higher BMI (PZ0.05), higher

later (P!0.001 and P!0.001, respectively).

levels of insulin (PZ0.026) and FSH (PZ0.000). The study groups did not differ in

Conclusion

terms of their TSH, fT4, ACTH and cortisol concentrations, and the only significant

Our data suggest that measurement of CTX and P1NP in premenopausal women

difference in lipidogram pertained to triglyceride level, higher in Group A

detects those patients who will suffer bone loss five years later.

(PZ0.032). Right handgrip strength in Group A correlated significantly with BMD

L1-4 (rZ0.1318, PZ0.0486), VAT volume (rZ0.1478, PZ0.0360) and BMD

DOI: 10.1530/endoabs.49.EP227

Total (rZ0.1921, PZ0.0154). These findings suggest that handgrip strength may

constitute a predictor of osteoporosis in patients with TS.

DOI: 10.1530/endoabs.49.EP229

EP228

Bone mineral density in hospital male physicians over the age of 65

Noa Sylvetsky, Chen Futeran, Meir Frankel & Gabriel Munter

Endocrine Unit-Shaare Zedek Medical Center affiliated with Faculty nof

Medicine-Hebrew University, Jerusalem, Israel.

EP230

Volumes of visceral adipose tissue, gynoid and android fat as predictors

Background

of reduced bone mineral density in women with menstrual disorders

Hospital physicians are indoor workers, with higher prevalence of vitamin D

Malgorzata Syrenicz, Elzbieta Sowinska-Przepiera, Elzbieta Andrysiak-

deficiency as compared to community-based physicians. The correlation between

Mamos & Anhelli Syrenicz

vitamin D deficiency and osteoporosis later in life has not been fully studied, and

Pomeranian Medical University, Szczecin, Poland.

bone mineral density

(BMD) in elderly hospital physicians has not been

systematically examined.

Disorders of bone mineralization observed in women with ovarian insufficiency

Methods

are unlikely a simple function of decreased concentration of oestrogens.

A cross-sectional study measuring BMD in hospital male physicians aged 65 and

Published evidence suggests that adipose tissue is a central component within

older was carried out. BMD was measured at the hip, spine and distal forearm.

the complex system of metabolic and hormonal interactions responsible for

FRAX analysis with BMD was performed, using the IOF recommended FRAX

adequate mineralization of the bone. However, to the best of our knowledge, the

cut-offs for treatment (10-year probability of hip fracture R3% and 10-year

composite effects of specific substances synthesized within adipose tissue from

probability of major osteoporotic fracture R20%).

various anatomical compartments, ovarian hormones and insulin on bone

Results

turnover, have not been a subject of a complex analysis in women with menstrual

51 male physicians, employees and pensioners, participated in our study. The

disorders. Therefore, the aim of this retrospective study was to verify if volume

mean age was 71 years (median 69 years; range 65-86), all of them naive to

and distribution of adipose tissue may predict bone loss in this group. The study

specific treatment for osteoporosis. 14/51(27%) had osteoporosis, 7 of them

included 293 Caucasian women (mean age 26.7G4.4 years) with at least 6-month

defined only by distal forearm examination. 29 (56%) had osteopenia, 4 of them

history of secondary amenorrhea. Based on T-score values for bone mineral

defined only by distal forearm examination. According to their FRAX score, 9 of

density (BMD) in lumbar spine, the study subjects were divided into two groups,

the osteopenic examinees had high risk of major osteoporotic fracture and/or hip

with T-scores below K0.5 and at least 0.5. Univariate logistic regression analysis

fracture.

showed that lower bone mineral density (as shown by T-score below K0.5) was

Conclusion

associated with larger volumes of gynoid (odds ratio, ORZ7.45), android (ORZ

In elderly hospital-based male physicians, the prevalence of osteoporosis is higher

3.03) and visceral adipose tissue (ORZ1.55), as well as with higher values of

than expected. After adding the FRAX score results, 45% of the physicians would

body mass index (BMI, ORZ1.17), fasting concentration of insulin (ORZ1.08)

require specific treatment for fracture prevention, according to customary

and body weight (ORZ1.06). However, none of these variables turned out to be

international clinical guidelines. Using only hip and spine BMD, 31% would

an independent predictor of BMD deficiency on multivariate analysis. These

require treatment. Based on our data we suggest screening elderly physicians for

findings imply that excessive volume of adipose tissue, irrespective of distribution

osteoporosis.

thereof, is a strong determinant of reduced BMD in women with ovarian

DOI: 10.1530/endoabs.49.EP228

insufficiency. The lack of region-specific effects of adipose tissue volume on

BMD is probably associated with the influence of ovarian insufficiency on

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

systemic metabolism and endocrine processes, in particular with the development

kg/m²). Metabolic bone remodelling parameters were analysed: LDL, HDL,

of insulin resistance.

total cholesterol, HOMA_IR, insulin, glycaemia, alkaline phosphatase, osteocalcin

DOI: 10.1530/endoabs.49.EP230

and parathormone. It was determined the platelet and plasma serotonin

concentrations by ELISA.

5HTTVNTR was evaluated by PCR and the

5HT_2A_T102C by PCR-RFLP. Statistical analysis by SPSS 21.0.

Results

In osteoporosis, we found increased osteocalcin (PZ0.030) and plasma 5HT

concentration (PZ0.012) and decreased insulin (PZ0.023) and total cholesterol

(PZ0.027). In women with normal BMD, we found an association between

genotype 10/10 of 5HTTVNTR and decreased osteocalcin (PZ0.035). and

between genotype CC of 5HT_2A and decreased HDL (PZ0.029). Within this

group, we also found inverse correlations between HDL and alkaline phosphatase

(PZ0.030) and HOMA_IR (PZ0.018). In women with osteoporosis, we found

direct correlations between glycaemia and osteocalcin (PZ0.017) and HDL

EP231

(PZ0.049).

Effect of chronic atrophic gastritis on bone mineral density of Korean

Conclusion

women

In normal BMD, 5HTTVNTR and 5HT2A_T102C polymorphisms appear to

CB Lee¹, YC Jeon¹ & KY Lee²

modulate directly or indirectly some metabolic parameters associated with bone

¹Hanyang University Guri Hospital, Guri, Republic of Korea;²Incheon Gil

remodelling. These polymorphisms seem to have no effect in women with

Hospital, Incheon, Republic of Korea.

osteoporosis suggesting that they may play a relevant role in the susceptibility to

osteoporosis development by modulating metabolic bone remodelling

Hydrochloric acid has been demonstrated to be important for the absorption of

parameters.

calcium and the bone loss is often seen in human after total gastrectomy. The aim

DOI: 10.1530/endoabs.49.EP232

of our study was to document the change of calcium and bone metabolism in the

patients with decreased capacity of gastric acid secretion like chronic atrophic

gastritis.

The study sample consisted of chronic atrophic gastritis group and control group.

Chronic atrophic gastritis group was 20 post-menopausal females (age: 60.3G5.1

yr) who was confirmed by gastroscopic biopsy, demonstrating atrophic change of

gastric mucosal secretory tissue. Control group had 21 healthy females (age:

58.7G6.5 yr) with normal gastroscopic biopsy results. Gastric pH, serum levels

of calcium, phosphorus, total alkaline phosphatase, intact PTH, and bone mineral

density (Delphi, Hologic, USA) were monitored in all the patients in both group

before medication. There were no significant differences of gastric pH (3.9G0.6

EP233

3.3G1.0, PO0.05), calcium

(8.9G0.9

8.8G1.4 mg/dl, PO0.05),

phosphorus (3.2G1.5 vs 3.5G0.9 mg/dl, PO0.05), total alkaline phosphatase

The effect of mechanical assisted squat exercise on pulmonary function,

(72.5G24.5 vs 60.3G22.4 U/l, PO0.05) and intact PTH (29.3G5.1 vs 27.2G

muscle mass and function with or without sarcopenia

3.8 pg/ml, PO0.05) between chronic atrophic gastritis group and control group.

YunKyung Jeon, MyungJun Shin, InJoo Kim, BoHyun Kim &

Bone mineral density showed decreased average value in atrophic gastritis group

YongBeom Shin

comparing control group (0.78G0.27 vs 0.85G0.31 g/cm², PZ0.09).

Pusan National University Hospital, Busan, Republic of Korea.

In conclusion, chronic atrophic gastritis which have lower capacity of gastric acid

secretion may cause decrease of bone mineral density. And this mechanism may

Introduction

be one of the pathogenesis of senile osteoporosis.

Sarcopenia is a geriatric syndrome that causes age-related changes to muscle mass

DOI: 10.1530/endoabs.49.EP231

and function. Lung function is reduced in elderly patients with sarcopenia. We

explored whether a mechanically assisted squat exercise improved muscle

function and mass and pulmonary function in community-dwelling elderly

women with or without sarcopenia.

Methods

Participants were recruited via posters or the websites of regional health centers.

In total,

76 community-dwelling elderly subjects

(aged O60 years) were

screened. We finally included 47 subjects in this prospective study. They were

randomly assigned to exercise or non-exercise group as a ratio of 2:1. We

measured lung function, knee extensor strength, hand grip strength, and the body

composition before and after 6 weeks of mechanically assisted squat exercises

(3 days a week, 30 min per day).

Results

EP232

Subjects with sarcopenia had poor hand grip strength and knee extensor strength.

May serotonin metabolism polymorphisms 5HTTVNTR and 5HT_2A

Their lung function parameters

[including vital capacity, forced expiratory

have a clinical impact in osteoporosis development?

volume in 1 s (FEV1), and forced vital capacity (FVC)] were lower than those of

Raquel Simo˜ es1,2, Joana Freitas1,2, Ana Paula Barbosa3,4,

controls. After 6 weeks of squat exercises, the hand grip strength and knee

Rui Mascarenhas^3,4 & Manuel Bicho^1,2

extensor strength increased significantly in both the sarcopenia and control

¹Institute for Scientific Research Bento Rocha Cabral, Lisbon, Portugal;

groups. Appendicular skeletal muscle mass was increased in exercise group only

²ISAMB, Genetics Laboratory, Lisbon Medical School, Lisbon, Portugal;

in without sarcopenia group (PZ0.013). Leg fat mass was significantly decreased

³Clinic of Endocrinology, Diabetes and Metabolism, Lda., Lisbon, Portugal;

in both sarcopenia and non-sarcopenic group. However, leg lean mass was

⁴Department of Endocrinology, Diabetes and Metabolism, Santa Maria

significantly increased only in non-sarcopenic group after exercise. The FVC (L)

Hospital, Lisbon, Portugal.

and FVC (%) increased significantly only in the sarcopenia group (PZ0.019 and

PZ0.041, respectively), but not in the control group.

Objectives

Conclusion

To study the association of serotonin transporter gene (SLC6A4) polymorphism

Squat exercises improved not only lower extremity functionality, but also upper

5HTTVNTR and serotonin receptor 2A polymorphism 5HT2A_T102C with bone

extremity functionality, including hand grip strength. Muscle mass was

mineral density and metabolic parameters of bone remodelling.

significantly increased in without sarcopenia after exercise. The FVC increased

Materials and methods

in the sarcopenia group. Thus, squat exercises may improve lung function in

BMD (g/cm2) was measured by DEXA in 105 post-menopausal women: 35 with

patients with sarcopenia.

normal BMD (ageZ58.30G1.33 years; BMIZ28.18 [19.13-39.87] kg/m²) and

DOI: 10.1530/endoabs.49.EP233

with osteoporosis

(ageZ68.30G1.09 years; BMIZ28.90

[20.78-43.86]

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP234

EP236

Beta-2 adrenergic receptor (ADRB2) gene polymorphism Arg16Gly as

Differences in bone strength and metabolic parameters according to the

risk factor for osteoporosis

presence of hyperadiponectinemia and obesity in Korean adults: The

Raquel Simo˜ es1,2, Joana Freitas1,2, Ana Paula Barbosa3,4,

KoGES- ARIRANG study

Mário Mascarenhas^3,4 & Manuel Bicho^3,4

Jung Soo Lim¹, Eunhee Choi², Ji Hye Huh¹, Mi Young Lee¹, Jang Yel Shin¹,

¹Institute for Scientific Research Bento Rocha Cabral, Lisbon, Portugal;

Choon Hee Chung¹, Sang Baek Koh³ & Song Vogue Ahn³

²ISAMB, Genetics Laboratory, Lisbon Medical School, Lisbon, Portugal;

¹Department of Internal Medicine, Yonsei University Wonju College of

³Clinic of Endocrinology, Diabetes and Metabolism, Lda., Lisbon, Portugal;

Medicine, Wonju, Gangwon, Republic of Korea;²Smith Center for

⁴Department of Endocrinology, Diabetes and Metabolism, Santa Maria

Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center,

Hospital, Lisbon, Portugal.

Boston, MA, USA;³Department of Preventive Medicine, Yonsei University

Wonju College of Medicine, Wonju, Gangwon, Republic of Korea.

Objectives

To study the association of Beta-2

adrenergic receptor

(ADRB2) gene

Adiponectin has been thought to exert important influences in energy homeostasis

polymorphism Arg16Gly with bone mineral density and metabolic parameters

and insulin signalling pathway. Some obese individuals showed paradoxical

of bone remodelling.

hyperadiponectine-mia (HA), however, the effect of HA on bone metabolism has

Materials and methods

not been fully clarified.

BMD (g/cm²) was measured by DEXA in 105 post-menopausal women: 35 with

This study aimed to evaluate bone strength and metabolic parameters according to

normal BMD (ageZ58.30G1.33 years; BMIZ28.18 [19.13-39.87] kg/m²) and

the presence of HA and obesity in Korean adults. A total of 9,172 adults (59.4%

with osteoporosis

(ageZ68.30G1.09 years; BMIZ28.90

[20.78-43.86]

women) aged 40-70 years assessed in the Korean Genomic Rural Cohort Study

kg/m²). Metabolic bone remodelling parameters were analysed: LDL, HDL,

from 2005 to 2008 were examined. HA was defined as the levels of higher than or

total cholesterol, HOMA_IR, insulin, glycaemia, alkaline phosphatase, osteocalcin

equal to the upper tertile among metabolically healthy subjects with a bone mass

and parathormone. Arg16Gly polymorphism was evaluated by PCR-RFLP.

index (BMI) less than 23 kg/m².

Statistical analysis by SPSS 21.0. Statistical significance for P!0.05.

Moreover, obesity was defined as a BMI of more than or equal to 25 kg/m². The

Results

serum con-centrations of adiponecti-n were measured by radioimmunoassay. In

We found association between Arg16Gly polymorphism and osteoporosis with an

addition, bone status was assessed using the calcaneal quantitative ultrasound

increase of homozygous Gly/Gly in women with osteoporosis (PZ0.009). They

method. Obese subjects and those who have HA accounted for 40.3% and 15.7%,

showed a higher risk for the development of osteoporosis (ORZ6.517; CI95%

respectively; about twenty percent of the non-obese and 9.5% of the obese had

[1.663-25.539]). In osteoporosis, we found increased osteocalcin (PZ0.030) and

HA. Although most of metabolic parameters such as fasting glucose and lipid

decreased insulin (PZ0.023) and total cholesterol (PZ0.027). In women with

profiles were significantly better in the HA group compared with the non-HA

normal BMD, we found an association between genotype carriers of allele Arg

group, bone stiffness index (BSI) in the former was lower in the latter. In both the

(Arg/ArgCArg/Gly) and decreased total cholesterol (PZ0.018). We also found

non-obese and obese groups, individuals with HA had lower waist circumference

an association between carriers of allele Gly (Arg/GlyCGly/Gly) and decreased

and BSI. Moreover, obese subjects without HA showed the highest BSI levels

of glycaemia (PZ0.010). Within women with normal BMD, we also found

among the group-s, which was especially prominent in women. Our results

inverse correlations between HDL and alkaline phosphatase (PZ0.030) and

suggest that bone strength in obese individuals may be more negatively affected

HOMA_IR (PZ0.018). In women with osteoporosis, we found direct correlations

by high adiponectin levels. Further studies are necessary to confirm the effects of

between glycaemia and osteocalcin (PZ0.017) and HDL (PZ0.049).

adiponectin on bone health in subjects with obesity.

Conclusion

DOI: 10.1530/endoabs.49.EP236

Arg6Gly polymorphism of ADRB2 gene is associated with a higher risk for the

development of osteoporosis. This polymorphism also appears to modulate

directly or indirectly some metabolic parameters associated with bone

remodelling.

DOI: 10.1530/endoabs.49.EP234

EP237

Do the surgical outcomes change if the surgeon accompanies the

endocrinologist during the preoperative ultrasonography examination?

Ibrahim Kilic¹, Sefika Burcak Polat², Sevgul Faki², Mehmet Tokac¹,

Reyhan Ersoy², Mehmet Kilic³ & Bekir Cakir²

Department of Surgery, Ataturk Education and Research Hospital

Education and Research Hospital, School of Medicine, Ankara, Turkey;

EP235

²Department of Endocrinology and Metabolism, Yildirim Beyazit

Bone histomorphometry and bone marrow adipocytes in premeno-

University, School of Medicine, Ankara, Turkey;³Department of Surgery,

pausal women with type 2 diabetes

Yildirim Beyazit University, School of Medicine, Ankara, Turkey.

Vicente Andrade¹, Victoria Borba¹, Domingos Chula¹, Fellype Barreto²,

Cesar Boguszewski¹ & Carolina Moreira^1,2

¹Endocrine Division of Feral/University of Parana - SEMPR, Curitiba,

Introduction

Brazil;²LABORATORY PRO, Histomorphometry sivision, Pro Renal

Parathyroid surgical therapy differs because the glands are small and of variable

Foundation, Curitiba, Brazil.

number and location. Although localization studies have improved greatly, we may

not reliably determine the number and location of all diseased glands preoperatively.

Ultrasonography (US) is the most widely used imaging method. In this study, we

Few studies have evaluated bone histomorphometry in type 2 diabetic patients

aimed to demonstrate how the surgical outcomes change when the surgeon

(DM2) and none has established if the disease control plays a role on bone

accompanies the endocrinologist during preoperative ultrasonography examination.

morphology and bone marrow adipocytes. The aim of this study is to present

Methods

preliminary data on bone microstructure, bone formation rate and bone marrow

This prospective study included 50 patients with primary hyperparathyroidism

adipocytes in premenopausal women with DM2 with different levels of glucose

(PHPT) who underwent a minimally invasive parathyroid adenomectomy under

control. Bone biopsy, followed by tetracycline labelling, was obtained for

local anaesthesia at our institution from January 2014 to December 2015. The

analysis of static and dynamic parameters of bone histomorphometry and volume

patients were divided in two groups. In group A, all patients underwent neck US

of bone marrow adipocytes. To date, 12 bone biopsies and 6 histomorphometry

performed by an experienced endocrinologist and the surgeon on the day of

analysis were performed in a group of women with mean age of 40.9G6.0 yrs,

operation and the location of the lesion was specified by the surgeon. Group B

mean duration of DM2 of 6.8G2.6 years and median glycosylated haemoglobin

patients were operated according to the previous US performed by the

of 8,1% (range 6.5-12.3). Initial results have shown a normal bone volume,

endocrinologist only.

reduced bone formation and an increase in adipocytes content in comparison to

Results

normal premenopausal women values at the literature. Our preliminary results

There were 25 patients in Group A and 25 patients in Group B. The two groups

suggest that bone morphology and bone marrow adipocytes content is altered in

were similar in regard to demographical features, biochemical and hormonal

premenopausal women with DM2.

parameters. Postoperative parathyroid hormone (PTH), calcium and phosphorus

DOI: 10.1530/endoabs.49.EP235

levels didn’t differ between the groups. In group A operation duration was

significantly shorter compared to Group B (25.7 min vs 45 min, PZ0.00).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

adipose tissue percentage (FMR) was measured with DEXA. SPSS 16.0 was used

Preoperative detection of hyperactive parathyroid glands is useful for minimizing

for statistical data processing.

the extent of surgical intervention, reducing operation time and decreasing the

Results

risk of perioperative complication.

Patients were 33.7G8.9 years old (meanGS.D.), BMI was 24.6G5.2 kg/m²,

DOI: 10.1530/endoabs.49.EP237

CD4C were 475 c/ml (24-1,476) and viral load was 38 600 cp/ml (927-422 000).

Four patients (6%) presented with low testosterone levels (hypogonadotropic

hypogonadism) and one with newly diagnosed subclinical hypothyroidism

requiring therapy. Significant reduction of BMD was observed in 26 patients

(37%) from which 22 had osteopenia (Z score K1 to K2.5) and four had

osteoporosis (Z score !K2.5). Reduced BMD correlated positively with low

BMI (P!0.01), while no correlation was found with viral load, CD4C, smoking,

25OHD3 and gonadal hormones’ concentrations (PO0.05).

EP238

Conclusion

Teriparatide discontinuation in a patient with post surgical

In treatment - naïve HIV-infected male patients, the most frequently observed

hypoparathyroidism: a clinical challenge

endocrine disorder is reduced BMD, which does not seem to correlate with HIV

Alessandro Brancatella, Matteo Apicella, Emilio Fiore, Giovanni Ceccarini,

infection markers. In patients with low BMI, measurement of BMD would be

Edda Vignali, Claudio Marcocci, Paolo Vitti & Eleonora Molinaro

helpful for early diagnosis of reduced bone mass and the prevention of further loss

Department of Endocrinology and Metabolism, Univesity of Pisa, Pisa,

by using the most suitable antiretroviral therapy.

Italy.

DOI: 10.1530/endoabs.49.EP239

Context

Teriparatide may represent a possible treatment for hypoparathyroidism when

oral supplementation with calcium and calcitriol fail to maintain adequate serum

calcium level (SCL). The switch from teriparitide to oral calcium and calcitriol

could be challenging and there is no consensus for clinical management.

Case presentation

EP240

A 50-year-old man was admitted at our Department for teriparatide discontinuation.

Three years before admission, the patient underwent total thyroidectomy for a

Trabecular bone score is negatively associated with bone resorbtion

multinodular goiter. Three months after thyroidectomy, the patient was admitted to

markers in patients with primary hyperparathyroidism

the intensive care unit for the onset of symptomatic hypocalcemia. Laboratory exams

Daniel Grigorie^1,2, Mirela Ivan², Andra Caragheorgheopol², Diana Paun² &

were consistent with hypocalcemia related to post-surgical hypoparathyroidism. The

Alina Sucaliuc^1,2

patient was discharged with calcium carbonate and calcitriol therapy but in the

¹Carol Davila University of Medicine, Bucharest, Romania;

following months the patient was re-admitted several times to the E.R. for the

²National Institute of Endocrinology, Bucharest, Romania.

recurrence of symptomatic hypocalcemia. Therefore in addition to the oral therapy,

teriparatide was introduced. After two years of treatment, teriparatide has been

Objectives

discontinued in accordance to the national drug administration (AIFA) authorizing

Mean TBS (Trabecular Bone Score) values are generally lower in PHPT (primary

regulations. At the admission, the physical examination was normal. Laboratory

hyperparathyroidism) patients than controls. The aim of this study was to assess

exams were notable for low SCL and an elevated serum TSH level despite high dose

TBS from spine DXA images in patients with PHPT and look at its correlates.

of Levothyroxine supplementation (250 mcg/d). After teriparatide discontinuation

Methods

SCL progressively decreased (6,5 mg/dl) with the onset symptoms of hypocalcemia,

This was a cross-sectional study conducted in an osteoporosis referral center. One

despite high doses of calcium carbonate and calcitriol. Further investigations revealed

hundred and thirty six patients with PHPT were selected from our database

an atrophic autoimmune gastritis, confirmed at gastroscopy. It was decided to switch

(2010-2016) if they had a valid LS DXA scan. The patients were both females

from calcium carbonate to calcium citrate and to modify patient’s diet. SCL slowly

(20% premenopausal) and males (12%), mean age 59.4 yrs (range 16-83), with

increased up to 8,6 mg/dl so that the patient could be discharged. In six months, no

both asymptomatic and symptomatic PHPT (mean PTH 226 pg/ml, mean serum

symptomatic hypocalcemia occurred and the SCL were stable with oral therapy.

calcium 11.3 mg/dl); a third of the patients were severely vitamin D deficient

Conclusions

(!10 ng/ml). TBS indices were derived from LS-DXA images and cutoff points

Teriparatide discontinuation in patients treated for hypoparathyroidism is

used in term of fracture risk were those previously reported.

challenging and clinically does not differ from “hungry bone syndrome” after

Results

parathyroidectomy. Furthermore calcium citrate could be an alternative to

Mean TBS values of the group was 1.26G0.12. TBS Z-score was negatively

calcium carbonate in patients with achlorhydria.

and significantly correlated with serum PTH, serum Calcium, Osteocalcin

DOI: 10.1530/endoabs.49.EP238

(rZK0.275, PZ0.005) and mostly C-telopeptide

(rZK0.314, PZ0.001).

Actually TBS values and both T and Z scores correlated negatively and

significantly with serum C-telopeptide. TBS was in the partially degraded range

but did not differ by vitamin D status, even when compared with severely

deficient patients

(35 pts, mean TBS 1.25). PTH correlated negatively with

25OHD and TBS correlated strongly (rZ0.536) with aBMD.

Conclusion

We observed a good and negative correlation between TBS and serum

EP239

C-telopeptide which favor the notion that TBS might reflect degraded

Endocrine disorders in treatment-naïve male patients with HIV

microarchitecture.

infection

DOI: 10.1530/endoabs.49.EP240

Nikolaos Kalogeris¹, Markella Nezi¹, Maria Chini², Athina Lioni²,

Vissaria Sakka², Nikolaos Mangafas², Styliani Kaoustou², Marios Lazanas²

& Andromachi Vryonidou¹

¹Department of Endocrinology, Diabetes and Metabolism, Red Cross

General Hospital, Athens, Greece;²Infectious Diseases Unit, Red Cross

General Hospital, Athens, Greece.

EP241

Objective

Normocalcemic primary hyperparathyroidism (NPH)

To investigate endocrine disorders concerning bone metabolism, thyroid and

Cristina Corina Pop-Radu^1,2

gonadal axis in treatment-naïve HIV-infected male patients.

¹University of Medicine and Pharmacy, Tirgu Mures, Transilvania,

Subjects and methods

Romania;²Mures Clinic County Hospital, Tirgu Mures, Transilvania,

We studied 70 male, treatment-naïve patients (stage AZ60, stage BZ10) from

Romania.

the Infectious Diseases Unit of our Hospital. Anthropometric indices were

measured and BMI was calculated for each participant. Blood samples were

obtained after an overnight fasting for the evaluation of thyroid hormones,

Normocalcemic primary hyperparathyroidism (NPH) is characterized by normal

25OHD3, gonadotropins, total testosterone, sex hormone binding globulin

total and ionized serum calcium concentrations and consistently elevated PTH

(SHBG) levels. Free Androgen Index

(FAI) and bioavailable testosterone

levels. These patients have no obvious causes for secondary elevations of PTH,

(BAT) were calculated. Bone mineral density (BMD) in the lumbar spine and

such as renal disease, vitamin D deficiency or malnutrition. The group consisted

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

of 22 postmenopausal women, six premenopausal women, and two men, aged

Trabecular bone score (TBS) is a recent noninvasive analytical method, based

58G2 years (range 31-77) investigated between 2011 and 2016.

upon DXA images, related to bone microarchitecture or bone quality; together,

Results

TBS and DXA may evidence bone strength. Falls and osteoporotic fractures

All subjects had normal renal function and

25-hydroxyvitamin D levels

increase with ageing, while both BMD and vitamin D levels slowly decline. Data

O20 ng/ml (80% had levels O30 ng/ml); none used thiazide diuretics or lithium

about the influence of vitamin D on the TBS are scarce.

or demonstrated significant hypercalciuria. The reasons for referral included

Aim

elevated PTH discovered during the evaluation of low bone mass (nZ22), recent

To evaluate the influence of the blood vitamin D levels on the TBS in normal men.

fragility fracture (nZ2), nephrolithiasis (nZ6).

Material and methods

At the time of diagnosis, 70% had osteoporosis by BMD (measured at the lumbar

The lumbar spine BMD (g/cm²), and TBS (obtained from DXA scans) were

spine, hip or distal one-third of the non-dominant radius), 6.6% had documented

evaluated in a group of normal men more than 40 years old. Fasting blood was

fragility fractures, and

20% had nephrolithiasis. PTH was elevated, while

collected for osteocalcin, 25(OH)D and iPTH measurements. This group was

albumin-corrected serum calcium, serum phosphorus, alkaline phosphatase

divided in normal, insufficiency and deficiency vitamin D groups (ES Guidelines)

activity, and urinary calcium, were all in the mid-normal range.

and also in normal BMD, low BMD and osteoporosis groups. Total body fat and

Nine patients with positive localization studies

(cervical ultrasonography,

lean masses were also assessed by DXA. Adequate statistical tests were used

technetium 99 m sestamibi scanning) underwent successful parathyroidectomy,

(statistical significance P!0.05).

with operative findings of a single adenoma or hyperplasia. Twenty one patients

Results

who did not undergo surgery were followed for 3.1G0.3 years (annual serum

The mean (GS.D.) BMD and TBS of the vitamin D groups are shown in Table 1.

calcium, PTH and bone mineral density determinations). Hypercalcemia

Men of the deficiency vitamin D group were the heaviest and had the lowest TBS.

developed in 19% of these individuals. Two of the patients who developed

Significant relations were detected between the blood 25(OH)D vs. TBS, vs.

hypercalcemia and three additional patients with persistently normal serum

weight and vs. total fat mass but not vs. BMD.

calcium levels underwent successful parathyroidectomy. Fourteen patients were

Conclusions

without significant change in serum calcium or development of hypercalcemia,

Blood 25(OH)D levels may play an important role on the bone microarchitecture

PTH continued to remain elevated.

(by TBS) in vitamin D deficient men, as they have worse bone quality. These data

DOI: 10.1530/endoabs.49.EP241

suggest that further studies are needed on larger cohort of men and it might be

worth to investigate also elderly men with osteomalacia.

Table 1

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Groups

Normal

Insufficiency

Deficiency

Secondary hyperparathyroidism and its implication on bone mineral

Variable

(49.3%)

(37.7%)

(13.0%)

density in patients with different stages of chronic kidney disease

Natalia Karlovich

TBS L₁-L₄

1.044

(G0.14)

1.087

(G0.16)

1.079(G0.15)

0.0071

Minsk City Endocrinology Dispensary, Minsk, Belarus.

L₁-L₄ BMD

1.294

(G0.12)

1.323

(G0.12)

1.434

(G0.07)

NSD

g/cm²

Secondary (SHPT) is frequent in patients with chronic kidney disease and can

DOI: 10.1530/endoabs.49.EP243

predispose patients to low bone mineral density (BMD). Necessity of BMD

assessment in such patients is controversial.

The aim was to analyze BMD and PTH secretion in patients with different stages

of chronic kidney disease. We examined 311 patients, 161 f, 150 m; age 49.2G

14.4 yrs; 190 patients are on continuous dialysis due to end-stage chronic kidney

disease (mean dialysis duration 4.9G3.9 yrs), 121 patients with CKD 1-5 not on

dialysis. Serum PTH was measured and BMD was estimated by DEXA in lumbar

spine and in proximal part of femur, T score !K2.5 was classified as low BMD.

Median PTH level was 314.1 pg/ml (119.2; 770.7) in dialysis patients and 149.0

EP244

(65.2; 259.7) in patients with CKD 1-5 not on dialysis (P!0.05). PTH was above

Neutrophil lymphocyte ratio in 6 month teriparatide therapy of

upper limit of the reference range in all dialysis patients and in 51.6% of them was

osteoporosis

300 pg/ml and higher. SHPT was revealed in all patients with CKD 4-5, in 38.1%

Bengur Taskiran¹, Goknur Yorulmaz², Guven Baris Cansu¹ &

of patients with CKD 3; in 25.3% of those with CKD 1-2. In dialysis patients

Aysen Akalin²

low BMD was revealed in 24.7% of cases, significant implication of PTH level

¹Yunus Emre State Hospital, Eskisehir, Turkey;²Osmangazi University,

O300 pg/ml on low BMD development was revealed. In patients with CKD 1-2

Eskisehir, Turkey.

there were no cases of low BMD, with CKD 3-19.1%, with CKD 4 and CKD

5-33.3% (P!0.05). Prevalence of low BMD was 10.7% in non-dialysis patients

with normal PTH and 29.7% - with SHPT (P!0.05).

Aim

We can assume that frequency of low BMD is 25% and higher in patients with

Low BMD and atherosclerosis may share similar underlying biological

CKD 4-5 and secondary hyperparathyroidism significantly implicates on its

mechanisms including higher serum phosphate and inflammation. Neutrophil-

development. Future investigation is required to evaluate clinical implication of

lymphocyte ratio (NLR) as a simple marker of inflammation. There are scarce

DEXA in patients with SHPT for fracture risk assessment.

data indicating improved atherosclerosis and cardiovascular events with

biphosphonate and teriparatide therapy. We aimed to evaluate NLR before and

DOI: 10.1530/endoabs.49.EP242

after

6 months of teriparatide therapy in patients with severe established

osteoporosis.

Methods and materials

Electronic data of 53 (49 female, four male) patients with severe osteoporosis and

history of fracture of femur neck and/or lumbar spine were evaluated. None of

EP243

them were previously diagnosed with rheumatoid arthritis, DM, and secondary

Impact of vitamin D on the bone quality assessed by trabecular bone

osteoporosis. Sixteen had with HT and/or other cardiovascular disease.

score in men

Results

Mário Rui Mascarenhas^1,2, Ana Paula Barbosa^1,2, Nuno Duarte²,

Mean age was 74G9 years, baseline 25 OH vitamin D level 25.6G17.6 ng/ml,

Ana Wessling^2,3, Ana Raquel Coelho Gomes³, Carolina Faria³,

baseline NLR 2.22G0.89, 25 OH vitamin D level at 6th month 27.8G13.4 ng/ml,

Raquel Paixa˜o3, David Barbosa3, Catarina Silvestre3, José Poupino2,

NLR at 6th month 2.10G0.96.

Vânia Gomes³, Ana Sofia Osório³, Francisco Sampaio², Jacinto Monteiro²,

Mean baseline and

6^th month measurements of NLR,

25 OH vitamin D,

Didier Hans⁴, Manuel Bicho¹ & Maria João Bugalho^2,3

parathormone, ALP, ESR, and phosphorus were similar in patients with and

¹Endocrinology and Metabolic Diseases, Faculty Medicine of Lisbon,

without cardiovascular disease. NLR did not change significantly after 6 months

Lisbon, Portugal;²Fracturary Osteoporosis Outpatient Clinic - Endo-

of teriparatide therapy.

crinology, Diabetes and Metabolism Department, Santa University Maria

Conclusion

Hospital-Chln, Epe, Lisbon, Portugal;³Endocrinology, Diabetes and

NLR does not change in short term teriparatide therapy and association between

Metabolism Department, Santa University Maria Hospital-Chln, Epe,

osteoporosis and cardiovascular disease cannot be settled in advanced age.

Lisbon, Portugal;⁴Bone Center, Lausanne University Hospital, Lausanne,

DOI: 10.1530/endoabs.49.EP244

Switzerland.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

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Calcium & Vitamin D Metabolism

Analysis of DXA scans of males performed in clinical center of

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vojvodina

Management with Cinacalcet of non-surgical primary

Bojan Vukovic^1,2, Jovanka Novakovic Paro^1,2, Tijana Icin^1,2, Ivana Bajkin¹,

hyperparathyroidism in the elderly.

Djordje Popovic^1,2, Milica Medic Stojanoska^1,2, Radoslav Pejin^1,2 &

Juan Marti¹, Jose Luis Salsamendi¹, Jon Marti-Ayerdi² & LLuis Jordana¹

Edita Stokic^1,2

¹Hospital Zumarraga, Zumarraga, Spain;²Complejo Hospitalario Navarra,

¹Clinical Center of Vojvodina, Clinic for Endocrinology, Diabetes and

Pamplona, Spain.

Metabolic Diseases, Novi Sad, Serbia;²Medical Faculty University of Novi

Sad, NOvi Sad, Serbia.

Primary hyperparathyroidism (PHPT) is a common condition. The prevalence

since the introduction of multichannel analysers is approximately 1:1000, with the

The prevalence of osteoporosis among men is not well-documented. The aim of

older female being the typical patient. PHPT is predominantly a sporadic disorder.

this cross-sectional study is to analyze results of DXA scans preformed in males

Surgery remains the only curative approach to most primary hyperparathyroidism

in Clinical center of Vojvodina between years 2009 and 2016. Form the total of

(PHPT), medical treatment with cinacalcet has been proven to be an alternative

2006 fist DXA scans performed in 7 years period there was 14.8% of males. DXA

for patients with hyperparathyroidism.

scan was indicated by the rheumatologists, internists and endocrinologists

Objective

predominantly for suspected secondary causes of osteoporosis. We divided male

Analyze treatment with cinacalcet, in older patient with primary hyperparathyr-

subjects in groups by the age of life. In the group from 20 to 50 years of life there

oidism not tributary of surgery.

was 68 subjects with average BMI 26.5G6.30 kg/m² with average T score in L1-

Material and patients

L4 K0.8G1.4 S.D., bone mineral density (BMD) was 1.152G0.184 g/cm², and

Between 2011 and 2015, 13 patients with PHPT who were not suitable for surgery

femur neck K0.71G1.2 S.D., BMD 0.959G0.176 g/cm², 9 subjects had Z score

were identified. Data collected: age, gender, comorbidities, levels of calcium and

! 2 S.D. In the group form 50 to 70 year of life (average 60.38G4.82, BMI

PTH and follow-up.

27.93G5.31 kg/m²) there was 174 subjects with T score L1-4: K0.82G1.93 S.D.,

Results

BMD 1.120G0.231 g/cm², left femur neck: K1.41G1.36 S.D., BMD 0.887G

We present 13 patients 8 women and 5 man with a mean of age 80.5G6.59 year-

0.176 g/cm². 56 had osteopenia and 49 had osteoporosis. Group above 70 years of

old (range 71-92). Comorbidities, diabetes mellitus 50%, frailty 58%, heart

life (88 maximum, average 75.6G3.96, BMI 25.17G4.16 kg/m²) had 55 subjects

disease

40%, depression

33%, cognitive impairment

17%. Calcium levels

from whom 22 had osteopenia and 23 osteoporosis and average T score L1-L4

previous treatment was

11.85G0.28 mgr/dl and PTH

123G34 pg/ml. T

was: K0.85G2.12 S.D., BMD 1.115G0.255 g/cm², left femur neck: K1.84G

cinacalcet 30 mg. daily was initiated, in 12 patients and 60 mgr. in one. Patients

1.25 S.D., BMD 0.829G0.161 g/cm². Lower values of T score and BMD were

were followed for 1-4 years (2.75G1.21) calcium were adequately controlled

measured on left femur neck in older groups. There was very high percentage of

(9.98G0.78 mgr/dl), but PTH 112.4G42 pg/ml remains high, renal function was

osteoporosis and osteopenia in the oldest groups of males although all males

uncharged in all patients. Two patients died during the follow-up, not related with

referred to DXA scan were suspected to have osteoporosis.

hyperparathyroidism. Adverse events were observed in 1 patient (vomiting) that

DOI: 10.1530/endoabs.49.EP245

disappeared to diminishing doses.

Discussion

Geriatricians will readily recognize the clinical conundrum of an incidental

finding of PHPT in the older that was unexpected. Retrospective questioning may

identify some pertinent symptoms, but none strong enough on their own to have

made the diagnosis obvious prior to testing serum calcium. This group of patients

is hard to define and hence there is little published guidance on how to manage the

increasingly common clinical scenario of the frail, relatively asymptomatic, older

patient with PHPT.

Conclusions

Cinacalcet, the first available calcimimetic, increases the sensitivity of the

EP246

calcium-sensing receptor (CaR) to circulating serum calcium, thereby safely

Biological assessment and causes of secondary osteoporosis

reducing serum calcium and PTH concentrations in patients with mild-

Aicha Bouzid & Djamila Meskine

to-moderate PHPT, intractable disease, and also parathyroid carcinoma.

Dr, Algiers, Algeria.

Cinacalcet in a reasonable and safe alternative to treatment of PHPT not tributary

of surgery.

DOI: 10.1530/endoabs.49.EP247

Secondary osteoporosis accounts for 10-20% of the causes of osteoporosis in

menopausal women. The search for a possible etiology should not be neglected

before considering the therapeutic management of any osteoporosis. There is no

consensus on the first-line biological tests to be prescribed.

Goal

Determine biological abnormalities in postmenopausal women with osteoporosis.

Patients/methods

Postmenopausal women are enrolled, the mean age is 65.5G8.9 years. 305

patients are classified as osteoporotic according to the WHO criteria (T-score

%2.5). NFS, VS, CRP, serum calcium, phosphoric acid, 24-hour calcium, total

EP248

alkaline phosphatase, parathyroid hormone (PTH), serum protein electrophoresis,

Glucocorticoids regulate expression of lung calbindin-D9k in mouse

serum creatinine, liver function test, fasting blood glucose.

Jin Yong An, Jae-Hwan Lee, Seon Yong Park & Eui-Bae Jeung

Results

Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

6.2% (19/305) patients had an abnormality.

Distribution of anomalies

Monoclonal gammopathy five cases: two myeloma, two MGUS, one unlabeled

Introduction

case

Calbindin-D9k (CaBP-9k), which is a calcium ion buffering and transporter gene,

- HPT I: seven cases (two parathyroid adenomas confirmed by the anapath)

is known to be regulated by the vitamin D and steroid hormones, and is mainly

- 1 cases rheumatoid arthritis

expressed in mammalian intestine, kidney and uterus. However, CaBP-9k

- diabetes type two unknown: six cases, one case of intolerance to carbohydrates

expression in lung has not been studied. Maintaining lung structure using

Discussion/conclusion

pulmonary surfactant is important for pulmonary gas exchange. Steroids are

In the presence of a low BMD, it is recommended that a diagnostic survey should

known to accelerate maturation of the fetal lung and secretion of surfactant.

be carried out, including physical examination, clinical examination and routine

Otherwise the relationship between pulmonary function especially in surfactant

biological examinations, in order to eliminate malignant or metabolic osteopathy

secretion and CaBP-9k expression has not been researched. In this study, we

and to investigate the causes of secondary osteoporosis. In our study targeting a

investigate the CaBP-9k expression by sex steroid hormones and glucocorticoids

population of postmenopausal osteoporotic women followed in consultation, the

in mouse lung.

discovery by biological examination of a new condition that can lead to bone

Materials and methods

demineralization is quite common.

To confirm the effect of sex steroid hormones, the immature mice age from

DOI: 10.1530/endoabs.49.EP246

14 days to 16 days were respectively injected of estrogen (E₂) and progesterone

(P₄) for 3 days. To confirm the effect of glucocorticoids, the mature mice age from

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

11 weeks were respectively injected of dexamethasone (Dex). ER antagonist

EP251

(ICI187,780) and PR, GR antagonist (RU486) were injected 30 min prior to

Gitelman syndrome and primary hyperparathyroidism - a rare

steroid hormones. We compared the changes in the CaBP-9k expression of each

association

group using polymerase chain reaction.

Teresa Rego, Fernando Fonseca & Ana Agapito

Results

Endocrinology Department, Centro Hospitalar de Lisboa Central, Lisbon,

In the estrogen and progesterone treated immature mice lung, the CaBP-9k gene

Portugal.

expression had no significant change in mRNA and protein level but significantly

increased in Dex treated mice lung. It is suggested that glucocorticoids may play a

role in regulation of CaBP-9k expression in lung.

Gitelman’s Syndrome (GS) is a rare autosomal recessive salt-losing tubulopathy

Conclusion

of young adults, characterized by secondary hyperaldosteronism, hypokalemia,

Our results has significance to the regulation of CaBP-9k by Dex. By studying the

hypomagnesemia, hypocalciuria and metabolic alkalosis. It is caused by

effects on lung surfactant through the control of CaBP-9k, it may be presented as a

mutations in SLC12A3 gene. Hypercalcemia due to hypocalciuria in these

basis data of pulmonary surfactant associated disease or research.

patients is extremely rare and requires further evaluation.

DOI: 10.1530/endoabs.49.EP248

A 25-year-old normotensive female was referred to Endocrinology clinic for

evaluation of persistent hypokalemia. She presented history of malaise, fatigue,

myalgias, cramps and paresthesia. She denied diarrhea, recent treatment with

diuretics or laxatives. Her physical exam was normal. Laboratory workout

revealed: aldosterone 47.1 ng/mL (r.v. 4-31), active renin 374.7 mUI/ml (r.v. 4.4-

46.1), KC2.7 mEq/l (r.v. 3.5-5.1), 24 h urinary KC84.7 mEq/24 h (r.v. 25-125),

Mg2C0.71 mg/dl (r.v. 1.6-2.6), 24 h urinary Mg2C143.1 mg/24 h (r.v. 73-122),

Ca2C12 mg/dl (r.v. 8.4-10.2) and 24 h urinary Ca2C133 mg/24 h (r.v. 100-

EP249

300). GS was diagnosed and she was treated with spironolactone, oral K^C and

Vitamin D intoxication caused hypercalcemia: Case report

Mg^2C supplementation. Further investigation confirmed hypercalcemia due to

Kader Ugur¹, Hakan Artas², Mehmet Balin³, Esra Aykut⁴,

primary hyperparathyroidism

(parathyroid hormone

(PTH) 107.3 pg/ml (r.v.

Selcuk Demircan⁴, Bedrettin Orhan⁴ & Nevzat Gozel⁴

14.8-83.1)) caused by a large single parathyroid adenoma. Following

¹Firat Univercity Department of Endocrinology, Elazig, Turkey;²Firat

parathyroidectomy calcium profile normalized. The sequencing of SLC12A3

Univercity Department of Radiology, Elazig, Turkey;³Firat Univercity

gene detected the variant c.602-16GOA and the mutation c.2221GOA

Department of Cardiology, Elazig, Turkey;⁴Firat Univercity Department of

(p.Gly741Arg), both in heterozygosity. In this context genetic study of the

Internal Medicine, Elazig, Turkey.

progenitors was required. The father presents the variant c.602-16GOA and the

mother the mutation c.2221GOA (p.Gly741Arg), in SLC12A3 gene.

Introduction

The assotiation of hypokalemia, hypomagnesemia and hypercalcemia is

Vitamin D is a fat soluble prohormone and can be produced in the body with

uncommon but potentially lethal. Current knowledge favors that hypomagnese-

adequate sunlight exposure or taken up by consumed foods or supplements.

mia in GS’s patients protects them from hypercalcemia. In this context of multiple

Recently vitamin D deficiency has been seen in pandemic. A rare disease, vitamin

electrolyte imbalances, correction of hypomagnesemia is a challenge and should

be done carefully. Like in our patient hypercalcemia’s etiology should be prompt

D intoxication is usually iatrogenic. High levels of 25(OH) vitamin D increases

diagnosed and reversed.

the intestinal calcium absorption and causes severe and refractory hypercalcemia.

In this case report we presented a patient with pancreatitis and hypercalcemia

DOI: 10.1530/endoabs.49.EP251

secondary to vitamin D intoxication.

Case

79-years-old female patient presented to emergency department with generalized

pain, lack of appetite, dry mouth, nausea, vomiting and abdominal pain. Serum

calcium level was 13.8 mg/dl. In her medical history she used 12 ampules of

vitamin D-3 in the last month. In her physical examination there was abdominal

tenderness. Laboratory findings were as follows; 25-OH vitamin D-3: 455 mg/l

(20-150), WBC: 19 570 10e3/ml (3.8-8.6), Urea: 60 mg/dl (10-50), Creatinine:

2 mg/dl (0.6-1.2), Ca: 13.8 mg/dl (8.5-10.8), phosphorus: 2.9 mg/dl (2.6-4.5),

albumin: 3.7 mg/dl (3.5-5.5), amylase: 132 U/l (28-100), Lipase: 115 U/l (7-60),

Parathormone: 28 pg/ml (19.8-74.9). Abdominal CT scan showed interstitial

EP252

oedematous pancreatitis. In the follow up, patient was hydrated with isotonic

The volume of parathyroid adenoma is related to presurgical PTH and

saline infusion. To lower the calcium levels, intravenous furosemide infusion was

25OH-D3, but not calcium levels at patients with primary

used. Calculated QTc level when serum calcium is 9.1 mg/dl, was 443 msec.

hyperparathyroidism

According to literature we could see osborn wave in the ECG but we did not.

Cristian Velicescu¹, Cristina Gatu¹, Alexandru Grigorovici¹, Radu Danila¹,

Discussion

Valentin Munteanu², Voichita Mogos¹, Carmen Vulpoi¹, Cristina Preda¹,

Vitamin D toxicity develops when serum levels of 25 OH vitamin D-3 levels

Simona Mogos¹ & Dumitru D Branisteanu¹

reach 150 ng/ml or above and daily intake should exceed 10.000 IU. In the

¹University of Medicine and Pharmacy ‘Gr.T.Popa’, Iasi, Romania;

treatment, cessation of vitamin D intake and controlling of hypercalcemia is

²University of Medicine and Pharmacy ‘Iuliu Hatieganu’, Cluj, Romania.

mandatory. Limiting daily calcium intake, hydration, loop diuretics, corticoster-

oids, calcitonin and bisphosphonates can also be used. Dialysis can be performed

to those who are refractory to these treatment modalities.

Aims

Conclusion

We wanted to evaluate the correlations between the volume of the surgically

Uncontrolled and over the counter use of vitamin supplements is a common issue

removed parathyroid adenoma and the presurgical metabolic profile of patients

worldwide. Patients who need vitamin D supplements should be followed with

diagnosed with primary hyperparathyroidism.

laboratory and clinically.

Materials and methods

Prospective multicentric study, enrolling 52 patients with primary hyperpar-

DOI: 10.1530/endoabs.49.EP249

athyroidism from two medical units, proposed for surgery. Serum calcium and

PTH were evaluated in all patients before surgery, and 25OH-D3 was measured

only in the 33 patients recruited from one of the two surgery departments.

Parathyroid volume was measured immediately after excision, using the formula

of a rotating ellypsoid. Data were statistically evaluated by using Pearson

correlation analysis. Correlations were considered significant at P values lower

than 0.05.

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Results

We observed a significant correlation between the volume of parathyroid

adenomas and presurgical PTH (P!0.001) but not presurgical calcium levels at

Abstract withdrawn.

patients from the two medical units and in the whole group. Twenty-nine out of

the 33 patients diagnosed with primary hyperparathyroidism recruited from the

first medical unit had 25OH-D3 levels in the range of vitamin D deficiency or

insufficiency. 25OH-D3 was not significantly correlated with PTH or calcium

levels, but a significant negative correlation was found between the volume of the

parathyroid adenoma and serum 25OH-D3 levels (P!0.05).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

Objectives

The volume of parathyroid adenoma seems to be related to presurgical PTH and

To evaluate the efficacy and safety of cinacalcet in patients with PHPT who were

25OH-D3, but not calcium level. D hypovitaminosis is frequently found at

unfit for surgery, refused surgery or remain hypercalcaemic post-parathyroi-

patients with primary hyperparathyroidism and may contribute to particular

dectomy and not amenable to further intervention (complex PHPT).

disease profiles. Higher PTH and lower 25OH-D3 levels, as well as larger

Methods

adenomas may be accompanied by increased disease severity, or by a different

We assessed the demographic and clinical characteristics and biochemistry in 12

spectrum of disease complications.

patients seen in endocrinology and biochemistry clinics with complex PHPT at

DOI: 10.1530/endoabs.49.EP252

the commencement of cinacalcet and after approximately 1, 3, 6 and 12 months.

We also checked doses, tolerability and side effects of cinacalcet.

Results

Most patients (66.67%) needed small maintenance dose of cinacalcet once a day.

Mean baseline adjusted calcium level was 3.36 mmol/l (13.44 mg/dl) with a range

of 2.91-5.36 mmol/l (11.64-21.44 mg/dl). There was a significant reduction in

adjusted calcium levels at approximately 1 month (10.08%), 3 months (11.93%),

6 months (13.57%) and 12 months (20.17%). Calcium normalised in most patients

(83.33%), and one patient developed hypocalcaemia necessitating cinacalcet dose

reduction. All patients adhered to the treatment with two people experiencing

self-limiting nausea and vomiting.

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Conclusion

Our patient cohort indicates that cinacalcet is an effective and safe alternative to

Pseudohypoparathyroidism type Ib: a case of chronic severe

surgery in patients with complex PHPT. Cost-effectiveness analyses are needed to

hypocalcaemia and seizures diagnosed in adulthood

allow more widespread use in such patients. Further studies with long-term

Ana Cláudia, Martins, Paula Bogalho & Ana Agapito

follow-up are required to assess efficacy in preventing osteoporosis and renal

Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,

complications related to PHPT.

Portugal.

DOI: 10.1530/endoabs.49.EP254

Pseudohypoparathyroidism

(PHP) is a rare group of genetic disorders

characterised by end-organ resistance to parathyroid hormone

(PTH). We

describe the case of a 34-year-old Caucasian female with severe hypocalcaemia

presenting with a first generalised seizure. Her medical history was significant for

bilateral cataract. She had three healthy children, and no family history of note.

On examination, she had positive Chvostek’s sign. Biochemical analysis showed

serum calcium 4.5 mg/dl (n.r. 8.4-10.2 mg/dl), phosphorus 5.8 mg/dl (n.r. 2.3-

4.7;mg/dl), PTH 94.7 pg/ml (n.r. 14.76-73.1 pg/ml) and vitamin D 19.6 ng/ml

(n.r.

30-100 ng/ml), with normal serum albumin and normal alkaline

phosphatase. Electrocardiogram demonstrated prolonged corrected QT interval.

EP255

Brain imaging revealed basal ganglia and cerebellar calcifications, and

Is there a threshold of Vitamin D sufficiency that can prevent secondary

electroencephalography did not show paroxysmal activity. We excluded a

hyperparathyroidism?

number of causes of secondary hyperparathyroidism based on her medical history

André Amaral¹, Tatiana Nunes³, João Anselmo² & Rui César²

and investigations, and concluded that PTH resistance would be the most likely

¹Unidade de Saúde Ilha do Faial, Horta, Faial/Ac¸ores, Portugal;2Hospital

diagnosis. Since she lacked the typical clinical features of Albright hereditary

Divino Espírito Santo, Ponta Delgada, São Miguel/Ac¸ores, Portugal;

osteodystrophy and did not present with other hormones’ resistance, a genetic test

³Unidade de Saúde Ilha de São Miguel, Ponta Delgada, São Miguel,

was requested and identified abnormal methylation of the 20q13.32 region,

Portugal.

confirming the diagnosis of PHP type Ib. The patient is currently medicated with

calcium carbonate and calcitriol, maintaining a satisfactory calcium-phosphate

homeostasis. This case highlights the importance of PHP as a rare but significant

While nonskeletal benefits of vitamin D remain a matter o debate, its importance

cause of severe hypocalcaemia. The delayed diagnosis, as seen in this case, may

in bone health is known for decades. Secondary hyperparathyroidism is

result in serious consequences.

considered to play a significant role in the pathogenesis of age-related bone

DOI: 10.1530/endoabs.49.EP253

loss. In the present study we investigate the association between serum PTH,

25-hydroxyvitamin (25(OH)D) and other clinically related variables in a cross

sectional sample of patients followed in an Endocrine consultation during the year

2016. Patients with diseases or medications known to affect calcium metabolism

were excluded. 509 participants, 365 female and 145 male, were selected for

analysis. Mean ageGS.D. was 52G16 yrs (2-86); 47% were diabetics; 31%

suffered of thyroid disorders and 7% were obese. The meanGS.D. serum level of

25(OH) D was 20.4G10.2 ng/ml; 17.8G8.7 ng/ml in measurements during

winter months and 23.4G10.04 during summer. In 61 patients (12% of the

sample) with more than one determination, there was a 51.9% increase in 25(OH)

D from a mean level of 16.81G9.3 ng/ml during winter to 24.94G11.2 ng/ml

EP254

during summer months

(P!0.02). Patients treated with statins presented

significantly lower levels of

25(OH)D than non-treated patients,

15.9G

A practice review of the use of cinacalcet in primary

6.7 ng/ml and 26G10.1 ng/ml, respectively (P!0.01).This difference remained

hyperparathyroidism

statistically significant after adjusting for age, sex and disease.

Rahat Tauni^1,2, Nida Ali² & Ritwik Banerjee²

We found an inverse relationship between 25(OH)D and PTH. The best fitted line

Cambridge University Hospitals, Cambridge, UK;²Luton and Dunstable

was obtained as a logarithmic expression of 25(OH)D (rZ0.65; P!0.001). There

University Hospital, Luton, UK.

was no further significant decrease in PTH for serum levels of 25(OH)D of more

than 25 ng/ml. In conclusion, more than half of our patients were Vit D deficient

Background

(!20 ng/ml) particularly elderly people treated with statins, but serum levels of

The treatment of choice for primary hyperparathyroidism (PHPT) is surgical

25(OH)D above 25 ng/ml are needed in order to prevent secondary hyperpar-

parathyroidectomy. Cinacalcet is the first calcimimetic approved by European

athyroidism. This value can be considered as the lower limit of Vitamin D

Medicines Agency (EMA) in 2008 for use in patients with PHPT who are not fit

sufficiency in the sample studied.

for surgery or refuse surgery. British National Formulary (BNF) recommends it

DOI: 10.1530/endoabs.49.EP255

for hypercalcaemia in PHPT where parathyroidectomy is inappropriate. The main

aim of treatment with cinacalcet is to keep calcium levels at safe levels.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP256

patients is important because of the consequences of untreated hyperparathyroid-

ism, which include nephrolithiasis, osteoporosis and atraumatic fractures.

Spontaneous remission of parathyroid adenoma due to parathyroid

apoplexy: a case report

DOI: 10.1530/endoabs.49.EP257

Cem Onur Kirac, Suleyman Baldane, Suleyman Ipekci & Levent Kebapcilar

Division of Endocrinology and Metabolism, Selcuk University Faculty of

Medicine, Konya, Turkey.

Introduction

Primary hyperparathyroidism

(PHPT) is a disease that is characterized by

elevated calcium and parathyroid hormone levels. The most common cause of

PHPT is the paratiroid adenoma and the first line treatment option is surgical

EP258

removal of the adenoma. Rarely, the haemorrhage in the lesion may cause the

Parathyroid carcinoma: experience of a Portuguese centre

spontaneous remission of the disease.

Carlos Tavares Bello¹, Sara Donato², Susana Prazeres², Helder Simoes² &

Case report

Valeriano Leite²

A 54-year-old woman patient with fatigue was referred to our department due to

¹Hospital de Egas Moniz, Lisboa, Portugal;²Instituto Portugues de

calcium level of 11.4 mg/dl (normal range: 8.4-10.2) and PTH level of 76.1 pg/ml

Oncologia Lisboa Francisco Gentil, Lisboa, Portugal.

(normal range: 15-65). Neck ultrasound examination revealed a 10!5 mm mass

lesion in the posterior-inferior region of the left lobe of the thyroid. Sestamibi

Introduction

scan showed activity in the same region with neck ultrasound. Surgical resection

Parathyroid Carcinomas are rare malignant neoplasms, accounting for less than

of the parathyroid adenoma was planned but the patient refused surgical excision

1% of primary hyperparathyroidism cases. Apart from certain genetic mutations,

because of personal reasons. One year after the diagnosis of PHPT, her calcium

no additional risk factors are known. Diagnosis is challenging in the absence of

concentration returned into the normal range (9.4 mg/dl), at the same time neck

metastatic disease since no consensual histological criteria have so far been

MRI showed a mass with a size of 19!13 mm, which was attached inferiorly to

developed. These neoplasms typically present with severe hypercalcemia and

the left lobe of the thyroid. The mass was diagnosed as hemorrhagic parathyroid

markedly elevated serum PTH levels. Treatment is surgical and despite frequent

adenoma because the mass was imaged as a high intensity area by T₂-weighted

metastatic disease at diagnosis, clinical course is usually indolent. The authors

MRI. At that time the sestamibi scan was negative. Six months after the

report the experience of a tertiary reference centre in Portugal regarding

haemorrhage of the lesion, it was seen that the calcium level rose to 11.1 mg/dl

parathyroid carcinomas.

and the PTH level was 89 pg/ml so the PHPT has been recurred.

Methods

Conclusion

Observational, retrospective study. Patients with diagnosed parathyroid carci-

Parathyroid apoplexy can lead to spontaneous remission of the PHPT but the

noma from 1999 until 2016 were included. Clinical data was obtained from

remission is usually temporary and finally recurrence of the disease could be seen.

patient’s clinical, laboratory and imaging files. Descriptive statistical methods

DOI: 10.1530/endoabs.49.EP256

were used and results are presented as mean and standard deviation.

Results

The sample is composed of ten patients (five females) with a median age of 53G

16.9 years at the time of diagnosis. Clinical presentation was heterogeneous. All

patients had hyperparathyroidism (mean 1229G642 pg/ml), nine hypercalcemia

EP257

(13.4G2.2 mmol/l) and four hypophosphatemia (2.1G0.6 mol/l). Histological

Normocalcemic versus Hypercalcemic Primary Hyperparathyroidism:

findings: intratumoral septa (50%), vascular, capsular, perineural invasion (70%,

a comparative study

80%, 10% respectively), extraglandular extension (50%). Mitotic index was

Natalya Mokrysheva, Svetlana Mirnaya, Anna Eremkina, Julia Krupinova &

evaluated in four patients. CDC73 mutations were present in four patients.

Elena Kovaleva

Metastases were present in one patient. All patients underwent en bloc resection

Endocrinology Research Centre, Moscow, Russia.

and three received external beam radiotherapy due to recurrent loco-regional

disease. After a mean follow up of 9 years, 90% are in remission and no mortality

has been documented.

Introduction

Conclusion

Normocalcemic primary hyperparathyroidism (NPHPT) is defined as a condition

The authors describe a series of ten parathyroid carcinoma patients. Despite the

in which persistently normal serum calcium levels are observed in the presence of

clinical and biochemical severity at the time of diagnosis, most patients achieved

high levels of parathyroid hormone (PTH). NPHPT is a new entity which possibly

sustained remission. Genetic mutations were identified in a significant proportion

represents a clinically symptomatic disease and which has generated a

of patients, having important clinical implications. This series is noteworthy for

considerable scientific interest.

the good outcome of such an aggressive neoplasm.

Aim

DOI: 10.1530/endoabs.49.EP258

To compare the clinical and laboratory data between the normocalcemic and

hypercalcemic forms of PHPT.

Materials and methods

A comparative study of 357 patients with PHPT wich were separated into

normocalcemic (nZ56) and hypercalcemic (nZ301) subgroups on the basis of

their fasting serum total calcium value. Bone mineral density

(BMD) and

T-scores were evaluated by densitometry of the lumbar spine, femoral neck and

EP259

total of the radius. Nephrolithiasis and bone fractures were documented by a

review of the medical records.

Vitamin D prescribing bias in liver transplant referrals

Results

KJ Gan¹, Niamh O’Sullivan², Bernadette Hanley¹, Paul Armstrong¹,

Patients with NPHPT had, on average, a lower serum PTH concentration

Mark Kilbane¹, Diarmaid Houlihan² & Rachel Crowley¹

150 pg/mlG115

15-65, Me

114) and a lower serum calcium level

¹Department of Endocrinology, St Vincents University Hospital, Dublin,

2.44 mmol/lG0.08 (N 2.15-2.55) vs hypercalcemic PHPT - 408 pg/mlG651

Ireland;²Department of Hepatology, St Vincents University Hospital,

(Me 186) and 2.89 mmol/lG0.3 respectively. There was no significant difference

Dublin, Ireland.

in urine calcium excretion. The frequency of nephrolithiasis was

27% in

normocalcemic patients and 16% in the hypercalcemic ones (P!0.05). There

Vitamin D (VD) deficiency (25 OHD ! 50 nmol/l) is common is chronic liver

were no statistical differences in relation to BMD of the lumbar spine and femoral

disease at 64%-92% regardless of aetiology. The only guidelines for routine VD

neck, but BMD significantly differed in the total radius area. BMD in the total

supplementation are for cholestatic (C) liver disease; a population considered

radius was

0.423 g/cm²

(Me 0.415), mean T-score was K2.2

S.D. of the

being at high risk of low bone mineral density (BMD). BMD decreases further

normocalcemic patients, 51.8% had osteoporosis in at least one of the three sites

following orthotopic liver transplant (OLT). To assess VD intake in an at risk

evaluated. In addition, normocalcemic patients differed from hypercalcemic

population, retrospective analysis of intake was performed in OLT patients with C

patients by lower values of markers of bone turnover osteocalcin and b-C-

liver disease; this was excellent at 81%. Prospective analysis comparing C with

telopeptide, P!0.05. 20.4% of normocalcemic patients had a previous history of

non-cholestatic (NC) patients at time of dietetics referral at OLT assessment was

fractures compared to 20.3% of hypercalcemic patients (PO0.05).

then undertaken (nZ94, 27% C and 73% NC). Median 25OHD in C patients was

Conclusion

86.7 nmol/l compared to 24.7 nmol/l in NC (P 0.001).

36% of C patients

NPHPT is at present one of the most common reasons for consultation in bone

compared to 76% of NC had 25OHD measurement of !50 nmol/l (P !0.0001).

metabolism departments, especially in postmenopausal women. Identifying these

48% of C patients compared to 16% of NC were receiving VD supplementation

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

before OLT assessment. We have observed a prescription bias at referral to

regulatory region. We present a patient who was detected PHP while following

transplant hepatology; VD is prescribed more frequently to C than NC patients

for epilepsy.

with end-stage liver disease, although both populations are at risk of reduced

Case report

BMD.

A 17 years old male patient referred to endocrinology clinic with paresthesias of

DOI: 10.1530/endoabs.49.EP259

the hands. He had under treatment due to epilepsy for 3 years. He had normal

mental activity and phenotypic features. His family history had no specialty. His

laboratory examination revealed hypocalcemia and hyperphosphatemia with a

calcium level 7.4 mg/dl (reference range, 8.5-10.5 mg/dl), phosphorus 6.8 mg/dl

(reference range, 2.5-4.5 mg/dl), albumin 4.4 g/dl (reference range, 3.5-5.2 g/dl),

magnesium 2.06 mg/dl (reference range, 1.8-2.6 mg/dl), 25 hydroxyvitamin D

EP260

(25

OHD) 64.3 ng/ml (reference range,

30-70 ng/ml) and PTH

115 pg/ml

How to differentiate primary hyperparathyroidism with D

(reference range, 15-65 pg/ml). His rest of the laboratory findings and ophthalmic

hypovitaminosis from secondary hyperparathyroidism due to D

examination were normal. Brain computed tomography scan showed basal

hypovitaminosis?

ganglia calcifications. Calcitriol and calcium supplements were started to patient

Alina-Andreea Gatu¹, Cristian Velicescu^1,2, Cristina Preda^1,2,

whose biochemical findings support PHP diagnosis. Genetic testing of the patient

Carmen Vulpoi^1,2, Simona Mogos^1,2, Voichita Mogos^1,2, Valentin Zaharia²,

did not show GNAS coding region mutation and we planned methylation study in

Adrian Aancute² & Dumitru Branisteanu^1,2

terms of methylation abnormality in GNAS regulatory region.

¹Gr. T Popa University of Medicine and Pharmacy, Iasi, Romania;

Conclusion

²St. Spiridon Emergency Hospital, Iasi, Romania.

PHP is an uncommon cause of hypocalcemia. Blood electrolytes must be called to

mind in case of epilepsy or neurological evidence. Early diagnosis and treatment

of PHP prevent complications.

Background

D hypovitaminosis and primary hyperparathyroidism frequently coexist.

DOI: 10.1530/endoabs.49.EP261

Secondary hyperparathyroidism reactive to D hypovitaminosis is difficult to be

differentiated from primary hyperparthyroidism.

Aims

To differentiate patients with D hypovitaminosis and secondary hyperparathyr-

oidism.

EP262

Materials and methods

Long standing primary hyperparathyroidism consequences after

Prospective study involving 71 patients admitted in our department for 1 year

parathyroid surgery: fast recovery not only for bone mass

with the initial diagnosis of primary hyperparathyroidism. Serum and urinary

Cristina Stefan^1,2, Amalia Arhire¹, Luminita Cima^1,3 & Carmen Barbu^1,3

calcium and phosphate, PTH and 25OHD3 were evaluated at admission. Patients

¹Endocrinology Department, Elias Hospital, Bucharest, Romania;²Ghencea

with vitamin D levels under 30 ng/ml were repleted with 2000 IU/day of 25OHD3

Medical Center, Bucharest, Romania;³Carol Davila University, Bucharest,

for 1 month and 1000 IU/day for other 5 months. Values between groups were

Romania.

compared using student’s t test. Correlations were evaluated by using Pearson

correlation analysis.

Results

Background

Forty-eight of the 71 patients had vitamin D deficiency (! 20 ng/ml) and 15 had

Primary hyperparathyroidism is usually a long evolving disease before the

vitamin D insufficiency (between 20 and 30 ng/ml), only eight having 25OHD3 of

diagnosis, thus patients who are not diagnosed by routine screening tests may

over 30 ng/ml. Both 25OHD3 and PTH levels normalized after 6 months of

have a lot of complications affecting the bone, kidney, bone marrow.

repletion with vitamin D in only 24 of the 63 patients with initial low 25OHD3

Aim

levels and they were therefore diagnosed with secondary hyperparathyroidism

Pointing out the possibility of fast recovery not only for bone mass.

(group S), whereas in the other 39 patients PTH levels remained elevated despite

Material

normalization of 25OHD3 levels, setting the diagnosis of primary hyperpar-

We present a case of primary hyperparathyroidism, a female patient 66 years old,

athyroidism associated with D hypovitaminosis (group P). Initial PTH was

sent to emergency room, dehydrated, asthenic, with important hip pain, low back

correlated with serum calcium in both groups, but with serum phosphate only in

pain. Her CaZ14.3 mg/dl, PTHO4000 pg/dl, HbZ8.5 g/dl, CT: osteolotic

group P. Initial PTH and serum and urinary calcium were significantly higher,

lesion, pubis and ischium fracture, two osteolithic lesions on the right acetabulum

whereas serum phosphate and radius BMD were significantly lower in the patients

and the S1 vertebra, bone biopsy: perytrabecullar fibrosis, aspects of bone

from group P when compared with patients from the group S (P ! 0.05).

remodeling and normal medullar celularity, DXA T score: total hip -3, L1-L4 -

Conclusions

1.8, forearm

-4.4. The complication in the moment of diagnostic were:

Patients with secondary hyperparathyroidism reactive to D hypovitaminosis are

osteoporosis, spontaneous fragility fractures, medular fibrosis with normocytic

frequent. Their PTH and electrolyte profile are only mildly modified, with a

normochromic anemia.

milder impact on bone mass than in primary hyperparathyroidism. A clear

Results

diagnosis could be, however, set only after vitamin D repletion.

Surgery was successful with the normalization of blood calcium and PTH.

DOI: 10.1530/endoabs.49.EP260

Questions were raised regarding the high level of PTH(neoplasia was taken into

account) and also the impact of medular fibrosis the on the prognosis of the

patient. After one year BMD was in age range, DXA T score: total hip -1.2, L1-L4

-0.2, forearm -2, anemia have remitted HbZ12.5 g/dl, and maintained during 2

years follow up.

Conclusion

EP261

In spite of high level of PTH and dangerous medular fibrosis, our case show

Pseudohypoparathyroidism as an etiological cause for epilepsy:

surgical recovery of bone mass but also of medular complications.

a case report

DOI: 10.1530/endoabs.49.EP262

Naile Gokkaya¹, Arzu Bilen² & Habib Bilen¹

¹Division of Endocrinology and Metabolism, Department of Internal

Medicine, Faculty of Medicine, University of Ataturk, Erzurum, Turkey;

²Department of Internal Medicine, Erzurum Training and Research

Hospital, Erzurum, Turkey.

EP263

Associations of nitric oxide with vitamin D and other serological factors

Introduction

in healthy adolescents

Pseudohypoparathroidism

(PHP) is a condition mimics hypoparathyroidism

Nasser Al-Daghri¹, Sobhy Yakout¹, Naji Aljohani², Yousef Al-Saleh²,

biochemically with a hypocalcemia and hyperphosphatemia but differentiates

Omar Al-Attas¹ & Majed Alokail¹

from it an elevated parathyroid hormone (PTH) levels. PHP characterized by

¹King Saud University, Riyadh, Saudi Arabia;²King Saud bin Abdulaziz

targeted organ unresponsiveness to PTH and mainly subdivided two groups. PHP

University for Health Sciences, Riyadh, Saudi Arabia.

type 1a an autosomal dominant disease related to mutations of GNAS1. This

subtype has biochemical findings and characteristic somatic phenotype known as

Albright Hereditary Osteodystrophy (AHO). AHO include short stature, round

Nitric Oxide

(NO) has been considered a very important molecule in the

face, brachydactyly, shortened metatarsals, subcutaneous ossifications and

biological system because of its interaction with other molecules for mediating

reduced intelligence. PHP type

1b has laboratory findings but do not has

various bio-pathways. Its interaction with vitamin D in particular studied well in

phenotype of AHO. This disorder caused by methylation defects of GNAS1

animal models, cell lines and patients with various diseases. However, the

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

relationship between NO and vitamin D has never been studied in healthy

Ca values within the normal ranges, patients were divided into two groups

adolescents. We aimed to determine the association of NO with vitamin D and

according to their PTH values 6 months after surgey (elevated PTH (ePTH) group

other serological factors in healthy Saudi adolescents. We recruited

740

(PTH R65 pg/ml) and low PTH (lPTH) group (PTH !65 pg/ml)). Fifteen

individuals (245 boys and 495 girls) from Riyadh, Saudi Arabia. Socioeconomic

patients were classified as having ePTH and 20 as IPTH. The frequency of ePTH

status, food habits, BMI and data regarding major medical complications were

was determined as 42%. The mean pre and postoperative PTH levels in ePTH and

recoded. Blood samples were performed for estimation of vitamin D, traces of NO

IPTH groups were 265G119, 94G32 and 206G136, 39G17 pg/ml, respectively.

and other possible serological parameters. Data revealed that NO has inverse

The mean pre and postoperative 25(OH) vitamin D3 levels in ePTH and IPTH

correlation with vitamin D but showed significant and positive association with

groups were 12G7, 22G11 and 22G14, 32G12 ng/ml, respectively.

serum triglycerides and systolic blood pressure. Here, it is suggested that some

Results

unknown limiting factors may restrict the relationship of NO and vitamin D in

Although ePTH group had higher preoperative PTH values as well as lower pre

healthy individuals. Therefore, the factors which limit the NO association with

and postoperative 25 (OH) vitamin D3 levels, there was no statistically significant

vitamin D and other molecules should be investigated in vitro and in vivo.

difference between the groups. For the remaining parameters, two groups had

DOI: 10.1530/endoabs.49.EP263

similar results.

Discussion

Several hypotheses have been proposed to explain the etiopathogenesis of

persistently elevated PTH values despite normal Ca levels following parathyroid

surgery. Suggested causes of this phenomenon include 25 (OH) vitamin D3

deficiency, secondary hyperparathyroidism resulting from insufficient renal

EP264

function, stimulation of PTH secretion induced by relative hypocalcemia

Primary hyperparathyroidism in pregnancy

postoperatively, and increased bone turnover. However, this condition may also

Belgin Efe¹, Goknur Yorulmaz¹, Sevil Alaguney¹ & Bartu Badak²

indicate possible recurrence due to multiglandular hyperplasia rather than a single

¹Division of Endocrinology, School of Medicine, Eskisehir Osmangazi

parathyroid adenoma.

University, Eskisehir, Turkey;²Department of General Surgery, School of

DOI: 10.1530/endoabs.49.EP265

Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.

Introduction

Primary hyperparathyroidism is the most common cause of hypercalcemia in the

general population. Hypercalcemia during pregnancy can result in significant

EP266

maternal and fetal morbidity and mortality.

Primary hyperparathyroidism mimicking metastatic bone disease

Case

Ali Burkan Akyıldız¹, Seda Sancak², Nalan Okurog˘ lu1, Kerem

A 30-year-old pregnant female primigravida in the 31 weeks of gestation with

Yig˘ it Abacar1, Elif Sakcı1 & Ali Ozdemir1

complaint of obstinate constipation was admitted to our emergency department.

¹Department of Internal Medicine, Fatih Sultan Mehmet Training and

In laboratory tests, hypercalcemia was detected. She was a Syrian refugee and

Educational Hospital, Istanbul, Turkey;²Division of Endocrinology and

was unable to communicate in English and Turkish. The parathyroid hormone

Metabolism, Fatih Sultan Mehmet Training and Educational Hospital,

(PTH) and albumin-corrected serum calcium levels were high. The results were

Istanbul, Turkey.

203

(12-65) pg/ml and 15.1 (8.5-10.5) mg/dl respectively. Urinary calcium

excretion rate was 440 mg/per day. Tubular phosphorus reabsorption rate was

73%, and the chlor/phosphorus ratio was 54.7. In the light of all these data,

We would like to present a case of primary hyperparathyroidism presumably

primary hyperparathyroidism was diagnosed. Ultrasound imaging revealed a

present with clinically large cystic parathyroid adenoma with multiple destructive

parathyroid adenoma (6!6!19 mm) at the inferior of the left thyroid lobe. In

skeletal lesions, which is of course referred to bone metastases.

our case we started 3000 cc salin infusion and furosemid treatment but her

Case

calcium levels didn’t decrease to safe range. Intravenous calcitonin was added to

A 58-year-old male patient was admitted to the orthopedy polyclinic with left leg

treatment but calcium levels didn’t decrease. We started to hemodialysis but still

pain and on the MR imaging performed here, multiple lytic lesions compatible

was calcium level O12.5 mg/dl. We followed up the patient in hospital until the

with metastasis to the tibia and fibula were detected. He was directed to our

baby’s lung maturation is completed. When the gestation reached the 35th week,

internal medicine clinic for further investigation. The patient had complaints of

parathyroid adenoma excision and caesarean section were performed concur-

widespread bone pain, especially the left leg which lasted for 2 months and was

rently. Post-operative calcium levels decreased. Hypocalcemia improved with

suffering from polydipsia. Biochemical tests showed elevated serum calcium

medical treatment in the newborn.

values and increased intact parathyroid hormone (iPTH), low phosphorus, high

Discussion

alkaline phosphatise, compatible with primary hyperparathyroidism. Erosive and

The main treatment modality of hyperparathyroidism is surgery but if

brown tumour like lesions were detected in bone x-ray. On PET CT imaging,

hyperparathyroidism is diagnosed in third trimester surgical approaches have

extensive, lytic and expansile lesions were observed, especially in the kranium

high risk. Because of the high risk, we trained our patient with medical treatment

and ribs. On the neck ultrasonography, a 50!30 mm sized, septated, irregular

at the hospital until safe birth time. In the postpartum interval to avoid a

contour nodule was detected in the right lobe. Thyroid fine needle aspiration

parathyroid crisis, surgery and cesarean operation were performed simultaneously

biopsy was performed. Histopathological evaluation was benign and there were

during the safe period for the baby.

no findings indicating parathyroid pathology. Parathyroid scintigraphy showed no

DOI: 10.1530/endoabs.49.EP264

lesions compatible with neck or mediastinal adenoma. Due to resistant

hypercalcemia, the patient was given bilateral neck exploration. The parathyroid

mass was localized and resected intraoperatively in the lower pole of the thyroid

nodule extending mediastinum, and histopathological evaluation was compatible

with parathyroid adenoma. Biochemical results due to hyperparathyroidism

normalized after operation and complaints resolved.

EP265

Discussion

Eucalcemic parathyroid hormone elevation after parathyroid surgery

It should be considered that primary hyperparathyroidism may have bone lesions

for sporadic primary hyperparathyroidism

that mimic bone metastasis. Especially in cases where the thyroid nodule is

Gulsah Elbuken¹, Sibel Ozkan-Gurdal², Makbule Begum Balkan² & Sayid

visible but there is no evidence of parathyroid adenoma in parathyroid

Shafi Zuhur¹

scintigraphy intrathroidal parathyroid adenomas should be considered in the

¹Department of Endocrinology and Metabolism, Namik Kemal University

differential diagnosis of cystic neck lesions.

Medical School, Tekirdag, Turkey;²Department of General Surgery, Namik

DOI: 10.1530/endoabs.49.EP266

Kemal University Medical School, Tekirdag, Turkey.

Introduction

Serum parathormone (PTH) levels may remain elevated in some patients after

surgery despite achievement of normal serum Ca levels. The factors contributing

EP267

to this phenomenon have not been fully elucidated yet. In this study, we

Acute pancreatitis as the first presentation of primary

retrospectively analysed the data of patients whose serum Ca levels returned to

hyperparathyroidism

normal after parathyroid surgery in our center.

Alexandra Vieira, Marta Ferreira, Daniela Guelho, Teresa Pereira,

Patients and methods

Luis Filipe Silva, Estela Ferreira & Ana Inácio

Computer records of 35 patients who had undergone parathyroid surgery and

Leiria Hospital Center, Leiria, Portugal.

achieved normal serum Ca levels were retrospectively analysed. Despite serum

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

EP269

Hypercalcaemia due to primary hyperparathyroidism is a rare cause of acute

Prevalence of hypocalcemia in adults in Minsk, Belarus

pancreatitis, with a reported prevalence of 1.5-8%.

Elena Brutskaya-Stempkovskaya^1,2, Alla Shepelkevich¹ & Georg Kostin^1,3

Clinical case

¹Belarusian State Medical University, Minsk, Belarus;²Minsk City

A 25-year-old male patient was referred to the Endocrinology outpatient clinic for

Polyclinic N31, Minsk, Belarus;³Minsk Consulting and Diagnostic Centre,

hypercalcemia diagnosed in the context of acute pancreatitis. He had medical and

Minsk, Belarus.

surgical pathological antecedents of: clavicle fracture after car accident,

cholecystectomy and appendectomy, gastroesophageal reflux disease. Current

medications included proton pump inhibitor daily. Laboratory analysis reported

The prevalence of hypocalcemia among patients non-operated the thyroid and

serum calcium of 3.46 mmol/l (2.20-2.65), phosphorus of 0.70 mmol/l (0.81-

parathyroid glands has increased significantly with the introduction the screening

1.45) and intact parathyroid hormone of

569 pg/ml

(12-88). Biochemical

of calcemia. The main reasons for hypocalcemia are hypoproteinemia and

screening for type 1 and type 2 multiple endocrine neoplasia was performed

hypoparathyroidism.

and was negative. The neck ultrasonography showed a nodular heterogeneity with

Objective

hyperechogenic contours with cystic areas, and posteriorly and inferiorly to the

To study the prevalence of hypocalcemia in the adult in Minsk.

left lobe an hypoechogenic nodular formation, with 2.4 cm of greater axis, which

Materials and methods

may correspond to the parathyroid gland with increased dimensions. Bone

We studed 1207 people, average age 53.9G17.25 (892 women, 315 men) from 18

densitometry showed osteopenia. Sestamibi parathyroid scintigraphy revealed a

96 years. Examination: total calcium, total protein. Hypocalcaemia was

focus of significant radiopharmaceutical retention on the projection of the lower

detected in total calcium level !2.2 mmol/l.

left lobe pole, alteration compatible with parathyroid adenoma. A lower left

Results

parathyroidectomy and left lobectomy of thyroid was performed without

Hypocalcaemia was recorded in 40 people (3.3/100 adults), the mean age was

complications. The histopathological result confirmed the diagnosis of

42.9G17.63 years (32 women, men - 8). In the age group up to 30 years

parathyroid adenoma. At the last visit, he had normal PTH and calcemia values.

hypocalcemia was revealed in 12 cases (8.3%, in women - 10.3%); in the group

During the follow-up he had recurrent acute pancreatites episodes.

30-44 years - five cases (1.3%, in men - 4.7%, in women - 0.3%), 45-59 years -

Conclusions

three cases (1.1%, in men - 2.5%, in women - 0.5%); 60-74 years - ten cases

The authors present this case because of its rarity: hyperparathyroidism in a young

(2.5%, in men - 2.6%, in women - 2.4%); O75 years - one case (0.7%, in men -

patient whose presentation was of acute pancreatitis without the classic clinic

3.2%). The prevalence of hypocalcemia in the group up to 45 years - 6.6 per 100

manifestations of hypercalcemia.

adults. The prevalence of hypocalcemia in the group 45 years over - 1.7/100

adults. The results of the study indicate a significant occurrence of hypocalcemia

DOI: 10.1530/endoabs.49.EP267

in the age group up to 45 years (c²Z20.34, pZ0.00001).

Conclusion

The prevalence of hypocalcemia in the adult population of Minsk-city was

3.3/100 adults (33:1000). The prevalence of hypocalcemia in the age group up to

45 years was 6.6/100 adults, in the age group 45 years over was 1.7 per 100 adults.

The results of the study indicate a significant occurrence of hypocalcemia in the

age group up to 45 years.

DOI: 10.1530/endoabs.49.EP269

EP268

Gender difference in clinical presentation of primary

hyperparathyroidism

Laura Gianotti, Elena Castellano, Francesco Tassone, Claudia Baffoni,

Flora Cesario, Gianpaolo Magro, Micaela Pellegrino & Giorgio Borretta

EP270

Division of Endocrinology, Diabetology & Metabolism, S.Croce & Carle

Hospital, Cuneo, Italy.

Assessment of changing in the therapeutic attitude in patients with

primary hyperparathyrodism in conservative management after the

realization of radial densitometry

Objective

Jose Alvaro Romero Porcel, Guillermo Martinez De Pinillos Gordillo,

Primary hyperparathyroidism (PHPT) is one of the most common endocrine

Fernando Garcia Perez, Eyvee Arturo Cuellar Lloclla, Jose Ignacio

disorders, with a female to male ratio of 3:1. Currently most patients with PHPT

Fernandez Pen˜ a, Carmen Carretero Marin, Juan Manuel Garcia De Quiros,

are asymptomatic. However, data about the gender impact on the clinical

Ignacio Fernandez Lopez, Mariana Tome Fernandez-Ladreda & Maria

presentation of PHPT are lacking.

Victoria Cozar Leon

Methods

Hospital De Valme, Sevilla, Spain.

We evaluated the difference in symptoms and biochemical parameters between

men and women with PHPT in a single center series of 417 patients.

Results

Introduction and objectives

Male PHPT patients resulted significantly younger

(PZ0.046) and more

In the 4th Workshop on Primary Hyperparathyroidism, it is recommended to

frequently symptomatic than women (62.3% vs 47%, PZ0.016). Furthermore,

perform BMD by DXA of third radius as well as lumbar spine and hip DXA in the

renal stone incidence was higher in male than in female patients (50.5% vs 33%,

initial assessment and follow up of patients with primary hyperparathyroidism.

PZ0.003) while no difference was found in the incidence of osteitis fibrosa

This test is not available in many centers, which means that only T Score values of

cystica (21.5% vs 20.7%). Instead, osteoporosis, established as T score ! 2.5 at

the lumbar spine and hip are used to certify the absence of osteoporosis in

any site, was significantly predominant in women (56.5% vs 39.3%, PZ0.015)

asymptomatic patients wich conservative management is performed. Our

rather than in men. However, no differences were found in classical biochemical

objective is to evaluate if the recent addition of radius DXA has modified the

disease parameters (i.e. PTH, serum calcium, phosphorus, 24 h-urine for calcium)

management of this patients.

nor in creatinine and vitamin D levels. Finally, the proportion of patients with

Materials and methods

surgical indications (symptomatic patients and asymptomatic patients meeting

Retrospective study including patients in follow-up by primary asymptomatic

surgical criteria recommended by current guidelines) was similar in male and in

hyperparathyroidism in conservative management according to the Fourth

female PHPT patients (84,6% vs 84,9%).

Workshop criteria when radial densitometry for the first time in its evolution.

Discussion

Changes after the DXA results were evaluated.

Gender leads to a different clinical presentation in PHPT patients, male patients

Results

being usually younger and more frequently affected by a symptomatic form of the

20 patients (65.4 years G11.14, 90% women) with a follow-up of 3.95 years

disease. In addition, renal stones are significantly more frequent in men, while in

G1.97 were included. Blood calcium levels 11.05G0.45 mg/dl, mean PTH of

women osteoporosis is prevalent. On the other hand, PHPT biochemical

105.46 pg/ml G60.9. None presented lumbar and/or femoral T-Score scores

presentation seems not to be influenced by gender. Furthermore, surgical

values lower tan K2.5 DS (lumbar T K0.15 DS G2.17, femoral K0.77 DS

indication is reached equally in male and female PHPT patients.

G0.98). The radial T Score was K2.67 DS G2.45. The radial densitometry

Conclusions

results changed the clinical attitude in 70% of the patients, from the recommed

In male patients PHPT is less frequent but more commonly symptomatic than in

conservative management to surgical treatment in those with a T-Score lower

female patients. PHPT clinical presentation is influenced by gender, although

K2.5 DS in the distal radius and T-Score higher than K2.5 DS in the lumbar

there are no sex-related differences in its biochemical profile.

and/or femoral.

Conclusions

DOI: 10.1530/endoabs.49.EP268

Our study reinforces the importance of performing distal radius densitometry in

patients in which conservative management is giving to be performed, as is

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

recommended as recommended by international criteria. Lack of implementation

30.5% had severe hypercalcaemia

(cCa R3.50 mmol/l). Aetiology:

47.2%

may lead to conservative management in patients with osteoporosis.

malignancy related hypercalcaemia, 15.1% primary hyperparathyroidism, 5.6%

DOI: 10.1530/endoabs.49.EP270

secondary or tertiary hyperparathyroidism, 9.4% drug-related, 15.1% unknown.

Frailty was documented reason to withdraw further investigations in 62.5% of the

latter. Coexistent active prostate cancer and hyperparathyroidism was found in

two cases. Investigations: PTH was checked in 67.8% cases, Phosphate in 64.4%,

ALKP 100%. Of the cases with suppressed PTH, only 72.2% had serum

paraproteins checked, 55.5% urinary Bence-Jones proteins and 83.3% imaging

EP271

for malignancy. Vitamin D was only checked in 22.6%. Management: Patients

received an average of 3L intravenous fluids in the first 24 h. 62.7% received

A rare case: intrathymic parathyroid adenoma

intravenous bisphosphonates. 13.5% had less than 2L intravenous fluids prior to

Veysi Asoglu¹, Mehmet Celik², Buket Yilmaz Bulbul², Semra Ayturk²,

bisphosphonate. Second line treatment with Cinacalcet, steroids, Furosemide or

Ebru Tastekin³, Nuray Can³, Atakan Sezer⁴, Funda Ustun⁴ &

Calcitonin was used in

20.7% cases. There were no cases of rebound

Sibel Guldiken²

hypocalcaemia.

¹Trakya University, Medical Faculty, Department of Internal Medicine,

Conclusions

Edirne, Turkey;²Trakya University, Medical Faculty, Department of

Compliance with guidelines recommendations was suboptimal in certain areas,

Endocrinology and Metabolism, Edirne, Turkey;³Trakya University,

not entirely explained by the adoption of a palliative approach with focus on

Medical Faculty, Department of Pathology, Edirne, Turkey;⁴Trakya

symptom control in cases. Training opportunities will be devised locally to

University, Medical Faculty, Department of Surgery, Edirne, Turkey;

improve practice. Bisphosphonate use in the Emergency department should be

⁵Trakya University, Medical Faculty, Department of Nuclear Medicine,

controlled for the appropriate circumstances. Vigilance is recommended

Edirne, Turkey.

assigning causality in active malignancy, given that

11.1% of pre-existing

malignancy cases were found to have concurrent PTH driven hypercalcaemia,

Primary hyperparathyroidism in the most common cause of hypercalcemia. 87%

despite only 38.9% of them being investigated with a PTH level.

of the cases present with single adenoma, 9% of them have hyperplasia, while

DOI: 10.1530/endoabs.49.EP272

multiple adenomas and parathyroid malignancy are detected in 3 and 1% of the

cases, respectively. Although it is rare, parathyroid adenomas may be ectopic. The

most common locations for ectopic parathyroid adenomas are thymus,

tracheaesophageal cleft, carotis sheet, intrathyroidal and paraesophageal area.

In this study, we aimed to present an intrathymic parathyroid adenoma as a rare

case.

A 46-year old female patient who received hemodialysis for chronic renal failure

secondary to chronic glomerulonephritis for

years and then underwent

EP273

cadaveric renal transplantation in

2010 was presented for routine follow-up

Higher circulating parathyroid hormone concentration fascilitates

visit. Laboratory examination revealed urea:19 mg/dl(n:15-43),creati-

preoperative diagnostic imagings for localization in primary

nin:0.8 mg/dl(n:0.57-1.11)), calcium:11.5 mg/dl (n:8.6-10.2 mg/dl), phosphor-

hyperparathyroidism

us:2.7 mg/dl (n:2.4-5.1 mg/dl), albumin:4.2 g/l (n:3.2-4.8 g/l), iPTH:340 pg/ml

Kentaro Okamoto¹, Yoshihiko Itoh¹, Akiyuki Kawashima¹, Aya Amano¹,

(n:15-68), creatinin clerarance in 24-h urine: 82 ml/min, calcium in 24-h urine:

Kyoko Okazaki¹, Hiroyuki Murabe¹, Toshihiko Yokota¹, Risa Yoshimoto²,

410 mg/day. Neck ultrasonography was performed, which demonstrated 12!

Akiko Sahara², Junko Tomokuni² & Keita Hamamatsu³

9 mm sized well-circumscribed nodular lesion with heterogeneous echo at

¹Kurashiki Central Hospital, Department of Endocrinology and Rheuma-

inferior part of lower pole of left thyroid gland (thyroid nodule? Parathyroid

tology, Okayama, Japan;²Kurashiki Central Hospital, Department of

adenoma?). Femoral neck and L1-L4

vertebra were osteopenic on bone

Laboratory Medicine, Okayama, Japan;³Graduate School of Medicine

densitometry. Parathyroid scintigraphic examination detected no scintigraphic

and Faculty of Medicine Kyoto University, Department of Diabetes,

signs characteristic for parathyroid adenoma in the neck and mediastinum. The

Endocrinology and Nutrition, Kyoto, Japan.

patient underwent parathyroidectomy following surgical exploration. Histopatho-

logic examination of parathyroidectomy material revealed intrathymic para-

thyroid adenoma. The patient was scheduled for outpatientclinic follow-up with

Introduction

post-operative laboratory findings of iPTH: 38 pg/ml, Ca:9.9 mg/dl, P:2.5 mg/dl,

For minimally invasive surgery of primary hyperparathyroidism (PHPT), the

Alb:4.3 g/l, kreatinin:0.7 mg/dl.

identification of the accurate localization is required. As preoperative diagnostic

Annual incidence of primary hyperparathyroidism is 0.27%. Since Primerhi-

imagings, we perform ultrasound, technetium 99m-sestamibi scintigraphy and

perparatiroidizmin yıllık gorulme oranı

% 0.27dir. Since both thymus and

either or both of megnetic resonance imaging or computed tomography in all

parathyroid gland embrologically derive from

3rd pharyngeal cleft, ectopic

cases. The aim of the present study is to evaluate the clinical biochemical factors

parathyroid adenomas may locate within thymus. It is very important to pre-

that fascilitate preoperative diagnostic imagings for localization.

operatively determine the localisation of ectopic parathyroid adenomas to prevent

Methods

surgical errors.

We retrospectively searched the medical records of patients with PHPT who were

DOI: 10.1530/endoabs.49.EP271

admitted in our hospital from 2014 to 2016. Fifty-five patients were identified.

Four patients with parathyroid carcinoma, multiple endocrine neoplasia type 1,

familial hypocalciuric hypercalcemia, and detectable parathyroid hormone-

related protein were excluded. Fifty-one patients were included in the study. We

defined 36 patients as the ‘localized’ group, including 30 patients who underwent

curative operation and 6 non-operative patients whose suspicious adenoma was

EP272

consistently identified by two or more of diagnostic imagings. And other 15

patients were defined as the ‘non-localized’ group. We compared biochemical

Audit of emergency hypercalcaemia management in the acute

data including intact parathyroid hormone (iPTH), serum calcium, urine calcium,

medical unit

and tartrate-resistant acid phosphatase 5b.

Emanuela Bejinariu, Rahat Tauni, Tharanga Rathnayake, Vinit Shah,

Results

Shiu-Ching Soo & Ritwik Banerjee

iPTH was statistically higher in the ‘localized’ group (146 [103-195] vs. 98 [82-

Luton and Dunstable University Hospital, Luton, UK.

136] pg/ml: pZ0.010). Multivariate logistic regression analysis demonstrated

that the usefulness of preoperative diagnostic imaging was ensured only in higher

Introduction

iPTH (pZ0.014). When we set the cut-off value of iPTH to 150 pg/ml, sensitivity

We conducted a retrospective audit of emergency management of hypercalcaemia

was 48.6% and specificity was 87.5% (AUC: 0.73 [95% CI 0.59-0.87]). When we

presenting to the acute medical team and compared our practice against the

used whole parathyroid hormone (wPTH) in place of iPTH, we obtained similar

Society for Endocrinology guidelines September 2016.

results: the cut-off value 85 pg/ml with sensitivity 57.1% and with specificity

Method

87.5% (AUC: 0.84 [95% CI 0.72-0.96]).

53 adult patients with 59 corresponding medical admissions were identified from

Conclusion

tracking all biochemistry samples with corrected calcium (cCa) R3.0 mmol/l

Both iPTH and wPTH as circulating parathyroid hormone concentration are

processed between August 2015 and July 2016 trustwide. We conducted a

useful to predict whether preoperative diagnostic imagings can identify the

retrospective review of their admissions’ case records.

acurate localization of the parathyroid adenoma.

Results

DOI: 10.1530/endoabs.49.EP273

Characteristics: age 40-98 years old (median 79), 60.4% female, median length

of stay 7 days, presenting cCa range: 3.04-5.36 mmol/l (median 3.31 mmol/l).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP274

EP276

Calcifediol is more effective than cholecalciferol in the treatment of

The changing face of primary hyperparathyroidism

severe vitamin D deficiency in a patient submitted to malabsorbitive

Ifigenia Kostoglou-Athanassiou¹, Alexios Travlos², Evaggelia Vogiatzi² &

bariatric surgery: a case report

Eleni Pantazi²

Alessandro Brancatella, Daniele Cappellani, Edda Vignali,

¹Department of Endocrinology, Red Cross Hospital, Athens, Greece;

Domenico Canale & Claudio Marcocci

²Department of Endocrinology, Alexandra Hospital, Athens, Greece.

Department of Endocrinology and Metabolism, Univesity of Pisa, Pisa,

Italy.

Primary hyperparathyroidism is a disease which nowadays is being diagnosed

with increasing frequency. The diagnosis of primary hyperparathyroidism is

Context

based on routine calcium measurement, which if detected abnormally elevated

Vitamin D deficiency following malabsorptive bariatric surgery can lead to

leads to the screening of the patient for primary hyperparathyroidism. Therefore,

osteomalacia. We report a patient with severe vitamin D deficiency following

primary hyperparathyroidism is frequently detected early in the course of the

malabsorptive bariatric surgery successfully treated with calcifediol but not

disease. Consequently, severe musculoskeletal manifestations may be lacking in

cholecalciferol.

the modern world setting in patients with primary hyperparathyroidism.

Case description

The aim was to describe musculoskeletal manifestations in patients with primary

A 40-year-old woman, submitted to biliopancreatic diversion 20 years before and

hyperparathyroidism being followed up in a center of excellence in Athens.

chronically treated with 50 000 IU cholecalciferol weekly, was admitted to our

A cohort of 38 patients, 33 female and five male, with primary hyperparathyroid-

Endocrine Unit because of severe low-back pain, muscle weakness, generalized

ism aged 62.31G1.87 years, being followed up within a center of excellence in

muscular hypotrophy, associated with hypocalcemia and elevated PTH levels.

Athens was studied. Musculoskeletal manifestations were recorded in the cohort

Initial evaluation revealed low albumin-corrected serum calcium (7.4 mg/dl),

of the patients studied.

high serum PTH (240 pg/ml), bone-specific alkaline phosphatase (125 mg/l) and

Within the cohort of

38 patients with primary hyperparathyroidism being

1,25-dihydroxyvitamin D (112 pg/ml) concentrations, and undetectable serum

followed up within a center of excellence in Athens, 12 patients (31.58%) had

25-hydroxyvitamin D (!7 ng/ml). Bone mineral density (BMD) was markedly

osteoporosis, 2 (5.26%) had osteopenia, 7 (18.42%) had diffuse bone pain, 2

low. Normocalcemia was initially restored with i.v. albumin and calcium

(5.26%) had diffuse myalgia and 1 (2.63%) had suffered a wrist fracture. Within

gluconate. Treatment with calcitriol (0.5 mg three times daily) and oral calcium

the cohort studied

(47.37%) patients did not have any musculoskeletal

carbonate (1000 mg daily) was simultaneously started and cholecalciferol was

manifestations.

replaced with calcifediol

(125 mg

(5000 UI) daily)). During follow-up the

It appears that primary hyperparathyroidism does not have severe musculoske-

calcifediol dose was progressively tapered to 25 mg (1000 UI) daily and the

letal manifestations, such as osteitis fibrosa cystica, in the real world setting in

calcitriol dose progressively reduced and finally withdrawn. Serum biochemistry

patients followed up for the disease within a center of excellence in Athens.

normalized, BMD significantly increased and the patient’s clinical conditions

However, patients with primary hyperparathyroidism appear to have diffuse bone

progressively improved, with a substantial recovery of autonomy.

pain as well as osteoporosis, which may be complicated by a fracture in some of

Conclusions

the cases. Early detection and diagnosis of the disease seems to have altered the

Our data suggest that calcifediol migth be more efficacious than cholecalciferol

face of primary hyperparathyroidism in the real modern world setting.

for prevention and treatment of vitamin D deficiency in patients treated by

DOI: 10.1530/endoabs.49.EP276

malabsorptive bariatric surgery.

DOI: 10.1530/endoabs.49.EP274

EP277

Single center experience of intact parathyroid hormone determination

in washout samples of suspicious parathyroid adenomas

Mustafa Sahin¹, Asena Gokcay Canpolat¹, Elif Ediboglu²,

¸ ag˘ lar Keskin1,

EP275

S¸ ule Canlar1, Ozgur Demir1, Sevim Gullu1, Murat Faik Erdogan1,

The effect of 1,25(OH)₂D₃ on interferon i secretion by human

Rıfat Emral¹ & Demet Corapcioglu¹

mononuclear cells in vitro

¹Ankara University Faculty of Medicine, Department of Endocrinology and

Lambros Athanassiou¹, Andrianos Nezos¹, Ifigenia Kostoglou-Athanas-

Metabolism, Ankara, Turkey;²Ankara University Faculty of Medicine,

siou², Clio Mavragani¹, Panagiotis Athanassiou³ & Michael Koutsilieris¹

Department of Internal Medicine, Ankara, Turkey.

¹Department of Physiology, Medical School, University of Athens, Athens,

Greece;²Department of Endocrinology, Red Cross Hospital, Athens,

Greece;³Department of Rheumatology, St Paul’s Hospital, Thessaloniki,

Introduction

Greece.

Minimally invasive surgery is an alternative surgical approach for primary

hyperparathyroidism with less surgical trauma and anesthesia complications.

Neck ultrasonography and scintigraphy are still the first step tools for localisating

Vitamin D is a secosteroid hormone known for its skeletal effects. Recently, the

parathyroid lesions. Intact parathyroid hormone (PH) determination in washout

extraskeletal effects of vitamin D are under investigation. Vitamin D is thought to

samples is really very useful when parathyroid lesions can not be easily

exert an immunomodulatory effect, having multiple effects on the immune

distinguished from thyroid lesions or sometimes lymph nodes.

system. It is known to induce immune tolerance and also to enhance the immune

Method

response to bacteria.

In our clinic, we performed ultrasonography guided parathyroid fine needle

The aim was to study the effect of 1,25(OH)₂D₃ on interferon I secretion by

aspiration procedure for 119 patients diagnosed with primary hyperparathyroid-

human mononuclear cells in vitro.

ism between January

2005 and January

2016. Intact parathyroid hormone

Human mononuclear cells were separated from whole human blood from healthy

determination was performed in washout samples. 80 of the study group also had

female human subjects using the Lymphoprep protocol. Subsequently they were

a parathyroid scintigraphy. All of the patients underwent parathyroid surgery.

placed in wells 10⁶ cells/well and were cultivated for a period of 6 h at a

Results

temperature of 37 8C in a humidified environment of 5% CO₂ in the presence or

In 106 of the study group had positive parathyroid hormone washout (phw) results

absence of interferon alpha 400 U, 1,25(OH)₂D₃ 250 pmol, interferon alpha

according to blood PH levels. Significant difference was achieved in localisation

400 U and 1,25(OH)₂D₃ 250 pmol. Subsequently the content of the wells was

of the lesion (p:0.006), serum calcium levels (p:0.01) and PHW levels (p!0.001)

centrifuged and the precipitate was treated with Trizol for RNA extraction of

between washout negative and positive group. No difference was observed in

genes known to be stimulated by interferon alpha. Real time PCR was performed

gender, age, presence of stone, levels of serum phosphorus, creatinin, alkaline

for MX1, IFIT1, IFI44 and GAPDH as a control.

phosphatase, parathyroid hormone, vitamin D and 24 h urinary calcium levels. 28

Interferon alpha was shown to stimulate genes related to interferon I secretion, i.e.

patients in the scintigraphy group had negative scan whereas 47 of them had both

it was found to have a positive feedback on its own secretion. 1,25(OH)₂D₃ was

scintigraphy and PHW positive. 24 of the patients had positive PHW results but

found to modulate interferon I gene augmentation induced by interferon alpha

negative scintiscans.

treatment.

Conclusion

Vitamin D is being investigated for its immunomodulatory properties. In the

The present study represents that ultrasonography combined with PHW

present study vitamin D was found to modulate the response of human

evaluation seems to be more diagnostic according to parathyroid scintigraphy.

mononuclear cells to interferon alpha treatment.

DOI: 10.1530/endoabs.49.EP277

DOI: 10.1530/endoabs.49.EP275

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP278

exclusion of other conditions, such as familial hypocalciuric hypercalcaemia.

Symptomatic patients should usually be referred for parathyroidectomy. For

Primary hyperparathyroidism due to atypical adenoma: clinical,

asymptomatic patients there are clear guidelines for surgical referral, based on the

biochemical and histological features of an Italian cohort

Fourth International Workshop (2014) recommendations. This study evaluates

Federica Saponaro¹, Marina Di Giulio¹, Elena Pardi¹, Simona Borsari¹,

current practice for diagnosing and managing primary hyperparathyroidism

Gabriele Materazzi², Claudio Marcocci¹ & Filomena Cetani¹

compared to international guidelines, at a large UK teaching hospital.

¹Endocrinology Unit 2, University of Pisa, Pisa, Italy;²Endocrine Surgery,

Methods

University of Pisa, Pisa, Italy.

We evaluated all new cases of PHPT seen in outpatient endocrinology clinics

between January 2014 and July 2016. Data were collected using a standardised

Primary hyperparathyroidism (PHPT) is mostly due to a benign parathyroid tumor

proforma. Data fields included demographics, biochemistry and imaging. Follow-

(99%). Some have parathyroid ‘atypical adenomas’, rare tumors with histological

up data on surgical referrals, histology and outcomes were also collected.

features of parathyroid cancer (PC) (fibrous trabeculae, thick fibrous bands,

Results

mitotic figures in parenchymal cells), without local invasion or metastasis. We

Of the

121

patients, at diagnosis,

50.4% were symptomatic. Complete

evaluated 20 patients with histological diagnosis of atypical adenomas. Patients

investigation data were available for 117. 59.8% had all relevant investigations

were 13 women and seven males (mean age: 55G13 yrs). Nineteen patients had a

performed as recommended per guidelines. Urinary calcium was conducted in

sporadic PHPT and one a Familial Isolated PHPT (FIHP). At least one of the

67.5% of patients, of those, 44.3% had inappropriate vitamin D levels at the time

following symptoms was present in 8 (40%) patients: nephrolithiasis (nZ8),

of collection. At diagnosis, 30.0% patients had renal complications and 36.3%

clinical fragility fractures

(nZ1), neuropsychiatric symptoms (nZ6). In the

had osteoporosis. 84% of the 121 met criteria for surgery, although 58.8% were

remining patients (nZ12) PHPT was asymptomatic. Osteoporosis was detected in

actually referred. The most common reasons for non-referral were patient choice

(40%). Preoperative imaging was positive in 16 (80%) patients. The association

(33.3%) and fitness for surgery (45.5%). On imaging, 74% had a single adenoma,

with other tumors was recorded: papillary thyroid carcinoma (nZ4), adrenal

11.7% had no obvious adenoma. 75% had positive correlation between imaging

bilateral hyperplasia (nZ1), breast cancer (nZ1), Morton’s neuroma (nZ1).

and surgical findings. 3 months post-operatively, 91% of patients had normal

Biochemical tests at baseline were: albumin adjusted serum calcium 12.4G

calcium and 68% had normal PTH.

0.8 mg/dl, PTH 204 (160-277) pg/ml and 25OHD 13.4G7 ng/ml. All patients

Conclusions

underwent PTx. The histological diagnosis was of atypical adenoma (mean

This study shows that the majority of patients with PHPT are diagnosed and

diameter 24G10.6 mm) with the following features: fibrous trabeculae in two,

investigated as per guidelines. Almost all patients had a normal calcium 3 months

thick fibrous bands in 13, capsular invasion infiltration in seven and mitotic

post operatively, suggesting surgery was curative. However, urinary calcium

figures in two. All but one patients were cured after PTx and remained

estimation was performed without the correction of vitamin D levels in a

normocalcemic (mean follow-up 5 years). One patient, with apparently sporadic

significant percentage of patients, thereby affecting accuracy of interpretation.

PHPT, had persistent hypercalcemia and he is in follow-up. This study suggests

DOI: 10.1530/endoabs.49.EP280

that PHPT due to atypical adenoma is generally asymptomatic at diagnosis, it has

a moderate-severe biochemical profile resembling that of PC, it is a sporadic

disease and shows a benign prognosis in the majority of cases. We found an

association with other tumors, that will be evaluated in further studies.

DOI: 10.1530/endoabs.49.EP278

EP281

EP279

Fahr Syndrome and idiopathic primary hipoparathyroidism - clinical

Medullary vertebral compression in primary hyperparathyroidism

case

Fedala Saida, Meskine Djamila, Kedad Lamia, Fafa Nadira & Toubal Zakia

Ana Filipa Martins¹, João Martin Martins^1,2 & Sónia do Vale¹

Laboratory of Endocrinology and Metabolism (LEM 1), Algiers, Algeria.

¹Hospital de Santa Maria - CHLN, Lisboa, Portugal;²Faculdade de

Medicina de Lisboa, Lisboa, Portugal.

We report the case of an ectopic parathyroid adenoma, revealed by a medullary

vertebral compression by a brown spinal tumor in a 44-year-old women. Physical

Introduction

examination revealed a lower limb weakness, paresthesia and radicular lower

Fahr syndrome (FS) is a neuropsiquiatric condition due to progressive basal

extremity pain. Magnetic resonance imaging (MRI) showed osteolytic vertebral

ganglia calcification. Although physiopathology is not completely understood, it

lesions suggesting metastatic localizations. A thoracic CT scan identified a

may be secondary to infectious, metabolic and genetic diseases.

mediastinal mass measuring 6.2 cm in the major axis. Biological evaluation

Case report

revealed a hypercalcemia

(135 mg/l) with very high PTH

(1896 pg

/ml),

A 65-year-old male Caucasian was referred to the outpatient endocrine

parathyroid scintigraphy confirmed the mediastinal ectopic parathyroid. The

department because of hypocalcaemia. No perioral paresthesia or tingling of

patient underwent surgical resection of the mediastinal mass that proved to be a

the fingers and toes were noticed. He complained of longstanding hand tremor and

parathyroid ectopic adenoma. She showed a remarkable improvement in her

since one year ago apathy and gait instability were evident. Past medical history

clinical condition observed

months after parathyroidectomy. Medullary

revealed High Blood Pressure under treatment. He also referred previous use of

vertebral compression by a brown spinal tumor in primary hyperparathyroidism

anti-convulsivant medication since he was 15 because of diagnosed epilepsy.

is rare, surgery of parathyroid adenoma improved clinical condition without

Drugs were suspended at 20th with no further seizures. No previous cervical

resection of the brown tumor, However surgical decompression may be necessary

surgery or irradiation were done. Her death mother was also diagnosed of

in some cases.

epilepsy. Besides slow and rigid movement, physical examination was otherwise

DOI: 10.1530/endoabs.49.EP279

normal, with negative Chvosteck and Trouseau. Deafness, visual field defects or

dismorphisms were absent. Analytic evaluation confirmed albumin-corrected

hypocalcemia, hyperphosphatemia, normal serum magnesium, hypoparathyroid-

ism with sufficient 25OH-vitamin D levels. Slight ferropenia and chronic renal

disease grade

were diagnosed. Besides Hashimoto thyroiditis, no other

endocrinopathy was evident. Ecocardiogram evidenced left auricular dilatation

and reduced global systolic function. Cystic renal disease and slight cystic

EP280

calcifications were documented on kidneys ultrasound and cervical ultrasound

Management of primary hyperparathyroidism: Experience of a large

evidenced multinodular goiter. Bone densitometry of femur and lumbar spine was

UK teaching hospital

normal. craneoencephalic TC identified bilateral simetric parenquimatous

Rebecca Sagar, Amy Longhurst & Afroze Abbas

calcifications, both supra and infratentorial, with extensive involvement of

Leeds Centre for Diabetes and Endocrinology, Leeds Teaching Hospitals,

basal ganglia. I¹²³-SestaMIBI scintigaphy did not fixate in cervical imaging. Anti-

Leeds, UK.

NALP5 antibody was negative, as well as CASR activating mutation.

Discussion and conclusion

Background

Parathyroid hormone and calcium abnormalities are the most common metabolic

Primary hyperparathyroidism (PHPT) is a common cause of hypercalcaemia seen

disorders associated to FS. We describe a patient diagnosed of idiopathic

in outpatient endocrinology clinic. Diagnosis is based on biochemistry and

hypoparathyroidism. Basal ganglia calcifications support a long-standing

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

hypocalcemia, and chronic ion disturbance may have contributed to the absence

parathyroid carcinoma, In familial primary hyperparathyroidism, reoperative

of usual muscular complaints.

parathyroidectomy are challenging entities that require special consideration and

DOI: 10.1530/endoabs.49.EP281

expertise.

DOI: 10.1530/endoabs.49.EP282

EP282

EP283

Clinical presentations of four patients with familial isolated

When is it worthwhile to perform parathyroid SPECT/CT scintigraphy

hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome

in primary hyperparathyroidism?

Taner Bayraktaroglu¹, Utku Sentosun¹, Dilek Karakaya Arpaci¹,

Malgorzata Trofimiuk-Muldner^1,2, Anna Skalniak^1,2, Lukasz Kulczynski^1,2,

Ali Ugur Emre², Mertol Gokce³, Serkan Uysal³, Rabiye Uslu Erdemir⁴,

Aleksandra Zapendowska-Dudek², Aneta Budek², Monika Buziak-

Burak Bahadir⁵ & Guldeniz Karadeniz Cakmak²

1,2

Bereza^1,2, Anna Sowa-Staszczak^1,2 & Alicja Hubalewska-Dydejczyk

¹Bulent Ecevit University, Faculty of Medcine, Department of Internal

¹Chair and Department of Endocrinology, Jagiellonian University Medical

Medicine, Division of Endocrinology and Metabolism, Zonguldak, Turkey;

College, Krakow, Poland;²Endocrinology Department, University Hospital

²Bulent Ecevit University, Faculty of Medcine, Department of General

in Krakow, Krakow, Poland.

Surgery, Zonguldak, Turkey;³Bulent Ecevit University, Faculty of

Medcine, Department of Chest Surgery, Zonguldak, Turkey;⁴Bulent Ecevit

University, Faculty of Medcine, Department of Nuclear Medicine,

Introduction

Zonguldak, Turkey;⁵Bulent Ecevit University, Faculty of Medcine,

Observed increasing frequencies of asymptomatic or oligosymptomatic PHP

Department of Medical Pathology, Zonguldak, Turkey.

cases may increase the rate of false negative imaging results.

Aim

To determine the level of PTH and calcium at which an enlarged parathyroid

Introduction

gland can be detected by parathyroid SPECT/CT.

Primary hyperparathyroidism is commonly treated with targeted parathyroidect-

Material and methods

omy guided by preoperative imaging and intraoperative parathormone

A retrospective analysis of 117 patients diagnosed with PHP (100 females and 17

monitoring. Despite advanced imaging techniques, failure of parathyroid

males, aged 16-88 years) was performed. In each patient parathyroid SPECT/CT

localization still occurs. Hyperparathyroidism-jaw tumor syndrome and familial

after administration of

500 MBq of 99mTc-MIBI was conducted (Siemens

isolated hyperparathyroidism are a rare autosomal dominant tumor syndrome

Symbia T16). Serum calcium and parathormone (PTH) were measured in each

characterized by hyperparathyroidism. In this report, we present four patients

patient, serum phosphate was estimated in 109 subjects. Statistical analysis was

with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor

performed with Statistica 12 Software.

syndrome, below.

Results

Case 1

Median serum calcium level was

2.77 mmol/l

(LQ and UQ - 2.66 and

A 26-year-old man with left maxillary tumoral lesion is referred. He had the

2.87 mmol/l, respectively); median serum PTH level was 122.8 pg/ml (97.2 and

elevated serum calcium and parathormon levels, osteoporosis, rena anomalia,

191.9 pg/ml); median plasma phosphate was 0.84 pmol/l (0.74 and 0.98 mmol/l).

nephrolitiasis, Acording to the diagnosis of hyperparathyroidism jaw-tumor

(59.8%) patients an enlarged parathyroid gland was detected with

syndrome, imaging modalities included neck sonography, scintigraphy, compu-

SPECT/CT. There was a statistically significant difference in PTH levels (median

terized tomography indicaed that a ectopic parathyroidal adenoma, then it was

138.15 and 114.80 pg/ml, respectively; PZ0.02) and serum calcium levels

removed by videoscopic assisted medastinoscopy with temporarily hypo-

(median2.74 and 2.67 mmol/l, P!0.01) between patients with positive and

parathyroidism.

negative parathyroid SPECT/CT. Serum phosphate levels did not differ

Case 2

significantly

(PZ0.19). Receiver-operator curves

(ROCs) were drawn to

A 43-year-old-man who is a relative of Case 1 is presented with persistent

establish PTH and serum calcium cut-off levels for positive parathyroid

myalgia-arthralgia and nausea due to hypercalcemia caused by increased

SPECT/CT imaging. Sensitivity and specificity of parathyroid scintigraphy

parathormon levels. Sonographic and scintigraphical evaluations of the neck

were 38 and 89.6%, respectively, for PTH cut-off level of 191.9 pg/ml, and 52 and

showed that multiple irregular nodules of thyroid and suspected parathyroid

79%, respectively, for serum calcium cut-off level of 2.74 mmol/l.

adenomas. Fine neddle aspiration cytology of the nodules and pathological

Conclusions

lymphadenopathy revealed a suspect of the low differentiated thyroidal

Limiting parathyroid SPECT/CT to patients with significantly increased PTH

carcinoma with lymphatic invasion. In wash-out sampling from suspected

and/or serum calcium levels, particularly if surgical treatment is not considered,

parathyroid adenoma, parathormon levels were increased. Total thyroidectomy

may decrease false negative imaging rates and allow to avoid unnecessary

with central and lateral neck dissection in addition adenomectomy with hungry

radiation exposure. More precise determination of PTH and calcium cut-off levels

bone syndrome.

requires analysis of larger patients group data.

Case 3

A 600-year-old-man who is in relations with Case 1 and Case 2 is complained

DOI: 10.1530/endoabs.49.EP283

with nausea-vomiting and lower back pain with osteoporotic fractures of left

femur and left humerus. His serum levels of calcium and parathormon are highly

increased. Imaging modalities showed a suspected lesion in the inferior region of

the left thyroidal localization. After minimal invasive intervention and selective

parathyroid sampling, the second operation included exploration and thyroid-

ectomy with 3.5 paratyhroidectomy and implantation to sternocleidomastoid

muscles were performed. Postoperatively, he had hypothyroidism with elevated

serum calcium and parathormon levels. Thereafter hybrid nuclear modalities

EP284

showed a suspected paratrakeal lesion, the case referred to reoperation with

Parathormone (PTH) as a marker of vitamin D (VitD) deficiency

radioguided parathyroid surgery.

Malgorzata Trofimiuk-Muldner^1,2, Anna Skalniak^1,2,

Case 4

Malgorzata Kiec-Klimczak^1,2 & Alicja Hubalewska-Dydejczyk^1,2

The patient was a 51-year-old man (who is a brother of Case 3) presenting without

¹Chair and Department of Endocrinology, Jagiellonian University Medical

any symptoms. He had hypercalcemia (12.2 mg/dl) and hyperparathyroidism

College, Krakow, Poland;²Department of Endocrinology,

(247 pg/ml). Parathyroid lesion detected with sonography and scintigraphical

University Hospital in Krakow, Krakow, Poland.

evaluations, and it is referred to minimal invasive parathyroid adenomectomy.

Conclusion

Primary hyperparathyroidism is a common clinical problem for which the only

Introduction

definitive management is surgery. Diagnosis of the familial primary hyper-

VitD deficiency, the pandemics of which we currently observe, may result in

parathyroidism caused by CDC73 (formerly known as HRPT2) is based on the

secondary hyperparathyroidism even if not accompanied by hypocalcaemia.

biochemical findings of primary hyperparathyroidism, identification of ossifying

Aim

fibroma(s) of the maxilla and/or mandible on imaging studies, family history, and

To assess VitD levels as a cause of secondary hyperparathyroidism.

detection of a heterozygous germline CDC73pathogenic variant on molecular

Material and methods

genetic testing. The spectrum of CDC73-related disorders includes hyperpar-

257 healthy volunteers with normal kidney function (GFR! 60 ml/min) (28.4%

athyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism and

males), median age 57 years, were included. In each participant, serum calcium,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

phosphates, creatinine, PTH and total VitD levels, as well as urinary calcium in

EP286

urine morning sample, were measured. Daily calcium intake was estimated with

Diseases associated with hypercalcemia

a dietary questionnaire. Statistical analysis was performed with Statistica

Elena Brutskaya-Stempkovskaya^1,2, Alla Shepelkevich², Georg Kostin^2,3,

12 Software.

Eduard Chertko² & Janna Matsiushava²

Results

¹Belarusian State Medical University, Minsk, Belarus;²Minsk City

Median VitD level in the investigated group was

21.22 ng/ml; PTH

Polyclinic N31, Minsk, Belarus;³Minsk Consulting and Diagnostic Centre,

41.17 pg/ml, serum calcium - 2.39 mmol/l, serum phosphates - 1.12 mmol/l,

Minsk, Belarus.

serum creatinine - 68 mmol/l, and urinary calcium - 2.69 mmol/l. Median daily

calcium intake was

689 mg. There was statistically significant negative

correlation between VitD and PTH levels (rZK0.19, PZ0.0018), independent

Introduction

of serum creatinine. This relationship was particularly significant for measure-

According to modern studies, hypercalcemia is associated with an increased risk

ments performed during autumn/winter (rZK0.34, P!0.0001), while losing its

of urolithiasis, cholelithiasis, gastritis and peptic ulcer.

significance in study subjects subgroup investigated during spring/summer (rZ

Objective

K0.06, PZ0.5153). Kruskal-Wallis ANOVA analysis showed a statistically

To study the prevalence of urolithiasis, cholelithiasis, gastritis and peptic ulcer in

significant difference in PTH levels in relation to VitD deficiency severity

patients with hypercalcemia in Minsk-city.

(predefined ranges: !10; 10-19.9; 20-29.9 and R30 ng/ml) (PZ0.0078). A

Materials and methods

significantly higher PTH level was observed in subjects with severe VitD

we studied 1207 people, average age 53.9G17.25 (892 women, 315 men) from 18

deficiency (!10 ng/ml) when compared to subgroups with VitD levels of 20-

to 96 years. Examination: total calcium, total protein, creatinine, ultrasonography,

29.9 ng/ml (PZ0.0147) and R30 ng/ml (PZ0.0401). A significant negative

fibrogastroduodenoscopy, an analysis of morbidity.

correlation was found also between serum PTH and serum calcium (rZK0.13,

Results

PZ0.0447).

Hypercalcemia has been found in 31 people, mean age was 58.39G11.6 years.

Conclusions

Urolithiasis was detected in 141 cases (in patients with hypercalcemia - in nine

Lack of significant negative correlation between serum PTH and VitD, seen

cases) cholelithiasis was detected in 107 cases (in patients with hypercalcemia -

during spring and summer confirms that appropriate sunlight exposure is

in ten cases) gastritis was detected in 397 cases (in patients with hypercalcemia -

sufficient to correct VitD deficiency. Significant increase in PTH levels is seen

in 21 cases) peptic ulcer was detected in 102 cases (in patients with hypercalcemia

mostly in subjects with particularly low VitD levels, which may be an argument

- in nine cases).

for redefining the recommended normal range of VitD.

Significant differences was detected in the prevalence of urolithiasis (c²Z8.54,

DOI: 10.1530/endoabs.49.EP284

PZ0.0035), cholelithiasis

(c²Z19.33, PZ0.00001) gastritis

(c²Z16.41,

Z15.69, PZ0.0001) in patients with hypercalcemia

PZ0.0001) peptic ulcer (c²

compared all studied patients.

Conclusion

The results of the study show an increasing risk of urolithiasis, cholelithiasis,

gastritis and peptic ulcer in patients with hypercalcemia. The results may indicate

an important role of hypercalcemia in the pathogenesis of these diseases.

DOI: 10.1530/endoabs.49.EP286

EP285

Pathological basal ganglia calcification in isolated idiopathic

hypoparathyroidism: a case report

Gordana Pemovska¹, Tose Plaseski¹, Biljana Todorova¹,

Nadica Bozhinovska¹, Marija Zivkovic¹ & Radmila Nesovska²

EP287

¹University Clinic of Endocrinology, Diabetes and Metabolic Diseases,

PTH levels in vitamin D deficiency

Skopje, Macedonia;²City Hospital September 8th, Skopje, Macedonia.

Merve Catak¹, Derya Koseoglu², Ozden Ozdemir Baser¹ & Dilek Berker¹

¹Numune Education and Research Hospital, Ankara, Turkey;²Hitit

Introduction

Univercity Hospital, Corum, Turkey.

The isolated hyperparathyroidism (IHP) is a metabolism disorder characterized

by an absent or low parathormon (PTH) and hypocalcemia. It can be acquired,

Introduction

autoimmune, a result of some syndrome and as a part of a family (FIHP). FIHP is

High level of Parathormone (PTH) impair bone health by increasing the risk of

an extremely rear disease which is inherited auto somatic dominant or auto

fracture. The aim is to determine the threshold value of PTH elevation to

somatic recessive as a result of a mutation of one or several different genes.

accompany deficiency or failure of Vit D. This may be an important parameter in

Pathological calcifications in the cerebrum are a secondary form of calcification

assessing bone metabolism in clinical practice.

in patients with IHP.

Material and method

Material and methods

931 patients who were referred to the endocrinology clinic were retrospectively

We present two patients, a brother and a sister, age 44 and 42. The disease started

studied and 880 patients diagnosed with Vit D deficiency included to the study.

in both cases, with a series of epileptic attacks, the brother at the adolescent period

Patients were divided into three groups according to their vitamin D levels: !10

and the sister at age of 30. The diagnose was established based on a characteristic

ng/dL, 10-19.99 ng/dl, 20-29.99 ng/dl. The mean Ca, P, PTH, Vit D, ALP levels

symptoms: Fatigue, muscle weakness, paresthesis, convulsions, speech and

were calculated.

attitude disorder as well as cognitive deficit. The brother has cataract and the sister

RESULTS

has hirzutism and acne. Hormone and laboratory diagnostic tests. Radio

880 patients included in the study, 710 were female and 170 were male.

diagnostic on the kidneys, densitometry and psychological tests.

The mean PTH levels were 68.99, 56.10, 50.92 pg/ml when Vit D levels were

Results

!10 ng/dl,

10-20 ng/dl,

20-30 ng/dl and respectively and a statistically

The brother: PTHZ4.22 pg/ml (15-65), TCaZ1.08 (1.21-2.6), PosfZ2.01 (0.8-

significant difference was found between PTH levels (P!0.0001).

1.4 mmol/e), CaCCZ1.46 (1.3-10) mmol/l, Vit. D 14.35, Mg 0.69 (0.6-

When ROC analysis was performed, while Vit D level !5 ng/dl; PTH level was

1.1 mmol/l). Undergone cataract surgery. The sister: PTHZ1.2 pg/ml, TCaZ

O71.25 pg/ml (sensitivity 45%, specificity 78%), while the Vit D level was

1.92, PosfZ1.7. No signs for litiasa and nefrosclerosis. KT scan of the brain:

!10 ng/dl; PTH level wasO66.75 pg/ml (sensitivity 50%, specificity 77,4%),

calcification in the cerebellum, basal ganglia, par ventricular and sub cortical - M.

while Vit D level !20 ng/dl; PTH level was O61.1 pg/ml (sensitivity 40.3%,

Fahr. No signs of nefrocalcinosis. Radiology finding shows osteosclerosis of the

specificity 80.9%)

cranium, spine, long bones. Both of them have neuropsychological disorder with

Conclusion

limited intellectual capacity and light mental retardation.

As the Vit D level decreases, the calcium level decreases statistically significantly

Conclusion

while the parathormone level increases. Patients with Vit D deficiency have

IPH from an unknown etiology points to a family HypoPTH which needs to be

elevated PTH levels but PTH levels are still in the normal reference range.

confirmed by a genetic test. The tests were not performed due to financial

Prospective studies are needed to evaluate the effect of increased but still in a

limitations. Timely diagnose of IPH can prevent calcification in basal ganglia.

normal range PTH levels on bone with measurement of bone mineral density.

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Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP288

Conclusion

Endocrinologist operated US and PTH wash-out increases the number and

Renal complications in patients with chronic postoperative

success of focused surgery. Especially, patients with redo-surgery may benefit

hypoparathyroidism treated with oral calcium and active

from this procedure.

vitamin D metabolites

Filomena Cetani¹, Antonella Meola², Edda Vignali¹, Giovanni Guglielmi³,

DOI: 10.1530/endoabs.49.EP289

Irene Donato⁴, Antonio Matrone², Rossella Elisei² & Claudio Marcocci²

¹University Hospital of Pisa, Endocrine Unit, Pisa, Italy;²Department of

Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;

³University Hospital of Pisa Medicina Preventiva del Lavoro, Pisa, Italy;

⁴Department of Traslational Research and New Technologies in Medicine

and Surgery, University of Pisa, Pisa, Italy.

EP290

Patients with chronic hypoparathyroidism (HypoPT) treated with oral calcium

Weight has a weak influence on calcium-phosphorus metabolism in

and active vitamin D metabolites are at risk of renal complications, because of the

HIV-patients with vitamin d deficiency

Carolina García-Figueras Mateos & Manuel Cayón-Blanco

lack of action of PTH at the renal tubule. In the present study we evaluated

Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.

90 patients

(68

females and

22 males; age:

51.8G14.1 yrs) with chronic

postoperative Hypo (PO-HypoPT) diagnosed since at least 3 years. All patients

were treated with calcitriol and 35 (39%) with oral calcium two patients were also

Introduction

treated with thiazide diuretics. One-hundred forty-two healthy Hospital employ-

In contrast to general population, clinical consequences related to low levels of

ers, matched for age and sex, undergoing routine medical evaluation, were used as

25-hydroxyvitamin D in HIV-infected patients with overweight are not

control. Mean levels of Alb-Ca and ionized calcium were in the normal range and

established. The aim of our study was to investigate the influence of weight on

but 39 (43.3%) patients had values that did not meet the range recommended by

clinical parameters and on calcium-phosphorus homeostasis in HIV-patients with

the recent guidelines of the European Society of Endocrinology (ESE). Serial

vitamin D deficiency.

measurements of serum calcium prior to the present evaluation were available in

Methods/design

78 patients: only 9 (11.5%) patients had all values within the recommended ESE

Prospective study of HIV outpatients treated in our hospital. Vitamin D deficiency

range, and a large proportion of patients (32, 41.0%) had values greater than the

(D-DEF) was defined as serum 25-hydroxyvitamin D below 20 ng/ml. Patients

upper recommended value. The mean serum phosphorus and creatinine levels

were classified as “overweight/obesity” if body mass index (BMI) R25 Kg/m².

were in the normal range, but 7 (7.7%) patients had elevated values of phosphorus

Their clinical, metabolic and immunological data were compared to HIV-

and 22 (24.4%) of creatinine. The serum calcium-phosphate product was normal

individuals classified as “normal weight” (BMI: 18.5-24.9 Kg/m²).

in all patients. Forty-four (54%) patients showed increased 24-h urinary calcium

Results

excretion and 27 (30%) microlithiasis, mostly asymptomatic. Compared to the

One hundred and six HIV-infected individuals (86.8% male, mean age: 46.4G6.5

controls, patients had statistically significant lower mean serum Alb-Ca

years) were included. 51.9% were classified as “overweight/obese”. Levels of

(P!0.0001) and higher serum creatinine (PZ0.0008) and greater prevalence

vitamin D were lower in “overweight/obese”, but no significant difference was

of kidney stones (27/90 vs 7/142, P!0.0001, OR: 8.2 (3.4-19.9)). In conclusion,

observed between both groups (14.8G4 vs 15.3G1.8 ng/mL; PZ0.772). In

conventional treatment of chronic PO-HypoPT is suboptimal and associated with

overweight HIV-patients, although into the normal range, the serum phosphorus

an increased risk of renal complications. Careful monitoring of patients, as

levels were higher as compared as those without D-DEF (3.3G0.8 vs 2.9G

recommended by the ESE guidelines, should be therefore performed.

0.5 mg/dl; PZ0.04). Levels of i-PTH were also higher in overweight D-DEF

DOI: 10.1530/endoabs.49.EP288

patients (66.1G35.1 vs 48.9G19.8 pg/ml; PZ0.04). No others differences were

observed between these groups. Analyzing individuals with D-DEF only, there

was no difference in calcium, phosphorus or i-PTH levels between patients with

or without overweight.

Conclusions

In HIV-infected patients with low levels of

25-hydroxyvitamin D, BMI

R25 Kg/m² determines subtle changes on calcium-phosphorus homeostasis

which clinical significance remains to be determined. Further follow-up studies to

establish potential clinical implications of these findings are needed.

EP289

DOI: 10.1530/endoabs.49.EP290

The results of parathormone assay in parathyroid aspirates in

preoperative localization of parathyroid adenomas for focused

parathyroidectomy in patients with negative or suspicious sestamibi

scans

Aysenur Ozderya, Sule Temizkan, Kenan Cetin, Sule Ozugur,

Aylin Ege Gul & Kadriye Aydin

Kartal Dr Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey.

EP291

Chronic hypoparathyroidism disease profile from 492 patients in the

Objective

PARADIGHMe natural history global registry

In primary hiperparathyroidism (PHPT), increasing the number of patients treated

Bart L Clarke¹, Steven Ing², Aliya Khan³, Michael Mannstadt⁴,

by focused parathyroidectomy should be the main objective of pre-surgical

Michael McDermott⁵, Rebecca Piccolo⁶, Michael H. Shanik⁷,

imaging modalities. Suspicious or negative imaging results do not always mean

Tamara J Vokes⁸ & John Germak⁹

multiglandular disease, most of the patients may single adenoma and therefore

¹Mayo Clinic, Rochester, MN, USA;²Ohio State University Wexner

these patients may still benefit from focused parathyroidectomy.

Medical Center, Columbus, OH, USA;³McMaster University, Ontario,

Methods

Canada;⁴Massachusetts General Hospital and Harvard Medical School,

Retrospectively, we analyzed the data of 65 patients with PHPT with suspicious

Boston, MA, USA;⁵University of Colorado Hospital, Aurora, CO, USA;

or negative sestamibi scans who admitted at a tertiary reference center between

⁶Shire Human Genetic Therapies, Inc., Lexington, MA, USA;⁷Endocrine

January 2013 and December 2016. We excluded patients who had history of

Associates of Long Island, PC, Smithtown, NY, USA;⁸University of

chronic renal failure, renal transplant and multiple endocrine neoplasia. All

Chicago Medicine, Chicago, IL, USA;⁹Shire International GmbH, Zug,

patients underwent an endocrinologist operated ultrasonographic examination

Switzerland.

and parathyroid fine needle aspiration wash-out procedure.

Results

Of the 65 patients, 23 patients had nodular guatr disease. Fifty-four patients

PARADIGHM^e is a global registry (NCT01922440) of patients diagnosed with

had positive parathormone

(PTH) wash-out results. A total of

43 patients

hypoparathyroidism (HPT) R6 months regardless of aetiology and management.

underwent surgery. Of the 43 patients, four patients had redo-surgery. Of the

Routine medical care data were entered using electronic case report forms; the

operated patients,

40 had positive parathormone wash-out results and had

36-item Short Form Health Survey was completed by patients. Baseline-recorded

successful focused surgery. All of the patients with redo-surgery had positive

data are reported for 492 patients enrolled as of 1 December 2016 from 41 centres.

parathormone wash-out results and successfully re-operated. Three patients

At baseline, 78% were women, mean (S.D.) age was 49 (17) years, and mean (S.D.)

with negative PTH wash-out results, two of them had successful bilateral neck

BMI was 29.8 (8.6) kg/m². Medical histories included mood disorder (29%),

exploration, but a patient’s operation was not successful although bilateral neck

arthritis (16%), kidney stones (11%), fractures (8%), chronic renal disease (6%),

exploration.

and hypercalciuria (3%). 93% of patients had baseline symptom data (for the

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

previous 6 months), all reported R1 symptom; the most common were fatigue

approach. The gold standard is sestamibi SPECT/CT nowadays - but fails in

(40%), paraesthesia (30%), muscle twitching (24%), anxiety (20%), brain fog

approximately 10% cases. In last 3 years some case report with 18F-choline

(17%), muscle weakness (17%), back pain (16%), and headache (16%). HPT

PET/CT were published. We describe two cases with SPECT/CT invisible

management included oral calcium in 91% (calcium carbonate, 59%) and active

parathyroid adenoma.

vitamin D in 84% (calcitriol, 94%) of patients; 7% received recombinant PTH (1-

First case was 36y/o woman, with osteopenia diagnosed after pregnancy (was

84) in a clinical trial. 62% were taking R1 concomitant medication (45% thyroid

attributed to LMWH treatment in pregnancy) and no relevant health problems.

hormone,

4% hydrochlorothiazide,

1% psycholeptics,

!1% magnesium

Mild hypercalcemia (2.7 mmol/l) was found in 2014 in context with vitamine D

supplements). Key laboratory mean (S.D.) values were PTH 1.5 (1.5) pmol/l,

deficiency and patient was referred to our department. Primary hyperparathyroid-

albumin-corrected total serum calcium 2.1 (0.3) mmol/l, phosphate 1.4 (0.3)

ism was clearly stated (serum calcium 2.9 mmol/l; PTH 130 ng/l; 25-OH-D

mmol/l, magnesium 0.8 (0.1) mmol/l, and 24-hour urinary calcium 7.2 (4.6)

vitamine 69 nmol/l), bone turnover was also slightly elevated. According to age,

mmol/day. Among 330 patients who had imaging, calcifications were reported in

osteopenia and planned pregnancy we decided for surgery, but ultrasonography

40 patients (12%): kidney (nZ12), brain (nZ9), cardiovascular (nZ7), and other

and sestamibi SPECT/CT was without any parathyroid adenoma. Patient did not

sites (nZ12). In the previous 12 months, 47% of patients had 2K3 doctor visits

agreed with surgical revision of all four glands and we choosed conservative

and 49% had R1 emergency room visit owing to HPT. Mean (S.D., range) SF-

approach. In 2015, hypercalciuria was appeared, therefore next SPECT/CT and

36v2 summary scores for physical and mental components were 45.6 (10.7;

ultrasonography was performed, with still negative results. In 2016 we used

11.2K64.2) and 48.4 (11.0; 11.9K70.3). These real-world data for 492 patients

PET/MRI with 18F-choline for the first time in our hospital

- upper left

enrolled in the PARADIGHM^e registry provide valuable insight into disease

parathyroid adenoma was found (9!6 mm, SUVmax 5.8). Patient was referred to

variability, symptom burden, and HPT treatment approach.

surgery and histologic examination reveals parathyroid adenoma and patient went

DOI: 10.1530/endoabs.49.EP291

normocalcemic, normocalciuric and with normal PTH level, with continuing D

vitamine treatment due to osteopenia. No hungry bone syndrome was presented.

Second case was 59 y/o man, with primary hyperparathyroidism treated for 3

years by cinacalcet, with twice negative sestamibi SPECT/CT, repeatedly

negative ultrasonography. During the treatment was slightly hypercalcemic

(2.6 mmol/l), normocalciuric, with non-progressing osteopenia. PET/MRI

revealed 8mm left bottom parathyroid adenoma and patient was referred for

surgical resection, planned for March 2017.

EP292

Despite our limited experiences, 18F-choline PET seems to be a promising

Prevalence of cardiometabolic risk factors among Saudi Women with

diagnostic option. Using MRI instead of CT has some advantages - radiation load,

vitamin D deficiency

no risk of iodine contrast allergy and slightly better resolution in neck region.

Hanan Al Kadi¹ & Eman Alissa²

DOI: 10.1530/endoabs.49.EP293

¹Physiology Department, Center of Excellence for Osteoporosis Research,

King Abdulaziz University, Jeddah, Saudi Arabia;²Biochemistry

Department, King Abdulaziz University, Jeddah, Saudi Arabia.

Vitamin D deficiency is highly prevalent among Saudi women. The aim of this

study was to determine the prevalence of cardiometabolic risk factors in

apparently healthy Saudi women with vitamin D deficiency. A Retrospective

chart review was conducted in the “Center of Excellence for Osteoporosis

Research” (CEOR), King Abdulaziz University, Jeddah, Saudi Arabia. Only

healthy women 20-40 years old, with no history of previous illnesses and not on

any medications were included. Data on anthropometric measurements as well as

EP294

blood pressure (BP) were obtained. Body mass index (BMI) was calculated.

Severe hypocalcemia induced by Denosumab in a patient with

Laboratory results including fasting blood glucose (FBG), fasting lipid profile,

Osteroporosis after malabsorptive bariatric surgery

25-hydroxyvitamin D₃ (25(OH)D₃) and parathyroid hormone (PTH) were also

Ana Jiménez Portilla, Guillermo Serra Soler, Juan Ramón Urgeles Planella,

obtained. Vitamin D deficiency was defined as

25(OH)D3

concentration

María Soledad Gogorza Pérez, Mercedes Noval Font, Honorato

!50 nmol/l. Modified NCEP:ATPIII criteria were used to define cardiovascular

García Fernández, In˜ aki Arguelles Jiménez & Vicente Pereg Macazaga

risk factor cutoff points. A total of 305 women were included in the current

Universitary Hospital Son Espases, Palma de Mallorca, Spain.

analysis. Mean (G S.D.) age of the study group was 28.4G6.1 years and median

(IQR)

25(OH)D3 was 17.8 (11.9-28.2) nmol/l. Almost

97% of the study

participants were vitamin D deficient and 70% had values below 25 nmol/l.

Introduction

25-hydroxyvitamin D was significantly inversely associated with waist

Denosumab is a monoclonal antibody indicated in the treatment of postmeno-

circumference, systolic and diastolic BP and PTH

(PZ0.011,

!0.0001,

pausal osteoporosis. Hypocalcemia is a rare adverse effect.

!0.0001, !0.0001, respectively). Prevalence of cardiovascular risk factors

Case report

were higher among subjects who fell in the lowest tertile of 25(OH)D₃ except

We present the case of a 58-year-old woman with a clinical history of bariatric

total cholesterol and low density lipoprotein cholesterol, however only higher

surgery in 2001 and osteoporosis with multiple vertebral and hip fractures. Under

PTH was statistically significant (PZ0.022). The results of the present study

treatment with Zinc sulphate, Vitamin A, 25-OH-vitamin D, calcium and iron.

confirm the high prevalence of vitamin D deficiency among otherwise healthy

She came to the A&E for general malaise, generalized weakness, paraesthesia,

Saudi women. The results also suggest that the prevalence of selected

dysarthria and weight loss of some weeks of evolution. She was admitted due to a

cardiometabolic risk factors is higher among those with low vitamin D status.

severe hypocalcemia: calcium 5 mg/dl (8.4-10.2), ionic calcium 2.5 mg/dl (4.64-

Prospective studies are needed to determine whether such deficiency will be of

5.28), phosphate 1.2 mg/dl (2.3-4.7), magnesium 2.35 mg/dl (1.6-2.6), albumin

clinical significance with advancing age in this population, and whether vitamin D

38.8 g/l (35-50), PTH 284 pg/ml (15-65), 25-OH-vitamin D 22 ng/ml (30-100),

supplementation has beneficial effects.

alkaline phosphatase 360 U/l (40-150) and normal kidney function. The ECG

showed a prolonged QT. The signs for hypocalcaemia were negative. The patient

DOI: 10.1530/endoabs.49.EP292

had received treatment with subcutaneous Denosumab 60 mg 22 days before,

with prior calcium values of 8.4 mg/dl, phosphorous 3.1 mg/dl, 25-OH-vitamin D

25 ng/ml, PTH 76 pg/ml and Ca-urine 27 mg/24 h. Treatment was started with

intravenous calcium for 8 weeks, together with oral calcium, phosphorous and

25-OH-vitamin D. The patient improved symptomatically, with a normalization

of the QT and analysis with ionic calcium 4.6 mg/dl, phosphate 3.5 mg/dl,

magnesium 2.8 mg/dl, PTH 139 pg/ml, Ca-urine 2.3 mg/dl and 25-OH-vitamin D

EP293

39 ng/ml. The treatment to discharge was oral calcium

2.5 g/day and

25-OH-vitamin D 16.000 UI daily.

18F-choline PET/MRI in patients with primary hyperparathyroidism

Conclusions

and negative sestamibi SPECT/CT - report of two cases

Hypocalcemia after Denosumab is a rare adverse effect but it can be serious. The

Michal Krcma

patients who have undergone malabsortive bariatric surgery have a greater risk. It

Department of Internal Medicine I, Faculty of Medicine in Pilsen,

is important to monitor the 25-OH-vitamin D and calcium in patients who start

Charles University, Pilsen, Czech Republic.

treatment with Denosumab and at 15 days in patients who are at the greatest risk,

as is the case of this patient.

Primary hyperparathyroidism is a common disorder which is curable by surgery.

DOI: 10.1530/endoabs.49.EP294

Exact localisation of parathyroid adenoma is essential for minimal invasive

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP295

EP297

Performance characteristics of a new Waters MassTrake Vitamin D

Tc-99m sestamibi uptake by brown tumours in a patient with primary

assay

hyperparathyroidism

Norma Breen, Leanne Davey, Declan Roche, Philip Lambert,

Daniela Dias, Daniel Macedo, Rita Santos & Valeriano Leite

Danielle Cullen & Padhraic Rossiter

Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa,

Water Technologies Ireland Ltd, Wexford, Ireland.

Portugal.

The Waters MassTrak Vitamin D Kit is designed for the quantitative

Tc-99m sestamibi (MIBI) imaging is able to localize parathyroid adenomas/car-

determination of serum or plasma

25-hydroxyvitamin D3

(25OHD3) and

cinomas in patients with primary hyperparathyroidism. Brown tumours are one of

25-hydroxyvitamin D2 (25OHD2), which in combination provide the total

the skeletal manifestations of long standing hyperparathyroidism and its

25-hydroxyvitamin D concentration as an aid in the assessment of vitamin D

incidence has been reported to be 3%. Radiological features of these tumors

sufficiency.

may mimic bone metastasis. There are only a few reports showing brown tumours

The MassTrak Vitamin D Kit is validated for use with the Watersw ACQUITY

uptake in the whole-body Tc-sestamibi scan.

UPLCw I-Class/Xevow TQD IVD System and the sample preparation has

We report a 72-year-old female with a previous history of right nephrectomy for

been validated using the Tecanw Freedom 100/4 EVOw Offline Automated

renal lithiasis at age 49 and a left clavicle mass fracture. A neck and thoracic

Liquid Handling system. Screening for vitamin D deficiency is recommended

computed tomography (CT) scan revealed multiple lytic lesions of the skeleton

by the Endocrine Society Clinical Guidelines- Evaluation, Treatment and

(including in the left clavicle) and a pathological mandibular fracture, suggesting

Prevention of Vitamin D Deficiency by the Task Force for all individuals at

metastatic lesions.

risk for deficiency.

¹⁸F-FDG PET scan showed multiple skeletal hypermetabolic lesions and a

Vitamin D status (Total 25OHD, which is the sum of 25OHD2 and 25OHD3)

hypermetabolic nodule close to left lower pole of the thyroid gland. The biopsy of

has been a challenge to measure accurately because the antibodies used in

the lesion in the left clavicle revealed histiocytic proliferation with multinucleated

many immunoassays do not have 100% co-specificity for both 25OHD2 and

osteoclast-type giant cells compatible with a brown tumor. Laboratory data

25OHD3.

showed an elevated serum calcium of 12.8 mg/dl (8.4-10.2), alkaline phosphatase

Precision, sensitivity, linearity, potential interferents and carryover were all

of 264 UI/l (9-36), and parathyroid hormone of 1056 pg/ml (12-65).

assessed during the development of the MassTrake Vitamin D kit and found

Tc-99m sestamibi scintigraphy showed an uptake in the inferior left pole of the

to meet the performance criteria specified for the kit.

thyroid and in multiple bone lesions. The patient underwent a left inferior

To further assess the accuracy and performance of the MassTrake Vitamin D

parathyroidectomy. Histology revealed a 20 mm parathyroid adenoma.

kit assay, Waters enrolled in the CDC Vitamin D Standardisation Certification

In this patient with a long standing hyperparathyroidism the intense uptake of

Program (VDSCP) for 25(OH)D in serum, which assesses bias and precision of

brown tumors in both¹⁸F-FDG PET scan and MIBI can mimic a parathyroid

assays relative to reference measurement procedures.

carcinoma with bone metastases.

The MassTrake Vitamin D kit calibrator materials are traceable to NIST

DOI: 10.1530/endoabs.49.EP297

SRM2972a via a documented unbroken chain of calibrations. The accuracy of

this traceability to NIST SRM2972 has been verified through participation of

the Vitamin D Standardisation Certification Program (VDSCP).

DOI: 10.1530/endoabs.49.EP295

EP298

Thyroid supression in patients with primary hyperparathyroidism may

improve pre-surgical scintigraphy localisation

Mariana Tomé¹, Guillermo Martínez de Pinillos², Eyvée Arturo Cuéllar²,

Juan Manuel García de Quirós², Fernando García² & Ignacio Fernández²

Punta de Europa Hospital, Algeciras, Spain;²Valme Hospital, Seville,

Spain.

Introduction

EP296

The cause of primary hyperparathyroidism (PHPT) is a single adenoma in 85% of

Vitamin D intoxication complicated with parathormon treatment in

cases. Scintigraphy with technetium-sestamibi (MIBI) is the test of choice for

elderly: a case report

localising adenomas in patients with PHPT, allowing minimally invasive surgery

in most patients. Some articles recommend thyroid function supression to

S Nur Boysan, Burcu Altunrende, Levent Dalar, M Eren Acik,

I Polat Canpolat, C Selcan Akdeniz & M Sait Gonen

improve scintigraphy results.

Istanbul Bilim University, Istanbul, Turkey.

Methods

A prospective study was conducted in which 8 patients were included with

diagnosis of PHPT and negative scintigraphy for adenoma localisation. These

Parathormon treatment for osteoporosis is rarely complicated with hypercalce-

patients did not have a contraindication for thyroid hormone intake. We started

mia. Vitamin D treatment with high doses frequently can cause asymptomatic

treatment with a dose of 1 mcg/Kg per day with dose titulation until achievement

intoxication.We present a case with life-threatening hypercalcemia complicated

of TSH!0.3 mU/ml. Once the objective was reached, MIBI was repeated with the

both parathormon and high-dose vitamin D.

same technique and interpreted by the same specialist in Nuclear Medicine.

A 85-year old woman hospitalized for sudden-onset confusion. In history she had

Results

coronary-artery by-pass operation and a serebrovascular accedant. She was

75% of patients were women, mean age 51.9G20.55 years.

treated with teriparatide 20 mr subcuraneously and cholecalciferol 0.25 m per oral

De los eight pacientes incluidos en el estudio, 6 eran mujeres (75%), con una edad

for one year. She had a pulmonary infection one month before admission. Since

media de 51.9G20.55 an˜os. Mean preoperative calcium level was 11.49G

vitamin D is popular in media for public health, her daughter gave three doses of

0.61 mg/dl. Mean preoperative PTH level was 146.26G97.58 ng/l. Mean TSH

300 000 IU vitamin D for infection. She has hallucinations and hypoxia. Her

level before repeating scintygraphy was 0.17G0.08 mU/ml. Thyroxine suppres-

laboratory was; Ca 15.6 mg/dl, P 3.3 mg/dl, PTH 6.88 pg/ml, 25-(OH] vitamin

sion scan was positive in four of the eight patients (50%). Only two of these four

DO 70 ng/dl, 1.25(OH]₂ vitamin D 86.4 ng/l. She had also increased serum

patients underwent surgery for the moment. Minimally invasive surgery was

creatinine level. She was followed in intensive care unit fo

2 days. For

performed in these cases, confirming the existence of a parathyroid adenoma

hypercalcemia she had hydration, forced duresis, calcitonin and glucocorticoid

where the MIBI suggested. The level of calcium in these patients normalized after

therapy. Thorax CT showed bilaterally lineer atelectatic areas at basal zones. She

surgery.

continued to have nebulisation and oxygen after transmission from intensive care

Conclusiones

unit. Ejection fraction was 40% on echocardiography. She was discharged after 1

In our study suppression of thyroid function by thyroxine administration

week when serum calcium was 10.2 mg/dl and PTH was 16.37 pg/ml. Vitamin D

improved MIBI sensitivity for parathyroid adenoma localization in our patients

replacement, in elderly, could be life-threatening in megadoses. In this case,

with previous negative studies, however, a larger number of patients would be

parathormon treatment with vitamin D replacement complicated presentation.

required to confirm these results.

DOI: 10.1530/endoabs.49.EP296

DOI: 10.1530/endoabs.49.EP298

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP299

hyperuricemia (14.8 mg/dl). A 25-hydroxyvitamin D deficiency was also present

(6.5 ng/ml). The first neck ultrasound did not show abnormalities;

99mTc-

Serum vitamin D in overweight patients with normal and impaired

sestaMIBI scan was negative. Repetition of neck ultrasound revealed a left-

GFR

postero-inferior nodule likely to correspond to an enlarged parathyroid. The

Stelios Tigas¹, Athanasios Kitsos², Evangelia Dounousi²,

cytological evaluation supported this hypothesis. Pamidronate, antiemetics and

Rigas Kalaitzidis², Anna Challa³ & Costas Siamopoulos²

volume expansion with isotonic saline reverted the clinico-laboratory condition

¹Department of Endocrinology, University of Ioannina, Ioannina, Greece;

and served as a bridge to parathyroidectomy. Surgery went uneventful and a 3 cm

²Department of Nephrology, University of Ioannina, Ioannina, Greece;

inferior-left parathyroid was sent to anatomopathological examination. The final

³Pediatric Research Laboratory, Child Health Department, Ioannina,

diagnosis was parathyroid adenoma. In subsequent postoperative follow-up the

Greece.

patient was asymptomatic and had normal serum calcium levels (9.3 mg/dl) and

slightly upper-limit PTH (77.3 pg/ml).

Introduction

Conclusion

Obesity is a strong risk factor for incident chronic kidney disease

(CKD).

Despite the considerable size of the resected parathyroid, initial ultrasound failed

Furthermore, high body mass index (BMI) is consistently associated with low

to locate it. Seeking for a topographical diagnosis, a second ultrasound was

serum vitamin D in the general population. The aims of the present study were to i)

performed by a different operator in our hospital. This case highlights the

compare vitamin D metabolite levels in overweight/obese versus normal weight

importance of carefully selecting experienced centers to address parathyroid

individuals with normal to severely impaired renal function and ii) to assess the

preoperative studies. Furthermore, despite the adenoma size, its inferior location,

impact of 25(OH)D on the development of secondary hyperparathyroidism (SHPT).

and the associated severe hypercalcemia, the

99mTc-sestaMIBI scan was

Methods

negative, reminding of potential false-negative results of this method.

Serum 25(OH)D, 1,25(OH)₂D, PTH, calcium and phosphate were measured in 104

DOI: 10.1530/endoabs.49.EP300

CKD outpatients with BMIO25 kg/m². Participants were categorized according to

the eGFR (ml/min/1.73 m²): G1: R60 (nZ53), G2: 30-59 (nZ35) and G3: 15-29

(nZ16). Fifty normal-weight subjects with comparable eGFR levels composed the

control group (G1-nw - G3-nw).

Results

25(OH)D was lower in overweight/obese G1 patients compared to G1-nw (21.7G

EP301

6.5 vs 26.5G7.0 ng/ml, PZ0.02) and in G2 versus G2-nw (19.0G6.0 vs 25.0G

5.2 ng/ml, PZ0.005), whereas the level did not differ among G3 groups (15.8G

4.7 ng/ml vs 20.3G4.5 ng/ml, PZ0.49 in G3 vs G3-nw respectively). Mean

1,25(OH)₂D and PTH levels were similar in obese/overweight versus normal-

Abstract withdrawn.

weight individuals in each eGFR category. Multivariate regression analysis in the

entire cohort revealed that factors independently associated with low 25(OH)D

levels were BMIO25 kg/m², eGFR!30 ml/min/1.73 m²

and female gender

whereas low 1,25(OH)₂D levels were associated with eGFR!30 ml/min/1.73 m²,

older age and increased serum phosphate. Even though serum 25(OH)D levels were

suboptimal (!30 ng/ml) in both overweight and controls and in all eGFR groups,

significant SHPT was only observed in the groups with eGFR!30 ml/min/1.73 m².

Conclusions

Lower serum 25(OH)D but similar 1,25(OH)2D and PTH levels were observed in

overweight/obese compared to normal weight individuals and preserved or

EP302

moderately impaired renal function. Even though vitamin D insufficiency was a

Ectopic production of calcitriol by non-hodgkin lymphoma as a cause of

common feature across all eGFR categories, SHPT was only observed in those with

hypercalcemia: case report

severely impaired renal function.

Elvira Alarcón, Mariana Tomé, Carmen Bautista & Daniel González

DOI: 10.1530/endoabs.49.EP299

Punta de Europa Hospital, Algeciras, Spain.

Introduction

Hypercalcemia of malignancy usually appears in patients with osteolytic

metastasis and in those patients with humoral hypercalcemia due to secretion

of PTHrp by the tumor. Hypercalcemia due to calcitriol production by the tumor

is uncommon (!1% of cases of hypercalcemia of malignancy). It is the cause of

virtually all cases of hypercalcemia in patients with Hodgkin’s lymphoma and

approximately one third of cases in non-Hodgkin’s lymphoma. It has also been

described in some cases of ovarian dysgerminoma.

Methods

We describe the case of a patient with MALT Non-Hodgkin lymphoma admitted

to our hospital with severe hypercalcemia.

Results

EP300

Our patient was admitted to the hospital with calcium levels above 15 mg/dl.

After hydration, loop diuretics and zoledronic acid he reached calcium level of

The importance of ultrasound in the preoperative evaluation of patients

10.5-11 mg/dl but after withdrawal of intravenous hydration he presented

with primary hyperthyroidism: a case report

recurrence of hypercalcemia up to the initial values. Analytics showed very low

José Marçalo, Alexandra Araújo, Ana Wessling, Maria Raquel Carvalho &

levels of PTHi and 25-OH-Vitamin D (5.76 pg/ml, 3 ng/ml respectively). Imaging

Maria João Bugalho

tests (body CT) did not show osteolytic lesions suggestive of metastases. Given

Hospital de Santa Maria, Lisbon, Portugal.

the suspicion of humoral hypercalcemia we initiated treatment with Cinacalcet

60 mg daily and steroids (Prednisone 1 mg/kg per day) without a satisfactory

Introduction

response in reducing calcium levels. Analytical result showed undetectable levels

Primary hyperparathyroidism is the most common cause of hypercalcemia in the

of PTH-related protein (!1.1 pmol/l) and very high calcitriol levels (148 pg/ml,

outpatient setting, and a single parathyroid adenoma is usually the culprit.

N: 16-56 pg/ml). Our suspicion of calcitriol tumoral production associated with

Clinical presentation is commonly dictated by hypercalcemia. Symptoms can

lymphoma is therefore confirmed. In view of the poor response to medical

range from mild non-specific malaise and gastrointestinal disturbances, through

treatment and the need for intense hydration to maintain acceptable calcium levels

bone disease, kidney stones, cardiovascular and neuromuscular dysfunction to,

a splenectomy with cytoreductive objective

(19 cm splenomegaly) was

ultimately, coma and death. However, the vast majority of patients are

performed. After this, calcium levels reached the normal level (9.5-10.2 mg/dl)

asymptomatic.

and remained stable.

Case report

Conclusion

A 46-year-old female with a half-year endocrinology monitoring for type 2

Although tumor production of calcitriol is an uncommon cause of hypercalcemia,

diabetes and obesity, resorted to our hospital after 3 weeks’ evolution of persistent

it is usually related to lymphomas. We must think in this disorder in patiens with

nausea and vomiting. Laboratory workup showed increased PTH levels

lymphoma and hypercalcemia.

(596 pg/ml), severe hypercalcemia

(17.4 mg/dl), mild hypophosphatemia

DOI: 10.1530/endoabs.49.EP302

(2.4 mg/dl), acute kidney injury

(creatinine clearance

34 ml/min) and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP303

into consideration, since this can result from secondary hyperparathyroidism and

cause formation of calcificates.

Primary hyperparathyroidism: elective parathyroidectomy versus

Conclusions

conservative management; results of a retrospective cohort study

Vitamin D3 shout be tested in the first place during the treatment of any kind of

Melanie Nana, Holly Morgan, Natasha Shrikrishnapalasuriyar &

calcified nodular goiter, since calcificates can be caused not only by oncologic

Atul Kalhan

processes, but also secondary hyperparathyroidism.

Royal Glamorgan Hospital, South Glamorgan, UK.

DOI: 10.1530/endoabs.49.EP304

Background

The optimum management strategy for primary hyperparathyroidism remains

debatable especially in patients with mild or asymptomatic disease. We aimed to

compare the baseline characteristics and long-term outcomes of patients with

EP305

primary hyperparathyroidism who were either managed conservatively or

Pseudohypoparathyroidism (PHP) and GNAS gene mutations - clinical

underwent elective parathyroidectomy.

spectrum from PHP type 1a to pseudopseudohypoparathyroidism

Methodology

Ana Saavedra^1,2, Elisabete Rodrigues^1,2, Filipe Cunha^1,2, Miguel Le

˜o³ &

We carried out a retrospective cohort analysis of patients with primary

Davide Carvalho^1,2

hyperparathyroidism under follow-up at the Royal Glamorgan Hospital, Wales

¹Department of Endocrinology, Diabetes and Metabolism of Centro

from 1995 to 2016. The baseline characteristics were recorded from case records

Hospitalar de Sa˜o João, Porto, Portugal;2Faculty of Medicine, University of

while the clinical portal was used to collate biochemical and radiological data.

Porto, Porto, Portugal;³Department of Genetics of Centro Hospitalar de São

The patients were categorised into two main groups based on management

João, Porto, Portugal.

approach (conservative treatment vs elective parathyroidectomy group).

Results

Out of a total of 336 patients with confirmed primary hyperparathyroidism,

Introduction

(21.4%) underwent elective parathyroidectomy. Mean duration of follow up

Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of disorders

was shorter for the surgically treated patients as compared to the ones treated

that have in common end-organ unresponsiveness to parathyroid hormone (PTH).

conservatively (3.7 vs 5.2 years). There was no significant difference between

The most frequent form, PHP type 1, results from different genetic/epigenetic

mean calcium levels at diagnosis although the mean parathyroid hormone (PTH)

changes in the GNAS gene.

level at diagnosis was significantly higher in the surgical group (15.0 vs 11.4,

Case 1

PZ0.038). Despite age adjustment using binary logistic regression, prevalence of

Woman, 25 years-old, sent to Endocrinology from Genetics consultation after her

hypertension and ischaemic heart disease was significantly lower in patients

daughter had been diagnosed with PHP type 1a (heterozygous pathogenic variant

undergoing elective parathyroidectomy as compared to the group managed

at exon 13 of GNAS gene c.1174GOA (p.e392K)). Our patient and her father

conservatively.

present some clinical manifestations as observed in the child, suggestive of

Conclusion

Albright Hereditary Osteodystrophy (AHO), and both present the same mutation

There was a significant difference in prevalence of hypertension and ischaemic

as encountered in index case. We tested phosphocalcic metabolism of our patient

heart disease in patients managed conservatively as compared to the group who

and she presented normal serum calcium/phosphorus levels as well PTH levels.

underwent elective parathyroidectomy despite adjustment for age. The duration

Other pituitary hormones were evaluated, with normal results except elevated

of follow up for this group was relatively shorter which can potentially off-set

TSH (18.72 mUI/ml) in context of primary autoimmune hypothyroidism. Patient

costs associated with surgery. The higher PTH levels at baseline for the elective

started treatment with levothyroxine.

parathyroidectomy group may also signify a correlation of PTH levels with

Case 2

increased risk of complications. Prospective large randomised controlled trials

Male, 31 years-old (case 1 brother). He was sent to Endocrinology in December

need to be designed to assess cardiovascular outcomes comparing surgical versus

2015 for lymphocytic thyroiditis evaluation. During the physical examination, it

conservative management approach.

was recognized a phenotype suggestive of AHO, as was found in his relatives

DOI: 10.1530/endoabs.49.EP303

(round facies, brachydactyly and subcutaneous calcifications). Patient’s lab tests

showed normal serum calcium/phosphorus levels and high PTH in the context of

vitamin D deficiency. Other pituitary hormones levels were in normal range.

Patient performed genetic test - results ongoing.

Conclusion

Different pathological entities may result from mutations in the GNAS gene. PHP

type 1a is characterized by the presence of AHO and PTH resistance. However,

AHO manifestations may occur in patients without PTH resistance (pseudopseu-

dohypoparathyroidism), as in the two cases presented. This occurs when the

mutation is paternally transmitted. These cases somehow demonstrate de

EP304

complexity of GNAS gene mutations, which merited recently a new classification.

It is also highlighted that although pseudopseudohypoparathyroidism needs no

Calcium metabolism and autoimmune thyroiditis

treatment, genetic counselling should also be recommended.

Armine Khroyan^1,2, Edvard Toromanyan^1,2, Maria Badalyan^1,2 &

Mariam Khachatryan^1,2

DOI: 10.1530/endoabs.49.EP305

¹Muracan MC, Yerevan, Armenia;²Armenia MC, Yerevan, Armenia.

Objectives

The objective of our - investigation is to find out the role of D3 vitamin deficiency

- and calcium in patients with autoimmune thyroiditis and calcified nodules.

EP306

Methods

Hyperparathyroidism and cardiovascular risk

The research has been carried out at

“Muratsan” University Hospital and

Daniela Amzar¹, Melania Balas¹, Ioana Golu¹, Mihaela Vlad¹,

“Armenia” Medical Center, in 2013-2016.

Ramona Sandu² & Maria Cornianu³

80 patients (ages G4-0, of which 68 women and 12 men) with autoimmune

¹Department of Endocrinology, Victor Babes University of Medicine and

thyroiditis and calcified nodules have taken part in the clinical research.

Pharmacy, Timisoara, Romania;²Department of Endocrinology,

They have been tested on TSH, FT4, anti-TPO, vitamin D3, Ca^2C, PTH, as well

Emergency County Hospital, Timisoara, Romania;³Department of

as undergone a thyroid ultrasound, elastography.

Pathology, Victor Babes University of Medicine and Pharmacy, Timisoara,

Results

Romania.

TSH - 58%[, 42% N

FT4 - 60% Y, 40%N

Anti-TPO - 100%[

Background

Vitamin D3 - 84%Y, 16%N

Primary and secondary hyperparathyroidism (HP) are associated with increased

Ca^2C - 94%N, 6%Y

risk for cardiovascular complications and high mortality. Risk factors correlated

PTH - 89% [, 11%N

with hypertension in HP are hyperlipidemia, glucose intolerance, insulin

Thyroid ultrasound - Calcificates proved to be present in 76% of nodules, which

resistance, vitamin D deficiency, etc. The aim of the study was to assess the

have been formed on the background of autoimmune thyroidits.

incidence of cardiovascular complications in HP.

Thyroid elastography after 6 month taking vitamin D3 13% 3b elastography is go

Material and methods

to 3a. The increased level of PTH hormone and lower vitamin D3 should be taken

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

The study included 45 patients (15 men, 30 women), with a mean age of 45 years

hypertension. He is taking amlodipine 10 mg od. He is a non-smoker and drinks

(range 21-65 years). Thirty-two patients were diagnosed with primary HP and 13

alcohol in moderation. He was admitted with right leg swelling found to be a

with secondary HP due to chronic kidney disease (stages 3 and 4). The patients

new thrombosis. Incidental finding of extreme hypercalcaemia found on bloods

were evaluated by biochemical, hormonal parameters, imagistic tests, and cardiac

with raised PTH

(CorrCa 4.23 mmol/l, PTH 83.1 pmol/l.) Patient was

sonography.

completely asymptomatic. CT imaging of chest, abdomen and pelvis

Results

demonstrated extensive above knee thrombosis, renal calculi and a large

Vitamin D deficiency was documented in all patients with secondary HP and in

thyroid nodule. However, an ultrasound and Sestamibi confirmed spectacularly

24 patients with primary HP (75%). Other metabolic disturbances and risk factors

this was an enlarged parathyroid. He was anticoagulated with heparin and then

for cardiovascular diseases were as follows: diabetes mellitus (24.4%), smoking

oral anticoagulant. He was given aggressive i.v. fluids and bisphosphonate with

(28.8%), obesity (22.2%), and dyslipidemia (46.6%). The incidence of mitral

limited effect so cinacalcet was initiated. We were still unable to control

and/or aortic valvular stenosis (caused by calcifications) was similar in the two

calcium levels and so in patient parathyroidectomy was performed. At

groups, affecting 31.1% of the patients. Hypertension prevailed in the group of

operation the gland appeared grossly enlarged and vascular. However, there

secondary HP (12 cases), as compared to primary HP (10 cases, PZ0.0002,

was no tethering to adjacent tissues and easily removed weighing 43 g. Our

Fisher’s exact test). Peripheral atherosclerotic manifestations were noted in 11

patient made a good recovery with normalisation of calcium. Histology showed

cases (24.4%). Seven patients (15.5%) experienced an acute coronary event and

features in keeping with parathyroid adenoma rather than carcinoma. On

three patients underwent PTCA procedures with stent implantation. Ten patients

review in clinic two months later he remains normocalcemic. A DEXA has

showed ventricular hypertrophy (22.2%); the incidence was similar in the two

shown osteoporosis which we expect to improve in time.

groups (eight patients with primary HP, respectively two with secondary HP).

Our case is interesting as there are features of this case in keeping with

Conclusion

parathyroid malignancy rather than adenoma and we shall discuss this.

Our study shows that hyperparathyroidism is associated with higher incidence of

DOI: 10.1530/endoabs.49.EP308

severe cardiovascular complications, occurring at younger ages as compared to

general populations.

DOI: 10.1530/endoabs.49.EP306

EP309

Hungry bone syndrome after treatment of severe primary

EP307

hyperparathyroidism

Risk factors associated with osteoporosis in beta-thalassaemia major

El Mghari Ghizlane & El Ansari Nawal

patients

Chu Med6, Marrakech, Morocco.

Elena Mirela Iancu, Alice Ioana Albu & Irina Nicolaescu

Elias University Clinical Hospital, Bucharest, Romania.

Introduction

Persistent hypocalcemia after surgery for severe hyperparathyroidism are not

uncommon and may be secondary to transient or permanent hypoparathyroidism

Beta-thalssaemia major (BTM) is a rare disease that encompasses a vast

but may also be due to bone pathology.

range of endocrinological complications, despite of the improvement of

Observation

treatment protocols. The aim of this study was to identify the clinical and

Patient of 44 years old was hospitalized for fractures of the pelvis, and shaft of left

hematological parameters associated with osteoporosis, a frequent compli-

femur, spontaneous without trauma turned out. Laboratory tests shows severe

cation found in beta-thalassaemia patients.

hypercalcaemia to 156 mg/l, serum phosphorus at 22 mg/l, elevation of PTH to

Patients with BTM were evaluated in the Endocrinology Department of

1150 pg/ml and proper renal function with a serum creatinine to 8 mg/ml. PAL is

Elias Hospital between February 2004 and March 2016. Only patients who

increased to 709 U/l.

provided written informed consent were included in the study. A complete

A spot of médiastinal fixation compatible with ectopic parathyroid adenoma was

physical and hormonal evaluation was performed on all patients, and data

seen on the MIBI scintigraphy with several brown tumors. Ectopic mediastinal

regarding treatment of hematological disease were collected. The bone

parathyroidectomy was made after medical preoperative treatment with bispho-

density was evaluated using dual energy X-ray absortiometry (DXA).

sphonates, vitamin D and active metabolite of vitamin D.

Forty-nine patients were included in the study (median age 28.37 years;

In postoperative period a severe hypocalcemia reaching 65 mg/l at the fifth day

range

12-47). We found that

patients

(71.4%) had osteoporosis

was observed, the PTH was (9.9 pg/ml) and PAL are increased to 560 U/l with a

documented using DXA, 16 of them (45.7%) had fragility fractures caused

lowered serum phosphorus.

by decreased BMD.

The difficulty of standardization of serum calcium despite supplementation of

Patients with osteoporosis were older (median age 31.51 vs 20.5 years,

calcium element and 1 alpha and vitamin D, high PAL and the presence of diffuse

PZ0.05) and started the iron chelation therapy at an older age compared

bone lesions guide to The diagnosis of HBS.

with subjects without this condition

(105.72 months vs 63.58 months,

Conclusion

P!0.05). Although the levels of serum ferritin were higher in patients with

HBS is a heightened greed bones for calcium. It occurs in situations of

osteoporosis (1062 vs 777 ng/ml), the difference did not reached statistical

demineralization and intense bone remodeling.

significance. Hypogonadism was significantly more frequently found in

DOI: 10.1530/endoabs.49.EP309

patients with osteoporosis (30 pts, 85.7% vs 5 pts, 14.3%) in comparison to

patients without osteoporosis

(PZ0.014). The risk of developing

osteoporosis was six times greater in hypogonadal study subjects.

Our data show that osteoporosis is a highly prevalent complication among

Romanian b-thalasaemia patients, its presence being associated with older

age, delayed initiation of iron chelation therapy and the presence of

hypogonadism.

DOI: 10.1530/endoabs.49.EP307

EP310

Clinical review of nine cases of pseudohypoparathyroidism

David Barbosa¹, Brígida Robalo², Carla Pereira² & Lurdes Sampaio²

CHLN - Hospital de Santa Maria, Endocrinology, Diabetes and

Metabolism Department, Lisbon, Portugal;²CHLN - Hospital de Santa

Maria, Pediatric Endocrinology Unit, Lisbon, Portugal.

EP308

Giants walk amongst us

Objective

Raj Tanday¹, Bonnie Grant¹, Akin Ojo², Edel Casey¹ & Khash Nikookam¹

To analyze the clinicopathological features of pseudohypoparathyroidism (PHP),

¹Department of Endocrinology, King George Hospital, London, UK;

that would help clinicians to consider this rare condition in children.

²Department of Surgery, King George Hospital, London, UK.

Methods

A retrospective review of nine patients with PHP (including seven males and

three females) admitted to our hospital between 1990 and 2014 was conducted.

We present the case of a 51-year-old gentleman who had a giant parathyroid

Clinical and biochemical parameters along with epidemiological data were

adenoma. He has a past medical history of deep vein thrombosis and

extracted and analyzed.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

Objective

The mean age at diagnosis was 61.8G26.1 months, ranging from 4 to 114 months.

To study the prevalence of cardiovascular disease in patients with hypercalcemia.

The most frequent clinical features were: round lunar face and obesity (77.7%),

Materials and methods

followed by brachydactyly and learning/behavior disabilities (66.7%). Subcu-

We studied 1207 people, average age 53.9G17.25 (892 women, 315 men) from

taneous calcifications, although a landmark of PHP, were only present in four

18 to 96 years. Examination: total calcium, total protein, creatinine, cholesterol

patients (44.4%). Afebrile seizures occurred in two cases, despite the majority

and triglycerides, HbA1C, ambulatory blood pressure monitoring, ECG, an

showed multiple intracranial calcifications on cranial CT scan. Laboratory tests at

analysis of morbidity

(hypertension, coronary heart disease, cardiovascular

diagnosis revealed most frequently hypocalcemia (mean 7.4G1.9 mg/dl; 8.6-

events).

10.2), hyperphosphatemia (mean 7.9G1.7 mg/dl; 2.7-4.5) and high PTH levels

Results

(mean 366.3G218.4 pg/ml; 14-72). Subclinical hypothyroidism was present in

Hypercalcemia has been found in 31 people, mean age was 58.39G11.6 years.

eight out of nine patients (88.8%) with a mean TSH of 9.45G4.2 uU/ml (0.35-

Arterial hypertension was detected in 677 cases (in patients with hypercalcemia -

5.5) and a mean free T4 of 0.95G0.1 ng/dl (0.8-1.9). Vitamin D3, and calcium

in 23 patients), coronary heart disease was detected in 599 cases (in patients with

when needed, were prescribed to all patients to prevent symptomatic

hypercalcemia - 21), acute myocardial infarction - in 52 cases (in patients

hypocalcemia and presumably to stop disease progression by lowering the PTH

with hypercalcemia - 1), acute cerebrovascular accident - in 39 cases (in patients

levels, although it is not clear whether this normalization is beneficial. Genetic

with hypercalcemia - 1).

testing was performed in six children.

Significant differences in the prevalence of arterial hypertension

(c²Z4.03,

Conclusion

PZ0.0447); in the prevalence of coronary heart disease (c²Z3.87, PZ0.046) in

PHP is a rare and heterogeneous genetic disease with a high rate of misdiagnosis

patients with hypercalcemia were detected. In the same time the differences in the

and no specific treatment. It should be considered in children presenting with a

prevalence of acute myocardial infarction

(c²Z0.09, PZ0.8) and acute

round face, obesity, brachydactyly, learning/behavior disabilities, subcutaneous

cerebrovascular accident (c²Z0, PZ1) in patients with hypercalcemia were

calcifications and subclinical hypothyroidism. Laboratory evaluation of blood

not revealed.

calcium, phosphorus, PTH and thyroid hormones should be ordered as soon as

Conclusion

possible, as well as neuroimaging and a genetic profile for further confirmation.

The results of the study show an increasing risk of arterial hypertension and

DOI: 10.1530/endoabs.49.EP310

coronary heart disease in patients with hypercalcaemia. In the same time the risk

of acute cardiovascular events is not increased. The results may suggest the

influence of hypercalcemia on the development of cardiovascular disease.

DOI: 10.1530/endoabs.49.EP312

EP311

Severe hypercalcemia revealing an atypical parathyroid adenoma

El Ansari Nawal & Bouchra Rafiq

Department of Endocrinology, Diabetology Metabolic Diseases and

Nutrition Laboratory PCIM, FMPM, Cadi Ayyad University,

UHC Mohamed VI, Marrakech, Morocco.

Introduction

EP313

Primary hyperparathyroidism is a common cause for hypercalcemia, however

Vitamin D levels in obese adults and cardiovascular risk

severe hypercalcemia remain a rare complication. The atypical parathyroid

Andreia Domingues¹, Bruno Oliveira^2,3 & Flora Correia^2,4

adenoma is an uncommon cause to severe hypercalcemia. We report a case of a

¹Hospital das Forças Armadas - Polo Lisboa: Unidade de Nutrição e

40-year-old male with very high serum calcium due to a possible atypical

Dietética e Serviço de Endocrinologia e Diabetes, Lisboa, Portugal;

parathyroid diagnosed after a spontaneous fracture.

²Faculdade de Ciências da Nutrição e Alimentac¸ão da Universidade do

Case report

Porto, Porto, Portugal;³LIAAD INESC-TEC, Porto, Portugal;⁴Centro

A 40-year-old male was admitted to the traumatology department for the

Hospitalar de S. Joa˜o EPE, Porto, Portugal.

management of spontaneous fracture of the humerus. The clinical history revealed

clinical symptoms of hypercalcemia

(abdominal pain, neurologic irritation,

asthenia, etc.). The initial blood work up found a severe hypercalcemia (203 mg/l)

Introduction

hypophosphoremia (23 mg/l) and high ALP. Parathyroid hormone level were of

The prevalence of vitamin D deficiency is high, and yet still little recognized and

749 pg/ml. The patient underwent a surgical en bloc resection after the

treated. Cardiovascular diseases are the leading causes of morbidity and mortality

localization of a right inferior parathyroid adenoma. Pathology showed a mixed

worldwide and the emergence of evidence with the link suggesting an association

picture consistent with possible atypical adenoma versus parathyroid carcinoma.

between vitamin D deficiency and cardiovascular risk (CVR), it is pertinent to

However, due to the absence of local structures involvement, atypical parathyroid

better understand this association.

adenoma was more likely. The immunohistochimie: paratyhroidien adenoma

Objective

atypical. The evolution was marked by the improvement of the clinical signs and

This study aimed to relate the levels of 25 (OH) D in obese patients with the

calcium normalization.

cardiovascular risk.

Conclusion

Methodology

It can be very difficult to distinguish between atypical parathyroid adenomas and

Cross-sectional observational study with a sample of 31 individuals between

parathyroid carcinomas as in our case and no clear-cut guidelines yet exist to

and

years, of both sexes diagnosed with obesity. They evaluated

differentiate the two based on histology. Close follow-up is mandatory to detect

sociodemographic data, solar exposure and use of sunscreen, skin color phototype

any local recurrence.

of skin color, sources of vitamin D, physical activity, anthropometric data,

clinical and biochemical and CVR.

DOI: 10.1530/endoabs.49.EP311

Results

The average value of 25(OH) D was 15.6 ng/ml, 71.0 and 22.6% had deficiency

and insufficiency, respectively. We observed lower levels of

25(OH) D in

smokers, those with less solar exposure time, with a higher waist-to-height ratio

and in those with lower levels of DBP. We did not find a statistically significant

Cardiovascular Endocrinology and Lipid Metabolism

association between vitamin D and CVR.

Conclusions

EP312

We found a high prevalence of vitamin D deficiency in our sample of patients

Hypercalcemia and cardiovascular disease

with obesity and a significant association with the waist-to-height ratio. Despite

Elena Brutskaya-Stempkovskaya^1,2

the evidence that suggests that vitamin D deficiency is associated with an

¹Belarusian State Medical University, Minsk, Belarus;²Minsk City

increased CVR, we found this association but without statistical significance. The

Polyclinic N31, Minsk, Belarus.

measurement of total 25(OH) D routinely in people with central obesity can help

identify those who are at most CVR.

Introduction

Keywords: vitamin D cardiovascular risk; obesity; SCORE; metabolic syndrome.

According to modern studies, patients with hypercalcemia have an increased

DOI: 10.1530/endoabs.49.EP313

cardiovascular risk.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Clinical Case Reports - Pituitary/Adrenal

CD was suspected. Serologic test for anti-gliadin antibodies was positive. Another

examination of the biopsy after the first endoscopy revealed extensive collagen

EP314

depositions in the lamina propria of the small bowel, giving the diagnosis of CD.

Partial gigantism: case report

Also antibodies against Transglutaminase were positive. After gluten-free diet the

Munira Karimova & Zamira Khalimova

above mentioned symptoms disappeared and patient’s anemia and blood clot

Center for the Scientific and Clinical Study of Endocrinology, Department

markers as well as parathormone and Ca level were well controlled.

of Neuroendocrinoloy, Mirzo Ulugbek str. 56, 100125, Tashkent,

Conclusion

Uzbekistan.

The presence of other immune-related diseases in our case suggests that

immunological mechanism plays a crucial role in CD. We recommend active

specific screening in older patients belonging to at risk-group like other

The aim

autoimmune disorders. Disappeared and patient’s anemia and blood clot markers

To study case of partial gigantism.

as well as parathormone level were well controlled.

Methods

To evaluate the patient’s condition we conducted hormonal and biochemical

DOI: 10.1530/endoabs.49.EP315

investigations, as well as total blood and clinical urine analysis; Doppler

sonography and multislice computed tomography were performed.

Results

STH - 25.8 mIU/l (normal range: 2.0-20 mIU/l); IGF - 2.9 mg/l (normal range

for the age: 13-100 mg/l); ALPase - 160 U/l (normal range: up to 644 U/l); total

calcium

2.08 mmol/l

(normal range:

2.5-3.0 mmol/l); phosphorous

1.42 mmol/l

(normal range:

1.3-2.26 mmol/l). Doppler sonographyof left

extremity demonstratedpresence of hyperechoic(circular) layer in the projections

of the first and second left toes.

Multislice computed tomography

(MSCT) of left extremitydemonstrated

enlargement of the first and second left toes with the metatarsal involvement.

EP316

The soft tissues of the area contain multiple poorly demarcated thin-wall cyst-like

Optic neuritis as presenting complaint in primary hypoparathyroidism

formations with cystic content density of

-120C34 HU. Cortical layers of

Muhammad Fahad Arshad¹, Steven Kang¹, Nauman Arif Jadoon² &

adjacent toe or metatarsal bones demonstrated no disruptions of continuity.

Rehmat Karim²

Spacing intervals between the first and second toes and metatarsal bones are

¹Doncaster Royal Infirmary, Doncaster, South Yorkshire, UK;²Hull Royal

enlarged. Middle phalanx of the second toe is laterally displaced. Boundaries of

Infirmary, Hull, UK.

bones are well defined; no disruptions of cortical layer or periosteal reaction can

be seen. The soft tissues of right extremity have no changes. Total blood and

Background

clinical urine analysis, ECG and brain MRI demonstrated no deviations.

Papilledema and raised intracranial pressure has been reported frequently in

Conclusions

patients with hypoparathyroidism but very rarely optic neuritis (1).

Due to few similar cases and limited experience for their managing, it is necessary

Clinical case

to:

We report a case of 63-year-old male who presented to ophthalmology with right-

- choose the wait and see approach. The excessive growth making a patient’s

sided visual loss and a relative afferent pupillary defect. He was diagnosed with

movements hard progresses, correcting surgical procedures and appropriate

optic neuritis and underwent MRI brain which showed bilateral white matter

footwear are necessary,

changes with the possibility of demyelination. He was initially diagnosed with

- let the closure of growth zones be accomplished for correcting surgical

relapsing-remitting multiple sclerosis by the neurologist but was later found to

reconstruction to be performed; the body part disproportionally enlarged should

have severe hypocalcaemia (adjusted calcium 1.32 mmol/l (2.20-2.60)) and

be surgically removed after that, generate a databank to generalize the results,

idiopathic primary hypoparathyroidism (PTH!0.3 pg/ml (1.6-7.2)). Cerebrosp-

and to develop drug and radiotherapy regimens.

inal fluid examination was entirely normal with negative oligoclonal bands. The

DOI: 10.1530/endoabs.49.EP314

initial MRI changes were thought to be secondary to severe hypocalcaemia as per

neuroradiology MDT and subsequently, the diagnosis of multiple sclerosis was

reversed. Although the underlying mechanism is not very clear, we believe there

is an association between optic neuritis and primary hypoparathyroidism,

especially in the absence of any other underlying cause for optic neuritis.

Conclusion

Although rare, but primary hypoparathyroidism can present as optic neuritis.

Clinical Case Reports - Thyroid/Others

Therefore, serum calcium should be checked in patients with no clear cause of

optic neuritis.

EP315

Reference

An unique case of celiac disease with hypocoagulation and secondary

1. Bajandas FJ, Smith JL. Optic neuritis in hypoparathyroidism. Neurology 1976

hyperparathyreodism in elderly patient - a case report

26(5) 451-454.

Gocha Barbakadze, Lali Tigishvili, Levan Ramishvili, Nani Tsikarishvili &

DOI: 10.1530/endoabs.49.EP316

Koba Burnadze

Enmedic Clinic, Tbilisi, Georgia.

Introduction

Celiac disease

(CD) an autoimmune disorder of the small intestine, was

considered as a disease of childhood. The symptoms can be obvious. That is the

main reason why CD is underdiagnosed in elderly patients.

Aims & Methods

The purpose of our study was to demonstrate a clinical case of CD which was

EP317

diagnosed in a 41-year-old female patient. The patient attended our clinic with

The parathyroid carcinoma in a young adult male

complains of weakness, tenderness, abdominal distension, weight loss.

Sevde Nur Firat¹, Anara Karaca¹, Nujen C¸ olak Bozkurt1 & Hatice Unverdi2

Laboratory tests find severe iron deficiency anemia (HB -9 g/dl, Ery- 3.1!

¹Ankara Teaching and Research Hospital, Endocrinology and Metabolism,

10¹²/l, serum iron 4 mmol/l) and severe hypocoagolopathy (prothrombine index-

Ankara, Turkey;²Ankara Teaching and Research Hospital, Pathology,

48%, INR-2.98, but mild thrombocytopenia 130!10/l). She had suffered with

Ankara, Turkey.

these symptoms for 2 years.

Results

Number of investigations was performed. We also checked parathormone which

Introduction

revealed secondary hyperparathyroidism

(parathhormon

187 pg/ml, Ca-

Parathyroid carcinoma is a rare malignancy of the parathyroid glands. Parathyroid

1.01 mmol/l). The hemolytic anemia was excluded (haptoglobin was in normal

carcinoma may be suspected, but it usually cannot be confirmed prior to operation.

range). Stool examination revealed no pathogens.

Case

It was believed that she has these symptoms due to her anemia. After 2 weeks

A 35-year-old male was consulted to Endocrinology department with persistant

occurred the oedema of abdomen and diarrhea of 3-4 watery stools daily and

kidney stones. He was operated five times in 10 years for recurrent kidney stones.

night tremor and seizure due to hypoglycaemia

(2.3 mmol/l). Ultrasound

His lab results are as follows; Ca:13(8.8-10.6), P:2.2 mg/dl(2.5-4.5),

investigation of abdomen showed very rush peristalsis of small and large

ALP:84U/L(30-120), parathormone:179 pg/ml(14-72),

25(OH)Dvit:8.2 ug/

intestines, but no ascites, significant meteorism.

l(10-80). Urine Ca: 1159 mg/24 h(100-300), urine P:134 mmol/24 h(13-42).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Neck USG revealed 17!11!12 mm PTH adenoma with cystic components, but

Congenital fibrous dysplasia is a rare disease with a broad spectrum of

with no pathological cervical lymphodenopathies.

manifestations, including various endocrinopathies;precocious puberty,

Radionuclide scan confirmed increased parathyroid gland activity on the right

hyperthyroidism, excess growth hormone, hypophosphatemia mediated by

inferior of the thyroid gland.

FGF23.

The patient underwent right inferior parathyroidectomy. Postoperative PTH!6,

We present the case of a 33 year old male, who presented in our endocrinology

Ca:8.17,which confirmed successful remove of the pathological parathyroid gland.

service with infertility and bone pain. He was diagnosed at the age of years old

The histological findings reported marked pleomorphysm in the cells, divided by

with congenital fibrous dyplasia and suffered multiple surgeries for bone

the typical fibrotic septae and Ki-67: 4-5%. All those findings were consistent with

decompression. Blood tests showed vitamin D insufficiency (16,01 ng/ml), very

parathyroid carcinoma.

high levels of alkaline phosphatise

(919 U/l), normal levels of calcium,

After 4 months his last lab results were as follows; PTH: 57.8 pg/ml, Ca:8.8 mg/dl,

phosphorus and parathormone. Bone mineral density was low at the femoral

P:4.6 mg/dl, urine Ca: 124 mg/24 h.

neck: BMD 1.385 g/cm², TscoreZK2.4, ZscoreZK2.3.

Conclusion

His semen analysis showed a normal aspect, volume and viscosity, but with a low

There is a challenge in the diagnosis of parathyroid carcinoma, because it is

A mobility of spermatozoa and a low percentage of normal form spermatozoa.

commonly confirmed with histological evaluation. Although, parathyroid

His testosterone was within the normal range (3,44 ng/ml), with a TSH of

carcinoma is a rare disease, it should be kept in mind even in young adults.

4,10 microUI/ml. We further performed a karyotype analysis, wich showed the

DOI: 10.1530/endoabs.49.EP317

presence of an extra X chromosome in 10% of the studied metaphases, with the

diagnosis of mosaic Klinefelter:47XXY(10%)/46 XY (90%).

This is the first description of a case with congenital fibrous dysplasia which

associates mosaic karyotype 46XY/47XXY. Although the link between the two

conditions is not known, further investigations are necessary to establish a

possible correlation between them. It remains to establish if karyotype analysis

should be a routine investigation for those diagnosed with fibrous dysplasia.

DOI: 10.1530/endoabs.49.EP319

EP318

Clinical case of atypical parathyroid adenoma with severe

hypercalcemia and multiple fragility fractures

Anna Eremkina, Natalia Mokrysheva, Julia Krupinova, Svetlana Mirnaya &

Iya Voronkova

Endocrinology Research Centre, Moscow, Russia.

Introduction

Atypical parathyroid adenoma (APA) is rarely encountered cause of primary

hyperparathyroidism (PHPT). No definite criteria are considered to distinguish

preoperatively APA from parathyroid typical adenoma or carcinoma.

The aim

To describe the clinical course of a patient with an atypical parathyroid adenoma

with severe hypercalcemia and multiple fragility fractures.

Case presentation

EP320

A 61-year-old woman was evaluated for multiple fractures, skeletal deformities,

Parathyroid nodular hyperplasia: when imaging exams fail

pain in the large joints and bones, tachycardia, oppressive chest pain. She had

Ana Sofia Osório¹, José Rocha², Carolina Faria¹, David Barbosa¹,

severe hypercalcemia

(calcium level

14.7 mg/dl), hypophosphatemia (serum

Ema Nobre¹ & Maria Joa˜o Bugalho1

phosphate 2.1 mg/dl) with an elevated intact parathyroid hormone level of

¹Serviço de Endocrinologia, Diabetes e Metabolismo; Hospital de Santa

1871 pg/ml. Ultrasonography revealed a large structure (4.7 cm) of the right

Maria; Centro Hospitalar de Lisboa Norte, Lisboa, Portugal;²Serviço de

parathyroid gland. 99mTc-sestamibi SPECT/CT showed the lesion 43!34!

Cirurgia I; Centro Hospitalar de Lisboa Norte, Lisboa, Portugal.

40 mm behind the middle and lower third of the left thyroid lobe. Renal function

was impaired, GFR

46 ml/min/1.73 m². Whole-body Tc-99m bone scan

demonstrated multiple skeletal changes accepted as parathyroid osteodystrophy.

Introduction

As a result of the determination of severe hypercalcemia, heart rhythm

Parathyroid hyperplasia is the second cause of primary hyperparathyroidism (PH),

disturbances (permanent form of atrial fibrillation), a high risk of hypercalcemic

representing 15-20% of all cases. The scintigraphy with Tc-99m-Sestamibi is a

crisis, intravenous hydration was started with no significant effect. Patient

preoperative exam used to identify parathyroid adenomas or hyperplasia. It has a

received denosumab 60 mg s.c. She underwent a surgical resection of parathyroid

sensibility of 50-90%, which increases with larger parathyroid size. The neck

adenoma and intra-operative PTH levels fell to 20.9 pg/ml. In the postoperative

ultrasonography (US) has also an important role detecting parathyroid enlarged

period serum calcium was decreased to 8.9 mg/dl. On pathological examination,

glands with 70% sensibility. We report a case of parathyroid hyperplasia where the

the tumor consisted mainly of chief cells. Capsule invasion, peripherical vascular

imaging exams fail to detect a 40 mm parathyroid.

and perineural invasion of the adjacent tissue, high mitotic activity or large bands

Case report

of fibrosis were not observed. Ki67 immunostaining was generally positive in

75-year-old woman with osteoporosis, spontaneous bone fracture and osteoarti-

about 3% of the tumor. Tumor vessel invasion was detected in the central node

cular pain. Laboratory evaluation showed a parathormone (PTH) of 145 pg/ml

part. These changes corroborated the diagnosis of atypical parathyroid adenoma.

(range 14-72), a serum calcium of 12,0 mg/dl (range 8,6-10,2) and a phosphorus

Conclusion

of 2,2 mg/dl (range 2,5-4,5). A neck US was performed revealing a 17 mm

APA are rare and have been a challenge for diagnosis. They have some features of

hypoechogenic vascularised nodule consistent with the inferior left parathyroid,

carcinoma but lack the indisputable evidence of malignant disease like invasion

also visible in the Tc-99m-Sestamibi. Patient was submitted to inferior left

or metastases. They have unpredictable clinical course, long-term follow up is

parathyroidectomy. The intraoperative exploration conducted to the additional

prudent to assess for local recurrence and metastatic disorder to distinguish

finding of an enlarged superior right parathyroid with 40 mm also removed. The

between benign and malignant parathyroid disease.

final diagnosis was nodular hyperplasia of both glands. Retrospectively, a detailed

familial history was taken and considered negative for hyperparathyroidism

DOI: 10.1530/endoabs.49.EP318

and/or endocrine tumours. After 2 months post surgery, the patient is under

Vitamin D and Calcium and mentioned improvement in symptoms.

Conclusion

Coincidental results of an anatomic exam (US) and a functional one (Tc-99m-

Sestamibi), suggesting the involvement of a single gland, do not exclude

EP319

pluriglandular HP. Vitamin D and Calcium were started considering the bone

Congenital fibrous dysplasia and Klinefelter syndrome: coincidence

disease; discontinuation and tapering of therapy will be managed according to

or not?

calcium and PTH levels.

Maria Alexandra Grama¹ & Constantin Dumitrache^1,2

DOI: 10.1530/endoabs.49.EP320

¹Institute of Endocrinology IC Parhon, Bucuresti, Romania;²University of

Medicine and Farmacology Carol Davila, Bucuresti, Romania.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP321

gene, suggesting the diagnosis of FHH. This mutation has never been reported in

literature or in the Human Gene Mutation Database. In the follow up of the patient

As clear as mud: an atypical case of primary hyperparathyroidism

30 mg/day cinacalcet treatment was started and increased up to 60 mg/day due to

Jessica Lai^1,2, Navin Niles^1,3 & Namson Lau^1,4

the persistant symptomatic hypercalcemia. Plasma calcium levels were

¹Liverpool Hospital, NSW, Australia;²South Western Sydney Clinical

normalized and PTH levels decreased slightly after the treatment.

School, University of New South Wales, NSW, Australia;³Macquarie

Conclusions

University Hospital, NSW, Australia;⁴LIVE DIAB CRU, Ingham Insitute

FHH is a rare disorder, but it is clinically important because it can be confused

of Applied Medical Research, NSW, Australia.

with asymptomatic primary hyperparathyroidism. FHH is usually asymptomatic

but rarely symptoms of fatigue, weakness, and excessive thirst and concentration

Objective

problems are experienced. Cinacalcet is potentially a useful treatment of patients

A young woman presented with marked hyperparathyroidism with post-operative

with intractable hypercalcemia caused by mutations in the CaSR gene.

course complicated by hungry bone syndrome and diagnostic and management

DOI: 10.1530/endoabs.49.EP322

challenges of ongoing hypocalcaemia with hyperparathyroidism.

Method

ML, a 32-year-old Fijian Indian female, was referred with severe hypercalcaemia,

following one-year history of migratory debilitating bone pain. Initial labs

showed corrected calcium (C.Ca) 3.17 [2.10-2.60 mmol/l], parathyroid hormone

(PTH) 305.4 [2.0-6.0 pmol/l] and 25-hydroxyvitamin D (25-VitD) of 22 [40-

EP323

80 nmol/l]. Acute management included admission for intravenous fluids and

Parathyroid carcinoma can be misdiagnosis with medullary thyroid

bisphosphonates, which normalised C.Ca. A parathyroid SESTAMIBI/CT-

cancer: how is that possible?

SPECT demonstrated a 31!9!33 mm soft tissue mass in anterior superior

Natalia Mokrysheva, Julia Krupinova, Ekaterina Pigarova,

mediastinum with focal uptake at T3. Further CT neck demonstrated 10!5!

Nadezhda Platonova, Iya Voronkova & Kirill lanschakov

5 mm mass between left common carotid and subclavian arteries.

Endocrinology Research Centre, Moscow, Russia.

Results

ML’s surgical resection of the mediastinal mass was immediately complicated by

Background

generalised bony pain, pleural effusions and despite aggressive replacement of

Hypercalcemia may stimulate thyroid’s C-cells to produce the calcitonin, that

calcium, marked hypocalcaemia

(Day

C.Ca

1.99); consistent with an

could lead to misdiagnosis of medullary thyroid cancer.

exaggerated ‘hungry bone syndrome’. ML has been followed closely for on-going

Clinical case

optimisation of calcium and vitamin D; three-month labs showed elevated PTH

A 47-year-old woman suffered from fracture of the left knee. She could not walk

(30.7 pmol/l), despite normalisation of 25-VitD (79 nmol/l) and improved C.Ca

and used a wheelchair. CT scan in a public hospital detected multiple bone lytic

(2.04 mmol/l). Her pre-operative DEXA scan showed T-scores: lumbar spine

changes in the ribs and vertebrae (mts?), tumor in the liver (mts?) and node in the

K5.1SD and bilateral femoral necks K5.6SD. A MRI cervical spine

thyroid gland 2.6*1.9 cm. Thyroid biopsy showed follicular neoplasia (cancer?).

demonstrated widespread lytic lesions including, a lesion in the C2 spinous

At the same time, blood analysis showed high level of serum calcitonin 190 pg/m

process and posterior pedicles, considered consistent with pathological fracture.

(0-5.5). Thus, her state was determined as the medullary thyroid cancer (MTC)

Histopathology reported a

70!65!51 mm; 41 gm mass with no invasive

with mts in bone and liver and she was sent to our center for surgery of MTC.

features. Parafibromin was positive, whilst PGP9.5 was negative; other patterns of

Medical examination uncovered primary hyperparathyroidism

(PH): total

staining were normal, making HRPT2/CDC73 mutation unlikely.

calcium - 3.78 mmol/l (2.10-2.55), PTH K1513 pg/ml (15-65) in combination

Conclusion

with 3.7*2.9*2.4 cm tumor behind the thyroid gland showed by the US exam.

This case highlights: 1) the diagnostic challenge of marked hyperparathyroidism

Osteitis fibrosa cystica was suspected after radionuclide bone imaging. Renal

with a clinical picture suggestive of malignancy, but histological evidence not

functions were impaired, GFR 10 mL/min/1.73 m². Given the fast progress of the

supporting invasion; 2) the management issues of moderating post-operative

disease the parathyroid cancer (PC) was suspected, so “en bloc” removal of the

severe hypocalcaemia and hungry bone phenomenon; and 3) the on-going

tumor was performed. The diagnosis was confirmed by histological examination.

diagnostic and management of post-operative hyperparathyroidism with

PTH, total serum calcium levels as well as calcitonin were decreased down to the

hypocalcaemia. In summary, atypical primary hyperparathyroidism presents

reference level after the surgery. The liver biopsy shows no tumor cells. PET/CT

unique diagnostic and management challenges.

did not observe the abnormal accumulation of 18FDG in the liver and in bones.

DOI: 10.1530/endoabs.49.EP321

The patient’s condition has significantly improved 4 month after the surgery - she

can walk without a wheelchair.

Conclusions

High level of calcitonin caused by hypercalcemia in combination with nodules in

the thyroid gland can lead to incorrect diagnosis. It is important to exclude

hypercalcemia in case of high levels of calcitonin.

DOI: 10.1530/endoabs.49.EP323

EP322

Familial hypocalciuric hypercalcemia with a new heterozygous

missense mutation of CaSR gene and cinacalcet treatment

Sinem Kiyici¹, Burçin Uygun¹ & Orhan Gorukmez²

¹University of Health Sciences, Bursa Yuksek Ihtisas Education and

EP324

Training Hospital, Department of Endocrinology and Metabolism, Bursa,

Clinical case of pachydermoperiostosis

Turkey;²University of Health Sciences, Bursa Yuksek Ihtisas Education

Munira Karimova & Zamira Khalimova

and Training Hospital, Department of Genetics, Bursa, Turkey.

Center for the Scientific and Clinical Study of Endocrinology, Department

of Neuroendocrinoloy, Republic of Uzbekistan, 100125, Tashkent,

Mirzo Ulugbek str. 56.

Introduction

Familial hypocalciuric hypercalcemia (FHH) is an autosomal-dominant genetic

disease caused by an inactivating mutation in the gene encoding the calcium

The aim

sensing receptor (CaSR). The loss of function leads to increased circulating level

To study the case of Pachydermoperiostosisis.

of PTH and subsequent hypercalcemia.

Material and methods

Case report

We report a case of a 24-year old male complaining of marked changes in

20-year-old male patient referred to our center with hypercalcemia which was

appearance due to the disfiguring thickening and wrinkling of skin, excessive

found after the syncope. His serum calcium level was

11.7 mg/dl and the

greasiness and perspiration, marked horizontal creases on the forehead, with deep

phosphorus was 2.4 mg/dl (normal: 2.5-4.5). The serum PTH was 131 pg/ml

furrows between them, increase in the thickness of eye lids, “senile expression” of

(normal: 10-65), 25-hydroxyvitamin D3: 12.2 ng/ml and 24-h urine calcium

the face, thickening of distal parts of extremities, fingers and toes. The patient is

excretion was below 200 mg/day. His calcium/creatinine clearance ratio was

unsocial, aloof and focused on his emotions.To evaluate the patient’s condition

0.005. After replacement of vitamin D, calcium/creatinine clearance ratio was

we conducted hormonal and biochemical investigations, as well as total blood and

still ! 0.01. The family screening planned for FHH. Both his 49 year-old father

clinical urine analysis; MRI of pituitary and ultrasonography of inner organs were

and 22 year-old brother had also slightly elevated PTH in spite of moderately

performed.

increased serum calcium levels. Their calcium/creatinine clearance ratios were

Results

!0.01. Patient is tested for mutations in the CaSR gene. The patient was found to

GH - 2.2 (normal range: 0-20 mIU/l); IGF -114.6 (normal range: 219-644 mg/l);

have a heterozygous missense mutation (p.Ser182Pro/c.544T OC) in the CaSR

prolactin

5.3

(normal range:

1-18 ng/ml), TSH

0.87

(normal range:

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

0.17-4.05 mIU/l), free T4 - 15.5 (normal range: 11.5-23 pmol/l). The patient was

and false positive preoperative imaging might influence the extent of preoperative

diagnosed with pituitary microadenoma, mastoiditis, ethmoiditis, and sinusitis;

evaluation and the choice of surgical approach in PHPT.

US revealed chronic cholecystitis, pancreatitis, and reactive hepatitis. Total blood

DOI: 10.1530/endoabs.49.EP326

and clinical urine analysis demonstrated no deviations. The patient presented

pachydermia of scalp with moderately painful, rough skin folds in the parietal-

occipital region, resembling cerebral gyri, thickening and enlargement of eyelids

due to hypertrophy of the cartilage tissue, dystrophic changes of the conjunctiva,

atrophy of the tarsal glands with formation of cysts and granulomas in them. The

patient is unsocial, aloof and focused on his emotions.

Conclusions

EP327

Although the prognosis for patients with pachydermoperiostosis is unfavorable,

Parathyroid carcinoma: a report of cases

and there are no specific prevention techniques, they can maintain the ability to

İlknur Ozturk Unsal, Erman Cakal, Bekir Ucan, Mustafa Calıskan,

work for a long time and live to old age if the appropriate treatment is applied (the

Esra Tutal, Melia Karakose, Muyesser Sayki Arslan & Mustafa Ozbek

latter can be achieved by a thorough medical and genetic counseling of families of

Saglik Bilimleri Universty Diskapi Yildirim Beyazit Traning and Research

patients. Some cases, severe articular syndrome may cause permanent disability.

Hospital, Ankara, Turkey.

DOI: 10.1530/endoabs.49.EP324

Background

Primary hyperparathyroidism (PHPT) is one of the most common endocrine

diseases. Parathyroid carcinoma, a rare entity, comprises a small percentage

of patients with hyperparathyroidism and represents 0.005% of all cancers and

!1% of cases of PHPT.

Material and methods

Patients was diagnosed at the Endocrinology Department of Diskapi Yildirim

EP325

Beyazit Training and Research Hospital between 2010 and 2016. Ultrasound and

Vascular dementia in a 57-year old woman with adenoma of

99mTc-Sestamibi confirmed the suspicion of a parathyroid mass. Parathyroid

parathyroid gland

gland volumes were calculated by multiplication of three diameters and the

Mubina Hodzic

constant value

0.52. Intraoperative findings and pathology confirmed the

Cantonal Hospital, Zenica, Bosnia and Herzegovina.

diagnosis of parathyroid carcinoma.

Results

Of the patients eight were female and three were male. The patient’s ages were

Dementia describes a set of symptoms such as memory loss, difficulties with

between 27-76 years. Parathyroid gland volume of two patients were lower than

thinking, problem solving or language. Vascular dementia is a second most

other cases

(respectively

8.92-10.17 ml). Despite small lesion size on

common type of dementia, rare under 65 year old. I report a case of 57- year-old

ultrasonography, these two patients have moderate-high PTH values. The

woman with diagnosed dementia vascularis in Neurology department. Beside

demographic characteristics and biochemical parameters of the patients.

neurological diagnostic methods(brain scan-CT, MRI, Color Doppler of carotids,

Conclusion

she had hypercalcaemia (2.96-3.04 mmol/l; normal range 2.20-2.60) as high

Pre-operatively, parathyroid carcinoma can be expected based on factors

calciuresis/24-hour

(concentration

6.98 mmol/l). Her parathyroid hormone is

including a larger tumor size, palpable mass, severe primary hyperparathyroidism

elevated (hyperparathyroidism) due to adenoma of right inferior parathyroid

(PTH 3-15 times the normal upper limit) and hypercalcemia (O14 mg/dl) often

gland (PTH is 95 pg/ml). Because of progression on patient’s physiological and

with renal and bone involvement by the onset of presentation. Biochemical or

clinical state, immobility, difficulty to communicate and feeding with nasogastric

ultrasonographic features (lesion size, very high serum calcium and parathyroid

tube, an operation of adenoma of parathyroid gland was not an option. She ended

hormone levels) may predict aggressive disease, but this is not always the case.

with stones in her left urether and postsurgery complications.

DOI: 10.1530/endoabs.49.EP327

Keywords: dementia vascular; adenoma of parathyroid gland; hypercalcemia;

hyperparathyroidism; parathyroid hormone.

DOI: 10.1530/endoabs.49.EP325

EP328

A rare case of giant parathyroid adenoma: diagnostic and therapeutic

aspects

EP326

Cristina Alina Silaghi¹, Horatiu Silaghi², Gheorghe Cobzac³,

Equivocal preoperative imaging including 18F-fluorocholine PET-CT

Svetlana Encică⁴, Romina Alina Rădi⁵, Daniel Tudor Cosma⁶, Anca Ciurea⁷

in primary hyperparathyroidism and nodular thyroid disease - case

& Carmen Emanuela Georgescu¹

report

¹Department of Endocrinology “Iuliu Hatieganu” University of Medicine

Katerina Zajickova

and Pharmacy Cluj-Napoca, Cluj Napoca, Romania;²5th Departament of

Institute of Endocrinology, Prague, Czech Republic.

Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-

Napoca, Cluj Napoca, Romania;³Clinic of Nuclear Medicine, County

Emergency Hospital, Cluj-Napoca, Cluj Napoca, Romania;⁴Department of

66-year old woman came first for an evaluation of nodular thyroid disease.

Pathology, “Niculae Sta˘ncioiu” Heart Institute, Cluj Napoca, Romania;

Primary hyperparathyroidism (PHPT) was incidentally diagnosed during the

⁵Clinic of Endocrinology, County Emergency Hospital, Cluj-Napoca, Cluj

entrance lab test with total calcium

2.62 mmol/l and PTH 93 ng/l. Serum

Napoca, Romania;⁶Diabet, Nutrition and Metabolic Diseases Clinical

creatinine was normal and 25 OH vitamin D was 97 nmol/l. Dual-energy X-ray

Center Cluj-Napoca, Cluj Napoca, Romania;⁷Department of Radiology

absorptiometry was carried out and revealed osteoporosis at lumbar spine.

“Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca,

Moreover, there were two low-trauma fractures in a recent patient history.

Cluj Napoca, Romania.

Although hypercalcemia was mild, the presence of osteoporosis constituted an

indication for surgical treatment of PHPT. Neck ultrasound found a

hypoechogenic lesion of 0.2 ml behind the cranial third of the left thyroid lobe

Parathyroid adenomas (85% of cases of primary hyperparathyroidism) are usually

evocative of a left superior hyperfunctioning parathyroid gland. 99mTc-MIBI

small in size (weigh 70 mg - 1 g). Giant parathyroid adenomas (GPTA) weighing

double-phase scintigraphy was, however, negative. Due to inconclusive

more than 3.5 g are very rare, more common in males, in the 6^th decade of life,

conventional imaging

18F-fluorocholine PET-CT was recommended and

generally affect one parathyroid gland, are oxyphilic and ectopic in 50% of cases.

localized four abnormal parathyroid foci suggestive of parathyroid hyperplasia

We report the case of a 53-year-old woman presented for asthenia, fatigue,

and/or multigland parathyroid disease. Basic assessment of hereditary forms of

tingling in the arms and legs without other symptoms of hypercalcaemia.

PHPT was, therefore, carried out. Prolactin, IGF1, chromogranin A and calcitonin

Laboratory analysis showed: ionized calcium 6.5 mg/dl (normal: 4.2-5.4 mg/dl),

were normal; calcium/creatinine excretion ratio was 2,2%. No relatives affected

total calcium

13.9 mg/dl

(normal:

8.8

10.0 mg/dl), hypophosphoremia

with hypercalcemia were found. In a postmenopausal woman with normal renal

2.0 mg/dl (normal: 2.3 to 4.7 mg/dl) and 809 pg/mL intact-parathyroid hormone

functions and sufficient vitamin D level a sporadic form of PHPT with a single

(normal:

11.0

67.0 pg/ml). Calcitonin, thyroxin and thyroid-stimulating

adenoma would be the most expected. The result of 18F-fluorocholine PET-CT

hormone levels were normal. Cervical ultrasonography revealed a solid

was probably modified by thyroid nodules present in both thyroid lobes. The

hypoechoic nodule located postero-inferior of the right thyroid lobe with

definitive diagnosis will be made by a surgeon during bilateral cervical

retrosternal extension. An ectopic GPTA localised in para-aortic region of

exploration. The present case shows how a combination of both false negative

superior mediastinum stretching down to the bifurcation of the trachea was

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

detected using technetium-99m sestamibi scintigraphy and single photon

polyuria or polydipsia. She did not have any history of hypertension,

emission computed tomography/computed tomography

(SPECT/CT). GPTA

nephrolithiasis, renal failure or bone fracture; and she was taking risedronate

measuring 8.5!4!4.5 cm was removed via cervical approach. Histopathology

for one week for osteoporosis. On physical examination, vital signs and

indicated an atypical GPTA with main cells, oncocytic cells, follicular areas, Ki67

systemic findings were normal. Blood count revealed mild anemia

! 5% (rarely, in very small areas Ki67 was up to 10%); chromogranin and

(hemoglobin:10 gr/dl, MCV:80 fL); and in biochemical analysis, creatinine

cytokeratin AE1/3 were positive; carcinoembryonic antigen, thyroid transcription

was

0.65 mg/dl, Ca:12 mg/dl, P:2.2 mg/dl, Mg:2.07 mg/dl, albu-

factor1, and thyroglobuline were negative.

min:3.1 gr/dl, ALP:738 U/l. Hormonal parameters showed biochemical

The peculiarities of this case: GPTA but poor symptomatology of hypercalcemia and

primary hyperparathyroidism

(PTH:1938 pg/ml,

25(OH)D3:!3 ng/ml).

moderately elevated serum calcium levels; ablation of GPTA by cervical incision

BMD showed severe osteoporosis in lumbar vertebra (T score K4.0).

although mediastinal expansion; mild hungry bone syndrome postoperatively (not

There were osteopenia in bone X-rays and

“Brown tumor” in fifth

correlated with GPTA volume). In conclusion, GPTA is a very rare condition but

metacarpal bone of right hand. No nephrolithiasis or nephrocalcinosis

their size is not an argument in favour of malignancy. Cervical incision should be

were found in abdominal sonography. Neck sonography revealed a large

considered before sternotomy and thoracic/mediastinal approach.

(37!24 mm), vascular, heterogenous nodule having both cystic and solid

DOI: 10.1530/endoabs.49.EP328

areas in right lobe of the thyroid gland. 99mTc-sestamibi scintigraphy

showed MIBI uptake in the nodule, making us to define the nodule as

intrathyroidal parathyroid adenoma. Then, the patient underwent to surgery,

and right hemithyroidectomy was done; and postoperative pathological

examination confirmed the parathyroid adenoma. Postoperative calcium and

PTH levels were 7.3 mg/dl and 24.3 pg/ml.

EP329

When clinical and biochemical findings point to primary hyperparathyroid-

Autosomal dominant hypocalcemia in a Portuguese family: novel

ism, we should keep in mind that intrathyroidal nodules may be parathyroid

mutation in the calcium-sensing receptor gene

adenoma.

Vânia Gomes, Florbela Ferreira, Catarina Silvestre, Raquel Castro &

DOI: 10.1530/endoabs.49.EP330

Maria João Bugalho

Santa Maria Hospital, Lisbon, Portugal.

Introduction

Autosomal dominant hypocalcemia

(ADH) is a rare condition, caused by

activating mutations in the calcium-sensing receptor (CASR) gene. Affected

EP331

individuals have hypocalcemia with inappropriately low parathyroid hormone

(PTH) levels.

The rare cause of primary hyperparathyroidism: Parathyroid

Case report

Carcinoma

A 50-year-old woman, asymptomatic, was referred to our Endocrinology

Nagihan Bestepe¹, Didem Ozdemir², Sefika Burcak Polat², Berna Evranos¹,

department for investigation of hypocalcemia detected in routine blood analysis

Reyhan Ersoy² & Bekir Cakir²

(serum corrected calcium was 7.4 mg/dl - normal: 8.6-10.2). There was also

¹Ankara Ataturk Training and Research Hospital, Department of

hyperphosphatemia (5.4 mg/dl - normal: 2.4-5.1) and abnormally low PTH

Endocrinology and Metabolism, Ankara, Turkey;²Ankara Yildirim

(9.9 pg/ml - normal: 14-72).

Beyazit University Medicine Faculty Department of Endocrinology and

Her past medical history was irrelevant except for depression in the past. She

Metabolism, Ankara, Turkey.

denied taking any prescription. There was no history of neck surgery/radiation or

known family history of hypocalcemia. Thyroid function, morning serum cortisol

Introduction

and 24-h urinary cortisol, fasting glucose, 25-hydroxyvitamin D, renal function,

Parathyroid carcinoma (PC) is a rare endocrine malignancy which accounts for

serum magnesium, sodium and potassium were normal. Auto-antibodies against

0.005% of all cancers and less than 1% of primary hyperparathyroidism cases.

thyroid, parathyroid and adrenal gland were negative. Brain computed

This uncommon tumor usually occurs during the fifth decade of life, with equal

tomography identified basal ganglia calcifications. A few first-degree relatives

frequency in both sexes, and has an indolent but progressive course. It’s

(74-year-old mother, sisters aged 44 and 49, and 30-year-old son) were also

frequently symptomatic and patients may have high values of serum calcium and

screened for hypocalcemia. The mother and the younger sister, both

parathyroid hormone (PTH) with a palpable cervical mass. PC generally occurs as

asymptomatic, had hypocalcemia and inappropriately low PTH. The mother

a sporadic disease, and less frequently in the setting of genetic syndromes such as

also presented basal ganglia calcifications. The son and the older sister had normal

hyperparathyroidism-jaw tumor syndrome and multiple endocrine neoplasia. In

calcium levels. Genetic analysis identified a novel heterozygous CASR variant:

this study we present five different PC cases followed in our clinic.

c.2269GOA (p.Glu757Lys) in the proband, her mother and younger sister

Cases

whereas it was not identified in the son and older sister. Affected individuals

There were 2 female and 3 male patients with PC. The mean age of the patients was

started calcium replacement aiming to a low-normal calcium level (8-8.5 mg/dl).

50.4G13.7(38-65). They had presented with weakness, headache, nausea and

Conclusion

vomiting, and widespread bone pain. One of the patients had bone fracture and one

The co-segregation of the novel CASR variant with the hypocalcemic phenotype

other patient had nephrocalcinosis.The mean serum calcium, phosphorus and PTH

in the family favor its pathogenic role. Clinical investigation and diagnosis of this

levels were 15.3G2.7 mg/dl (ranging between 11.6 and 18.9 mg/dl), 2.4G0.8 mg/dl

condition can be challenging, but treatment and long-term monitoring are

and 869.4G991.9 pg/ml (ranging between 87 pg/ml and 2500 pg/ml), respectively.

essential to prevent complications, such as neurological.

Histopathologically, mean tumor size was 29.2G11.1 (15-44) mm. Plasma calcium,

DOI: 10.1530/endoabs.49.EP329

phosphorus and PTH levels were in the normal range and 36 months after surgery in 2

patients. Local recurrence was observed in 2 patients and reoperation was performed.

One other patient withlung and bone metastasis had still high serum Ca and PTH

levels despite recurrent surgeries for six times.

Conclusion

PC is usually that of a slowgrowing neoplasm and indicates progressive end-organ

EP330

damage from disturbed calcium homeostasis. While some patients present with

A case of intrathyroidal parathyroid adenoma presented with severe

mild increases in serum calcium and PTH levels, some might have very severe

25(OH)D3 deficiency, bone pain and high PTH

hypercalcemia and hyperparathyroidism. Similarly, prognosis varies from cure to

Omercan Topaloglu¹, Bahri Evren¹, Ibrahim Sahin¹ & Bulent Unal²

life threatening unresectable and metastatic disease depending on the presentation

¹Inonu University Medical Faculty, Department of Endocrinology, Malatya,

and surgical success.

Turkey;²Inonu University Medical Faculty, Department of General

Surgery, Malatya, Turkey.

DOI: 10.1530/endoabs.49.EP331

The most frequent pathology of primary hyperparathyroidism presented

with the findings of hypercalcemia is parathyroid adenoma. Some patients

EP332

having the signs of primary hyperparathyroidism may have intrathyroidal

parathyroid adenoma and it may be overlooked. We present a case of

A parathyroid adenoma presented with diffuse bone lesions and anemia

intrathyroidal parathyroid adenoma presented with bone pain.

Irem Kok, Fatma Dogan, Soner Cander, Ozen Oz Gul, Erdinc Erturk &

47-year-old female patient referred to our clinics with bone pain and she had

Canan Ersoy

no pruritus, dry mouth, dyspepsia, abdominal pain, nausea, vomiting,

Uludag University Medical School, Bursa, Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Primary Hyperparathyroidism is a common endocrine disorder characterized with

EP334

high parathyroid hormone (PTH) and calcium (Ca) levels. Although most of the

Broken bones and blindness- a rare cause of osteoporosis

patients are asymptomatic, some patients may be presented with renal,

Rebecca Sagar & Afroze Abbas

gastrointestinal, musculoskeletal, neurologic or cardiovascular signs associated

Leeds Centre for Diabetes and Endocrinology, Leeds Teaching Hospitals,

with hypercalcemia or elevated parathyroid hormone related findings such as

Leeds, UK.

bone disease, nephrolithiasis, hypophosphatemia increased production of

calcitriol, hypomagnesemia, hyperuricemia and anemia. Brown tumor is one of

the manifestations of Primary Hyperparathyroidism and is more commonly found

Case History

in trabecular bone pattern of the mandible, bones of the upper and lower

A 37 year-old gentlemen was referred to metabolic bone clinic due to recurrent

extremities and ribs.

recent fragility fractures. He had several fractures throughout childhood, and

Case

these had continued to occur into his adult life. He was blind in his left eye since

A 54 year-old female with a history of recurrent nephrolithiasis was referred with

birth. He felt that this had contributed to his fractures, due to falls. There had been

fragile bones fractures. Biochemical assay revealed an increased value of serum

no other previous major health problems. His brother had a similar eye condition.

PTH 1570 pg/ml and calcium 13.5 mg/dl. The serum phosphorus level was

There were no other risk factors for osteoporosis. There was nothing of

3.4 mg/dl, ALP:14 IU/l, 25OH vitamin D:!8 mg/l.

significance to find on examination.

Direct radiographies revealed multipl lesions of the upper and lower extremities,

Investigations & Results

iliac bones, femoral heads, sacrum, sternum, ribs and vertebrae. A complete blood

DXA scan- Spine L1-L4 T-score K3.6, Left hip T-score K2.4. CTX 0.24 mcg/L

count (CBC) of the patient revealed a low hemoglobin and hematocrit levels

(normal), P1NP 34 mcg/L (normal). Spine X-rays: T11 grade 1 fracture & T4

(Hg:6.93 g/dl, Htc:20.00%). There was no evidence of neutropenia or leucopenia.

grade 2 fracture. No other secondary cause of low bone mass identified (normal

After consulting to Hematology department, it was reported that anemia was

levels of testosterone, parathyroid hormone, vitamin D, calcium, phosphate and

associated with diffuse bone lesions and it was not possible to make bone marrow

coeliac antibodies)

biopsy due to diffuse bone lesions. Follow up of anemia for recovery after

Discussion

parathyroidectomy was also suggested. Ultrasound of neck revealed mass of 3 cm

This is a case of a young man with seemingly unexplained fragility fractures and

associated with parathyroid adenoma. After erythrocytes transfusions, the patient

low bone mass. The clue to the aetiology for low bone mass was the gentleman’s

was planned for surgery.

hereditary eye condition. The eye problems are caused by a condition known as

Multipl bone lesions are common in Primary Hyperparathyroidism and Brown

Familial Exudative Vitreoretinopathy (FEVR); a rare genetic disorder affecting

tumor may also be a part of this clinical condition. These lesions are usually

retinal angiogenesis that can cause progressive visual loss. FEVR may be

localized and have a tendency for recovery of the primary disease. It should be in

mediated by mutation in LRP5 coding for the LRP5 transmembrane receptor.

mind that diffuse bone marrow lesions may be seen resulting progenitor cells

LRP5 plays a key role, alongside Frizzled protein, in the Wnt signalling pathway,

failure in bone marrow and cytopenia.

which has effects on cellular proliferation, adhesion and migration. Importantly,

Wnt signalling is also known to regulate bone mass. Therefore, it is the defect in

DOI: 10.1530/endoabs.49.EP332

this pathway that is the common denominator for this gentleman’s blindness and

bone problems. We speculate that upcoming new drugs that target Wnt signalling

in osteoporosis, such as Romosuzumab

(a Sclerostin inhibitor), may be

particularly beneficial in patients with low bone mass associated with FEVR.

DOI: 10.1530/endoabs.49.EP334

EP333

Common bone lesions may be a sign of parathyroid carcinoma in the

primary hyperparathyroidism

Soner Cander¹, Ozen Oz Gul¹, Pinar Sisman² & Canan Ersoy¹

¹Uludag University Medical School, Bursa, Turkey;²Kars State Hospital,

EP335

Kars, Turkey.

An usual cause of post operative hypocalcemia

Fatma Mnif, Wajdi Safi, Nabila Rekik, Houcem Mrabet, Hamza Elfekih,

A 60-year-old male patient who presented with left hip and knee pain was found

Nadia Charfi, Mouna Mnif & Mohammed Abid

to be compatible with primary hyperparathyroidism (PTH:2233 pg/ml, calcium:

Department of Endocrinology, Hedi Chaker University hospital, Sfax,

15.7 mg/dl, phosphorus:

2.9 mg/dl creatinin:1.99 mg/dl,

25-OH-D:9.7 mg/l,

Tunisia.

ALP:532 mU/ml). Bone grafts of the patient showed multiple lytic lesions in

the pelvis, cranium and long-bones. Neck ultrasonography showed hypoechoic

solid nodule with cystic areas, 2!2 cm with size in the left thyroid gland inferior

Introduction

region and delayed wash-out was detected by the parathyroid scintigraphy. Bone

The otorhinolaryngologist can be confronted to multiple surprises after a thyroid

scintigraphy was suspicious in terms of metastasis. Left hemi thyroidectomy and

surgery

left inferior parathyroidectomy was performed. In thorax lytic lesions compatible

Case description

with multiple metastases in bone structures were observed. Thoracal and lumbar

We report the case of a 48 year-old woman admitted with post operative

vertebral MR imaging also showed lesions compatible with metastasis.

hypocalcaemia (after thyroidectomy?). The patient has a history of hypothyroid-

Histopathological examination revealed parathyroid carcinoma with invasion to

ism since 5 years. She then presented a cervical swelling. The ultra-sound

the thyroid gland.

confirmed the presence of a suspicious thyroid nodule measuring

4 cm. A

Primer hyperthyroidism has been increasing in recent years as a laboratory

thyroidectomy was then conducted. Post operative, the patient presented with

diagnosis the contribution of asymptomatic cases has increased. Frequent routine

symptoms of hypocalcaemia, confirmed by low level of blood calcium at

examinations have also led to the early recognition of the disease, and osteitis

1.59 mmol/. The anatomopathological examination showed no sign of thyroid

fibrosa cystica and bone lesions such as brown tumor, which are among the

tissue, along with the presence of five adenomatous parathyroid nodules. Post

complications of primary hyperparathyroidism, are increasingly rare. Primer

operative scintigraphy showed a conserved thyroid tissue, with absence of

Hyperparathyroidism is often associated with solitary parathyroid adenoma,

parathyroid glands. Hungry Bone Syndrome was confirmed led to the prolonged

hyperplasia or multiple adenomas, mostly seen with the genetic syndromes.

and severe hypocalcaemia, associated to the adenomatous aspect of the

Parathyroid carcinoma is very rare and is recognized only by the presence of

parathyroid measuring more than 6 cm. Because of the family history of pituitary

metastases or histopathologically significant invasion findings, such as those

prolactinoma, primary hyperparathyroidism and multinodular goitre and the

present in our case. Clinically, incompatibility in tumor size and serum PTH

personal history of uterine fibroma and hypothyroidism, Multiple Endocrine

levels, extremely high PTH levels may be a sign of parathyroid carcinoma. Apart

Neoplasia 1 (MEN1) was suspected. Genetic confirmation is underway.

from this, common bony lesions which are rarely seen in primary hyperparathyr-

Conclusion

oidia due to early diagnosis and noisy clinical picture can be considered as

This is the case of an asymptomatic hyperparathyroidism discovered by a severe

malignancy findings as it is in our patient. Therefore, in patients with widespread

post-thyroidectomy hypocalcaemia. This hyperparathyroidism is due to multiple

pain and common bony lesions, the patient should be carefully examined for

parathyroid adenomas misdiagnosed as thyroid nodules, and probably falls within

parathyroid carcinoma and an appropriate approach should be sought.

a multiple endocrine neoplasia type 1.

DOI: 10.1530/endoabs.49.EP333

DOI: 10.1530/endoabs.49.EP335

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP336

and lower tubular calcium reabsorption, and decreased excretion of zoledronate

due to acute renal failure. Considering the high prevalence of vitamin D

Brown tumor in a normocalcemic patient

deficiency and the sudden nature of hypocalcaemia, these and other risk factors

Pinar Sisman¹, Ozen Oz Gul², Soner Cander², Erdinc Erturk² &

should be considered when using bisphosphonates in order to prevent this

Canan Ersoy²

potentially fatal complication. Further studies may clarify the overall risk and

¹Harakani State Hospital, Endocrinology and Metabolism Clinic, Kars,

approach to this situation.

Turkey;²Uludag University Medical School, Department of Endocrinology

and Metabolism, Bursa, Turkey.

DOI: 10.1530/endoabs.49.EP337

Background

Brown tumor of bone is a non-neoplastic lesion resulting from abnormal bone

metabolism in hyperparathyroidism. Brown tumor, as the only and initial

symptom of normocalcemic primary hyperparathyroidism is extremely rare.

Case presentation

A 69-year-old female patient was admitted to the hospital with a mass in the right

thigh. A mass lesion of the right distal femur with bone and soft tissue infiltration

EP338

was observed in the lower extremity magnetic resonance imaging (MRI). The size

Transient hyperglycemia during the course of primary

of the mass was measured as approximately 10!3.7!4.6 cm. Apart from this

hypoparathyroidism: Case study

lesion, nodular lesions were detected in various dimensions on the right femur,

Magdalena Urbanczuk^1,2, Marcin Lewicki^2,3, Agnieszka Zwolak^2,4,

left femur and left patella. Brown tumor was detected in pathologic evaluation of

Marcin Urbanczuk⁵, Joanna Swirska^2,4, Monika Lenart-Lipinska^2,6 &

the mass of the right distal femur. The patient was examined for hyperparathyr-

Jerzy S Tarach²

oidism. Serum parathormone (PTH) level was 2698 pg/mL (reference range

¹Chair and Department of Clinical Pathomorphology of Medical University

15-68), calcium level was 8.8 mg/dL (8.4-10.2), phosphorus level was 2 mg/dL

of Lublin, Lublin, Poland;²Department and Clinic of Endocrinology of

(2.4-4.4) and 25-OH D level was 10 mg/L. Vitamine D treatment was given to the

Medical University of Lublin, Lublin, Poland;³Chair and Department of

patient. 24-hour urine calcium could not be assessed because of the patient’s low

Epidemiology and Clinical Research Methodology of Medical University of

compliance. The total lomber T score was K4.7 and the femur neck T score was

Lublin, Lublin, Poland;⁴Department of Internal Medicine and Internal

K5.5 in the bone mineral density. Localization studies were performed and neck

Medicine in Nursing, Medical University of Lublin, Lublin, Poland;⁵Chair

ultrasonography and parathyroid scintigraphy revealed a parathyroid adenoma in

and Department of Family Medicine of Medical University of Lublin,

the inferior right lobe. Patient underwent parathyroidectomy surgery and in

Lublin, Poland;⁶Department of Laboratory Diagnostics of Medical

histopathological evaluation solitary parathyroid adenoma was observed. The

University of Lublin, Lublin, Poland.

follow-up of the patient whose postoperative PTH decreased to 161 pg/mL is

being continued.

Introduction

Discussion

Calcium ions (Ca^2C) play an essential role in process of correct b-cell insulin

Cytologically, it is difficult to separate the brown tumor from any other giant cell

secretion. Hypocalcemia impairs insulin secretion leading to glucose metabolism

lesions. To prevent unnecessary surgical procedures, PTH assay is necessary in

disorders and insulin resistance.

any patient with expansive lytic lesion of the bone, even if serum calcium level is

Case study

normal.

62 -year old female patient with 18 years history of type 2 diabetes, treated with

DOI: 10.1530/endoabs.49.EP336

insulin, suspected of hypoparathyroidism, was admitted to the Department and

Clinic of Endocrinology, Medical University of Lublin because of hypocalcae-

mia. She was experiencing latent tetany signs like muscle tremors, paresthesia and

an unpleasant tingling sensation in her hands, additionally persistent dry cough.

Clinical observation and laboratory findings with classic constellation of

symptoms (hypocalcemia, hyperphosphatemia, undetectable concentrations of

parathyroid hormone (PTH), latent tetany signs, history of nephrolithiasis and of

subcortical nuclei calcifications) have confirmed the diagnosis of late onset

primary hypoparathyroidism. Significant clinical improvement following intro-

EP337

duction of calcium and active form of vitamin D supplementation were achieved.

Symptomatic bisphosphonate-induced hypocalcaemia after severe

Based on normal blood glucose levels with relatively low daily insulin

idiopathic hypercalcaemia

requirement an attempt at discontinuing insulin therapy was made. In spite of

Joana Lima Ferreira, Teresa Tavares, Rui Moc¸o & Pedro Melo

hypoglycemic therapy cessation, patient’s glucose levels remained in the normal

Hospital Pedro Hispano, ULS Matosinhos, Portugal.

range. For the purpose of diagnosis verification oral glucose tolerance test

(OGTT) was performed, and did not reveal any glucose metabolism disorders.

These observations led us to conclude that recognized hyperglycemia was

Introduction

secondary to prolonged hypocalcemia.

Bisphosphonates, generally considered as safe drugs, are potent inhibitors of bone

Conclusions

calcium outflow used to treat osteoporosis and hypercalcemia associated with

The optimal concentrations of organism’s cytosolic Ca^2C are required for

malignancy. Bisphosphonate-induced hypocalcaemia is an increasingly reported

appropriate b-cell insulin release. Hypocalcemia is regarded as a factor

complication, but it has not yet been a subject of comprehensive research.

implicated in pathogenesis of glucose metabolism disorders thus normalizing

Case report

serum calcium levels allows for restoration of adequate insulin secretion.

A 65-year-old woman had a history of Crohn’s disease and ankylosing spondylitis

medicated with prednisolone and etanercept. Due to vitamin D deficiency she had

DOI: 10.1530/endoabs.49.EP338

been taking calcium and vitamin D supplementation. At a consultation she

presented with difficulty in concentration and balance, and blurred vision.

Analysis revealed severe hypercalcemia (ionized Ca^2C2.18 mmol/l), elevated

serum creatinine and normal parathyroid hormone (PTH). She was treated with

intravenous fluids and a single intravenous dose of zoledronate, resulting in

calcium normalization and clinical remission. Five days later she returned for

delirium, tetany, perioral paraesthesia and carpopedal spasm. Chvostek’s sign was

positive. Hypocalcaemia

(ionized Ca^2C0.97 mmol/l), vitamin D deficiency,

EP339

elevated PTH, hypomagnesaemia, hypophosphataemia and hypokalaemia were

Hyperparathyroidism jaw tumour syndrome (HPT-JT)

detected. She required intravenous calcium and long-term oral calcium and

KS Ahmed, M Sherlock, L Stassen, C Timon & ML Healy

vitamin D supplementation with gradual but sustained improvement. Densito-

¹Department of Endocrinology, St. James Hospital;²Department of

metry revealed femur and lumbar spine osteoporosis. Study was negative for

Endocrinology, Adelaide and Meath Hospital;³Department of Maxillofacial

neoplasms and despite extensive study, aetiology of hypercalcemia remains

Surgery, St. James Hospital;⁴St. James Hospital. Department, Dublin,

unclear.

Ireland.

Discussion

This case illustrates a serious but still poorly recognized complication of

hypercalcaemia treatment. Most patients do not develop hypocalcaemia due to

Hyperparathyroidism jaw tumour syndrome (HPT-JT) is an autosomal dominant

compensatory mechanisms that could be affected in this case: vitamin D

disease with variable penetrance. Onset is typically in late adolescence or early

deficiency, diminished intestinal calcium absorption (corticoids and zoledronate)

adulthood. Primary hyperparathyroidism is typically caused by a single

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

parathyroid adenoma but parathyroid carcinoma occurs in 10-15%. Ossifying

Methods

fibroma of the mandible or maxilla occurs in 30-40%, and may be locally

We report the case of a 37-year-old man admitted to the hospital with a neck mass

aggressive. 15% of patients have renal manifestations which include polycystic

of 48 mm.

kidney disease, Wilms tumour and renal cell carcinoma. In women there is an

Results

increased risk of uterine tumours. The gene causing HPT-JT, HRPT2, is located

Our patient presented with neck pain and an hipoechogenic nodule on ultrasound

on chromosome 1q31.2a, coding for parafibromin (tumour suppressor gene)

(US) on the left side of the neck adjacent to the lower pole of the left thyroid lobe.

found in 50-75%.

An US-guided fine-needle aspiration was performed and follicular cells where

We recently identified a patient with HPT-JT which led to detection of a kindred

described. Measurement of TSH, T4L and AbTPO had a normal result. Given the

with the CDC73 pathogenic variant. A

54-year-old male presented to the

suspicion of thyroid nodule O4 cm surgical treatment was decided. While

maxillofacial services for surgical removal of a jaw tumour. Histology confirmed

waiting for surgery an US was performed and we observed markedly reduction on

an ossifying fibroma of the maxilla. During his admission he was noted to have

the size of the nodule (28 mm) and the radiologist suggested the possibility of a

hypercalcaemia (Ca^CC3.2 mmol/l, PTH 110 pmol/l).

parathyroid adenoma. Our patient referred prior episodes of nephrolitisis a few

On review of previous history, he described poor dentition since the age of 20, and

years ago and that he had been told to had high serum calcium levels but did not

he reported that his sister had died at the age of 35 from metastatic parathyroid

undergo further studies. We measured PTHi levels and Calcium (100,5 pg/ml;

carcinoma. Diagnosis of primary hyperparathyroidism was established and he

10 mg/dl) showing a normocalcemic hyperparathyroidism. Left thyroid

underwent parathyroid surgery with normalisation of Ca^CC and PTH. Histology

lobectomy was performed showing a normal left thyroid lobe, a parathyroid

was consistent with parathyroid adenoma.

cyst and ectopic thymus.

His genetic analysis detected a mutation in the CDC73 gene (Exon 7 c.664 C to T

After nodule resection PTHi levels went back to normal and calcium levels

leading to protein PArg222Ter). Family members were screened, which

remain less than 10 mg/dl.

confirmed CDC73 mutation in one daughter and one son, and 1 son was

Conclusion

mutation negative.

PCs are rare lesions and often considered as thyroid cysts. Diagnosis is best made

DOI: 10.1530/endoabs.49.EP339

by monitoring serum calcium levels and sending cyst fluid for PTH analysis.

Therefore, PCs must be included and be remembered within the differential

diagnosis of all neck masses.

DOI: 10.1530/endoabs.49.EP341

EP340

Fahr syndrome revealing a pseudohypoparathyroidism

Imen Sakka, Ibtissem Oueslati, Meriem Yazidi, Malika Chihaoui,

Fatma Chaker, Ons Rjeb & Hedia Slimane

Department of Endocrinology, La Rabta Hospital, Tunis, Tunisia.

Introduction

EP342

Fahr syndrome is a rare entity characterized by the presence of bilateral

“Pseudo or not”: differential diagnosis of hyperparathyroidism with

intracranial calcifications with predilection for the basal ganglia and dentate

severe electrolyte imbalance in transgender patient: a challenging case

nuclei. It is commonly associated with endocrine disorders, particularly

report

parathyroid and Vitamin D disturbances. Herein we report a case of

Ieva Ruza^1,2 & Linda Kundzina²

pseudohypoparathyroidism revealed by Fahr syndrome.

¹Riga Eastern Clinical University Hospital, Riga, Latvia;²Riga Stradins

Observation

University, Riga, Latvia.

A 29-old-year male was referred to our department for symptomatic

hypocalcemia. He showed a decrease in his school performances with memory

and concentration impairement. Computed tomography scan of the brain revealed

Introduction

bilateral, symmetric basal ganglia calcifications. Ophthalmic examination

Differential diagnosis between secondary hyperparathyroidism (SHPTH) and

showed bilateral cortical cataract.

possible pseudohypoparathyroidism can be challenging in case of insufficient

Physical examination showed positive Chvostek and Trousseau’s signs. The rest

diagnostic tools and co-existing medical conditions. We report a diagnostic road

of clinical examination was normal in particular no typical findings of Albright’s

to final diagnosis.

hereditary osteodystrophy were observed.

Case report

Laboratory investigations revealed severe hypocalcemia of

44 mg/l (normal

A 48-years old white male-to-female transgender patient was admitted to our

range: 85-105), hyperphosphatemia of 48 mg/l (normal range: 25-45), elevated

clinic for evaluation due to mental deterioration, general fatigue, slowly

parathormone level of 218 pg/ml (normal range: 15-68.3), normal renal function,

progressing bilateral upper arm and epigastric area cramps over last 2 years,

normal serum albumin and normal 25 OH Vitamin D level (46 mg/l, normal range:

pain in the lumbal area and right hip region leading to reduced mobility. No

30-80 mg/l). Thyroid function was normal. Urinary cyclic adenosine mono-

remarkable history, except crural DVT during estrogen therapy, received from

phosphate level and Gsa subunit assay were not available Considering laboratory

2004-2015 without any specialist’s supervision, not any therapy used in last year.

findings, the diagnosis of pseudohypoparathyroidism was established. Patient was

Possible previous delusion episodes since head trauma during teenage years were

put on substitutive therapy.

reported by patient’s brother. The patient was severely obese.

Conclusion

Biochemical tests revealed low calcium (1.74 mM/l [2.2-2.55]) and potassium

In the absence of chronic renal failure, the coexisting of hypocalcemia,

(3.12 mM/l

[3.3-5.5]), normal phosphate, creatinine and glucose level.

hyperphosphatemia, elevated PTH and normal vitamin D level is consisting

Preliminary suspected Cushing’s and Fahr’s syndromes were excluded after

with the diagnosis of pseudohypoparathyroidism.

seeing suppressed cortisol axis and elevated PTH (624.2 pg/ml [12-68]). No

substantial changes in other tests. No electrolyte loss with 24 h urine was seen.

DOI: 10.1530/endoabs.49.EP340

Thyroid and gonadic axis were unchanged. Head CT scan revealead no basal

ganglia calcinosis. No data of paratadenoma. In spite of high normal phosphate

level and not characteristic phenotype, our first suspected diagnosis was

pseudohypoparathyroidism. Additional tests showed low 25(OH)-vitamin-D (!

7 ng/ml [30-50]) and elevated alkaline phosphatase (320 U/l [44-147]). Pelvic

MRI showed left femoral periosteal cyst formation and right hip joint synovitis.

EP341

Though we were restricted in many diagnostic tools due to multiple factors, no

further data strongly supported evidence of pseudohypoparathyroidism.

Parathyroid cyst: the forgotten diagnosis of a neck mass

Based on these findings we suggest the final diagnosis of secondary

Esperanza Miranda, Mariana Tomé, Carmen Bautista & Daniel Gonzalez

hyperparathyroidism with severe osteomalacia. Treatment was continued with

Punta De Europa Hospital, Algeciras, Spain.

calcitriol, cholecalciferol, oral calcium. Some improvement of symptoms was

seen over the hospitalization course.

Introduction

Conclusion

The differential diagnosis of cystic cervical masses includes thyroid cyst, thymic

We would like to stress the importance of multi-focused investigation for bone-

cyst, thyroglossal duct cyst, branchial cleft cyst, bronchogenic cyst, lymphan-

metabolic problems.

gioma and parathyroid cyst (PC). PC is one of the less common causes of the

DOI: 10.1530/endoabs.49.EP342

cervical masses.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Developmental Endocrinology

were not different between groups(6.39G0.4 mmol/l vs. 6.39G0.9 mmol/l, PZ

NS). OC had a positive correlation with ucOC (rZ0.3, PZ0.03). In contrast, CRP

EP343

was not correlated with OC and ucOC (PZ0.2, PZ0.3, respectively).

Adolescent onset distal renal tubular acidosis presenting with significant

Conclusion

growth retardation without rickets

We conclude that circulating OC has a potential use as a sensitive diagnostic

Sagarjyoti Roy, Sandipan Banik, Indira Maisnam, Aniruddha Ray &

biomarker for early detection of breast cancer.

Apurba Kumar Mukherjee

DOI: 10.1530/endoabs.49.EP344

R G KAR Medical College and Hospital, West Bengal, India.

Introduction

Distal renal tubular acidosis (RTA) can have varied presentation. Onset in infancy

is usually severe. However, adolescent onset has variable presentation ranging

from hypokalemia to nephrocalcinosis, and rarely with rickets or growth

retardation. We describe a girl with distal RTA presenting with hypokalemia

and growth retardation.

EP345

Case

Gross CDC73 deletions in young patients with primary

12 year old girl presented with recurrent episodes of weakness of all four limbs

hyperparathyroidism in Russia

and failure to gain height and weight for last 4 years. There was no sensory or

Elizaveta Mamedova, Natalya Mokrysheva, Evgeny Vasilyev,

autonomic involvement. She had normal birth history and developmental

Iya Voronkova, Elizaveta Orlova, Maria Kareva, Zhanna Belaya,

milestones, no dysmorphism or bony abnormality, no sensorineural deafness

Liudmila Rozhinskaya & Anatoly Tiulpakov

and a negative family history. Nutritional status was average. Height and weight

Endocrinology Research Center, Moscow, Russia.

were below Indian Academy Of Paediatrics 3rd percentile.

Investigations

K^CZ2.9 mmol/l; Urine KZ30 mmol/24 hr (increased). pHZ7.324, HCO3^-Z

Introduction

12.4 meq/l, pCO₂ Z23.9 mm-Hg; anion gapZ10 mmol/l Urine pH Z7.0. UAG:

Hyperparathyroidism-jaw tumour syndrome (HPT-JT) is a rare disorder, which is

Positive (28 meq/l), urine calcium:creatinine ratioZ0.63(N!0.2) ANA & ENA:

frequently characterized by the development of parathyroid carcinomas and

negative. Genetic testing not done due to non-availability CBC, LFT, serum

atypical parathyroid adenomas and, thus, severe course of primary hyperpar-

25-OH Vitamin D & iPTH, Ca^CC, PO_3-, alkaline phosphatase, FT4/TSH, IGF-1

athyroidism (PHPT).

were all normal. X-ray of wrist: no evidence of rickets. USG Abdomen Z

Case reports

Medullary Nephrocalcinosis in both kidneys.

Two patients (1 male and 1 female, 18 y.o. and 13 y.o. at the time of diagnosis of

Diagnosis

PHPT, respectively) among a cohort of young patients (!40 y.o.) with PHPT,

Growth retardation with hypokalemic periodic paralysis in a case of distal RTA of

underwent next-generation sequencing (NGS) (Ion Torrent^TM PGM^TM, Thermo

adolescent onset based on normal anion gap acidosis with high urinary pH with

Fisher Scientific-Life Technologies, USA) using a custom-designed Ion

positive urine anion gap.

AmpliSeq^TM gene panel. NGS did not reveal any pathogenic variants in genes

Treatment

associated with familial PHPT in these two patients, but the analysis of the

She was managed successfully with intravenous potassium and is on oral sodium

sequence data by the ExomeDepth program [Plagnol V et al, 2012] allowed us to

bicarbonate 500 mg twice daily. Her clinical response is good.

assume the existence of large deletions in CDC73

gene. To confirm this

Conclusion

observation MLPA (MRC-Holland, the Netherlands) of CDC73 on ABI 3500xL

The take home points are that every child presenting with hypokalemia should be

Genetic Analyzer (Applied Biosystems, USA) was performed. In a male with

evaluated for RTA. The presentation of distal RTA can be subtle to severe. Even

severe PHPT (serum total calcium 4.49 mmol/l (2.15-2.55), ionized calcium

in the absence of bony involvement like rickets children can suffer from

2.03 mmol/l (1.03-1.29), PTH 1833 pg/ml (15-65), osteitis fibrosa cystica) and

significant growth retardation. Growth failure should be actively searched for

histological diagnosis of atypical parathyroid adenoma, a gross deletion including

even in asymptomatic patients.

the entire CDC73 gene and four additional genes (TROVE2, GLRX2, B3GALT2

DOI: 10.1530/endoabs.49.EP343

and LINK0103) was detected. In a female with severe PHPT (serum total calcium

3.57 mmol/l, ionized calcium 1.58 mmol/l, PTH 1550 pg/ml, osteitis fibrosa

cystica) and histological diagnosis of parathyroid carcinoma, the deletion of 1-10

exons of CDC73 gene was detected. The patients’ mother also had PHPT due to

parathyroid adenoma.

Conclusion

These two cases illustrate that NGS data could be successfully applied for indirect

assessment of large gene deletions which could be further confirmed by MLPA.

Search for CDC73 mutations is necessary among patients with parathyroid

carcinomas and atypical parathyroid adenomas, which could occur at any age.

Endocrine Tumours and Neoplasia

DOI: 10.1530/endoabs.49.EP345

EP344

Differential roles of carboxylated and uncarboxylated Osteocalcin in

stage I breast cancer as a diagnostic biomarker

Anara Karaca¹, Nese Ersoz Gulcelik¹, Filiz Bakar², Giray Akgul³,

Zeynep Sahiner¹ & Mehmet Ali Gulcelik³

¹Ankara Teaching and Research Hospital, Endocrinology and Metabolism,

Ankara, Turkey;²Ankara University, School of Pharmacy, Biochemistry,

Ankara, Turkey;³Ankara Oncology Teaching and Research Hospital,

EP346

General Surgery, Ankara, Turkey.

Multiple endocrine neoplasia type 1 phenocopies: role of the genes

associated with familial primary hyperparathyroidism

Elizaveta Mamedova, Natalya Mokrysheva, Evgeny Vasilyev,

Objective

Vasily Petrov, Zhanna Belaya, Liudmila Rozhinskaya & Anatoly Tiulpakov

The finding of new biomarkers is needed to have an early diagnosis of breast

Endocrinology Research Center, Moscow, Russia.

cancer. In this study we evaluated serum levels of carboxylated osteocalcin (OC)

and uncarboxylated osteocalcin(UcOC), CRP as a diagnostic biomarker for breast

cancer.

Introduction

Design and methods

The genetic causes of development of multiple endocrine neoplasia type 1 (MEN-

Blood samples of 39 women with newly diagnosed breast cancer with stage I were

1) phenocopies remain largely unknown.

obtained before surgery and 39 age and BMI matched health women were

Aim of the study

selected as controls.

To evaluate the role of genes associated with familial primary hyperparathyroid-

Results

ism (PHPT) in the development of MEN-1 phenocopies with the combination of

The mean age was 52G7 years (PZ0.8). Circulating logOC was significantly

PHPT and pituitary adenomas (PA).

lower in breast cancer patients compared to controls (2G1.1 mg/ml vs. 3G

Materials and methods

1.23 mg/ml, P!0.05), while logCRP levels were significantly higher in breast

20 patients (19 females and 1 male) were included in the study. All patients had

cancer patients than controls (0.8 vs. K0.6, P!0.05). Serum levels of logUcOC

biochemically confirmed PHPT in combination with PA of different types of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

secretion:

GH-secreting,

ACTH-secreting,

PRL-secreting,

non-

¹University Hospital of Pisa, Endocrinology Unit, Pisa, Italy;²Department

functioning PA. Median age at the time of inclusion was

61 years [Q25-

of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;

Q75;min-max:57-66.5;54-79], median age at the time of PHPT diagnosis was 57

³Department of Surgical, Medical and Molecular Pathology and Critical

years [Q25-Q75;min-max:54-62;51-72], median age at the time of PA diagnosis

Area, University of Pisa, Pisa, Italy;⁴Fondazione Pisana Per La Scienza

was 47 years [Q25-Q75;min-max:40.5-57.5;21-61]. Five patients had mild

Onlus, Pisa, Italy.

PHPT, 15 - manifest PHPT (though it was difficult to assess the role of PHPT in

osteoporosis development due to concomitant menopause and Cushing disease in

some cases). Imaging techniques revealed: in 15 patients - solitary parathyroid

Familial Isolated Hyperparathyroidism (FIHP) is a hereditary disorder charac-

tumour, in 2 patients - two parathyroid tumours, in 3 patients parathyroid tumours

terized by primary hyperparathyroidism

(PHPT) with no evidence of other

were not visualized. In the majority

(nZ16) of patients PA was the first

endocrine disorders. Germline MEN1, CDC73 and CASR mutations have been

identified, but the majority of FIHP has still unrecognized causes. The aim of this

manifestation, only in 4 patients PHPT was diagnosed before PA. In all patients

study was to identify, by whole-exome sequencing, novel gene alterations in a

no MEN1 mutations were identified by Sanger sequencing, confirming diagnosis

large FIHP kindred. The family’s proband, her sister, brother and niece were

of MEN-1 phenocopy. Next-generation sequencing of a custom-designed Ion

affected by PHPT. The proband was negative at MEN1, CDC73 and CASR gene

AmpliSeq^TM panel of genes associated with familial PHPT (MEN1, CASR,

mutations by Sanger analysis. The proband, her sister and niece were also affected

CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D) using

by papillary thyroid carcinoma, the brother had Non-Hodgkin Lymphoma and

semiconductor sequencer PGM^TM Ion Torrent

(Thermo Fisher Scientific,

bladder cancer. The proband had also a moderate colorectal polyposis and the

USA) was performed. ANNOVAR was used for variant annotation.

niece a renal angiomyolipoma. We analyzed the proband, two affected and two

Results

healthy family’s members with the Illumina NextSeq550 platform. The raw data

No pathogenic or likely pathogenic variants in the abovementioned genes were

were converted using Bcl2toFastq tools. Data analysis was performed by the

identified.

SeqMule pipeline. The three affected individuals, but not the healthy relatives,

Conclusion

shared 57 rare genetic variants. A more stringent filter related to genes involved in

Mutations in the genes associated with familial PHPT are unlikely to have

hereditary cancer detected one missense variant in the APC gene (V530A) in the

any role in the development of MEN-1 phenocopies with combination of PHPT

three affected patients, subsequently confirmed by Sanger analysis. Moreover, the

and PA.

other affected relative and 2/15 healthy members carried the variant. The APC

DOI: 10.1530/endoabs.49.EP346

gene is involved in familial polyposis (FAP), an inherited disease marked by

thousands colorectal polyps. The APC variant was predicted deleterious by three

statistic model. Although the affected individuals don’t have classical FAP

features, the proband had the excision of two colonic polyps. We might speculate

that the presence of non-truncating mutation could lead to a mild colonic

phenotype, as showed in the attenuated FAP, characterized by the presence of

!100 polyps. FAP tumor spectra is highly various, in about 2% of cases papillary

EP347

thyroid carcinoma and bladder cancer have been reported.

Recurrent ectopic parathyroid carcinoma

DOI: 10.1530/endoabs.49.EP348

Julia Krupinova, Natalia Mokrysheva, Anna Eremkina, Ekaterina Pigarova

& Svetlana Mirnaya

Endocrinology Research Centre, Moscow, Russia.

Background

In most cases of parathyroid carcinoma (PC) only recurrence could be a credible

feature of malignancy.

Clinical case

At the age of 19 years a woman was diagnosed with urolithiasis. At the age of 22

EP349

years she had a surgical resection of the neck nodule at the right site in the

Parathyroid cancer - clinical presentation, prognostic factors and

projection of carotid triangle. After the histological study, ectopic parathyroid

long-term evolution

tumor was misdiagnosis with paraganglioma (material is available for review). At

Beata Jurecka-Lubieniecka¹, Barbara Michalik¹, Grzegorz Bula²,

the age of

37 years the patient noted deteriorating state of health: severe

Jacek Gawrychowski², Dariusz Kajdaniuk³, Bogdan Marek³,

weakness, nausea, vomiting (10 times per day), rapid loss of body weight (10 kg

Andrzej Tukiendorf⁴ & Barbara Jarzab¹

in 6 months). She noted the appearance of nodule in the neck to the right in the

¹Department of Nuclear Medicine and Endocrine Oncology, Maria

projection carotid triangle again. A month later she was diagnosed with a primary

Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,

hyperparathyroidism: total calcium - 3.0 mmol/l (2.19-2.55), PTH-786 pg/ml

Gliwice, Poland;²Department of General and Endocrinal Surgery, Bytom,

(15-65). CT-scan showed two tumors sized up to

3.3*1.7 cm;

3.2*1.3 cm

Silesian Medical University, Katowice, Poland;³Department of Pathophy-

between right m. sternocleidomastoideus and the common carotid artery. The

siology and Endocrinology, Silesian Medical University, Katowice, Poland;

next day the hypercalcemic crisis developed (total calcium - 5.33 mmol/l) and

⁴Department of Epidemiology and Silesia Cancer Registry, Maria

therefore, ectopic parathyroid tumors were urgently resected in our center. PC

Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,

was diagnosed after a histological examination. At the age of 47 years the local

Gliwice, Poland.

recurrence was diagnosed: total calcium - 3.51 mmol/l, PTH-450 pg/ml. PET/CT

showed a focus with the pathological accumulation of 18FDG in singles upper

jugular lymph node on the right at the level of C3-4, 16,7*19,7 cm. After another

Background

surgery, the tumor went through the immunocytochemical analysis which showed

Parathyroid carcinoma (PC) is a rare endocrine malignancy affecting 0.5-5% of

a diffuse intensive expression of PTH, Ki-67- 15%.

all patients with primary hyperparathyroidism. Due to the rarity of PC there is still

Conclusions

lack of prognostic implications of the disease and clear consensus regarding

The diagnosis of PC is challenging due to the lack of credible diagnostic criteria.

management. Our purpose was to evaluate prognostic factors and treatment

The treatment of choice in PC is an en bloc resection of the mass with total

outcomes of patients treated at the Department of Nuclear Medicine and

ipsilateral thyroid loboistmectomy and central compartment lymphadenectomy

Endocrine Oncology.

and timely detection and resection of mts.

Methods

The target group covered 44 patients with parathyroid carcinoma treated in years

DOI: 10.1530/endoabs.49.EP347

1995-2016 at the department of Nuclear Medicine and Endocrine Oncology.

Results

All the patients were treated surgically, 17 of them repeatedly, however, only in

19 patients the en bloc resection was performed, 25 patients underwent only

parathyroidectomy. During an average 10-year-observation among all the patients

operated non-radically the recurrence of the disease appeared. Deaths occurred

EP348

only in this group, despite radio- and chemotherapy. An interesting clinical

Exome analysis of a large family with familial isolated primary

observation are benefits resulting from cinacalcet treatment: taking the medicine

hyperparathyroidism (FIHP) and multiple cancers

for 2-4 years resulted in stabilization and ever remission of the disease in four

Filomena Cetani¹, Elena Pardi², Simona Borsari², Federica Saponaro²,

patients with metastasis. To predict outcome histopathology results, biochemical

Liborio Torregrossa³, Chiara Mazzanti⁴, Paolo Aretini⁴, Marco La Ferla⁴,

and clinical features were analyzed. Due to a limited number of patients, a

Sara Franceschi⁴, Francesca Lessi⁴, Prospero Civita⁴ & Claudio Marcocci⁴

parametric Weibull’s regression was adopted. Among the analyzed risk factors

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

distant metastasis and organ complications, mainly renal failure were statistically

in G (1.29G0.12 g/cm² vs 1.23G0.02 g/cm² (PZ0.5). Ribs BMD were higher in

crucial in patients survival. Occurrence of distant metastasis increases the risk of

group 1 children compared to group 2 (B 0.72G0.08 g/cm² vs 0.59G0.06 g/cm²

early death seven times (HR Z6.82, PZ0.02) whereas in renal failure the risk

(PZ0.02); G 0.71G0.05 g/cm² vs 0.65G0.06 g/cm² (PZ0.05)). There were no

increases nine times (HR Z8.92, PZ0.008).

significant differences in hand BMD (G 0.87G0.10 g/cm² vs 0.85G0.13 g/cm²

Conclusions

(PZ0.836); B 0.93G0.14 g/cm² vs 0.85G0.15 g/cm² (PZ0.360)); total (G

In patients with parathyroid carcinoma, definition of prognostic factors and the

1.18G0.09 g/cm² vs 1.11G0.13 g/cm² (PZ0.29); B 1.17G0.13 g/cm² vs 1.06G

role of the radiation, chemotherapy and cinacalcet treatment still has to be

0.14 g/cm² (PZ0.21)) in obese children compared to control. A significant

elucidated. In our analysis distant metastases and renal failure were critical factors

increase in Ca levels were in obese B compared to control (2.48G0.07 vs 2.41G

regarding increased risk of death.

0.001 mmol/l (PZ0.001)) with no differences in G (2.43G0.09 vs 2.41G

DOI: 10.1530/endoabs.49.EP349

1.2 mmol/l (PZ0.86)). There were no differences in P (G 1.23G0.22 vs 0.95G

0.64 mmol/l (PZ0.78); B 1.32G0.27 vs 1.30G0.18 mmol/l (PZ0.85)), and AlP

(G 108.06G26.66

85.13G65.64 IU/l

(PZ0.46); B

217.93G57.24

157.27G26.41 IU/l (PZ0.68) in two groups.

Conclusions

A significant increase in ribs and legs BMD, Ca levels were found in children with

obesity compared to normal weight control.

DOI: 10.1530/endoabs.49.EP351

EP350

A suspicious case of multiple endocrine neoplasia

Teresa Alves Pereira¹, Inês Furtado², Ana Amado¹, Lia Ferreira¹,

Raquel Almeida¹ & Isabel Palma¹

¹Endocrinology Department, Centro Hospitalar e Universitário do Porto,

Porto, Portugal;²Internal Medicine Department, Centro Hospitalar e

Universitário do Porto, Porto, Portugal.

Paediatric Endocrinology

EP352

Introduction

Multiple endocrine neoplasia (MEN) syndromes are rare entities characterized by

Progressive osseous heteroplasia in a child with

the occurrence of tumors involving two or more endocrine glands in a single

pseudohypoparathyroidism type I

patient. These syndromes are classified as type 1 or 2 according to specific

Madalina Vintila, Iuliana Gherlan, Cristina Dumitrescu, Anda Dumitrascu

phenotypic characteristics. MEN2

encompasses three different subtypes:

& Camelia Procopiuc

MEN2A, MEN2B and familial medullary thyroid carcinoma. More recently a

CI Parhon National Institute of Endocrinology, Bucharest, Romania.

syndrome related to mutations in the CDKN1B gene has been described - the

syndrome of multiple endocrine neoplasia 4. It is characterized by tumors of the

Introduction

parathyroid and pituitary glands.

Progressive osseous heteroplasia (POH) is a rare genetic condition of progressive

The case

heterotopic ossification

(HO), from skin and subcutaneous tissues into deep

A 36-years-old woman was submitted to parathyroidectomy and adrenalectomy

skeletal muscles. Most cases are caused by heterozygous inactivating mutations

in September/2010 due to suspected parathyroid adenoma and pheochromocy-

of GNAS gene. Related disorders are Albright hereditary osteodystrophy (AHO),

toma, both confirmed posteriorly by histology. The patient did not have a positive

pseudohypoparathyroidism (PHP), and primary osteoma cutis. Distinction from

family history of pheochromocytoma, parathyroid adenomas or thyroid medullary

other GNAS-based conditions is made by the extension of HO from superficial to

carcinoma and, furthermore, genetic testing for MEN1 and MEN2 was negative.

deep tissues in POH.

Genetic investigation for MEN

is pending. After surgery PTH levels

Case report

normalized. However, there is a slow increase in PTH levels since 2012 and

We present the case of a 10-year-old girl who came to medical attention at

sestamibi scintigraphy shows signs of right parathyroid adenoma.

3-months of age for lumbar and scapular subcutaneous ossifications. The biopsy

Conclusion

confirmed osseous metaplasia of the connective tissue. The ossification process

This case is highly suggestive of a MEN 2A due to the symbiotic appearance of

progressed in size, depth and area, up to painful swelling and mechanical

parathyroid adenoma and pheochromocytoma in the same patient. A negative

compression in the shoulder. She underwent surgical resection of the scapular

genetic test, however, raises suspicion for a possible different diagnosis - MEN4

lesion at 3-years of age but the ossification recurred 2 years later. There were no

or even another genetic mutation.

congenital hallux valgus or other skeletal deformities. She had clinical features of

DOI: 10.1530/endoabs.49.EP350

AHO: round facies, flat nasal bridge, short neck, brachydactyly, obesity. Lab tests

revealed mild elevated TSH (4.98 mU/ml) at 5-years of age and later, at 8-years of

age, elevated parathyroid hormone

(395.9 pg/ml) with hypocalcemia

(CaZ

8.1 mg/dl) and hyperphosphatemia

(PZ7.18 mg/dl). She was diagnosed as

Endocrine Tumours and Neoplasia

having PHP most probably type Ia/c based on the typical clinical findings of AHO

phenotype and biochemical profile. She received treatment with calcitriol and

EP351

levothyroxine. Follow-up examinations revealed moderate progression of the

Bone mineral density in obese children

heterotopic ossifications and favourable clinical course with spontaneous puberty

Hanna Mikhno¹, Anzhalika Solntsava¹, Olga Zagrebaeva¹ &

and no other hormone resistance identified yet at age of 12.

Natalia Vasilieva²

Conclusions

¹Belarusian State Medical University, Minsk, Belarus;²Republican Center

Overlapping features of POH and PHP type I can be present, as part of the

of Medical Rehabilitation and Balneotherapy, Minsk, Belarus.

spectrum of the heterogeneous GNAS related disorders. Awareness and

distinction of these conditions are important for appropriate management.

Aim

DOI: 10.1530/endoabs.49.EP352

To evaluate bone mineral density (BMD) and its relationship with calcium (Ca)

and phosphorus (P) metabolism in children with obesity.

Methods

We examined 105 children in the University Hospital (Minsk) from 2011 to 2015

yrs. Their anthropometric parameters (height, weight, BMI) were determined.

Body composition with evaluating of mineral component were made by dual

energy X-ray absorptiometry with the calculation of feet, hands, spine, ribs, hips

BMD (g/cm²), Z-test. The levels of Ca and P, alkaline phosphatase (AlP) were

Steroid Metabolism C Action

determined. All children were divided into two groups: group one - children with

obesity (nZ75, boys(B)/girls(G) Z47/28, age 15.34G2.12 yrs, BMI 32.7G

EP353

5.3 kg/m²; group 2 - normal-weight control (nZ30, B/GZ19/11, 15.08G2.47

Genetic variations in the HSD11B1 gene in patients treated with

yrs (PZ0.3), 19.4G2.4 kg/m² (PZ0.0001)).

glucocorticoids show associations with bone mineral density

Results

Heide Siggelkow^1,2, Martina Blaschke^1,2, Gabriele Armbrecht³,

Legs BMD were increased in boys with obesity (0.94G0.11 g/cm² vs 1.13G

Friederike Thomasius³, Oliver Bock³, Mladen Tzvetkov⁴, Claus-C Gluer⁵

0.17 g/cm² (PZ0.03)) compared to control group without significant differences

& Dieter Felsenberg³

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Clinic of Gastroenterology and Gastrointestinal Oncology, University

glucocorticoids due to rheumatoid arthritis or asthma (64%), or other rheumatic,

Medical Center, Gottingen, Germany;²MVZ Endokrinologikum, Gottingen,

gastrointestinal or pulmonary disorders. An equivalent glucocorticoid dose was

Germany;³Center for Muscle and Bone Research, Charite, Berlin,

calculated for the different glucocorticoids used. BMD of the spine or femoral

Germany;⁴Institute of Clinical Pharmacology, University Medical Center

neck, and the number of fractures and falls were correlated to the HSD11B1

Gottingen, Gottingen, Germany;⁵Section Biomedical Imaging, Department

SNPs.

of Radiology and Neuroradiology, MOINCC, Kiel, Germany.

Results

BMD, the number of fractures and falls did not show an association with daily or

cumulative equivalent dose or type of glucocorticoid. Since the three genetically

Introduction

linked SNPs in intron 5 of the 11b-HSD1 gene - rs11811440, rs1000283, and

Physiological glucocorticoids play an essential role in bone formation but can

rs932335 HSD11B1 highly correlated, only rs11811440 was further analyzed. In

cause osteoporosis if present in excess. The key enzyme converting inactive

patients treated with the glucocorticoids prednisolone or methylprednisolone the

cortisone into the active cortisol and vice versa is

11-beta-hydroxy-steroid-

presence of the A-allele was associated with lower BMD levels.

dehydrogenase (11b-HSD1). We have reported that genetic variations in the

Discussion

HSD11B1 gene correlate with increased cortisol levels in dexamethasone

Our results suggest that in patients treated with glucocorticoids the function of

suppression and with changes in bone mineral density

(BMD) suggesting

11b-HSD1 is dependent on HSD11B1 polymorphisms. Hence, inactivation of

individual differences in 11b-HSD1 activity caused by polymorphisms. In this

prednisolone or methylprednisolone by 11b-HSD1 would be the crucial step for

study we investigated the effect of HSD11B1 SNPs on BMD in patients on

BMD levels in glucocorticoid-treated individuals.

glucocorticoid therapy.

DOI: 10.1530/endoabs.49.EP353

Methods

246 patients treated with different glucocorticoids the HSD11B1

SNPs

rs11811440, rs1000283

und rs932335

were determined. Patients received

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Calcium & Vitamin D Metabolism

can be useful to alleviate either a medical condition diagnosis confirmation or

unraveling of its etiology.

EP354

Aim

We present a case 30 years old male, presented with nausea, vomiting and diffuse

abdominal pain. Three months before hospital admission, patient was

Abstract withdrawn.

unsuccessfully treated for painful, reddish skin lesions

5mm in diameter,

dispersed on abdominal wall, arms and legs, interpreted as ‘viral papillomata’.

Out of mentioned skin lesions-eruptive xanthomata, hypotension, light abdominal

tenderness and moderate distention, other physical examination was normal.

Results

Laboratory findings revealed lipemic serum, elevated inflammatory, pancreas and

liver necrosis markers, hyperglycemia, hyponatremia and hypocalcaemia.

Performed imaging procedures (ultrasound and computed tomography) showed

enlarged pancreatic body and tail, and left pleural effusion. Lipemic serum and

eruptive xanthomata taken together with other case findings pointed to life-

threatening acute pancreatitis caused by mixed dyslipidemia, obviously serious

Cardiovascular Endocrinology and Lipid Metabolism

(lipids could not be measured initially). In association with aggressive pancreatitis

EP355

management, nil-by-mouth treatment with plasmapheresis successfully lowered

lipids and enabled their measurement (triglycerides 19.9 mmol/l and cholesterol

Metabolic syndrome in digestive neoplasms

10.8 mmol/l). After plasmapheresis, diet and fibrate, triglycerides and cholesterol

Soumaya Mrabet, Nour Elleuch, Aya Hammami, Hanen Jaziri,

levels were 4.04 and 3.99 mmol/l, respectively. Patient was referred to lipid

Aida Ben Slama, Ahlem Braham, Salem Ajmi, Mehdi Ksiaa & Ali Jmaa

clinic, gastroenterologist and surgeon (formed pancreatic cyst).

Sahloul University Hospital, Sousse, Tunisia.

Conclusions

Adequately interpreted eruptive xanthomata can act as a shortkey for faster

Introduction

confirmation of acute pancreatitis. Treatment of serious pancreatitis and

The metabolic syndrome (MS) is a real public health problem on a global scale.

dyslipidaemia is done at the same time. Plasmapheresis, as well lifelong diet

People with MS are at increased risk not only for cardiovascular diseases but also

and pharmacotherapy later, are the mainstay for management of dyslipidaemia

for neoplasia. The aim of our study is to determine the prevalence of MS in

that caused pancreatitis (presumably mixed one).

patients with digestive neoplasia and to study the impact of MS on the

DOI: 10.1530/endoabs.49.EP356

epidemiological, clinical profile and prognosis of digestive neoplasms.

Material and methods

This is a retrospective study including patients with digestive neoplasia who were

hospitalized in our department between January 2015 and June 2016. For all

patients, BMI, waistline, systolic and diastolic blood pressure, HDL cholesterol,

triglycerides, and blood glucose levels were determined. A MS was defined

according to the criteria of the International Diabetes Federation IDF 2005.

Results

78 patients were included (40 men and 38 women), with an average age of 61.7

years (between 28 and 89 years). The digestive neoplasias found were: colorectal

cancer (CRC) (nZ21.27%), hepatocellular carcinoma (CHC) on cirrhosis liver

(nZ18.23%), gastric cancer (nZ13.16.7%), Cholangiocarcinoma (nZ10.12.7%),

pancreatic cancer (nZ9.11.5%), oesophageal cancer (nZ3.8%), small bowel

lymphoma and a Cancer of the gall bladder in two cases each (nZ2.6%). The mean

tumor size at diagnosis was 6.2 cm (1.5-18 cm). The tumor was metastatic in 26

cases (33.3%). MS was present in 29 cases (37.2%). The analytical study found that

EP357

MS was more frequently found in female patients (50% versus 25%, PZ0.022),

Metformin and changes in blood pressure and heart rate in lean patients

older patients (68.2 years versus 58 years, PZ0.001) and having a CRC (57%

with polycystic ovary syndrome (PCOS)- preliminary study

versus 29%, PZ0.027). However, the presence of a MS did not influence the

Marta Kialka¹, Tomasz Milewicz¹, Marek Klocek² & Rita Tomczyk¹

average survival of patients (10.3 months versus 8 months, PZ0.138).

¹Department of Gynecological Endocrinology, Jagiellonian University,

Conclusion

Medical College, Cracow, Poland;²Department of Cardiology and

In our study, more than one-third of patients had MS. It was associated with an

Hypertension, Jagiellonian University, Medical College, Cracow, Poland.

older age, the female sex and the CRC. However, diagnosis and management of

MS remains difficult in these patients because of the malnutrition and weight loss

caused by the disease.

Introduction

The aim of our study was to assess the value of blood pressure and heart rate using

DOI: 10.1530/endoabs.49.EP355

the 24-h blood pressure monitoring (ABPM) before and after treatment with

metformin to patients with polycystic ovary syndrome (PCOS) and normal lean.

Material and methods

20 patients received metformin 1500 mg/day in three divided doses. ABPM was

performed to each patient with PCOS twice: before and after 6 months of

treatment with metformin.

Results

EP356

In patients with PCOS and normal lean after treatment with metformin we

Dyslipidemia-associated skin lesions as a short key for etiology

observed: statistically significant lower systolic blood pressure

(120.2G

unraveling and management of life-threatening acute pancreatitis

22.33 mmHg vs 113.22G21.43 mm Hg, PZ0.0248); lower systolic blood

in young male

pressure of daily measurements (127.1G32.13 mmHg vs 116.1G22.08 mmHg,

Zoran Gluvić¹, Bojan Mitrovi

´¹, Vladimir Samard

ˇic´1, Jelena Tica Jevtić1,

PZ0.0062); reduction in average arterial pressure MAP daily measurements

Marina Vujović¹, Vesna Popović-Radinovic´1, Aleksandar Stanojević2 &

(95.52G22.76 mmHg vs

88.36G16.41 mmHg, PZ0.048); oscillometric

Esma R. Isenovi

´³

pressure reduction (96.27G27.93 mmHg vs 87.82G21.61, PZ0.0004 mmHg);

¹Division of Internal Medicine, Department of Endocrinology, Zemun

oscillometric pressure reduction of daily measurements (102.1G27.93 mmHg vs

Clinical Hospital, School of Medicine, University of Belgrade, Zemun,

91.85G21.61 mmHg, PZ0.0032); oscillometric pressure reduction in the

Serbia;²Division of Internal medicine, Department of Gastroenterology,

measurement of the night

(88.81G24.85 mmHg vs 82.22G20.54 mmHg,

Zemun Clinical Hospital, School of Medicine, University of Belgrade,

PZ0.0089). In women after treatment with metformin has also been observed

Zemun, Serbia;³Laboratory for Molecular Endocrinology and Radio-

higher average heart rate (65.82G13.48/min vs. 70.71G16.04/min; P !0.01).

biology, Institute for Nuclear Sciences ‘Vinča’, University of Belgrade,

The calculations included 500 measurements.

Belgrade, Serbia.

Conclusion

Treatment with metformin in patients with PCOS and normal lean leads to lower

Background

blood pressure and increases the frequency of heart rate.

After the gall bladder stones and alcohol abuse, dyslipidemia is among most

DOI: 10.1530/endoabs.49.EP357

frequent causes of acute pancreatitis, especially in youngsters. Some clinical signs

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP358

characterized by: higher (P!0.05) serum TCH, lower (P!0.05) hepatic TCH

and its biosynthetic precursors, lower (P!0.05) hepatic7a-hydroxycholesterol

Screening for type 2 diabetes mellitus as a method of secondary

but elevated (P!0.05) 27- and 24- hydroxycholesterol in comparison to YA IC.

prevention of cardiovascular lesions

Both GEN and DAI decreased (P!0.05) hepatic 27-hydroxycholesterol, with no

Lev Prystupiuk, Liudmyla Naumova, Maksym Prystupiuk,

effect on any other parameter of cholesterol metabolism. We obtained age-related

Iuliia Onofriichuk & Marianna Naumova

reduction of serum estradiol, which was reversed by both soybean phytoestro-

Bogomolets National Medical University, Kyiv, Ukraine.

gens. In conclusion, age-related dyslipidemia was associated with reduced

7a-hydroxycholesterol, main intermediate of neutral pathway, and higher

In patients with type 2 diabetes mellitus (T2DM), cardiovascular lesions are 3-4

27—hydroxycholesterol, main intermediate of alternative acidic pathway of

times more often than in non-diabetics. Screening for T2DM in 1564 people from

Chol degradation to bile acid. Both GEN and DAI lowered hepatic

27-

all Ukraine revealed that 12% had HbA1c at 6.1-6.4% and 16% had HbA1c above

hydroxycholesterol, which might be associated with elevated serum estradiol

6.5%. Those with HbA1c above 6.5% were examined for BMI, glycemia, total

concentrations. Further research is needed to examine this possibility.

cholesterol, HDL-C, non-HDL-C. Dyslipidemia was defined as total cholesterol

DOI: 10.1530/endoabs.49.EP359

over 5.20 mmol/l, HDL-C - less than 1.02 mmol/l for males and less than

1.29 mmol/l for females. Total cholesterol averaged

6.41G0.03 mmol/l in

screened men and 6.23G0.01 in women. HDL-C was respectively 1.89G0.08

and

1.88G0.07 mmol/l. Whereas non-HDL-C was

4.60G0.02

and

3.38G

0.05 mmol/l respectively. As for total cholesterol, objects were divided into the

following groups (in mmol/l): 5.2; 5.3-6.5 and over 6.5. Males with these

indicators were distributed:

38%, 57%, 5%; females - 28%, 64% and 8%

respectively. According to correlation of total cholesterol to fasting glucose, men

with glycemia under 6.1 mmol/l had cholesterol 5.70G0.01 mmol/l, those with

glycemia 6.2-7.8 mmol/l had cholesterol 5.90G0.05 mmol/l and those with

glycemia over 7.8 mmol/l had cholesterol 5.99G0.04 mmol/l. While in women,

cholesterol levels were (mmol/l): 4.86G0.03, 6.50G0.03, and 7.50G0.03 in

EP360

relation to the above mentioned levels of glycemia. In accordance with division of

Awareness and prevalence of metabolic syndrome among high-risk

BMI into normal weight, overweight and obesity, cholesterol levels in males were

individuals attending internal medicine clinics across Jordan

(mmol/l): 5.81G0.06, 6.12G0.04 and 6.10G0.05 respectively, while in females

Rania Efaishat¹, Rana Abu Farha² & Eman Alefishat³

5.48G0.04, 5.56G0.02 and 5.77G0.01. Consequently, dyslipidemias were found

¹Medical Supply Department, Directorate of Royal Medical Services,

in 70% of our group with T2DM of both sexes. They are induced by increase in

Amman, Jordan;²Department of Clinical Pharmacy and Therapeutics,

non-HDL-C, correlate with degree of compensation of diabetes and with BMI.

Faculty of Pharmacy, Applied Science Private University, Amman, Jordan;

Therapeutic correction of dyslipidemias in patients with T2DM should be:

³Department of Biopharmaceutics and Clinical Pharmacy, Faculty of

normalization of glycemia and body weight. Screening for T2DM and its active

Pharmacy, The University of Jordan, Amman, Jordan.

treatment are most suitable method of secondary prevention of cardiovascular

lesions caused by T2DM.

DOI: 10.1530/endoabs.49.EP358

Purpose

To examine the prevalence and awareness of metabolic syndrome (MetS) in high-

risk individuals attending 30 internal medicine clinics in Amman, Jordan, and also

to evaluate the various factors associated with increased risk of MetS among

them.

Methods

This retrospective cross-sectional study was carried out across Amman, Jordan

from October to December

2014. During the study period,

900 high-risk

individuals (with hypertension, diabetes, central obesity and/or dyslipidemia)

were recruited from thirty internal medicine clinics in Amman, Jordan. Data

collection forms were filled based on patient interview and medical case file.

Results

The prevalence of MetS among high-risk individuals was around 40% (361/900),

with around 79% (284/361) of MetS patients unaware of their condition. Older

age, lower income and family history of premature cardiovascular diseases were

EP359

associated with a higher prevalence of MetS.

Conclusion

Soybean phytoestrogens reduce 27-hydroxycholesterol concentration in

Although MetS was found to be highly prevalent among high-risk individuals in

the liver of middle-aged female rats

this study, the awareness of the condition in this group is very poor. These

Branka

ˇ oši

´-Jurjevi

´¹, Sne

ˇana Jankovic´2, Dieter Lutjohann3, Ivana Jarić1,

findings support the need for educational programs that involve both health care

Marko Miler¹, Branko Filipovic´1, Vladimir Ajdžanović1 &

providers and patients. These programs should especially target those at risk of

Verica Miloševi

´¹

MetS, in order to improve awareness of the concept of MetS.

¹Institute for Biological Research ‘Siniša Stanković’, University of

Belgrade, Belgrade, Serbia;²Institute for Science Application in

DOI: 10.1530/endoabs.49.EP360

Agriculture, University of Belgrade, Belgrade, Serbia;³Institut fur Klinische

Chemie und Klinische Pharmakologie Universitatsklinikum Bonn, Bonn,

Germany.

Hypercholesterolemia is associated with athero-thrombotic disease, a leading

cause of mortality worldwide. Advances in both dietary and pharmacological

interventions contribute to prevention and treatment of modifiable risk

factors.Purified soybean phytoestrogens, isoflavones genistein

(GEN) and

daidzein (DAI), were reported to exert moderate cholesterol-lowering effect. In

EP361

this research first we studied age-related modifications in hepatic cholesterol

Nine months of practice in California - self-referrals in endocrinology

metabolism and serum estradiol concentration of acyclic middle-aged (MA)

Jelena Maletkovic

female rats. Then we tested if purified isoflavones may prevent or reverse these

UCLA, Los Angeles, California, USA.

changes. Serum and hepatic total cholesterol (TCH), bile acid and cholesterol

precursors were determined by comparing data obtained for MA with young adult

(YA) intact (IC) females. Effects of subcutaneously administered GEN or DAI

Objective

(35 mg/kg per daily during four weeks) to MA rats were evaluated vs vehicle

A great number of patients are self-referred to endocrinologist. Most of these

(sterile olive oil) - treated MA females. After decapitation, perfused rat livers and

patients had some research of their symptoms and have a specific diagnosis that

serum were used to determine total cholesterol (TCH), its oxidative metabolites

they want to investigate.

(7a-, 27- and 24-hydroxycholesterol) and precursors (lanosterol, desmosterol,

Methods

dihydro-lano sterol and lathosterol), using gas chromatography/mass spec-

A retrospective chart review of 628 new consults conducted in one outpatient

trometry. Serum estradiol was determined by ECLIA. MA IC females were

endocrine office at University of California, Los Angeles was conducted.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

possible FH were 18.4%, 66.0% and 15.6%, respectively. Although the majority

Of the 628 new patients 326 were referred by another physician and were

of the patients (93.9%) were aware of their high LDL-C levels, only about half of

excluded from further review. Of 302 self-referred patients 248 patients had a

them (nZ75, 51.0%) were under treatment. Of all the patients who were

preexisting endocrine diagnosis and were excluded. The remaining 54 patients

interviewed, 21% (nZ31) had never taken, and 28% (nZ41) had stopped taking

were seeing endocrinologist for the first time and these patients were included in

lipid-lowering drug.

further study. Most common complaints were: weight gain (78% of patients),

Conclusion

fatigue

(72%), cold intolerance (46%), heat intolerance (31%), constipation

The results of this pilot study show that, undiagnosed or undertreated FH patients

(24%). Other common complaints observed were hair loss, low libido, erectile

can practically be detected from the high LDL-C registries of the Hospital

dysfunction, anxiety, palpitations, weight loss, hirsutism, acne, muscle weakness,

Laboratories. Nationwide implementation of this method may help us reach and

stretch marks, buffalo hump and polydipsia. When asked if they had a specific

manage these high-risk patients.

hormone abnormality in mind most of the patients reported that their main

DOI: 10.1530/endoabs.49.EP362

concern is hypothyroidism (69%), high cortisol level (13%), low testosterone

(10%), low cortisol

(5%), hyperthyroidism

(5%), diabetes insipidus

(4%),

diabetes mellitus (2%). After conducting endocrine studies based on presenting

symptoms none of the 54 patients were found to have confirmation of suspected

diagnosis. Four patients were found to have elevated TPO antibodies but thyroid

functions tests were normal. Six patients were found to have diabetes mellitus that

was previously not diagnosed or suspected. Two patients were found to have

elevated cholesterol.

Discussion

Common problems lead to online research that offers a number of endocrine

conditions as a possible underlying problem. With access to subspecialist care

oftentimes unnecessary work-up is done.

Conclusion

A longer period of investigation would add valuable data in determining the

impact of self-referrals on subspecialty practices as well as health care in United

EP363

States in general.

The effect of admission hyperglycemia on clinical outcome of ischaemic

DOI: 10.1530/endoabs.49.EP361

stroke patients

Vina Yanti Susanti¹, Iswandi Darwis² & Fidha Rahmayani³

Internal Medicine Department, Universitas Gadjah Mada/Sardjito General

Hospital, Yogyakarta, Indonesia;²Resident on Internal Medicine Depart-

ment, Universitas Gadjah Mada/Sardjito General Hospital, Yogyakarta,

Indonesia;³Resident on Neurology Department, Universitas Gadjah

Mada/Sardjito General Hospital, Yogyakarta, Indonesia.

Background and objective

Hyperglycemia exacerbates multiple deleterious derangements and this process

would influence the clinical outcome in diabetic patient. The objective of this

study is to know the effect of admission hyperglycemia on clinical outcome of

ischamic stroke patients admitted in Sardjito General Hospital.

Method

Observational cohort study over

5 months’ period from August 1-2016 to

EP362

December 31-2016 was done. All patients 18 years old and above, admitted as

stroke ischaemic patients in Sardjito General Hospital Yogyakarta were screened.

Identifiying underdiagnosed or undertreated patients with familial

In order to qualify, patient were subjected to initial random blood sugar

hypercholesterolemia from the central laboratory registries

determination upon admission and monitored to 48-72 h. Capillary blood glucose

Cem Haymana¹, Hamza Berlik², Yalcin Gunes², Orhan Enes Tuncez²,

was monitored using blood glucose monitor device by Bayer. Hyperglicemia

Cihat Aytekin², Zafer Tapikara², Huseyin Guzel², Ozlem Ozturk³,

status is blood glucose above 200 mg/dl. Clinical outcome was evaluated and

Cem Barcin⁴, Taner Ozgurtas³, Omer Azal¹ & Alper Sonmez¹

recorded using The National Institutes of Health Stroke Scale (NIHSS) on day 1

¹Department of Endocrinology and Metabolism, Gulhane Training and

and discharge. Participants who are below 18 years old, previously stroke, or

Research Hospital, Ankara, Turkey;²Gulhane School of Medicine, Health

those with acute co-morbid disease like acute myocardial infarction, pneumonia,

Sciences University, Ankara, Turkey;³Department of Biochemistry,

or critical infection, ketoacidosis diabeticum, hyperglicemia hyperosmolar state

Gulhane Training and Research Hospital, Ankara, Turkey;⁴Department of

were all excluded. All patients managed according to guidelines for stroke and

Cardiology, Gulhane Training and Research Hospital, Ankara, Turkey.

hyperglycemia.

Result

Objective

Sixty four eligible subjects admitted at Sardjito General Hospital, 12 (19.35%)

Familial hypercholesterolemia

(FH) is a life-threatening genetic disease

were hyperglycemia and 50 (80.65%) normoglycemia. The mean value of blood

associated with elevated low density lipoprotein cholesterol

(LDL-C) and

glucose at admission are 153.45C69.09 mg/dl. Patients who have worsening

premature coronary heart disease that is globally underdiagnosed and

clinical outcome at dischare are 18 (29.03%) based on NIHSS. Six patients

undertreated. This study aimed to search for the demographical characteristics,

(44.44%) who had hyperglicaemia had worsening clinical outcome and four

awareness and treatment adherence of underdiagnosed or undertreated FH

patients (9.09%) did not have worsening clinical outcome (P-value 0.003; OR 8;

patients from the records of the central biochemistry laboratory.

min 2 001-max 31 988).

Methods

Conclutions

Patients with a central laboratory measurement of LDL-C O250 mg/dl were

Hyperglicaemia at admission have correlate with worsening of clinical outcome

identified. Patients with older than

18 years without secondary causes of

ischaemic stroke patients.

dyslipidemia were called by medical students and interviewed about demographic

Keywords

characteristics, awareness of dyslipidemia and treatment adherence.

Hyperglycemia; Ischaemic stroke patients; The National Institutes of Health

Results

Stroke Scale.

A total of 147 patients

(mean age 51.7G16.6 years, 59.2% female) were

DOI: 10.1530/endoabs.49.EP363

interviewed. The mean LDL-C levels were 292.8G49.9 mg/dl. According to the

Dutch Lipid Clinic Network Criteria, the patients with definite, probable and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP364

the heart rate (HR) hardly changed at this constant rate. Since, saliva lactate levels

in an AT training are independent of heart rate and mostly of effort intensity.

Deleting genomic region of Hsd17b1 in mice results into a hypomorphic

Naglu allele, and consequently to a phenotype mimicking a lysosomal

DOI: 10.1530/endoabs.49.EP365

storage disease

Heli Jokela¹, Janne Hakkarainen¹, Pirjo Pakarinen^1,2, Suvi Ruohonen¹,

Fuping Zhang² & Matti Poutanen^1,2

¹University of Turku, Turku, Finland;²Turku Center for Disease Modeling,

Turku, Finland.

EP366

Abstract

Hydroxysteroid

17-beta dehydrogenase

(HSD17B1) is an enzyme

The effect of tocilizumab - an interleukin-6 receptor antagonist - on

catalyzing the reduction of estrone

(E1) to estradiol

(E2), as well as

lipid levels in rheumatoid arthritis

androstenedione (Adione) to testosterone (T). To elucidate the physiological

Ifigenia Kostoglou-Athanassiou¹, Lambros Athanassiou²,

function of HSD17B1, we generated knockout mice with disrupted Hsd17b1

Aikaterini Tzanavari², Charoula Katsavouni², Markos Kostopoulos²,

Dimitrios Pantelidis² & Panagiotis Athanassiou²

gene using targeted ES cells (clone 10231) obtained from KOMP repository

¹Department of Endocrinology, Red Cross Hospital, Athens, Greece;

(www.komp.org). In these ES cells the whole coding region of Hsd17b1 was

²Department of Rheumatology, St Paul’s Hospital, Thessaloniki, Greece.

replaced with LacZ/Neo cassette, expressing the reporter gene. As

previously shown by us, the homozygous Hsd17b1-LacZ/Neo females

were found to be subfertile and have a defect in pseudopregnancy

Tocilizumab is an interleukin-6 receptor antagonist used in the treatment of

maintenance, likely caused by the imbalance in ovarian steroid synthesis.

rheumatoid arthritis

(RA). It is known to induce remission and inhibit

In addition, the Hsd17b1-LacZ/Neo males present with a metabolic

radiographic progression in RA. Tocilizumab may be administered either

phenotype, including reduced adipose mass, increased lean mass and lipid

intravenously or subcutaneously. Its effect on lipid levels and the cardiovascular

accumulation in the liver. During the characterization of the metabolic

risk has not been fully investigated. The aim was to study the effect of tocilizumab

phenotype, it became evident that the expression of N-acetyl-alpha-

i.v. on disease activity, lipid levels and cardiovascular risk in RA patients.

glucosaminidase

(Naglu) gene, located

8399-739

bp upstream of the

Tocilizumab was administered i.v. once monthly in 25 patients with RA for a

Hsd17b1 transcription start site, was severely reduced (13-40-fold) in all

period of 1 year. Inflammation indices, ESR and CRP and lipid levels were

tissues analyzed in Hsd17b1-LacZ/Neo mice. Furthermore, similar results

measured before and 1 year after tocilizumab administration. The DAS28 disease

were obtained from Hsd17b1-LacZ mice after removing the Neo cassette or

activity index was also calculated.

by crossing the Hsd17b1-LacZ/Neo mice with transgenic mice constitutively

Inflammation indices ESR and CRP decreased from 34.3G4.04 mm/h and 2.02G

expressing human HSD17B1. Deficiency of the Naglu gene causes the

0.34 mg/dl before to

8.3G1.62 mm/h and

0.27G0.07 mg/dl, respectively

accumulation of glycosaminglycans

(GAGs) in several tissues, and

(P!0.001) after tocilizumab administration. The DAS28 disease activity index

accordingly, GAG accumulation was observed in all the above mentioned

decreased from 5.02G0.26 to 2.42G0.26 after tocilizumab (P!0.001). Total

mouse models lacking the genomic region coding for Hsd17b1.

cholesterol and HDL cholesterol increased from 207.4G8.53 mg/dl and 57.68G

Furthermore, biochemically and morphologically similar metabolic pheno-

2.65 mg/dl before to 231.08G12.30 mg/dl and 72.51G4.76 mg/dl, respectively

type, mimicking lysosomal storage disease, was observed both in Naglu

(P!0.001) after tocilizumab administration, LDL cholesterol and triglyceride

knockout mice (with the presence of active HSD17B1), and all the mouse

levels increasing from 128.6G7.45 mg/dl and 108.48G7.83 mg/dl before to

models lacking 2.3 kb long genomic region of Hsd17b1 gene. Thus, the data

136.17G9.39 mg/dl and 130.58G15.82 mg/dl, respectively

(P!0.001) after

indicate the presence of a strong Naglu enhancer inside the Hsd17b1 gene,

tocilizumab. No acute cardiovascular events were recorded during the study.

and the metabolic phenotype in mice lacking the Hsd17b1 genomic region is

Tocilizumab administered i.v. in patients with RA was shown to decrease

caused by the off target effect.

inflammation indices and disease activity. Lipid levels increased significantly.

DOI: 10.1530/endoabs.49.EP364

However, total cholesterol increased in parallel with HDL cholesterol.

Cardiovascular events were not observed during the study period. It appears

that tocilizumab may be accompanied by lipid level alterations, cardiovascular

risk not increasing as the adverse effects of total cholesterol may be counteracted

by HDL cholesterol.

DOI: 10.1530/endoabs.49.EP366

EP365

Salivary lactate levels during anaerobic threshold (AT) training

Hugo Ogando Berea¹, Laura Toba Estevez¹, Juan Fandin˜o Gómez1, Yolanda

Diz Chaves¹, Jose Luis García Soidán², Lucas Gonzalez Matías¹ & Federico

Mallo Ferrer¹

EP367

¹Labendo, Cinbio, Vigo University, Campus Lagoas-Marcosende s/n 36310

Homocystein-significant marker of metabolic syndrome and

Vigo, Spain;²Faculty of Educational Sciences and Sports, University of

atherosclerosis risk

Vigo, Campus a Xunqueira, s/n 36005 Pontevedra, Spain.

Branko Sreckovic¹, Vesna Dimitrijevic-Sreckovic^2,7, Ivan Soldatovic^3,7,

Hristina Janeski⁴, Nenad Janeski⁵, Jasna Gacic¹, Mirjana

6,7

Sumarac-Dumanovic^2,7 & Igor Mrdovic

Anaerobic threshold (AT) is defined as the point of maximum intensity at which

¹Clinical Center Bezanijska Kosa, Belgrade, Serbia;²Clinic for

lactate is being produced but does not accumulate in blood during exercise.

Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia,

Training at this intensity is common in athletes. Lactate is currently regard as

Belgrade, Serbia;³Institute for Medical Statistics and Informatics, Belgrade,

indicator of effort intensity. It is usually quantified by reflectometry of capillary

Serbia;⁴University Children’s Hospital, Belgrade, Serbia;⁵Clinical

blood. This procedure although not very invasive, may be annoying during

Hospital Center Zemun, Belgrade, Serbia;⁶Clinic for Cardiovascular

repeated measurements. Saliva is proposed as an alternative sample.

Diseases, Clincal Center of Serbia, Belgrade, Serbia;⁷Faculty of Medicine,

The objective of the present study is to quantify the variation of salivary lactate

Belgrade University, Belgrade, Serbia.

levels during AT training, in order to prove its usability in this field.

10 male subjects (32G2.96 years) performed a treadmill test recording intensity

(watts/min), VO2 and heart rate (HR) to determine AT. After two days resting

Background

they performed 6 running series of 1km at AT rhythm with 2 minutes of resting

Obesity is followed by insulin resistance (IR) and low grade inflammation. In

between series. Saliva samples by Salivette system (SARSTEDT, Germany) and

patients with metabolic syndrome

(MS) and clinicaly evident vascular

HR were taken at pretest, the end of each series, and 3, 6 & 9 min of resting after.

complications homocystein values are higher. Hyperhomocysteinemia correlates

Eating, smoking, drinking (except water) or teeth brushing was forbidden in 2 h

with hyperinsulinemia and IR, resulting in oxidative stress, which causes

previous to start.

endothelial lesions and dysfunction, promoting atherosclerosis and hypertension.

Salivary lactate concentrations increased significantly from 1st to 3rd series

Objectives

(PZ0.002). Afterwards, a plateau of saliva lactate concentration was observed in

To examine homocystein levels in patients with and without MS, and find

all subjects up to the end of the series (4th-6th). After a small reduction, an

correlation between factors of MS and homocystein values.

additional increase in saliva lactate was also consistently observed after 6 min of

Methods

rest. HR hardly changed during the exercise series. Since we can conclude that:

The study included 76 obese individuals (age over 30, BMI O25 kg/m²) classified

The salivary lactate was increased according to the accumulated workload despite

into two groups: I- with MS (35 patients); II- without MS (41 patients). OGTT

exercise was performed at constant intensity (AT). That was confirmed because

was used to evaluate the extent of glucoregulation disorder. IDF classification was

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

applied for diagnosing MS. Si MS risk score by Soldatovic I et all 2016 was used.

exists between CAC with coronary vascular disease (CVD), Agatston score being

IR was determined by HOMA IR. Serum CRP was measured by immunometric

an independent predictor of CVD. Including CAC may improve CV risk

assay. Microalbuminuria was determined immuno-nephelometrically. Homo-

prediction in addition to conventional risk factors. The AIM of our study was to

cistein was determined by immunoassay FPIA-Abbot.

assess CAC in subjects with prediabetes (preDM) at the beginning of the long

Results

term follow-up for occurrence of cardiovascular disease.

Patients with MS had increased WC:(I-110.6G15.4, IIG15.4 cm), BMI:(I-

Methods

35.3G6.6, II-30.4G7.4 kg/m²), blood pressure (I-136.4G13.9 /90.5G9.5, II-

After diagnosing preDM with oral glucose tolerance test and HbA1c, ECG was

118.4G12.2/78.1G9.7 mmHg), glycaemia

(I-5.4G1.6, II-4.8G0.8 mmol/l),

performed and subjects were evaluated for CVD risk. Score charts were used to

HOMA IR (I-8.8G9.4, II-5.3G3.8 mmol/mU per ml), triglycerides (I-2.17G

calculate the CVD risk. Thereafter, all subjects were appointed for multislice CT

0.95, II-1.45G0.7 mmol/l), CRP (I-7.0G0.0, II-3.7G3.8 mg/l), microalbumi-

to obtain the CAC.

nuria (I-87.4G81, II-56.4G56.9 mg/24 h), homocysteine (I-13.0G3.2, II-11.8G

Results

3.7 mmol/l) and decreased HDL (I-1.07G0.2, II-1.35G0.35 mmol/l). Statistical

70 subjects with preDM were screened for CVD. CAC score of 0 was present in

significance between groups was found for WC, BMI, systolic and diastolic

32 subjects. Minimal calcifications with a CAC score of 1-10 AU were present in

pressure, triglycerides, HDL-cholesterol (P!0.01) and CRP, Apo B, HOMA IR

12 subjects with pre DM. Moderate calcification of11-100 AU were present in 15

(P!0.05). Correlations: Homocysteine with systolic and diastolic pressure, Apo

subjects. Nine subjects had significant calcifications with 101-400 AU. Two

B and hyperlipoproteinemia (P!0.05). Si MS risk score with homocysteine

subjects had a CAC score of 100 AU which meant significant calcifications. Score

(P!0.01), rZ0.263.

risk below 2% was present in only 19 subjects, while a score risk of 15% and more

Conclusion

was present in 23 subjects. No significant correlation was found between Score

Abdominal obesity, hypertension, hypertriglyceridemia, inflammation factors,

charts and CAC. However, a trend of finding more calcifications in those with a

IR, homocystein and microalbuminuria as markers of endothelial dysfunction

10% and above Score risk was noted.

were increased in patients with MS. Correlation of homocystein values with si MS

Conclusion

risk score indicates that it is significant co-founding factor of MS. Correlation of

An approach to risk assessment that combines the traditional risk factor-based

homocystein with hypertension and hyperlipoproteinemia indicates importance of

paradigm with a more personalized atherosclerosis-imaging model may be

homocystein as significant marker for atherosclerosis.

appropriate for high risk individuals, such as subjects with pre diabetes.

DOI: 10.1530/endoabs.49.EP367

DOI: 10.1530/endoabs.49.EP369

EP368

Graft vs host disease and insulin resistance after bone marrow

transplantation

EP370

Panagiotis Athanassiou¹ & Ifigenia Kostoglou-Athanassiou²

Cardiometabolic risk and female sexuality: focus on clitoral vascular

¹Department of Rheumatology, St Paul’s Hospital, Thessaloniki, Greece;

resistance

²Department of Endocrinology, Red Cross Hospital, Athens, Greece.

Elisa Maseroli¹, Egidia Fanni¹, Sarah Cipriani¹, Irene Scavello¹,

Francesca Pampaloni¹, Cesare Battaglia², Massimiliano Fambrini¹,

Graft vs host disease is a disorder in which the graft, i.e. bone marrow, attacks the

Edoardo Mannucci¹, Emmanuele A Jannini³, Mario Maggi^1,4 &

host after bone marrow transplantation. It has various manifestations, one being

Linda Vignozzi^1,4

skin and muscle involvement with cutaneous sclerosis and diffuse muscle pain.

¹University of Florence, Florence, Italy;²University of Bologna, Bologna,

The aim was to describe the case of a patient with graft vs host disease

Italy;³Tor Vergata University of Rome, Rome, Italy;⁴Istituto Nazionale

complicated by insulin resistance and metabolic syndrome, after bone marrow

Biostrutture e Biosistemi, Rome, Italy.

transplantation for the treatment of acute lymphoblastic leukemia.

A patient, male, aged 2.5 years old, developed acute lymphoblastic leukemia. He

The relation between sexual and cardiovascular health in women is not well

was treated and the disease went into remission. At the age of 7 years, the patient

defined. Clitoral colour Doppler ultrasound

(CDU) with assessment of the

had a recurrence. He was found to be compatible with his elder brother and bone

pulsatility index (PI), reflecting resistance to blood flow, has been proposed as an

marrow transplantation was performed. During the following months the patient

objective measurement of sexual functioning. We aimed to investigate the

developed a skin eruption, diffuse cutaneous sclerotic lesions, muscle edema and

associations between clitoral PI and cardiometabolic risk factors. Seventy-one

pain.

adult heterosexual women attending our clinic for sexual dysfunction were

He was treated with thalidomide and cyclosporine and clinical manifestations of

consecutively recruited. Clitoral PI was positively correlated with BMI

graft vs host disease improved. Diffuse skin and muscle involvement improved.

(P!0.0001), waist circumference (WC; P!0.0001), glycaemia (PZ0.029),

The patient developed hypertriglyceridemia and insulin resistance. Metformin

insulin (PZ0.002), homeostatic model assessment index (PZ0.005), triglycer-

and fenofibrate were administered. The patient developed also hypothyroidism.

ides (PZ0.011), total cholesterol (PZ0.010), and LDL-cholesterol (PZ0.016).

Thyroxine was administered. At the age of 29 the patient developed psoriasis like

All relations, with the exception of glycaemia, retained statistical significance

lesions in the maxilla and the external genital organs.

after adjusting for age, smoking habit, and years since menopause (P!0.0001 for

In conclusion, the case of a patient is described with graft vs host disease after

BMI, WC and triglycerides; P!0.05 for all other associations). Analysis of

bone marrow transplantation for the management of acute lymphoblastic

covariance, after adjusting for confounders, showed that women with obesity or

leukemia. Graft vs host disease may have various clinical manifestations. In the

metabolic syndrome (MetS) showed significantly higher PI values (obesity:

case described skin and muscle involvement, along with insulin resistance and

PZ0.001; MetS: PZ0.019). In particular, a stepwise increase of PI was found as

metabolic syndrome were the predominant manifestations.

a function of increasing MetS components (PZ0.007). Clitoral PI was negatively

DOI: 10.1530/endoabs.49.EP368

associated with Female Sexual Function Index arousal

(PZ0.014) and

satisfaction

(bZK0.289, PZ0.026) scores and positively associated with

Middlesex Hospital Questionnaire somatized anxiety symptoms, even after

adjusting for confounders (PZ0.011). A positive association also was observed

between PI and the Body Uneasiness Test (BUT) positive symptom distress index

(PZ0.039) and BUT for dislike of the womb, genitals, and breast (P!0.0001;

EP369

P!0.0001; P!0.0001, respectively). After introducing WC as another covariate,

Coronary artery calcium score in prediabetes - preliminary results

the associations between clitoral PI and the BUT positive symptom distress index

Milica Marjanovic Petkovic¹, Ivana Sasic³, Miljanka Vuksanovic^1,2 &

and BUT dislike of the womb, genitals, and breast retained statistical significance

Teodora Beljic Zivkovic^1,2

(PZ0.038 for positive symptom distress index; P!0.0001 for dislike of womb,

¹Zvezdara University Medical Center, Belgrade, Serbia;²Belgrade

genitals, and breast). Clitoral vascular resistance is positively associated with

University School of Medicine, Belgrade, Serbia;³Institute of

MetS (in particular insulin resistance), decreased sexual arousal, body image

Cardiovascular Diseases Dedinje, Belgrade, Serbia.

concerns, and increased somatized anxiety symptoms. Further studies are needed

to establish whether treatment of metabolic abnormalities might improve clitoral

CDU indices and sexual outcomes.

Introduction

Coronary artery calcium (CAC) is examined through multislice CT. Calcifica-

DOI: 10.1530/endoabs.49.EP370

tions indicate late-stage subclinical coronary atherosclerosis. An association

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP371

EP373

Metformin and changes in serum lipid profile in lean patients with

The role of leptin signalling in the development of cardiovascular

polycystic ovary syndrome (PCOS)

diseases in obesity

Marta Kialka¹, Tomasz Milewicz¹, Anna Wajda¹, Patrycja Czekanska¹,

Stephanie Simonds & Michael Cowley

Barbara Zdzierak¹ & Sandra Mrozinska²

Monash University, Melbourne, Victoria, Australia.

¹Department of Gynecological Endocrinology, Jagiellonian University,

Medical College, Cracow, Poland;²Department of Metabolic Diseases,

Cardiovascular diseases are the greatest cause of death globally. Obesity

Cracow, Poland.

significantly increases the risk for the development of cardiovascular diseases.

However research does not under stand the physiological and molecular

Introduction

connections of these diseases. We have identified that the hormone leptin in

The aim of our study was to assess the values of total cholesterol, HDL-C, LDL-C

obesity plays a key role in elevating blood pressure in obesity. However recent

and triglycerides before and after treatment with metformin in patients with

findings in humans treated with leptin in the disease state of lipodystrophy, did not

polycystic ovary syndrome (PCOS) and normal lean.

result in the elevation of blood pressure. In the research present here we suggest

Material and methods

that one reason as to why leptin fails to increase blood pressure in lipodystrophy

32 patients received metformin 1500 mg/day in three divided doses. Lipids

patients is that plasma leptin concentration in not increasing high enough. For the

measurements were performed to each patient with PCOS twice: before and after

development of cardiovascular complications in obesity plasma leptin concen-

6 months of treatment with metformin.

tration needs to increase significantly to concentrations similar to that of obese

Results

animals (ten times the concentration measured in lean animals). In rodents we

In patients with PCOS and normal lean after treatment with metformin we

dose dependently demonstrate the differing effects of concentrations of leptin on

observed: statistically significant lower LDL-C levels (4.16G0.79 mmol/l vs

changes in body weight, food intake, brown adipose tissue temperature, blood

3.4G0.86 mmol/l, P!0.05) and triglycerides levels (1.8G0.53 mmol/l vs 1.12G

pressure and heart rate. We can demonstrated in obese hypertensive mice that

0.64 mmol/l, P!0.05). We observed an increase in HDL values and a decrease in

changes to the signaling components of specific neurons within the Dorsomedial

total cholesterol values, but these changes were not statistically significant (1.5G

Hypothalamic leptin receptor expressing neurons in the brain can substantially

0.71 mmol/l vs

1.71G0.69 mmol/l, PZ0.09;

5.87G0.92 mmol/l vs

5.69G

change leptin’s influence on cardiovascular control. Hence we can control in

0.97 mmol/l, PZ0.11).

rodents the development of hypertension in obesity, via manipulating the

Conclusion

responsiveness of leptin receptor responsive neurons. We are mapping the

Our study showed that treatment of 1500 mg metformin for about 6 months

connections of this specific subset of neurons and are gaining a true understanding

among PCOS women result in improvement in serum lipids. We observed a

on how the adipose derived hormone leptin plays a key role in the development of

significant decrease in LDL-C and triglycerides values after metformin treatment.

cardiovascular diseases.

DOI: 10.1530/endoabs.49.EP371

DOI: 10.1530/endoabs.49.EP373

EP372

Prevalence of major cardiovascular risk factors among people living

EP374

with HIV in a low risk country for cardiovascular disease

Influence factors on lipid profile among patients with rheumatoid

Carolina García-Figueras Mateos & Manuel Cayón-Blanco

arthritis

Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.

Manuel Cayón-Blanco¹, Carolina García-Figueras Mateos¹,

Raúl Menor-Almagro² & Mario H Cardiel Ríos³

Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain;

Introduction

²Universitary Hospital Virgen del Rocío, Seville, Spain;³Hospital Dr.

It is well known that the prevalence of major cardiovascular risk factors has

Miguel Silva, Morelia, Mexico.

increased in HIV-infected people since improvement of antiretroviral therapy.

Currently, Spain is defined as a ‘low risk country’ for cardiovascular diseases

(CVD) by 2016 European Guidelines on cardiovascular disease prevention. The

Introduction

objective of this study is to assess the prevalence and characteristics of CVD risk

Patients with rheumatoid arthritis (RA) face an increased risk of developing

factors and risk for CVD in a cohort of HIV-infected adults living in the South of

premature cardiovascular disease and limited ability to modify risk factors such

Spain according to current guidelines.

exercise or dietetic habits. Influence of exercise, dietetic habits or treatment on

Methods/design

lipid profile has been little studied in patients with RA. Here we aim to determine

Cross-sectional study. Measurements included anthropometry, blood pressure,

differences in lipid profile between two cohorts of patients with RA with different

fasting lipids and glucose assessment. Demographic, clinical, immunological, and

habits and patterns of treatment.

antiretroviral therapy data were obtained from electronic medical records. 10-year

Methods/design

risk of heart disease or stroke was calculated using the SCORE- European low

Cross-sectional study. Lipid profiles of 50 RA out-patients from South Spain were

risk chart.

compared with 50 age and sex matched controls from Central Mexico. Traditional

Results

risk factors were analyzed such as overweight or obesity, smoking status and

218 patients were evaluated. Hypertriglyceridemia was the most prevalent

hypertension. Glucose and lipid profiles as well as dietetic habits and physical

disturbance (44.3%) found, followed by low HDLc levels (41.7%). 8.7% of the

activity were recorded.

cohort had hypertension and 6.9% had type 2 diabetes. 68.5% were current

Results

smokers. High risk (10-year risk of fatal CVD O10%) was found in 13.3% of the

RA patients from Spain were more likely to practice physical activity (66.7% vs

cohort. People at higher risk were mostly men (100% vs 81%; PZ0.005), had

33.3%; PZ0.001), had lower BMI

(24.9G4.6 kg/m²

26.7G3.6 kg/m²;

higher BMI (25G2.3 vs 23G2.7 kg/m²; PZ0.04) and had a lower CD4 count

PZ0.004). No significant differences in smoking status, prevalence of diabetes

(405.5G156.2/mm³ vs 551.5G211.7/mm³; PZ0.035) and were more likely to

(steroid induced diabetes or type 2 diabetes), alcohol consumption or mean dose

receive protease inhibitors (48% vs 30%; PZ0.04).

of steroid treatment were found. Regarding to lipid profile, Mexican patients had

Conclusions

lower levels of LDLc (86G31.5 vs 128.7G24.9 mg/dl; P!0.001) In contrast, the

According to our results, the prevalence of major risk factors for CVD is high in

European population had lower levels of triglycerides (124.9G14.6 vs 145.3G

HIV-infected patients of our area, especially among those with worse immunity

3.6 mg/dl; P!0.001) and higher HDLc (60.5G12.8 vs 52.1G21.4; P!0.005).

and higher BMI. Physicians should screen their patients for metabolic and

Conclusions

cardiovascular risk at the regular visits to reduce CVD risk among people with

In patients with RA, exercise can modulate lipid profile favourably irrespective of

HIV. Changes in antiretroviral therapy to more metabolic neutral antiretroviral

corticoid dose or steroid induced diabetes. More accurate studies focusing on

drugs may also be considered.

specific nutrients would be useful to confirm our results.

DOI: 10.1530/endoabs.49.EP372

DOI: 10.1530/endoabs.49.EP374

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP375

obtained with a high fat diet (HFD), treatment with the dual FXR/TGR5 agonist

INT767 reduced visceral adipose tissue (VAT) accumulation, insulin resistance,

hypercholesterolemia and nonalcoholic steatohepatitis (NASH). In liver, INT767

reduced the high macrophage M1 (pro-inflammatory)/M2 (anti-inflammatory)

Abstract withdrawn.

ratio observed in MetS. Furthermore, INT767 increased the expression of: IL10

and FOXP3, markers of M2 macrophage and Treg cell, respectively; PPARa,

marker of hepatic fatty acid metabolism; VAMP4 and Syntaxin5, markers of lipid

droplet formation; IRS1

and STAMP2, markers of insulin signaling while

decreased lipogenesis markers. Moreover histomorphological sign of NASH were

significantly improved by INT767.

MetS induced insulin resistance, which shows VAT derangements like adipocytes

hypertrophy and reducted GLUT4 translocation to membrane. Treatment with

INT767 counteract these VAT alterations and induced the expression of brown

adipocytes markers. The analysis of preadipocytes

(rPADs) obteined from

INT767-treated rabbit and HFD rabbit revealed that INT767 improved insulin

sensitivity and mitochondrial ultrastructure and dynamic whereas reduced

superoxide production. In rPADs, when compared to HFD, INT767 increased

EP376

the expression of CIDEA and TMEM (brown fat markers); TFAM and NRF1

Oxidative stress and metabolic profiles assessment after melatonin and

(mitochondriogenesis markers); SDHB (membrane respisatory chain marker) and

irbesartan co-administration in a novel pharmaceutical formulation

MFN2 and FIS1, (mitochondria fusion/fission markers).

Cristina Manuela Dragoi, Alina Crenguta Nicolae, Daniela Elena Popa,

To conclude, INT767 significanlty improves NASH and VAT alterations induced

Ion-Bogdan Dumitrescu, Andreea Letitia Arsene, Corina Grigore &

by HFD, restoring insulin sensitivity and inducing the differentiation of rPADs to

Cristina Elena Dinu-Pirvu

a metabolically healthy phenotype.

University of Medicine and Pharmacy ‘Carol Davila’, Faculty of Pharmacy,

DOI: 10.1530/endoabs.49.EP377

Bucharest, Romania.

The concurrence of glucose intolerance, hypertension, dyslipidemia and obesity

has been termed metabolic syndrome. Each component of the metabolic

syndrome is an independent risk factor for cardiovascular disease and diabetes

type 2, the combination of these risk factors elevating the rates and severity of

cardiac pathology.

The therapeutic use of irbesartan, a selective blocker of the AT1 receptors,

administered in arterial hypertension, coronary heart disease and diabetic

nephropathy, is extremely important due to the presence of these receptors both

centrally and in the periphery.

Melatonin is an endogenous indoleamine hormone synthesized by the pineal

gland. Melatonin release into the circulation is augmented in darkness and

decreased during exposure to light, and facilitates the synchronization of the

body’s physiologic systems to circadian patterns. Melatonin shows properties of a

EP378

powerful antioxidant, at sufficiently high concentrations as a direct radical

Prevalence of metabolic syndrome and its relation to physical activity

scavenger, but, at lower, near-physiological levels, as a regulator of redox-

and nutrition in Azerbaijan

relevant enzymes, suppressor of prooxidant excitatory and inflammatory

Afruz Mammadova^1,2, Selen Yilmaz İ¸ikhan³, Aylin Acikgoz⁴ &

processes and as a mitochondrial modulator. Increased oxidative stress has

Okan Bulent Yildiz^1,5

emerged as playing a central role in metabolic syndrome and its component

¹Department of Internal Medicine, Hacettepe University School of

pathologies and may be a unifying factor in the progression of this disease.

Medicine, Ankara, Turkey;²Azerbaijan Medical University Therapeutic

In the present study, we evaluated in a hamster experimental model, the influence

Training Clinic, Baku, Azerbaijan;³Department of Biostatistics, Hacettepe

of irbesartan and melatonin, co-administered in a novel pharmaceutical

University School of Medicine, Ankara, Turkey;⁴Department of Nutrition

multiparticulate formulation, on metabolic markers and oxidative profile. Our

and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara,

results depicted blood glucose, serum cholesterol and triglycerides lowering

Turkey;⁵Division of Endocrinology and Metabolism, Hacettepe University

effects, being maximum for the new formulation irbesartan and melatonin,

School of Medicine, Ankara, Turkey.

revealing a potentiating effect of the two drugs. On the oxidative status, the new

formulation presented a tremendous decreasing effect, due to the simultaneous

release in the bloodstream the two medicines, depicting a synergic unique effect,

Aim

reasoning the use of the two molecules in a single pharmaceutical formulation.

Metabolic syndrome is a major public health challenge associated with an

DOI: 10.1530/endoabs.49.EP376

increased risk for cardiovascular disease and type 2 diabetes. The prevalence of

metabolic syndrome in Azerbaijan is unknown. The purpose of this study was to

examine the prevalence of metabolic syndrome and its relation to physical

activity and nutrition in a representative sample of adult population in Azerbaijan.

Methods

The study population consisted of 288 adults, 20 years of age and over, from

Guba, Azerbaijan recruited between January and April of 2016 by random

EP377

sampling in line with the gender and age distribution.

Revised NCEP/ATP III criteria were used to define metabolic syndrome and

The dual FXR/TGR5 agonist INT-767 counteracts nonalcoholic

prevalence estimates of each individual component were determined. Physical

steatohepatitis and visceral adipose tissue dysfunction in a rabbit model

activity and food consumption were assessed with validated questionnaires and

of high fat diet-induced metabolic syndrome

their relations with components of metabolic syndrome were evaluated.

Paolo Comeglio², Ilaria Cellai², Sandra Filippi¹, Annamaria Morelli⁵,

Results

Erica Sarchielli⁵, Luciano Adorini⁴, Mario Maggi^2,3 & Linda Vignozzi^2,3

The participants were 159 women and 129 men (mean GS.D. age of 43.1G15.2 y

¹Interdepartmental Laboratory of Functional and Cellular Pharmacology of

(range

20-83 y)). Overall prevalence of metabolic syndrome was

28.4%.

Reproduction, Department of Neuroscience, Phychology, Drug Research

Abdominal obesity was the most common individual component (49% and 85.4%

and Child Care, University of Florence, Florence, Italy;²Sexual Medicine

in whole population and in those with metabolic syndrome respectively).

and Andrology Unit, Department of Experimental and Clinical Biomedical

Interestingly, it was also the only component that was more common in women

Sciences, University of Florence, Florence, Italy;³I.N.B.B., Rome, Italy;

than men (P!0.05 for both whole population and patients with metabolic

⁴Intercept Pharmaceuticals, New York, USA;⁵Department of Experimental

syndrome) whereas the other components did not show a gender difference. The

and Clinical Medicine, University of Florence, Florence, Italy.

odds ratio for having metabolic syndrome was 0.56 (95% CI, 0.34-0.95) in

moderate-high physical activity group compared to low physical activity group

The nuclear Farnesoid X receptor (FXR) and the G protein-coupled bile acid

suggesting a reduced risk of metabolic syndrome with increased physical activity.

receptor

(TGR5) are bile acids receptors that play a key role in energy

Total calorie intake, protein, fat and carbohydrate consumption did not show a

metabolism. In an animal model of non-genomic metabolic syndrome (MetS),

significant difference in participants with and without metabolic syndrome.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

Informed Consent Forms, the intermittent interstitial glucose reading device

Metabolic syndrome in Azerbaijan is common and associated with low physical

(IPro2 - Medtronic/USA) was implanted and simultaneous electrocardiographic

activity. Preventive measures should be taken to address this public health

recording was performed by the Holter system (Cardios Systems/Brazil). The

problem and related risk factors in the country.

patients were monitored for hypoglycemia

(defined as interstitial glucose

DOI: 10.1530/endoabs.49.EP378

value !70 mg/dl according to the International Diabetes Federation without

any induction for this occurrence and arrhythmia detection for 24 hours. Twenty-

two patients were studied. From these eight patients (36.3%) did not have

hypoglycemia: two patients (25%) also had no arrhythmia, while six patients

(75%) had arrhythmias interpreted as non-significant. Hypoglycemic events were

detected in the other 14 patients (63.7%), corresponding in this scenario from 4%

(55 minutes) to 68% (16 hours) of total monitoring time. In this group, seven

patients (50%) presented no arrhythmia, while the other seven patients (50%) had

some non-significant arrhythmia that is common in non-diabetic subjects, being

more prevalent as ventricular and supraventricular extrasystoles, isolated/paired

with low frequency and sinus tachycardia. In the evaluated group, we find no

EP379

relation between episodes of hypoglycemia and clinically relevant cardiac

arrhythmia.

Isolated low HDL-Cholesterol in patients with type 2 diabetes about

168 cases

DOI: 10.1530/endoabs.49.EP380

El Ansari Nawal, Habra Bahia & El Mghari Ghizlane

Endocrinology, Diabetes and Metabolic Diseases Mohammed the 6th

University Hospital, Faculty of Medicine, Cadi Ayyad University,

Marrakesh, Morocco.

Introduction

Lipid abnormalities in diabetics both quantitative and qualitative contribute to the

increased cardiovascular risk.

EP381

Aim

Family hypercholesterolemia: about 4 cases

The aim of this study is to determine the prevalence of isolated hyoHDLémie in

Aicha Bouzid & Djamila Mineesk

type 2 diabetics and assess cardiovascular risk in two populations of type 2

Dr, Algiers, Algeria.

diabetes with and without Low HDL-Cholesterol isolated.

Patients and methods

Familial hypercholesterolemia (HF) is a rare hereditary dyslipidemia charac-

Prospective study started in diabetic patients seen in diabétologic consultation at

terized by a major elevation of LDLc, cutaneo-tendinous xanthomas and

the University Hospital of Marrakech.

atheromatous manifestations. This anomaly exposes a high vascular risk, more

Preliminars Results

than 50% for men and 30% for women, occurring early.

One hundred and sixty eight patients were identified, 72% female, The average

Observations

age of patients was

55 years, average duration of diabetes was

7 years,

We report four cases of HF from the same family, three girls and one boy and

hyoHDLémie was found in 40.4% of cases (68 patients), the prevalence of

whose parents are affected by hypercholesterolemia. The average age of patients

isolated hyoHDLémie is estimated at

26.19%

(44

cases), with overall

is 11 years. Only the eldest siblings present tendon xanthomas. The mean total

cardiovascular risk estimated at more than 20% in the group of patients with

cholesterol is 3.45 g/l, the average LDLc is 2.80 g/l, the mean HDLc level is

isolated Low HDL-Cholesterol.

0.37 g/l, the average triglyceride level is 1.30 g/l. The search for vascular and

Discussion

cardiac repercussions was negative outside aortic narrowing in the elder. For lack

Lipid disturbances are widely studied in diabetic patients, but few studies have

of means the genetic diagnosis could not be made.

examined the Low HDL-Cholesterol isolated. In diabetic patients, current

Discussion

treatment guidelines target low-density lipoprotein cholesterol (LDL-C) with

Xanthomas were the main manifestation in this family. The presence of these

statins. In patients with elevated TGs, non-HDL-C is considered a secondary

clinical signs led to the prescription of a biological check-up in search of a lipid

target of therapy. Despite the use of statin therapy in diabetes, a significant

perturbation and of early vascular pathologies. Familial hypercholesterolemia

number of fatal and nonfatal coronary heart events still occur, indicating the need

to target other modifiable risk factors for coronary heart disease, including Low

results from a lack of binding and internalization of LDL through the LDL

receptor. Identification of the mutation should be systematically performed.

HDL-Cholesterol. This study shows a high prevalence of isolated diabetics

Genetic diagnosis provides diagnostic certainty and facilitates family screening.

correlated with cardiovascular risk also important that the interests of the target

Low HDL-Cholesterol by lipid-lowering therapy to reduce cardiovascular

DOI: 10.1530/endoabs.49.EP381

morbidity and mortality in diabetics.

DOI: 10.1530/endoabs.49.EP379

EP382

Description of an educational intervention lifestyle program in reducing

cardiovascular risk factors

EP380

Eduardo Oliveira

Can hypoglycemic episodes in type 1 diabetics trigger cardiac

Universidade Estadual do Pará, Belém, Pará, Brazil.

arrhythmias?

Goals

Kelly Regina Lainetti, João Pimenta, Márcio Faleiros Vendramini &

The purpose of this article is to describe an educational program of lifestyle

José Luiz B. Cassiolato

intervention rather successful, taught for 25 groups of customers of a private

Hospital do Servidor Público Estadual, São Paulo/SP, Brazil.

hospital in Amazon, for a total of 2,215 individuals between 2008 and 2014, 1448

being female and male 767 and briefly assess its results in relation to some of the

Type 1 diabetes mellitus (DM1) accounts for 5 to 10% of DM cases, and can

main risk factors.

occur both in childhood and adults. Studies show an association between severe

Methods

hypoglycemia and increased vulnerability to cardiac arrhythmias due to

The PVS - Programa Vida Saudável, promotes evaluations and individual and

conduction disorders, interval ST-segment changes, and even sudden death.

group counselling, consisting of two phases, the first being, with eight meetings of

The aim of this study is to evaluate the occurrence of cardiac arrhythmias during

the group with the multidisciplinary team in 12 weeks, followed by the second

episodes of hypoglycemia. A prospective study with DM1 patients under insulin

phase, with monthly meetings during 52 weeks for a total of 15 months. Clinical

therapy for at least 5 years, aged 18-60 years, of both sexes. Before study

evaluations occur with individual counselling and laboratory dosages at the

initiation, all patients underwent a two-dimensional echocardiogram and

beginning and end of each phase, as well as an assessment of reaction to the end of

laboratory tests, and those who did not present structural heart disease or any

each of the sessions. The goals of the intervention were presented progressively

hormonal alterations that could cause arrhythmias, were included. The study was

and easy to perform encouraging the adoption of habits and health principles,

approved by the Research Ethics Committee of the Institution and after signed the

widely established.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

80/50 mmHg. Biochemistry revealed fasting glucose:95 mg/dl, Na:127 mmol/l,

We analyse those who obtained 75% or more of the meetings frequency

K:5.35 mmol/l, Hb:16.6. CT abdomen showed normal adrenal gland morphology

(nZ1723) in 15 months and as controls, those who did the assessments and

with no local masses or infectious pathology. Pituitary MRI demonstrated

exams, however, did not participate in the educational program

(nZ132).

enlarged heterogeneous gland with 9 mm height, probably due to high ACTH

Preliminary results showed a significant evolution in the percentage of each risk

levels. All findings were consistent with Addison disease, which was confirmed

factor in patients with blood glucose reduction, improvement in cholesterol, with

with morning cortisole of 2.44 mg/dl (normal range 6-22), ACTH: 1250 pg/ml

reduction in LDL-c reduction in triglycerides, reduction in blood pressure and

(0-46).

weight reduction.

Once Addison’s disease had been confirmed, other autoimmune diseases

Conclusion

regarding APS were undertaken. Subclinic hypothyroidism with automimmune

Based on studies of the data, this program of health education (PVS) presented a

thyroiditis; TSH:8

(0.4-5.3), fT₄:

0.9 ng/dl

(0.6-1.25), anti-TPO:1016 IU/ml

good adhesion of the customers and proved to be effective to reduce the risk levels

(0-9) was detected. Despite his normoglycemia; C-peptit:1.69 ng/ml, fasting

in its active participants.

insulin:22.3 uIU/ml, A1c:5.6%, he had high anti-GAD and anti-islet cell

DOI: 10.1530/endoabs.49.EP382

antibodies, widely used as a diagnostic and predictive tool for type 1 diabetes

mellitus, indicating that he may develop type 1 diabetes mellitus in future.

After a week of steroid replacement his physical discomforts were alleviated with

improved electrolytes.

Discussion and Conclusion

Herein, we reported an uncommon case, who had complete two-glandular

deficiency with third component; predicted type 1 diabetes. This patient is being

monitored closely on glycaemic state. Therefore, once an autoimmune disease is

identified, the early screening for antibodies against associated disease such as

anti-TPO, GADA, ICA, and antibodies to 21-hydroxylase is crucial, which

EP383

facilitate the diagnosis of further disorder at an early stage.

Role of lactate dehydrogenase-A (LDH-A) in atherosclerosis

DOI: 10.1530/endoabs.49.EP384

Keun Gyu Park, Yeon Kyung Choi, Kwi Hyun Bae & Jung Beom Seo

Kyungpook National University Hospital, Dae Gu City, Republic of Korea.

Pathological proliferation and migration of vascular smooth muscle cells

(VSMCs) has been implicated in the pathogenesis of accelerated atherosclerosis

in patients with diabetes mellitus. Increased aerobic glycolysis is a key feature of

cellular phenotypes including cancer and immune cells. However, it remains

largely unknown about the role of aerobic glycolysis in atherogenic phenotype of

VSMCs. Here, we investigated the role of lactate dehydrogenase-A (LDH-A),

which is a key enzyme for glycolysis, on proliferation and migration of VSMCs.

Clinical Case Reports - Thyroid/Others

Activation of VSMCs with platelet-derived growth factor (PDGF) or fetal bovine

EP385

serum (FBS) resulted in cellular proliferation and migration and increased

glycolytic activity accompanied by the increased expressions of glucose

Insulin autoimmune syndrome (Hirata Disease) triggered by a tyrosine

transporter 1 (GLUT1), hexokinase (HK) 2 and LDH-A in primary rat VSMCs.

kinase inhibitor drug in a Latin American patient

Through wound healing assay, actin stress fiber staining and transwell migration

Susana Mallea Gil, Carolina Ballarino, Daniel Lotero Polesel,

assay, we observed that both pharmacological inhibition (oxamate) and siRNA-

Maria Teresa Kleine, Emilio Batagelj & Nicolas Picon

mediated knockdown of LDH-A

(siLDH-A) effectively inhibited cellular

Hospital Militar Central, Buenos Aires, Argentina.

migration. Oxamate reduced PDGF stimulated glucose uptake, lactate production,

ATP production and NAD/ nicotinamide adenine dinucleotide (NADH) ratio.

Hirata syndrome is a rare cause of spontaneous hypoglycaemia, more prevalent in

Nicotinamide mononucleotide (NMN), nucleotide precursor of NADC, partially

Japanese population, very infrequent in Caucasian patients. It has been described

but significantly recovered oxamate treatment or siLDH-A induced inhibition of

that it can be triggered by medication with sulfhydryl compounds or a-lipoic acid.

VSMC proliferation and migration, suggesting NADC involvement in LDH-A

A 73-year-old male patient was sent to the Endocrinology Division in December

mediated VSMC proliferation and migration. Taken together, this study shows

2015 because he had been presenting with episodes of sweating, palpitations and

that enhanced aerobic glycolysis in PDGF- and FBS-stimulated VSMCs plays an

feeling hungry for

months; these symptoms improved when he ate

important role in their proliferation and migration and suggests that LDHA can be

carbohydrates. In the last 15 days before his visit, the episodes worsened, every

a potential therapeutic target for the prevention of vessel lumen constriction in the

3 hours. The patient had a history of a synchronous bilateral clear cell renal

course of atherosclerosis or restenosis.

carcinoma, the right kidney was removed in 2007, and the left renal carcinoma

DOI: 10.1530/endoabs.49.EP383

was not surgically removed because he presented worsening of a large

thoracoabdominal aortic aneurysm and the patient refused to be operated due to

the high risk involved in this surgery. He was treated with sunitinib, but this drug

was switched to sorafenib because of adverse effects in 2008. In 2013, he

presented cancer progression and he began treatment with pazopanib but there

was no response and the oncologist decided to switch to axitinib 10 mg/day in

Clinical Case Reports - Pituitary/Adrenal

2014. A year later the patient began with endocrine symptoms. Pancreatic CT

EP384

and MRI were normal. Lab tests: glycaemia 41 mg%, insulin O 1000 uU/ml

(N: 0-12) C-peptide: 5.4 ng/ml (N: ! 2.6). Insulin antibodies were performed:

Prediction of type 1 diabetes in autoimmune polyglandular syndrome

O50 U/ml (N: !1) which confirmed the diagnosis of Hirata disease. Axitinib

type 2

was stopped immediately and fractional eating was indicated. The hypoglycaemic

Anara Karaca, Nese Ersoz Gulcelik, Tulay Omma, Isilay Taskaldiran,

episodes became progressively less frequent and some days there were no

Sevde Nur Firat & Nujen Bozkurt

episodes. HLA analysis revealed the HLA-DRB1*04:15 allele. As the patient

Ankara Teaching and Research Hospital, Endocrinology and Metabolism,

improved, insulin antibodies were repeated but they remained elevated. The

Ankara, Turkey.

patient had renal cancer progression and died a year after.

Conclusions

Introduction

Episodes of hypoglycaemia with very high levels of insulin in a non-diabetic

Autoimmune Polyglandular Syndrome (APS) is a very rare endocrinopaty,

patient suggest a probable autoimmune origin. This is the first report of Hirata

characterized by the coexistence of at least two glandular autoimmune mediated

disease triggered by Axitinib, a drug not previously involved in this syndrome.

diseases. In this case a patient presented with hyperpigmentation of the whole

Another novel finding is that HLA phenotype results in HLA-DRB1*04:15 allele,

body, significant weight loss for last 6 months.

which has not been described before neither in Asian nor in European patients and

Case

this may be due to the fact that this patient is Latin American.

A-49 year old male were refered to our deparment with loss of appetite, fatigue,

DOI: 10.1530/endoabs.49.EP385

nausea, weight loss and with marked buccal pigmentation. Blood pressure was

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP386

EP388

Fulminant diabetic ketoacidosis complicating nivolumab

Diabetic patient with suppurative thyroiditis caused by Salmonella

immunotherapy

enterica complicated with acute kidney injury

Ploutarchos Tzoulis¹, Justin Stebbing², Elly Baker¹, Daniel Heaton¹ &

Aleksandra Hernik¹, Ewelina Szczepanek-Parulska¹, Bogusz Falkowski¹,

Richard Corbett¹

Hanna Komarowska¹, Anna Wejman-Matela², Michal Drews² &

¹Whittington Hospital, London, UK;²Imperial College/Imperial Healthcare

Marek Ruchala¹

NHS Trust, London, UK.

¹Department of Endocrinology, Metabolism and Internal Medicine, Poznan

University of Medical Sciences, Poznan, Poland;²Department of General,

Endocrine and Gastrointestinal Oncological Surgery, Poznan University of

A 56-year-old woman, recently commenced on immunotherapy as second-line

Medical Sciences, Poznan, Poland.

treatment for advanced non-small cell lung cancer, presented at the hospital

critically unwell with severe diabetic ketoacidosis (DKA) (glucose 47 mmol/l,

blood ketones 7.5 mmol/l, pH 6.95, bicarbonate 6.6 mmol/l). One week prior to

Incidence of acute thyroiditis is about 0.1% of thyroid gland conditions requiring

presentation, she was clinically well with random glucose of

6.1 mmol/l.

surgical treatment. Main pathogen causing acute thyroiditis is Staphylococcus

Following admission to Intensive Care Unit, she responded well to standard

aureus while Salmonella enterica is extremely rare.

treatment for DKA and discharged on basal bolus insulin regime. Her anti-GAD

Herewith we report a 61-year-old obese woman with sore throat and fever. She

antibodies were

12 kU/l

(0-5 kU/l), while islet cell antibodies and serum

had chronic atrial fibrillation, hypertension, and well-controlled type 2 diabetes

C-peptide were undetectable. Nivolumab has been recommenced without the

mellitus (HbA1C 5.5%) for 3 years (on metformin and gliclazide). Her medical

development of other immune-mediated phenomena to date.

history was negative for thyroid and renal disorders. Ultrasound examination

Besides metastatic lung adenocarcinoma diagnosed 3 years ago, she had no

(US) of the neck demonstrated mixed solid/cystic lesion. Moreover, empirical

personal/family history of diabetes mellitus (DM), while venous glucose had been

therapy with clindamycin was introduced (1.2 g/day) and the patient was referred

normal at numerous measurements. She was initially treated with Pemetrexed and

to the endocrinonogy department. On admission she was weakened and

Cisplatin followed by Pemetrexed as maintenance chemotherapy which was

dehydrated. Physical examination revealed restricted, swollen, tender and painful

discontinued due to side-effects two months prior to her emergency presentation.

lesion in the lower part of the neck. Laboratory tests indicated inflammation, acute

At that stage, Nivolumab every 2 weeks was initiated. She has maintained good

kidney injury and hyperthyroidism. Fine-needle aspiration biopsy (FNAB) of the

radiological and clinical response to treatment.

lesion was performed. Cytological diagnosis was consistent with acute thyroiditis,

Nivolumab is an anti-PD-1 monoclonal antibody and as a checkpoint inhibitor

while microbiologically Salmonella enterica was identified as pathogenic factor.

acts as an immunomodulatory antibody that augments the anticancer immune

Blood and stool cultures were negative for Salmonella. Neck CT revealed thyroid

response through downregulation of T-cell inhibition. Immunotherapy has a

lesion 6.8 cm in size. Patient received adequate therapy for acute kidney injury

beneficial effect in an increasing number of tumour sites, but is associated with

(most probably clindamycin-induced). I.v. treatment with ceftazidime according

immune-mediated endocrinopathies. Development of new-onset type 1 DM after

to antibiogram and thiamazole was administered. The patient was qualified for

receiving anti-PD-1 antibodies, especially as single agent, is extremely rare.

incision and percutaneous drainage. She was discharged after

11 days of

This patient developed fulminant type 1 DM leading to severe DKA and remains

hospitalization presenting significant clinical improvement. A year later on US six

insulin dependent. Both endocrinologists and oncologists need to recognise this

mixed solid/cystic lesions of size below 1 cm were visualized, benign on FNAB.

potentially life-threatening complication and to monitor patients for hyperglycae-

She remains clinically and biochemically euthyroid. Typical infections with

mia prior to and periodically during immunotherapy. Further studies examining the

Salmonella concern gastrointestinal tract, while conditions associated with

pathophysiology and natural history of immunotherapy-associated diabetes are

atypical infections are: HIV infection, transplant recipients, diabetes mellitus,

warranted in order to guide optimal patient monitoring and management.

thyroid gland disorders

(e.g. multinodular goiter, after FNAB), anatomical

DOI: 10.1530/endoabs.49.EP386

abnormalities

(piriform sinus fistula), corticosteroid therapy, advanced age,

neoplastic disease and contact with breeding animals. The only risk factor for

acute thyroiditis in our patient was diabetes mellitus, although it was well-

controlled.

DOI: 10.1530/endoabs.49.EP388

EP387

Dyslipidemia and antiretroviral therapy: a case report

El Meghari Ghizlane, Elbahi Meryam, Rafii Sana & El Ansari Nawal

Faculty of Medecine and Pharmacy, Marrakech, Morocco.

Introduction

EP389

The use of highly active antiretroviral therapy in 1996 helped greatly reduce the

Improved xanthomas after leptin replacement short therapy in

morbidity and mortality in patients infected by HIV. Very quickly, secondary

congenital lipodystrophy patient

metabolic complications to this same treatment have been described.

Antonio F Oliveira-Filho¹, Irla A Dantas⁴, Renata N Velloso³,

Dyslipidemia occupy a large part of these complications and give the patients

Sofia N P de Oliveira², Diego F F Candido⁴ & Adriana Nunes³

an atherogenic profile favouring the occurrence of acute coronary events. We

¹Paraiba Health State Department, Campina Grande, Brazil;²Federal

report a case that illustrates the lipid abnormalities associated with anti retroviral

University Campina Grande, Campina Grande, Brazil;³Federal University

treatment.

Rio Grande Norte, Natal, Brazil;⁴Faculty of Health Sciences, Joao Pessoa,

Case report

Brazil.

The subject was 54 years old woman, diabetic for 8 years, without history of

hypertension or smoking, BMI was 29 Kg/m², diagnosed as HIV infected for 1

year, treated by antiretroviral therapy. Her initial lipid profile reveals a moderate

Berardinelli-Seip syndrome is an autosomal recessive disorder characterized by

hypertriglyceridemia of 2.5 g/l, total cholesterol was 1.7 g/l and HDL cholesterol

generalized lipoatrophy, extreme insulin resistance with dyslipidaemia in

was 0.3 g/l. High plasma viral loads persisted after 6 months of antiretroviral

childhood and development of diabetes and hepatic steatosis in adolescence.

therapy, thus the patient was considered to have a treatment failure. The control of

The metabolic derangements can be severe and lead to substantial comorbidities,

her lipid profil, after 2 months of a second-line combination therapy, reveals an

including acute pancreatitis, hepatic cirrhosis, and premature cardiovascular

aggravation of her previous dyslipidemia with a severe hypertriglyceridemia of

disease. Other manifestations can include polycystic ovarian syndrome,

6.36 g/l, an hypercholesterolemia of 2.72 g/l and HDL cholesterol was 0.4 g/l.

acanthosis nigricans, and eruptive xanthomas. Lipodystrophy syndromes have

Discussion

caught interest because adipose tissue has been found to secrete a variety of

While the retroviral infection itself, especially at the AIDS stage, is responsible

cytokines/hormones such as leptin, adiponectin, resistin, and many others. Here

for an increase in triglycerides and a decrease in total cholesterol, antiretroviral

we describe a dramatic response to treatment with leptin. A 15-year-old girl was

therapy exacerbates abnormal lipid metabolism. This is mainly dyslipidemia with

given the diagnosis of Berardinelli-Seip congenital lipodistrophy syndrome

predominant hypertriglyceridemia, associated with an increase in total cholesterol

(BSCL). She presented generalized lipoatrophy, muscle hypertrophy, xanthomas

and LDL-cholesterol; HDL-cholesterol is either lowered or slightly modified,

in elbows legs and soles, umbilical hernia, hirsutism, hyperphagia, acanthosis

these abnormalities are partly due to increased hepatic synthesis of large VLDL

nigricans and hepatomegaly. Her BMI was 20.67 kg/m², body fat was 5.72%, and

and decreased purification of remnants rich in triglycerids. The Knowledge of

BMR was 1 440.3 Kcal. Computer tomography revealed hepatic steatosis, one

lipid abnormalities induced by antiretroviral treatment is critical for better patient

cyst on the right kidney, and absence of subcutaneous and adipose tissues. Patient

management between infectiologist, biologist and endocrinologist.

had difficult to manage metabolic parameters, requiring 300U of insulin and

DOI: 10.1530/endoabs.49.EP387

combined therapy. She started a leptin-replacement therapy (1 ml/day). After ten

days, her xanthomas became vanished, cholesterol levels decreased from 550 to

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

196 mg/dl, and triglycerides

5.000

840 mg/dl. She observed progressive

Conclusions

reduced fasting blood glucose and insulin dose simultaneously with improvement

The clinical features of this syndrome was according to those described in the

in clinical signs, symptoms and quality of life. In a ten days course, leptin

literature. Metabolic and endocrine disorders should not be interpreted as isolated

replacement showed to be able to manage metabolic state of the patient and

pathology, but as possible pathogenetic factors. We underline the essential role of

xanthomas.

MRI in detecting the disease correlated with intense headache. The neurological

DOI: 10.1530/endoabs.49.EP389

symptoms and psychiatric symptoms were correlated with the severity of internal

frontal hyperostosis and cortical atrophy.

DOI: 10.1530/endoabs.49.EP391

EP390

Resistant hypertension in an obese type 2 diabetic male with obstructive

sleep apnea: resolution with CPAP, weight loss and Dulaglutide

EP392

Claudia Arnas-Leon¹, Ana Delia Santana-Suarez¹, Alba Rodriguez-Perez²,

Continuous glucose monitoring in glycogen storage disease type Ia - a

Manuel Nivelo-Rivadaneira¹, Agnieszka Kuzior¹, Sara Quintana-Arroyo¹,

major improvement for patients

Carmen Acosta-Calero¹ & Francisco Javier Martinez-Martin¹

Diana Martins¹, Diana Oliveira¹, Carla Baptista¹, Sandra Paiva¹,

¹Endocrinology and Nutrition, Hospital Doctor Negrin, Las Palmas de Gran

Nuno Vicente¹, Luís Cardoso¹, Adriana Lages¹, Mara Ventura¹,

Canaria, Spain;²Internal Medicine, Hospital Doctor Negrin, Las Palmas de

Nelson Cunha¹, Sónia Moreira², Hugo Clemente², Helder Esperto² &

Gran Canaria, Spain.

Francisco Carrilho¹

¹Department of Endocrinology, Diabetes and Metabolism of Coimbra

Hospital and Universitary Centre, Coimbra, Portugal;²Department of

A 49-year-old male was referred to our Hypertension Clinic with uncontrolled

Internal Medicine of Coimbra Hospital and Universitary Centre, Coimbra,

hypertension, treatment Valsartan/Amlodipine/Hydrochlorothiazide 80/10/25 mg

Portugal.

C Doxazosine 4 mg. Mean home BP was 156/103 mmHg. Personal history:

dyslipidaemia, central obesity and type 2 diabetes, with mild diabetic retinopathy,

persistent microalbuminuria and preserved renal function. Treatment: Metfor-

Introduction

min/Sitagliptin

1000/50 mg BID; Pravastatin/Fenofibrate

40/160 mg. Height

Glycogen storage disease (GSD) type Ia (von Gierke’s disease) is an inherited

172 cm, weight 112 kg, BMI 37.8 kg/m², waist 126 cm, clinic BP 165/99, HR 77;

metabolic disorder of glycogen metabolism, caused by defects in the glucose-6-

unremarkable physical exam except abdominal adiposity. Glycemia 132 mg/dl,

phosphatase complex, with associated risk of severe hypoglycemia within 3-4 h

HbA_1C

7.2%, Cr

0.92 mg/dl, GFR

(CKD-EPI)

97 ml/min per

1.73 m²,

after a meal.

Cholesterol

166

mg/dL

(HDL 38, LDL 96), Triglycerides

161

mg/dl,

The aim of the present study was to evaluate the efficacy of continuous glucose

Albuminuria 126 mg/g Cr; TSH, Metanephrines, Aldosterone, PRA and ratio

monitoring (CGM) system in determining the magnitude of hypoglycemia in

were normal. Heart US: normal function, mild LVH (PW and IVW 14 and

patients with GSD type Ia.

13 mm). 24 h. ABPM: Awake BP 157/96, Sleeping 146/89, non-dipper.

Methods

The treatment changed to Perindopril/Indapamide 8/2.5 mg, Eplerenone 50 mg

We retrospectively analyzed data from three patients with GSD type Ia, who

and Doxazosine 4 mg. Four months later, the patient had lost 2.5 kg with

underwent CGM with iProTM2 CGM device (Medtronic, Northridge, CA), over a

diet/exercise, but BP and HbA_1C had not improved. Dulaglutide 1.5 mg/week was

7.0 days period, under real life conditions.

substituted for Sitagliptin. The patient’s wife reported heavy snoring with

Results

apparent pauses, and the patient was referred to polysomnography. A severe OSA

A total of 5.520 glucose data points were analysed. Concerning to low glycemic

was diagnosed, and CPAP was initiated.

excursions (!70 mg/dl), we identified 15 episodes (three of them below 55 mg/dl

Six months later, weight was 98.5 kg (IMC 33.1 kg/m²); waist 114 cm, and home

and reaching 40 mg/dl in one case). Most of the episodes of hypoglycaemia were

and office BP were normal. New ABPM: Awake 132/76, sleeping 116/69, dipper.

asymptomatic and occurred 3 or more hours after meals or during the nocturnal

Glycemia was 114 mg/dl, HbA_1C 6,7%, Cr 0.91 mg/dl, GFR 98 ml/min per

period. The individual CGM analysis revealed a mean area under the curve of

1.73 m², Chol. 153 mg/dl (HDL 43, LDL 79), Trigl. 156 mg/dl, Albuminuria

blood glucose below 70 mg/dl (AUC!70) respectively of 0.1, 0.5 and 0.8. One

23 mg/g Cr. New heart US: PW and IVW 11 and 10 mm.

patient presented with important glycemic variability: MAGE 3.11 (reference

The diagnosis was resistant hypertension with target-organ damage (albuminuria,

range 0.0-2.8).

LVH) associated to OSA, plus type 2 diabetes, central obesity, and dyslipidemia.

Conclusions

With CPAP, weight loss and Dulaglutide, BP and glycemic control were achieved

The analysis of continuous glucose monitoring data revealed significant periods

and target-organ damage was reversed.

of asymptomatic hypoglycemia and provided better perception into glycemic

DOI: 10.1530/endoabs.49.EP390

variations therefore, it may serve as a safe and useful tool for the long-term

management of patients with GSD type Ia. We suggest that CGM can be used as

an instrument to detect hypoglycemia, especially in the nocturnal period, helping

patients with GSD to modify their nutritional regimens if necessary.

DOI: 10.1530/endoabs.49.EP392

EP391

Morgagni-Stewart-Morel Syndrome in a 61-years patient: case report

Mihaela Stanciu

Lucian Blaga University of Sibiu, Sibiu, Romania.

EP393

Introduction

Diabetes mellitus: one train may hide another

Morgagni-Stewart-Morel syndrome is a disorder defined by the presence of

Sara Vandewalle^1,2, Nike Van Doninck¹ & Peter Coremans¹

internal frontal hyperostosis, variably associated with metabolic disorders,

¹AZ Nikolaas, Sint-Niklaas, Belgium;²Ghent University Hospital, Ghent,

endocrine and neuropsychiatric disorders. Hyperostosis frontalis interna (HFI)

Belgium.

is a morphological change of the frontal bone like a single or multiple bilateral

nodules on the inner lamina, characteristically sparing the diploe and the midline

calvaria.

A 26-year-old Chinese male with autism spectrum disorder and mental

Case presentation

retardation, was referred to start insulin therapy for uncontrolled diabetes

We present a 61-years old women with hypertension and diabetes mellitus (with

mellitus (DM) (HbA1c: 9%; C-peptide: 1.75 ng/ml; anti-GAD AB: negative)

oral antidiabetic therapy), obesity, osteoporosis; also the patient was operated in

treated with oral antidiabetic drugs since 2012.

2005 for a multinodular goiter (total thyroidectomy), treated with L-thyroxin

Clinical examination revealed a tall man with overweight and truncal obesity in

100 mg per day. She was referred to our department for severe frontal headache

light of his ethnicity. We withheld facial dysmorphism with hypertelorism, scarce

which she had suffered for several years, with gradually worsened, failing to

facial hair, and clinodactyly. He had a true gynaecomastia and acanthosis

respond to nonsteroidal anti-inflammatory drugs in last six months and a history

nigricans. Tanner genital stage was IV, however testicular volume was !4 ml.

of psychotic disorders. MRI demonstrated the internal hyperostosis frontalis with

Blood results showed hypergonadotropic hypogonadism

(LH:14.1 U/L,

compression of the cerebral cortex and a small image in the pituitary gland, which

FSH:25.3 U/L, testosterone: 195 ng/dl, free testosterone: 5.71 ng/dl). Additional

is now under observation.

genetic testing showed 48 XXYY karyotype.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Based on medical questionnaires, DM is described in 18% of 48 XXYY males.

A 45-year-old female presented with recurrent episodes of neuroglycopaenic

Following pathophysiological mechanism is proposed: low tota l and free

symptoms 6 years after Roux-en-Y gastric bypass surgery. Her symptoms

testosterone levels are associated with truncal obesity leading to metabolic

occurred during both the fasting and postprandial state. She had a history of

syndrome, insulin resistance and DM. Abdominal obesity and high C-peptide

Rheumatoid Arthritis. Her symptoms did not response to a complex carbohydrate

levels in our patient are arguments in favor of insulin resistance as possible

diet or Acarbose use.

etiological factor. Based on the pathophysiology, metformin and testosterone

Whipple’s triad was demonstrated during a 72 h fast; symptomatic hypoglycae-

could be considered as therapy. Our patient was initially treated with basal-bolus

mia

(1.8 mmol/l) occurred which resolved with glucose administration.

insulin therapy in combination with metformin to enhance insulin sensitivity.

Simultaneous C-peptide, IGF1, IGF2 and insulin samples were requested during

Although in-hospital blood glucose curves were perfect, global metabolic control

the hypoglycaemic episode.

remained poor (HbA1c: 8.5%) due to compliance problems partially by the

The Insulin level was 10 pmol/l, IGF1 level was 11.6 nmol/l, the IGF2 level was

complexity of treatment. Therefore therapy was simplified to a combination of

36.3 nmol/l, IGF2/I ratio was 3.1 (!10), C-peptide level was !94 pmol/l, GH

basal insulin and metformin. Metabolic control remained however poor. Some

was 7.5 mg/l and Sulphonlylurea screen was negative.

data suggest that testosterone treatment might improve metabolic control by

Ketones was

‘Zero’ confirming an insulin independent mechanism for

increasing skeletal muscle mass and decreasing abdominal obesity. In our patient,

hypoglycaemia. Hydroxcholoroquine for Rheumatoid Arthritis was discontinued

there was however no amelioration of metabolic control after start of testosterone.

which led to complete resolution of her symptoms.

Adequate DM therapy is complicated by mental retardation seen in 48 XXYY

This is the first case of severe hypoglycaemia in a patient who did not have

making it difficult to use complex insulin schemes. It seems reasonable to use

diabetes, who underwent bariatric surgery and developed hypoglycaemia due to

metformin in treatment as insulin resistance seems to play a role in the

hydroxycholoroquine therapy with complete resolution of symptoms on

pathophysiology.

discontinuing hydroxychloroquine.

DOI: 10.1530/endoabs.49.EP393

This case demonstrates the need for a structured approach to the evaluation of

hypoglycaemia. Roux-en-Y gastric bypass surgery is associated with subsequent

development of hypoglycaemia which can respond to a complex carbohydrate

diet or acarbose therapy. The lack of response however should prompt a thorough

evaluation. The demonstration of an insulin independent mechanism for

hypoglycaemia excluded post gastric bypass hypoglycaemia as a cause and

EP394

prompted a review of the medication list. Hydroxcholoroquine is associated with

Endocrine manifestations of Woodhouse-Sakati Syndrome - a

the development of hypoglycaemia and cessation resulted in complete resolution

Portuguese case

of symptoms which were occurring at a frequency of 3-4 times per week resulting

Diana Oliveira¹, Sandra Paiva¹, Pedro Louro², M Carmo Macário³,

in termination of employment and driving.

Joa˜o Durães3, Diana Martins1, Mara Ventura1, Adriana Lages1,

DOI: 10.1530/endoabs.49.EP395

Nelson Cunha¹ & Francisco Carrilho¹

¹Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital

and University Center, Coimbra, Portugal;²Medical Genetics Unit, Coimbra

Hospital and University Center, Coimbra, Portugal;³Neurology

Department, Coimbra Hospital and University Center, Coimbra, Portugal.

EP396

A case report of insulin autoimmune syndrome in a Caucasian

Introduction

Jaroslaw Jendrzejewski, Lukasz Obolonczyk, Martina Leczycka &

Woodhouse-Sakati Syndrome (WSS) is a very rare autossomic recessive disorder

Krzysztof Sworczak

caused by mutations in DCAF17 gene that primarily affects the endocrine and the

Medical University of Gdansk, Gdansk, Poland.

nervous systems. It is associated with hypogonadism, diabetes mellitus,

hypothyroidism, sensorineural hearing loss, alopecia and extrapyramidal findings.

Treatment is symptomatic and managed by multidisciplinary teams. Less than

The Insulin Autoimmune Syndrome (IAS) also called Hirata’s disease consists of

80 cases are reported to date.

hypoglycemia, high insulin concentration and presence of anti-insulin antibodies.

Case report

IAS is the third leading cause of spontaneous hypoglycemia among Japanese

We describe a 29-year-old woman with dysmorphic facial features, alopecia, mild

population. The syndrome is exceptionally rare among Caucasians, with !50

intellectual disability and sensorineural hearing loss, referred to the Endo-

cases described in literature.

crinology department for primary hypothyroidism with negative thyroid

In this report we showcase a 67 year-old female patient. She presented with

autoantibodies, hypergonadotrophic hypogonadism with ovaries not visualized

paroxysmal sweating, daily fatigue and weakness with no triggering factors for

on pelvic ultrasound and diabetes mellitus diagnosed at 19 years of age. She was

these symptoms. Her blood glucose levels during those episodes were below

under treatment with levothyroxine, drospirenoneCethynyl estradiol and oral

50 mg% measured by using a standard home glucometer device. Prolonged 72 h

glucose lowering agents. Worsening of metabolic control led to start of insulin

fast test showed extremely high insulin-glucose-ratio with moderate elevation of

therapy. Week positivity for Islet-cell cytoplasmic autoantibodies and positive

C-peptide levels. CT scans did not reveal any significant masses in the abdomen.

glutamic acid decarboxylase autoantibodies were detected. IGF1, GH, prolactin,

The subsequent laboratory analysis showed high levels of anti-insulin antibodies

cortisol and ACTH were normal. Progressive neurologic deficits included

with low insulin recovery by using polyethylene glycol precipitation method.

dysarthria, dysphagia, lower limb dystonia and spastic tetraparesis. Brain MRI

After treatment with low glycemic index diet and prednisone the average

showed generalized leukodystrophy. She was the only child of a consanguineous

glycemia has increased with the remission of the symptoms. There have been no

couple. Common genetic, metabolic and mitochondrial disorders were excluded.

incidents of hypoglycemia since the establishment of the treatment.

WSS was suspected. Sequencing of DCAF17 gene detected the homozygous

Our report indicates that at IAS should be considered in the differential diagnosis

variant c.1091C2TOC, not previously described in literature. However, since it

of spontaneous hypoglycemia in Caucasians. The treatment might lead to the

affects the splice donor site of intron 10 and probably causes exon 10 skipping, it

remission of the symptoms.

is likely to be pathogenic.

DOI: 10.1530/endoabs.49.EP396

Discussion

When in presence of several endocrine disorders associated with multisystem

involvement, it is fundamental to look for genetic disorders. Accurate clinical

evaluation allows genetic diagnosis and counseling. A new homozygous variant

of the DCAF17 gene was found in this case. The pathogenic mechanisms of the

disease are still unclear; diabetes-related autoimmunity is not found in previously

EP397

described cases. Also unlike other described cases, IGF1 was within normal

Acquired generalized lipodystrophy associated with latent autoimmune

limits. Endocrine consequences of WSS need frequent follow-up.

diabetes mellitus in adults: a new metabolic phenotype

Federica Ferrari¹, Marianna Maranghi², Giovanni Ceccarini¹,

DOI: 10.1530/endoabs.49.EP394

Silvia Magno¹, Caterina Pelosini¹, Margherita Maffei¹, Paolo Vitti¹,

Marcello Arca² & Feruccio Santini¹

Obesity and Lipodystrophy Center at the Endocrinology Unit, University

Hospital of Pisa, Pisa, Italy;²Department of Internal Medicine, Medical

Specialties, University La Sapienza, Rome, Italy.

EP395

Hypoglycaemia due to hydroxychloroquine in a patient who underwent

Roux-en-Y gastric bypass surgery

Introduction

Kamrudeen Mohammed & Altayeb Abdalaziz

Acquired generalized lipodystrophies (AGL) are rare syndromes characterized by

Hull Royal Infirmary, Hull, East riding of Yorkshire, UK.

complete loss of subcutaneous adipose tissue and very low serum leptin levels.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

AGL are complicated by severe insulin resistance, diabetes mellitus, dyslipidemia

EP399

and fatty liver. In most patients evidence exists of an autoimmune etiology.

Extensive venous thrombosis of the upper extremity in a newly

Case report

diagnosed type 2 diabetic female

We herein describe the case of a Caucasian woman who was diagnosed with

Daniel-Tudor Cosma¹, Cristina Alina Silaghi^2,5, Vlad Florin Bontea³,

lipodistrophy at 5 years of age, when she began to develop a gradual loss of

Calin Homorodean^3,5, Horatiu Silaghi⁴ & Ioan Andrei Veresiu^1,5

subcutaneous adipose tissue. At the age of

years insulin-resistance,

¹Center for Diabetes, Nutrition and Metabolic Diseases Cluj-Napoca,

hypertriglyceridemia and fatty liver were evident; diabetes mellitus was

Cluj-Napoca, Cluj County, Romania;²Endocrinology Clinic, Cluj-Napoca,

diagnosed when she was 28-years old, and 3 years after insulin therapy became

Cluj County, Romania;³1st Internal Medicine Clinic, Cluj-Napoca,

necessary in order to improve metabolic control of the disease. Genetic testing

Cluj County, Romania;⁴5th Department of Surgery, ‘Iuliu Hatieganu’

were negative for PPARG and LMNA/C mutations, ruling out the principal forms

University of Medicine and Pharmacy, Cluj-Napoca, Cluj County,

of congenital lipodystrophies. She came to our attention at the age of 35 years. At

Romania;⁵‘Iuliu Hatieganu’ University of Medicine and Pharmacy,

clinical examination a generalized loss of subcutaneous fat that included the face

Cluj-Napoca, Cluj County, Romania.

and the extremities was observed. Laboratory tests showed a poor glicemic

control. HbA1_c was 85 mmol/mol on high doses of insulin (150UI/die). Nuclear,

PMScl, Gastric Parietal Cell, and high titer Glutamic Acid Decarboxylase

Upper extremity deep vein thrombosis (UEDVT) is not infrequent and accounts

autoantibodies were detected.

for approximately 14% of deep vein thrombosis. The risk of pulmonary embolism

Discussion

is lower than in lower extremity DVT and prompt diagnosis is essential to select

AGL are frequently associated with other autoimmune disorders. The coexistance

those patients who deserve anticoagulant treatment. Previous studies indicated

with type 1 diabetes is very rare, but the association with a latent autoimmune

that type 2 diabetes (DM) patients carried greater risk of DVT development or

diabetes mellitus in adults

(LADA) has never been reported before. This

recurrence than the general population.

association generates an unusual metabolic pattern characterized by severe

A 49-years old female, with no previous medical history, was admitted to our

insulin-resistance due to ectopic-lipid accumulation and severe diabetes due to an

center via Emergency Room (ER) for optimizing glycemic control. At admission:

absolute insulinopenia. For these reasons the management of the metabolic

altered general status, bradylalia, bradypsychia, generalized edema, marked

syndrome in this case is extremely difficult and the association of insulin with

fatigability, BPZ140/90 mmHg, pulseZ96 b/min, holosystolic murmur in the

human recombinant leptin therapy seems to be more efficient than conventional

mitral area. Lab findings revealed: BGZ401 mg/dl, glycosuria

(1 g/dl),

drugs. This case shows the need to screen all patients presenting with an AGL for

proteinuria (300 mg/dl), low serum iron, mild normochromic and normocytic

associated autoimmune disorders including type 1/LADA diabetes.

anemia, high INR and NT proBNP levels, hypocalcaemia, low HDL cholesterol,

DOI: 10.1530/endoabs.49.EP397

slightly elevated CRP, cholestasis syndrome and A1cZ14.01% was consistent

with a sever glycemic imbalance in the last 3 months. Intravenous insulin infusion

and few boluses were needed to correct the hyperglycemic values followed by

initiation of a basal regimen with glargine insulin and metformin. On 3rd day

since admission, edematous swelling and cyanosis of the right arm with collateral

circulation at the shoulder girdle was observed. The echo-Doppler showed a

massive thrombosis from brachial to the brachiocephalic and internal jugular vein

and the CT pulmonary angiogram thrombi at the level of segmental arteries

bilaterally. Treatment with LMWHs was initiated and the patient was transferred

to the Cardiology department with a favorable outcome. The screening for

EP398

thrombophilia emphasized hyperhomocysteinemia and a slightly elevated S

protein activity.

Humalog Mix50^w massive overdose for suicidal purpose: a case report

Our case illustrates an extensive UEDVT and pulmonary embolism in a newly

Daniel-Tudor Cosma¹, Cristina Alina Silaghi^2,5, Horatiu Silaghi^4,5,

diagnosed type

2 diabetic patient. The modifications in the thrombophilia

Mihaela Mocan^3,5 & Ioan Andrei Veresiu^1,5

screening together with the hypercoagulable state induced by hyperglycemia

¹Center for Diabetes, Nutrition and Metabolic Diseases

might have led to the development of this extensive UEDVT.

Cluj-Napoca, Cluj-Napoca, Cluj County, Romania;²Endocrinology Clinic,

Cluj-Napoca, Cluj County, Romania;³1st Internal Medicine Department,

DOI: 10.1530/endoabs.49.EP399

Cluj-Napoca, Cluj County, Romania;⁴5th Department of Surgery, ‘Iuliu

Hatieganu’ University of Medicine and Pharmacy, Cluj-Napoca, Cluj

County, Romania;⁵‘Iuliu Hatieganu’ University of Medicine and Pharmacy,

Cluj-Napoca, Cluj County, Romania.

EP400

Intentional insulin overdose in diabetic patients is a rare critical situation. The

Early association of three autoimmune disorders in a young male with

severity is due to numerous neurological complications, electrolyte disturbances,

polyglandular autoimmune syndrome type IIIA

liver and lung damage or death.

Daniel-Tudor Cosma¹, Cristina Alina Silaghi^2,5, Mihaela Mocan^3,5,

A 76-years old female, with significant cardiac pathology, diagnosed with type 2

Horatiu Silaghi⁴ & Ioan Andrei Veresiu^1,5

diabetes and treated with Humalog Mix50^w 0-0-24 U/day, is admitted to our

¹Center for Diabetes, Nutrition and Metabolic Diseases Cluj-Napoca,

center via ER (emergency room) after an episode of severe hypoglycemia after

Cluj-Napoca, Cluj County, Romania;²Endocrinology Clinic, Cluj-Napoca,

administration of 1500U Humalog Mix50. She arrived in the ER one hour after

Cluj County, Romania;³1st Internal Medicine Department, Cluj-Napoca,

the overdose with a glycemic value of 111 mg/dl after 50 ml of glucose 33% and

Cluj County, Romania;⁴5th Department of Surgery, ‘Iuliu Hatieganu’

500 ml 10% glucose. At admission: altered general status, profuse sweating,

University of Medicine and Pharmacy, Cluj-Napoca, Cluj County,

multiple injection sites across her abdomen and thighs. Labs exams revealed:

Romania;⁵‘Iuliu Hatieganu’ University of Medicine and Pharmacy,

hypocalcaemia, hypokalemia, slightly elevated creatinine and BUN, mild

Cluj-Napoca, Cluj County, Romania.

normochromic, normocytic anemia, A1cZ6.29%. An infusion of 10% glucose

was begun at 1 L/h. The glucose infusion rhythm and concentration was adjusted

according to the glycemic profile with a total duration of infusion of 46 h.

Polyglandular autoimmune syndromes (PAS) are a heterogeneous group of rare

Besides, multiple boluses of glucose 33% were needed to avoid the hypoglycemic

diseases characterized by autoimmune activity against more than one endocrine

events. Hypocalcaemia and hypokalemia were corrected by intravenous (i.v.)

organ, although non-endocrine organs can be affected. In PAS III, autoimmune

administration of calcium gluconate and potassium chloride. Psychological

thyroiditis occurs with another organ-specific autoimmune disease, but the

evaluation diagnosed depression and recommended a psychiatric consult. On day

syndrome cannot be classified as PAS I or II.

3 since admission, the patient’s general condition worsened significantly with

A 29-years old man was refer to our center for diagnostic confirmation with the

severe hypotension (requiring continuous positive inotropic infusion), liver and

following complaints: xerostomia, polyuria, polydipsia, nocturnal enuresis, 10 kg

renal failure and she was transferred to the ICU. Despite intensive care

weight loss in the last 2 months, blurred vision and marked fatigability. One week

maneuvers, the patient died of cardiac arrest through electromechanical

before admission the lab exams revealed: blood glucose (BG) of 527 mg/dl,

dissociation.

severe dyslipidemia, glycosuria, ketonuria and a basal bolus regimen with insulin

Insulin overdose requires intensive and prolonged glycemic monitoring to prevent

glargine and lispro was started. Labs findings displayed: BGZ276 mg/dl,

recurrent hypoglycemia. The dose is correlated with a prolonged hypoglycemic

moderate hypertriglyceridemia, glycosuria, low sodium and chloride and the

risk higher than that deduced from the pharmacokinetics of insulin administered.

A1cZ17.73% was consistent with a sever glycemic imbalance in the last 3

To our knowledge this case represents the largest overdose with Humalog

months. The specific antibodies for type 1 diabetes (GAD, ICA, IA₂, anti-insulin)

Mix50^w ever reported.

were negative and the C peptide was low. The screening for other autoimmune

DOI: 10.1530/endoabs.49.EP398

diseases was positive for thyroiditis (high TPO antibodies) and celiac diseases

(high IgA anti-transglutaminase antibodies) and were confirmed by thyroid

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

ultrasound, gastroscopy

(paving stone duodenum) and histopathological

preservation of muscle mass and induction of satiety in non-bariatric subjects.

examination. In order to improve the glycemic control, the insulin doses were

Therefore, we investigated the effects of dietary protein, assessed by amino acid

adjusted according to the glycemic values and carbs ingestion. Nutritional

composition, on satiety, hunger and gastrointestinal hormones after gastric bypass

education was conducted emphasizing the importance of gluten-free diet and

surgery.

correct estimation of the carbs intake. The lipid profile normalized after

Methods

normoglycemia was achieved.

Participants who previously had undergone primary gastric bypass surgery were

Despite the lack of specific antibodies, the patient profile, lab exams and

studied during an oral Mixed Meal Tolerance Test (MMTT). Satiety and hunger

association with other autoimmune diseases support the diagnosis of type 1

were assessed every 30 min by means of a visual analogue scale. Blood samples

diabetes. The zinc transporter-8 (ZnT8) antibodies are not yet available in our

were collected at baseline, every 10 min during the first half hour and every

country. The evolution in these cases may be unpredictable and requires the

30 min till 210 min after the start. The plasma samples were assessed for 24

concomitant treatment of all the conditions involved in order to achieve the

amino acids including derivatives and four gastrointestinal hormones.

therapeutic success.

Results

DOI: 10.1530/endoabs.49.EP400

30 female and 12 male subjects aged 48G11 years, 31-76 months after surgery

with total weight loss of 30G9% completed the MMTT. After ingestion increases

in satiety, the hormones PYY, active GLP1, inactive GLP1 and most amino acids

were observed, while hunger, ghrelin and citrulline declined. Satiety scores above

the median were associated with increased plasma levels of PYY, active and

inactive GLP1. Hunger scores below the median (indicating less hunger) were

associated with increased levels of PYY and a reduced attenuation in ghrelin.

Higher concentrations of several plasma levels of amino acids especially

Developmental Endocrinology

histidine, serine, arginine, glutamine and glycine were observed in subjects

EP401

experiencing more satiety, higher levels of PYY, active or inactive GLP1.

Nutritional status in ambulatory patients by Medicine Laboratory

Additional analyses are underway.

Francisco Javier Merida De La Torre & Nieves Bel Pe

˜a

Conclusions

Health Management Area Serrania, Medicine Laboratory, Ronda, Malaga,

Our exploratory analysis shows positive associations between various plasma

Spain.

amino acids in groups with differences in satiety and gastrointestinal hormones.

This provides new insights to optimize the outcomes of bariatric surgery.

DOI: 10.1530/endoabs.49.EP402

Nutritional status has an important effect on the progression of any disease, not

only in hospitalized patients, even more in ambulatory patient of primary care.

Although there are many systems of evaluating nutritional status, they are costly

and subject to variability amongst individuals. The Medicine Laboratory can

correctly perform a nutritional evaluation in a quick an efficient manner.

Objective

Diabetes (to include Epidemiology, Pathophysiology)

Analyze the nutritional status by CONUT nutritional evaluation method

performed by the Medicine Laboratory in ambulatory patients of primary care

EP403

our Health Management Area in 2016.

The fatty acid profile in diabetic children

Materials and methods

Cíntia Castro-Correia¹, Sara Sousa², Sónia Norberto³, Cristina

The CONUT method for nutritional evaluation was used. This method is based on

Delerue-Matos⁴, Valentina Domingues², Manuel Fontoura¹ &

determining undernutrition according to levels of total lymphocyte count total

Conceição Calhau^3,4

cholesterol and serum albumin. During the study, the results of rutinary blood

¹Hospital S João - Unidade Endocrinologia Pediátrica, Porto, Portugal;

tests were used, not additional bllod tests were performed. The focus was a sample

²Requimte/LAQV-GRAQ - Instituto Superior de Engenharia, Instituto

size of all patient admitted in primary care centers, nZ1454 patients. Statistics

Politécnico do Porto, Porto, Portugal;³Department of Biochemistry, Faculty

data: accepted error 3.5%, C.I. 99%. The frequency of nutritional risk was

of Medicine, University of Porto, Centro de Investigac¸ão Médica, Porto,

calculated analysed alongside data on patients’ sex, age.

Portugal;⁴CINTESIS - Center for Research in Health Technologies and

Results

Information Systems, Porto, Portugal.

1454 patients were studied, 68.5%were not undernourished, 27,4% were mild

undernourished and 4,1% were moderate or severe undernourished. The mean age

of patients was 57.9 years, 60.9% were women and 39.1% were men. 6.7% of men

Several studies have shown a link between pro-inflammatory activity and the

were moderate or severely undernourished, only 2.3% of women studied were

presence or relative deficit of some fatty acids. A low amount of omega 3 fatty

moderate or severely undernourished. The statistics differences by gender were

acids, appears to promote an inflammatory profile. The omega 6 fatty acids have

significatives.

also the same effect. It is well known that a chronic low-grade inflammation is

Conclusion

associated to several diseases, namely, diabetes. The follow-up of children and

The nutritional evaluation performed by the Medicine Laboratory is an effective

young people with Type 1 diabetes involves the periodic evaluation of their

tool to evaluate nutritional status and take corrective measures. Although there are

lipidic profile, however it is not done regularly the evaluation of the profile on the

many experiences in CONUT nutritional evaluation in hospitalized patients, we

concentration of different types of fatty acids.

think that this method is useful in primary care too.

Objective

To characterize, and compare, fatty acids profile in children with Type 1 diabetes

DOI: 10.1530/endoabs.49.EP401

and healthy children.

The authors observed that the ratio of omega 6/omega 3 fatty acids was higher in

the control population. Omega 6 levels were higher in the diabetic children

compared to the control group. Several other differences in free fatty acid

composition were observed.

EP402

Conclusion

Satiety, hunger and gastrointestinal hormones after a test meal in

Our findings showed higher levels of alpha-linolenic acid, EPA and DHA, as well

patients after gastric bypass surgery: an association with amino acids

as mono and polyunsaturated fatty acids in diabetic children. This fact is

Merel van den Broek¹, Loek de Heide¹, Nic Veeger^2,3, Marloes Emous⁵ &

attributed to pharmacological therapy and nutritional management of these

André van Beek⁴

children. These findings reinforce the importance of a precocious nutritional

¹Department of Internal Medicine, Medical Center Leeuwarden,

attention and intervention in the diabetic child treatment.

Leeuwarden, The Netherlands;²Department of Epidemiology, University of

DOI: 10.1530/endoabs.49.EP403

Groningen, University Medical Center Groningen, Groningen, The

Netherlands;³Department of Epidemiology, Medical Center Leeuwarden,

Leeuwarden, The Netherlands;⁴Department of Endocrinology, University

of Groningen, Groningen, The Netherlands;⁵Department of Surgery,

Medical Center Leeuwarden, Leeuwarden, The Netherlands.

EP404

Background

Sitagliptin use may reduce oral cancer risk in patients with type 2

Nutrition is essential in achieving maximal treatment success after bariatric

diabetes

surgery, and is simultaneously beneficial for avoiding long-term complications.

Chin-Hsiao Tseng

Dietary protein could have an important role, because of its positive effects on

National Taiwan University Hospital, Taipei, Taiwan.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

Objectives

Whether sitagliptin may affect oral cancer risk has not been investigated.

To analyze the prevalence of episodes of diabetic decompensation in patients

Methods

admitted in Orthopedic Surgery and Traumatology (OST) area.

The reimbursement database of the National Health Insurance in Taiwan was

Material and methods

used. Diabetic patients newly treated with sitagliptin

(nZ50033) or other

Descriptive analysis of patients admitted to OST Service who presented

antidiabetic drugs (nZ277038) within 1999-2008 were followed for oral cancer

abnormally high or decreased blood glucose levels according to the criterion of

until December 31, 2011. The treatment effect was estimated by Cox regression

the Orthopedic Surgeon who performed the consultation.

adjusted for propensity score (PS) or using PS weighting by inverse probability of

Results

treatment weighting approach.

From June 2008 to December 2014, 1486 consultations were sent to Internal

Results

Medicine, Cardiology or Endocrinology, regarding patients admitted to the OST

The overall hazard ratios suggested a

20% lower risk without statistical

area who had suffered some type of medical decompensation during admission.

significance. In tertile analyses, the PS-adjusted hazard ratios for the first

Of these patients, 437 (29.4%) had a documented history of DM. The reason for

(!6.53 months), second (6.53-14.00 months) and third (O14 months) tertile of

consultation was poorly controlled DM in 124 patients (8.3%), with 111 patients

cumulative duration were 1.382 (0.899, 2.125), 0.908 (0.566, 1.456) and 0.464

(89.5%) presenting hyperglycemia and 13 (10.5%) presenting hypoglycaemia.

(0.272, 0.789), respectively; and were 1.324 (0.864, 2.030), 0.871 (0.545, 1.394)

However, since the consultations were made by the Orthopedic Surgeon who

and 0.447 (0.263, 0.760), respectively, for PS-weighted.

requested it, after the initial evaluation of all these patients, the diagnosis of

Conclusions

poorly controlled DM was only considered in 108 patients (7.4% of the total

Sitagliptin may reduce oral cancer risk when the cumulative duration is O14

decompensated patients), since the rest, despite presenting glycemia above 125 on

months.

fasting, were considered controlled taking into account their particular clinical

situation. This implies an actual decompensation of 24.7% of patients with

DOI: 10.1530/endoabs.49.EP404

known DM.

Conclusions

DM is a cause of medical decompensation in 8.3% of patients admitted to OST.

One in four known diabetics had abnormal blood glucose levels.

Together with previous studies in which we concluded that approximately one in

EP405

six known hypertensive patients is decompensated during admission to surgical

Does a first-degree family history of diabetes impact placental vascular

areas, we suggest that an early evaluation of blood glucose and blood pressure

circulation and placental inflammatory response?

performed by Cardiology, Endocrinology or Internal Medicine could be

Jacob Bar

beneficial in terms of morbidity.

WMC and Tel Aviv University, Tel Aviv, Israel.

DOI: 10.1530/endoabs.49.EP406

Background

Experimental and clinical studies have demonstrated that heritability of diabetes

is associated with marked hyperinsulinemia, impaired endothelial function, and

inflammatory up-regulation. However, no studies have examined whether a

EP407

family history of diabetes effects placental maternal and fetal vascular circulation,

Episodes of poorly controlled diabetes in 173 patients admitted in

or placental inflammatory response. The present study was designed to investigate

Vascular Surgery

the impact of first-degree family history of diabetes (FHD) on placental vascular

María Molina Vega¹, Pilar Losada Mora³, Alfonso M Garrido Castro²,

circulation and inflammatory lesions.

Jose M García Almeida¹, Juan L Carrillo Linares², Miguel Damas Fuentes¹,

Methods

Carmen Rodríguez García¹ & Cristina Díaz Perdigones¹

402 pregnant women were divided into two groups according to presence of of

¹Endocrinology, Hospital Virgen de la Victoria, Malaga, Spain;²Internal

first-degree FHD: Group 1 included 255 subjects without FHD, Group 2 included

Medicine, Hospital Virgen de la Victoria, Malaga, Spain;³Cardiology,

145

subjects with FHD. Placental histology was performed for vascular

Hospital Virgen de la Victoria, Malaga, Spain.

circulation and inflammation lesions of maternal and fetal origin.

Results

Maternal vascular supply

(MVS) abnormalities of the placental bed was

Introduction

significantly higher in subjects with FHD, compared to group 2 (33% vs 52%,

Episodes of poorly controlled diabetes (DM) are one of the most frequent medical

P!0.005). Fetal vascular supply (FVS) abnormalities as well as maternal and

complications during hospitalization in the elderly population.

fetal inflammatory lesions (MIR and FIR) did not differed significantly between

Objetives

groups. In the logistic regression analysis, FDH is an independent and significant

To analyze the prevalence of episodes of diabetic decompensation in patients

predictor predictor of maternal vascular supply abnormalities (PZ0.001) and

admitted to the area of Vascular Surgery and Angiology (VS).

more than doubles risk of this outcome

(OR 2.084, 95% CI 1.337-3.247,

Material and methods

PZ0.001). Gestational diabetes incidence was significantly higher in subjects

Descriptive analysis of patients admitted to the VS Service who presented

with FHD.

abnormally high or decreased blood glucose levels according to the criteria of the

Conclusion

Vascular Surgeon who performed the consultation.

We demonstrated that first-degree family history of diabetes is associated with an

Results

increased rate of maternal vascular malperfusion abnormalities.

From February 2011 to December 2014, 173 consultations were sent to Internal

Medicine, Endocrinology or Cardiology regarding patients admitted to the VS

DOI: 10.1530/endoabs.49.EP405

area who had suffered some type of medical decompensation during admission.

Of these patients, 94 (49.1%) had a documented history of DM. The reason for the

consultation was ‘poorly controlled DM’ in 8 patients (4.6%) of whom had

hyperglycemia 4 (50%) and hypoglycemia, 4 (50%) as well as ‘control of vascular

risk factors’ in 18 (10.4%). However, after analysis of all patients, only 22

(12.7%) were diagnosed as decompensated DM in the discharge report. This

implies a real decompensation of 23.4% of patients with known DM.

EP406

Conclusions

Episodes of poorly controlled diabetes in 1486 patients admitted in

DM is a single cause of medical decompensation in 4.6% of patients admitted to

Orthopedic Surgery and Traumatology

VS. However, associated with decompensation of other vascular risk factors, one

María Molina Vega¹, Pilar Losada Mora³, Alfonso M Garrido Castro²,

out of four known diabetics had abnormal blood glucose levels.

Jose M García Almeida¹, Juan L Carrillo Linares², Miguel Damas Fuentes¹,

Together with the previous studies in which we conclude that approximately one

Carmen Rodríguez García¹ & Cristina Díaz Perdigones¹

in six known hypertensive patients is decompensated during admission to surgical

¹Endocrinology, Hospital Virgen de la Victoria, Malaga, Spain;²Internal

areas, we suggest that an early evaluation of blood glucose and blood pressure

Medicine, Hospital Virgen de la Victoria, Malaga, Spain;³Cardiology,

performed by Cardiology, Endocrinology or Internal Medicine could be

Hospital Virgen de la Victoria, Malaga, Spain.

beneficial in terms of morbidity and hospital stay, since previous studies

associate the diabetic uncontrol in patients admitted to Vascular Surgery to an

average stay 9 days superior compared to non-diabetics.

Introduction

Episodes of poorly controlled diabetes (DM) are one of the most frequent medical

DOI: 10.1530/endoabs.49.EP407

complications during hospitalization in the elderly population.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP408

5. Ulysses SAFEGUARD IT now reports all insulin incidents monthly which are

discussed as part of Quality Improvement. A monthly junior doctor insulin/

Postprandial triglyceride responses and insulin resistance among night

prescription error alert (Aug’15) now mandates all error discussions with

shift health care workers

Educational Supervisors helping them reflect/learn from mistakes (11 insulin

Kiranmala Keithellakpam, Aslam Mohd, Brijesh Mishra, Rajat Jhamb &

incidents in Jan/Feb’16 vs 19 in Nov/Dec’15).

Madhu Sri Venkata

Thus, over a relatively short period of 1 year, we have shown that our simple, yet

Diabetes, Endocrinology and Metabolism Centre, Department of Medicine,

helpful, safety innovations can be very effectively applied to reduce diabetes

University College of Medical Sciences, New Delhi, Delhi, India.

errors, improve staff knowledge & satisfaction. Our approach can be easily

replicated by any NHS Trust to improve overall safety in insulin and diabetes

Background

management.

A higher cardiometabolic risk has been reported in night shift workers. Post

DOI: 10.1530/endoabs.49.EP409

prandial hypertriglyceridemia

(PPHTg) is recognized as an independent

cardiovascular risk marker. Few studies have shown that acute disruption of

circadian rhythm is followed by significantly altered insulin secretion and lipid

tolerance.

Aim and objectives

In this study we compared the postprandial triglyceride (PPTG) responses to

standard oral fat meal between health care night shift workers and non- night shift

EP410

workers to ascertain if it contributes to cardiometabolic risk in them.

Heterozygote c.313delC (p.H105TfsX11) mutation of Glucokinase gene

Methods

in patient with Waardenburg syndrome type 1

20 health care night shift workers (R4 night duties/month for last one year), aged

Huseyin Anil Korkmaz

20-40 years with normal glucose tolerance (NGT) following a 75 g glucose

Division of of Pediatric Endocrinology, Balikesir Ataturk State Hospital,

OGTT and 20 age and sex matched non-night shift workers who had not done

Balikesir, Turkey.

night duty in the last one year or ever were recruited. Anthropometric, OGTT,

HbA1c (%), insulin, HOMA-IR, HOMA-b (%), fasting lipids parameters and

inflammatory markers (IL-6 & Hs CRP) were measured. PPTG responses were

Background

obtained after a standard fat meal given at 8 am, and sampling done every two

Waardenburg syndrome is known as an inherited disorder associated with

hours for next 8 hours, that is at 0, 2, 4, 6 and 8 h and compared between the two

sensorineural deafness and pigmentary abnormalities affecting the skin, hair, and

groups.

eye. There are rare case reports of Waardenburg syndrome with diabetes mellitus

Results

in the literature.

Night shift and non-night shift workers were matched for age (29.70G3.92 years

Case

vs 29.70G2.23 years) and sex (M:F 12:8 vs 12:8). The duration of night shift

A 9-years-old boy from consanguineous family was admitted to pediatric

exposure was relatively short

(4.2G3.3 years) among cases. There was no

endocrine department because of fasting and postprandial hyperglycemia. In the

significant difference between the two study groups with respect to anthropo-

medical history, it was learned that his aunt and uncle had brilliant blue iris,

metric, glycaemic, fasting lipids parameters or inflammatory markers. However,

fasting and postprandial hyperglycemia. On physical examination; Height:

2 h postprandial glucose in health care night shift workers was comparatively

131.5 cm (10-25p), Height SDS: K0.76, Weight: 28.9 kg (25-50p), Weight SDS:

higher than non-shift workers (103.8G18.53 mg/dl vs 91.5G19.96) though it just

K0.29, Body mass index: 16.72, Body mass index SDS:0.16. On physical

fell short of statistical significance (PZ0.50). PPTG measures - PPTG area under

examination, the patient with a brilliant blue iris had dystopia canthorum, skin

the curve (TG AUC) and TG peak values were comparable in both the groups.

hypopigmentation, synophrys, broad nasal root, hypoplasia alae nasi and mild

PPTG response showed significant positive correlation with fasting insulin and

sensorineural hearing loss. When our patient was evaluated for Waardenburg

HOMA-IR indicating insulin resistance, and HOMA-b (%) indicating insulin

syndrome clinical criteria, Waardenburg syndrome was diagnosed with

secretion in night shift health care workers but not in others. There was no

Waardenburg Consortium. Blood glucose was 148 mg/dl (75-100), insulin was

significant correlation of PPTG parameters with any other clinical, biochemical

19.1 IU/ml (2-18) and serum C-peptide level was 3.72 ng/ml (1.1-4.4). HbA1c

and inflammatory measures.

value was 6.2%, anti insulin antibody was 0.01 U/ml (0-0.5U), anti-GAD was

Conclusions

!1 U/ml (! 1 U/ml) and islet cell antibody was negative. When our patient was

Postprandial triglyceride burden is significantly associated with insulin resistance

evaluated for maturity onset diabetes of the young, MODY type 2 was diagnosed

in night shift workers even with a relatively short duration of night shift,

with heterozygote c.313delC (p.H105TfsX11) mutation in glucokinase gene.

DOI: 10.1530/endoabs.49.EP408

Repaglinide was started for controlling blood glucose levels and blood glucose

regulation was achieved.

Conclusion

We reported the case of a patient with Waardenburg syndrome accompanied by

glucokinase gene mutation, To the best of our knowledge, we believed the first

reported Waardenburg syndrome patient with these concomitant disorder.

Keywords: Waardenburg syndrome type

1; glucokinase gene; MODY;

EP409

hyperglycemia.

Improving safety in diabetes management and reducing insulin errors

DOI: 10.1530/endoabs.49.EP410

in hospital - practically achievable or a utopian fantasy?

Wyn Burbridge, Lynne Braycotton, Amar Puttanna, Mahender Yadagiri,

Dee Ilsley, Sagnik Mukhopadhyay, Karthik Munichoodappa & Parijat De

Sandwell & West Birmingham NHS Trust, Birmingham, UK.

EP411

42 insulin related incidents were reported within our Trust in 2014. Subsequent

GLIS3 rs7020673 and rs10758593 polymorphisms interact in the

Root Cause Analysis revealed numerous insulin errors, hyperglycemia

susceptibility for type 1 diabetes mellitus

mismanagement and highlighted significant deficits in diabetes knowledge

Daisy Crispim^1,2, Guilherme Duarte^1,2, Tais Assmann^1,2, Cristine Dieter^1,2,

amongst nursing staff. To address the above issues, new safety interventions were

Bianca de Souza^1,2 & Luis Canani^1,2

introduced and five key outcomes are:

¹Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre,

1. A new stand-alone insulin prescription chart introduced May’15 has seen

Rio Grande do Sul, Brazil;²Post-graduation Program in Medical Sciences:

insulin incidents decrease from 60 (Apr’14 - May’15) to 37 (June’15 - Apr’16).

Endocrinology, Faculdade de Medicina, Universidade Federal do Rio

2. A new, abbreviated DKA protocol and DKA App launched Aug’15 has shown

Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

significant clinical benefits and crucially, helped earlier discharge by 3.2 days

(audit of 40 patients (13 between May - July’15 and 27 between Aug’15

Background and Aims

- Mar’16).

The transcription factor Gli-similar 3 (GLIS3) plays a key role in the development

3. A mandatory new “6 steps to insulin safety online module” introduced for all

and maintenance of pancreatic beta-cells as well as in the regulation of Insulin

junior doctors & nurses (Dec’15) - 91 staff have already completed the module.

gene expression in adults. Accordingly, genome-wide association studies

Our CCG has recently introduced this successful module for care home staff.

identified GLIS3 as a susceptibility locus for type 1 diabetes mellitus (T1DM)

4. Daily Hypoglycemia email alerts and Precision (Abbott) web database

and glucose metabolism traits. Therefore, the aim of this study was to investigate

introduced to specifically target & educate problem wards. A number of changes

the association of the rs7020673 (G/C) and rs10758593 (G/A) single nucleotide

have been already made as a result.

polymorphisms (SNPs) in the GLIS3 gene with T1DM in a Brazilian population.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

Wolfram syndrome, rare neurodegenerative disorder, is known to be DIDMOAD

Frequencies of the rs7020673 and rs10758593 SNPs were analyzed in 503 T1DM

(diabetes insipidus, diabetes mellitus, optic atrophy and deafness). There are rare

patients (cases) and in 442 non-diabetic subjects (controls). Genotyping was

case reports of Wolfram syndrome with chronic renal failure in the literature.

performed using Real-Time PCR and TaqMan MGB probes (Thermo Scientific).

A 19-year-old male patient was admitted to our pediatric emergency department

Haplotypes constructed from the combination of these SNPs were inferred using a

because of headache, chest pain and diurnal and nocturnal enuresis. He had been

Bayesian statistical method.

diagnosed with diabetes mellitus at

13 years of age

(Plasma glucose was

Results

386 mg/dl, urinary ketone negative, normal blood gases, serum C-peptide level

GLIS3 rs7020673C allele frequency was 47.3% in T1DM patients and 45.1% in

0.1 pmol/ml (0.15-1.10) and HbA1c value of as 9.6%) and had received four

the non-diabetic group (PZ0.365), while the rs10758593A allele was present in

doses of regular insulin (0.9 U/kg per day) treatment. Anti-insulin antibody was

43.3% of cases and 41.1% of controls (PZ0.341). Genotype distributions of these

3 U (0-8 U), anti-GAD 0.4 U/ml (!1 U/ml), and islet cell antibody negative at

SNPs were in agreement with those predicted by Hardy-Weinberg Equilibrium in

the diagnosis. In addition, fundus oculi examination had demonstrated bilateral

controls (all PR0.05), and did not differ significantly between groups (PZ0.468

optic atrophy and no sign of diabetic retinopathy at 13 years of age. He was the

and PZ0.279, respectively). In addition, frequencies of rs7020673

and

sixth child of apparently healthy consanguineous parents, born at full-term by

rs10758593 SNPs did not differ between groups under dominant, recessive or

normal vaginal delivery. Family history disclosed that his uncle, aunt and sister

additive inheritance models (all PR0.05). However, frequency of three or more

had diabetes mellitus. Physical examination: weight: 31 kg (!3 percentile),

minor alleles of the analyzed SNPs in haplotypes was higher in T1DM patients

height: 136.5 cm (!3 percentile), blood pressure: 160/80 mmHg and pulse rate

compared to non-diabetic subjects (6.2 vs 1.6%; PZ0.001). Presence of R3

96/dk. He had bilateral blindness. High renal function tests (BUN:78 mg/dl,

minor alleles remained independently associated with risk for T1DM after

creatinine: 4.7 mg/dl), serum electrolytes (Na: 133.7 mmol/l, K: 4.2 mmol/l, Cl:

adjustment for T1DM high-risk HLA DR/DQ haplotypes, age and ethnicity (ORZ

103.7 mmol/l, serum calcium: 8.4 mg/dl serum phosphorus: 8 mg/dl) and high

3.68 95% CI 1.22 - 11.12). Moreover, levels of glycated hemoglobin were higher

parathyroid hormone (PTH: 321.63 pg/ml range, 15 to 65) suggested chronic

in T1DM patients carrying the rs10758593A allele than patients with the G/G

renal failure. Urinary ultrasound imaging disclosed small kidney size. Glomerular

genotype (8.9G2.1 vs 8.2G2.0; PZ0.038). In conclusion, our results indicate

filtration rate was calculated as 13 ml/min/1.73 m². Audiometric examination for

that the rs7020673 and rs10758593 SNPs interact in the predisposition for T1DM.

Wolfram syndrome revealed bilateral sensorineural hearing loss. A known

DOI: 10.1530/endoabs.49.EP411

homozygous mutation (Y508fsX541, c.1523_1524delAT) in exon 8 of WFS1 was

found in the proband.

We reported a case with Wolfram syndrome accompanied by chronic renal

failure. Early diagnosis and appropriate management for Wolfram syndrome

would prevent development of complications.

DOI: 10.1530/endoabs.49.EP413

EP412

Vitamin D level in naïve Type2 Diabetes Mellitus in Fayoum University

Hospital

Eman Fahmy¹ & Mohamed Mashahit²

¹Faculty of Medicine, Helwan University, Cairo, Egypt;²Faculty of

EP414

Medicine, Fayoum University, Cairo, Egypt.

Hypoglycaemia in hospital is associated with longer hospital stay and

decline of renal function

Ricardo Fonseca, João Sequeira Duarte, Carlos Bello, Ricardo Capitão,

Vitamin D deficiency has become a worldwide problem, although vitamin D

Francisco Sousa Santos, Catarina Roque, Cátia Ferrinhos &

deficiency had associated with increased insulin resistance, obesity and HbA1c in

Carlos Vasconcelos

patients with T2D.

Hospital Egas Moniz, CHLO, Lisbon, Portugal.

It is uncertain whether vitamin D deficiency causes diabetes or its due to

confounding. The active metabolite 1a,25-dihydroxyvitamin D3 may affect the

receptors of pancreatic b-cells and hence affect insulin secretion, also it may have

Background and aims

impact on insulin sensitivity.

Hypoglycemia is a common complication of diabetes treatment and it’s

Several trials revealed that vitamin D improved glycaemic control in T2DM

associated with poor outcomes. A link between severe hypoglycemia and renal

patients. However, the outcome of these trials often was not clinically relevant.

dysfunction was suggested. No studies evaluated the impact of hypoglycemia of

The aim of this study is to reveal to the relation between vitamin D and naïve type

inpatients in microvascular or macrovascular complications. The aim of our work

2 DM. This is a case control study that was conducted on 90 Egyptian diabetic

was to study the evolution of renal function between admission and final visit, and

subject of both gender their ages was between 25 to 70 years, Exclusion criteria

the impact of nephropathy in the presence of hypoglycemia in inpatients.

are, post-menopausal females, pregnant & lactating females, presence of mal-

Materials and methods

absorption disorders like Crohn’s disease, celiac disease and cystic fibrosis,

Retrospective, observational study of consecutive patients with type 1 (nZ13)

presence of any endocrinal disorder, presence of renal and hepatic disorders.

and 2 Diabetes (nZ85), admitted to the medical specialties ward between 2011

First group included 47 naïve type 2 diabetic patients (HbA1C above 7) including

and 2015 (nZ106 admissions), who had their capillary glycemia written in the

51.1% male diabetic and 48.9% female diabetic patient and 46 healthy control

medical record (nZ14410). We evaluated the renal function (glomerular filtration

including 47.8% male subject and 52.2%female subjects.

rate determined by CKD-EPI formula; glicemic variability

(STD) and

The 47-diabetic group their mean age was 40G0.5 years and their mean BMI was

albuminuria) at admission and at the final visit as outpatients. We used

28G3.6 while the 26 control subjects their mean ages is 42G7.8 years and their

descriptive statistics

(Median G std), t-test and non-parametric tests for

mean BMI was 28G3.8.

continuous variables and Chi-squared distribution for categorical variables.

Vitamin D level was 22.47G10.5 and 23.57G9.7 ng/ml in diabetic group and in

Results

control group respectively, there were no statistically difference when comparing

We report 56 admissions with hypoglycemias, which were compared to 50

vitamin D level between the two groups. In this study, we found a negative

admissions without hypoglicemias in the same period. There were no differences

correlation between vitamin D level and hyperglycemia.

in the distribution of gender (64% were females), age (60.9G1.6 years), diabetes

Also, we found a positive correlation between vitamin D level and age, while

type (12.2% were type 1) or diabetes duration (5.0G1.0 years). In patiens with

vitamin D level was negative correlated with Body mass index.

hypoglicemia we found significant differences in glicemic variability (84 vs

DOI: 10.1530/endoabs.49.EP412

56 mg/dl, P!0.01), in GFRe at admission (94 vs 83 ml/min/1.73 m², PZ0.03),

GFRe decline (25 vs 7 ml/min/1.73 m², PZ0.03), and longer hospital stay (13 vs

6 days, PZ0.006).

Conclusion

Despite having the known limitations of a retrospective study, and some

heterogenecity of the population mainly in diabetes duration, we found significant

associations between occurrence of hypoglicemia during hospitalization and

longer hospital stay and decline of renal function. Other study design would be

required to investigate if it is only a marker of fragility or if hypoglycemia may

EP413

have a role in progression of microvascular complications, as suggested by some

Association of wolfram syndrome with chronic renal failure in a boy

investigators.

Huseyin Anil Korkmaz

DOI: 10.1530/endoabs.49.EP414

Balikesir Ataturk State Hospital, Balikesir, Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP415

EP417

Could we prevent insulin induced lipohypertrophy in diabetic patients?

Epidemiological and clinical study of diabetes in immigrants from

Natalya Volkova, Ilya Davidenko, Maria Porksheyan, Alexander Zibarev &

Bangladesh in Athens versus Greek patients

Alexey Harlamov

Georgios Papadakis¹, Thomas Zambelis², Kostas Konstantopoulos³ &

Rostov State Medical University, Rostov-on-Don, Russia.

Stylianos Chatzipanagiotou⁴

¹STEPS Stoffwechselzentrum, Biel/Bienne, Switzerland;²Department of

Neurology, Aeginition Hospital, Athens, Greece;³Department of

Introduction

Hematology, Laikon University Hospital, Athens, Greece;⁴Department of

Lipohypertrophy (LH) is a chronic complication of diabetes mellitus that caused

Medical Biopathology, Aeginition Hospital, Athens, Greece.

by frequent subcutaneous injections of insulin. Nowadays, on the basis of results

of ultrasonography of subcutaneous fat prevalence of LH in diabetic patients is

still high.

Objectives

Design

Diabetes risk for Asians is related to a greater tendency to adiposity, which

The aim has been to develop prevention of insulin induced LH in diabetic

increases insulin resistance. Various studies have highlighted the fact that people

patients. This study was done on 140 diabetic patients who had been under the

from South Asia have a younger age of onset of diabetes, greater upper-body

treatment with insulin a mean 8 years. On first stage all patients were divided into

adiposity and lower body mass index (BMI) and higher risk compared to those

two groups. First - 117 patients with LH, second - 23 diabetics without LH.

from other nations. Greece has experienced a large wave of immigration from

Further, all known LH risk factors were statistically processed using Spearman’s,

Asian countries, especially Bangladesh. The purpose of this study was to explore

Gamma rank correlation coefficients. Results were statistically significant when

the ethnic differences and special needs that must be taken into account when

P!0.05. On second stage 65 patients from first group were divided into two

treating patients with different cultural background.

subgroups. First - 50 patients with LH and corrected risk factors, second (control)

Methods

- 15 diabetics with LH and uncorrected risk factors. Ultrasonography of

A total of 166 randomly selected immigrants with diabetes from Bangladesh were

subcutaneous fat were used in assessing new LH in these subgroups after 3 and

compared with 123 randomly selected Greek Caucasian patients with diabetes.

6 month.

Results

Patients from Bangladesh had a mean duration of living in Greece of 10.34G6.2

As a result, 10 factors from 23 were remained after statistic analysis on first stage.

years. The Bangladeshi group was younger compared with the Greek group

Statistically insignificant parameters were eliminated (PO0.05). On next stage, in

(44.05G8.1 vs 48.75G9.2 years old, PZ0.009) and had an earlier age at onset of

first subgroup only two patients (4%) had new LH, while in second - 9 diabetics

diabetes (39.3G7.3 vs 41.7G10.1 years old, PZ0.025). The reported duration of

(60%) had new pathologic areas of subcutaneous fat after 3 month. And in first

diabetes was lower in the Bangladeshi group (4.86G4.5 vs 7.34G6.21 years,

subgroup only 6 patients (12%) had new pathologic areas of subcutaneous fat,

P!0.05). The Bangladeshi group had a significantly lower BMI (24.19G3.3 vs

while in second - 12 diabetics (80%) had new LH after 6 month.

29.04G8.7 kg/m², PZ0.01), and waist circumference (92.2G8.9 vs 103.1G

Conclusions

15.7 cm, P!0.001). Bangladeshi group had a slightly worse, but not statistical

Nowadays, primary prevention of LH is necessary for diabetic patients under the

significant, glycemic control as compared with the Greek group (A1CZ7.74G

treatment with insulin. There were stated that only 10 risk factors strongly

1.6% vs 7.55G1.7%, PZ0.3). A significant number of Bangladeshis stated that

influence on LH progress. Correction of these risk factors doesn’t lead to

they rarely checked their self-monitoring blood glucose as compared with the

development of new subcutaneous fat pathological changes and could be used to

Greek group (1.26G2.6 vs 8.87G9.9 times per week, P!0.01). There were also

prevent LH in diabetic patients in clinical daily practice.

no significant differences between the two groups for most laboratory findings,

DOI: 10.1530/endoabs.49.EP415

although Bangladeshis had higher mean levels of glucose (190.3G72 vs 160.8G

81 mg/dl, PZ0.4), cholesterol (199.8G44.4 vs 178.86G44.9 mg/dl, PZ0.9),

LDL (129.3G33.2 vs 110.62G33.9 mg/dl, PZ0.8) and triglycerides (231.4G

213 vs 181.95G166 mg/dl, PZ0.07). In the Bangladeshi group, the mean HDL

level was significantly lower as compared with the Greek group (33.99G9.4 vs

44.05G10.43 mg/dl, PZ0.037).

Conclusions

Bangladeshi immigrants are less likely to engage self-care behaviors and have

worse glycemic control and less access to medication, laboratory test and

healthcare units.

DOI: 10.1530/endoabs.49.EP417

EP416

Relation between serum leptin concentration and insulin resistance

syndrome in patients with type 2 diabetes mellitus

Tamer Shebl, Nour El Dein Abd El Azeem & Hosny Abd El Kareem

Alazhar Univesity, Assuit, Egypt.

Type 2 diabetes mellitus is known for its morbidity and mortality all over the

globe. It has been demonstrated in recent studies that abnormal levels of

EP418

adipocytokines may contribute to insulin resistance and type 2 diabetes.

Vitamin D levels in newly diagnosed type I diabetes mellitus and

Objectives

relationship with organ specific autoimmune disorders

The aim of the present study was to assess the relation between serum leptin levels

Belgin Efe¹, Gonca Akdere² & Goknur Yorulmaz¹

and insulin resistance syndrome in type 2 diabetic patients.

¹ESOGU Faculty of Medicine Department of Endocrinology, Eskisehir,

Methods

Turkey;²ESOGU Faculty of Medicine Department of Internal Medicine,

Eighty persons were enrolled in this study and were divided into two groups.

Eskisehir, Turkey.

Twenty healthy persons as a control group and 60 patients with type 2 diabetes

mellitus as a disease group. The disease group were further divided into those who

have evidence of metabolic syndrome (30 patients), and those who do not (30

Based on the effects of Vitamin D on immune system it has been suggested that

patients). Parameters like age, sex, anthropometric measurements and

vitamin D may play a role in the pathogenesis of type I diabetes mellitus (T1D)

biochemical indicators such as fasting and post prandial blood sugar, HbA1c,

and other organ specific autoimmune disorders. In our study, we aimed to show

lipid profile, leptin and fasting insulin were determined.

the effect of Vitamin D deficiency in the development of newly diagnosed T1D

Results

and other autoimmune disease that may associated with T1D such as autoimmune

Higher Leptin and insulin levels were observed in patients with metabolic

thyroid disease (ATD), celiac disease, Addison’s disease, vitiligo and atrophic

syndrome (P!0.001).

gastritis. In addition to 50 newly diagnosed T1D patients and 60 healthy controls,

Conclusion

we evaluated the data of the formerly diagnosed 50 T1D patients. The frequency

High serum leptin is a good indicator and could provide a minimally-invasive

of vitamin D deficiency in newly diagnosed T1D patients was found 88%. 30% of

marker for early detection of the insulin resistance syndrome.

these patients were anti parietal cell antibody (APA) positive which is marker for

Keywords

pernicious anemia,

24% of had ATD, 10% of was positive for anti-tissue

leptin concentration; insulin resistance syndrome; type 2 diabetes mellitus.

transglutaminase IgA which is marker for celiac disease and 2% of had vitiligo.

DOI: 10.1530/endoabs.49.EP416

Levels of 25(OH)D were statistically significant lower in newly diagnosed T1D

patients with positive APA than patients with negative APA. Frequency of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

vitamin D deficiency was 66.7% in healthy controls and 84% in formerly

The aim

diagnosed T1D patients. When we considered all T1D patients, we found the

To evaluate the efficacy of Nucleo CMP Forte

(Cytidine

- 5’- disodium

frequency of ATD was 25%, frequency of positive APA was 28%, frequency of

monophosphate and Uridine - 5’- trisodium triphosphate) in the combined

positive anti-tissue transglutaminase IgA was 10% and frequency of vitiligo was

treatment of patients with DPNP.

2%. We found that ATD and predisposition of celiac disease were much frequent

Methods

in T1D patients than healthy controls. Vitamin D levels were found lower; in

It was examined 59 (41-79 years old) patients with type 2 DM and DPNP. They

patients with T1D than healthy controls; when we evaluate all subjects we found

were compared into two groups: A - 30 patients received standard treatment, B -

that patients with ATD had lower vitamin D levels than patients without ATD and

29 diabetics additionally were taken Nucleo CMP Forte (1 capsule three times a

also patients with ATD and positive APA had lower vitamin D levels than patients

day). Patients filled questionnaire of life quality EQ-5D-3L

(Ukraine 2004,

without ATD and negative APA.

EuroQol) on the first and tenth day of treatment. We used non-parametric test c²

DOI: 10.1530/endoabs.49.EP418

to evaluate efficacy of therapy. Significance was set at P!0.05.

Results

All patients revealed positive changes after 10 days of treatment. Thus, the

problems with walking decreased in 16.6% of the group A patients (c²Z1.164.

PO0.05) and 33.3% (c²Z6.171, P!0.05) of the group B, the relief in

performing of daily activity was marked by 25% (c²Z2.286, PO0.05) and 50%

(c²Z2.859, PO0.05) of ones respectively, pain/discomfort bothered less than

25% (c²Z4.267, P!0.05) patients of the group A and 33.3% (c²Z6.171,

EP419

P!0.05) of the group B, anxiety/depression decreased in 58.3% (c²Z6.063,

Is secreted frizzled-releated protein 4 (SFRP-4) a possible biomarker

P!0.05) and 66.7% (c²Z6.954, P!0.05), respectively.

for b cell dysfunction?

Conclusion

Suleyman Baldane¹, Suleyman Ipekci¹, Sedat Abusoglu², Ali Unlu² &

Patients of both groups noted the positive effect of treatment. Usage of Nucleo

Levent Kebapcilar¹

CMP Forte in the combined treatment of patients has more expressed positive

¹Division of Endocrinology and Metabolism, Selcuk University Faculty of

influence on problems with walking.

Medicine, Konya, Turkey;²Department of Biochemistry, Selcuk University

DOI: 10.1530/endoabs.49.EP420

Faculty of Medicine, Konya, Turkey.

Introduction

SFRP-4 is a recently described inflammatory cytokine influencing insulin

secretion from human b cells as an extracellular modulator of Wingless (Wnt)

pathway. The aim of this study is to compare serum SFRP-4 levels in patients with

normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2

diabetes (T2DM), and to investigate its relation with other parameters.

Methods

The study included 152 patients who applied to the endocrinology outpatient

EP421

clinic of our hospital. Eighty-two patients who had history of T2DM constituted

Effect of glucose ingestion on serum fractalkine levels in healthy

the T2DM group. Patients who underwent OGTT within the last three months

subjects and diabetic patients

were categorized in either IGT (nZ34) or NGT (nZ36) groups according to their

Suleyman Baldane¹, Ismail Can Kendir², Suleyman Ipekci¹, Gulsum Tekin³,

test results. All patients provided blood samples between 08 am and 09 am

Ali Unlu³ & Levent Kebapcilar¹

following overnight fasting. Fasting insulin, fasting glucose, HbA1c and SFRP-4

¹Division of Endocrinology and Metabolism, Selcuk University Faculty of

levels were measured.

Medicine, Konya, Turkey;²Department of Internal Medicine, Selcuk

Results

University Faculty of Medicine, Konya, Turkey;³Department of

T2DM group had significantly higher serum SFRP-4 levels compared to BGT and

Biochemistry, Selcuk University Faculty of Medicine, Konya, Turkey.

NGT groups (0.282 ng/ml vs

0.183 ng/ml, PZ0.001; and

0.282 ng/ml vs

0.170 ng/ml, PZ0.004, respectively). In comparison of BGT and NGT groups,

although serum SFRP-4 levels were higher in BGT group, the difference was not

Introduction

statistically significant (0.183 ng/ml vs 0.170 ng/ml, PZ0.630). SFRP-4 level

Current studies suggest that fractalkine (FKN) could be a pathogenic factor

showed significant positive correlation with fasting glucose (rZ0.274, PZ0.001)

associated with adipocyte dysfunction and type 2 diabetes (T2DM) and have

and HbA1c (rZ0.291, PZ0.002) levels.

shown that FKN serum levels are increased in T2DM patients. The aim of this

Conclusion

study was determined as evaluating the change of FKN levels that will occur with

Progressive b cell dysfunction is observed during the normal course of T2DM,

oral glucose tolerance test (OGTT).

and inflammatory cytokines are held responsible. Recent studies have

Methods

demonstrated the association between increased SFRP-4 expression on b cells

The study included 67 patients to whom OGTT was applied. The patients with the

and reduced insulin release. Additionally, studies have found an association

history of diabetes mellitus, malignity or inflammatory disease were excluded. All

between serum SFRP-4 levels and high fasting glucose level and impaired insulin

subjects were given 75 g of glucose orally after an overnight fasting and blood

sensitivity in non-diabetic individuals. We found increased serum levels of SFRP-

samples were taken for glucose and FKN levels at 0 and 120 min. According to

4 in patients with T2DM in our study, and SFRP-4 level was positively correlated

OGTT results, the patients were divided into the groups of NGT (nZ33) and

with fasting glucose and HbA1c levels in the whole study group. We think our

newly diagnosed T2DM (nZ34).

results support the idea that increased plasma SFRP-4 levels may be a good

Results

indicator of b cell dysfunction and insulin resistance.

The basal level of FKN (OGTT at 0 min) was found to be significantly higher in

DOI: 10.1530/endoabs.49.EP419

T2DM group than NGT group (0.374 ng/ml vs 0.259 ng/ml, PZ0.012). The FKN

level at 120 min of OGTT was significantly higher also in T2DM group compared

to NGT group (0.367 ng/ml vs 0.229 ng/ml, PZ0.001). No significant changes in

FKN levels during OGTT were observed in both T2DM and NGT groups (0 and

120 min change) (0.374 ng/ml vs 0.367 ng/ml, PZ0.433 and 0.259 ng/ml vs

0.229 ng/ml PZ0.06, respectively). A significant positive correlation was noted

between the levels of FKN and glucose at

120 min of OGTT (rZ0.331,

PZ0.006).

Conclusion

EP420

Acute hyperglycemia or food intake is known to lead to an increase in circulating

The clinical efficacy of the nucleo CMP forte usage in the combined

levels of many inflammatory cytokines such as IL-1, IL-6, TNF-a. Fractalkine

treatment of diabetic peripheral neuropathy

(FKN) is a recently defined inflammatory cytokine. The results of our study, there

Larysa Martynyuk, Nadiya Makarchuk, Mykola Shved & Lesia Mykhailiv

was no change of serum FKN levels during OGTT in T2DM and NGT patients but

I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine.

there was a significant correlation between the levels of FKN and glucose at

120 min of OGTT. We believe that long-term studies with broad participation and

serial measurements are needed to determine the role of FKN in the pathogenesis

Introduction

of T2DM.

The protocols of medical care of diabetic peripheral neuropathy (DPNP) are

developed but positive effect cannot be achieved in all patients. New medications

DOI: 10.1530/endoabs.49.EP421

in DPNP have to be studied.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP422

Conclusion

Prediabetes and T2D were detected in the majority of patients undergoing

Epidemiological features of type 1 diabetes in children and adolescents

coronary angiography without previously known glycemic disorders. Therefore,

in the Republic of Armenia

HbA1c should be determined in all patients hospitalized for possible CAD,

Yelena M Aghajanova, Gayane M Bayburdyan, Lusine V Navasardyan,

regardless of the history for diabetes.

Renata L Markosyan & Lusine G Kalantaryan

Yerevan State Medical University, Yerevan, Armenia.

DOI: 10.1530/endoabs.49.EP423

Background

Diabetes is the most prevalent chronic metabolic disorder in children and

adolescents, and incidence rates for both type-1 and type-2 diabetes are increasing

worldwide. In recent years, the number of patients with type 1 diabetes is

increasing mainly due to children under 5-years-old.

Objective

To study the epidemiological indicators of T1DM among children of the Republic

EP424

of Armenia (RA) from 2007 to 2016. Methods: Retrospective analysis of the

The relation between type II diabetes and chronic depression in

Republican Children’s Endocrinology Center database using conventional

primary care practice in Jordan

statistical methods.

Abdallah Alzoubi, Renad Abu Naser, Ady Khasawneh & Aws Khasawneh

Results

Jordan University of Science and Technology, Irbid, Jordan.

During the period 2007-2010 in Armenia there was a relatively stable incidence

of diabetes in children 0-18 years: 7.1 in 2007, 6.45 in 2008, 6.3 in 2009 and 6.8

in 2010 (per 100 000 child population), while during 2010-2016 period increased

Diabetes is a major health problem that affects 8.5% of adults worldwide,

incidence is seen (6.7 in 2011, 9.4 in 2012, 8.7 in 2013, 9.99 in 2014, 10.69 in

and 13.2% of adults in Jordan. Studies suggest a bidirectional relationship

2015). The study of age-specific morbidity in children with T1DM in RA showed

between diabetes and chronic depression. Diabetic patients are twice as

that the maximum incidence in different years was at the age of 5-9 or 10-14

likely to suffer from depression that is symptomatically worse when

years. According to the Republican Children’s Endocrinology Center data

compared to nondiabetic individuals. Depressed diabetics suffer from poor

rejuvenation of type 1 diabetes can be traced. Mean age of patients in 2007 was 11

glycemic control and increased risk of diabetes complications. Because little

years. In 2014 mean age was 8.9 and 9.8 in 2016. The incidence rate in children of

is known about the bidirectional relationship between diabetes and chronic

younger age group (0-4 years) increased from 2.24 in 2007 to 5.05 in 2010, 7.14

depression in Jordan, we screened for depressive disorders among diabetic

in 2014 and 5.8 in 2016 (per 100 000 child population).

patients using the Patient Health Questionnaire-9 (PHQ-9) and screened for

Conclusions

diabetes among depressed individuals by measuring their HbA1c, in a cross-

In RA an increased incidence of type 1 diabetes among children and adolescents

sectional study design. A total of

146 diabetic patients (74 males, 72

is seen. The highest incidence occurs in the age groups 5-9 and 10-14 years.

females) participated in the study, with a mean age of 56G8.5 years. Almost

Further studies are needed to look into the cause of these changes.

60% of participants were uncontrolled for diabetes (HbA1c R 7%) with a

DOI: 10.1530/endoabs.49.EP422

mean HbA1c of 8.9%G1.7 and a mean PHQ-9 score of 6.2G5.5. The

remaining 40.4% were controlled for diabetes (HbA1c % 7%) with a mean

HbA1c of 6.1G0.6 and a mean PHQ-9 score of 6.7G4.5. The prevalence of

chronic depression (PHQ-9 score R 10) among diabetic patients was 27.4%.

No correlation was found between PHQ-9

scores and HbA1c levels

(Spearmen’s rZK0.03, PZ0.75). Additionally, 20 depressed patients were

recruited from the psychiatry clinic with a mean age of 41.7G8.3 years, and

were then screened for diabetes by measuring HbA1C levels. None of these

EP423

was found to be diabetic, with a mean HbA1C of 5.4%G0.4. In conclusion,

High incidence of glucose metabolism disorders in patients undergoing

our results thus far deny a correlation between depression and diabetes.

coronary angiography without history of diabetes

However, our future plan of examining the effect of treating depression on

Stavroula A Paschou¹, Sotirios Kiokas², Grigorios Avdikos²,

glycemic control and diabetes complications, and the effect of improving

Efstathios Lazaris² & Andromachi Vryonidou¹

glycemic control on the severity of depression, might improve our

¹Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital,

understanding of this relationship.

Athens, Greece;²2nd Department of Cardiology, Hellenic Red Cross

DOI: 10.1530/endoabs.49.EP424

Hospital, Athens, Greece.

Introduction

The aim of this study was to investigate the incidence of glycemic disorders in

patients undergoing coronary angiography with no prediagnosed type 2 diabetes

(T2D), as well as the association of the glycemic status with the extent of the

coronary artery disease (CAD).

EP425

Patients and methods

Anti-islet cell antibodies in a sample of Egyptian females with

We studied 170 consecutive patients (134M/36W), 63.9G13.1 (23-95) years old,

gestational diabetes and its relation to development of type 1 diabetes

with not known T2D, who underwent coronary angiography. HbA1c was

mellitus

measured and patients were classified into 3 groups accordingly: i) normal

Hanan M Amer¹, Rania S Abd elbaky¹, Merhan S Nasr¹, Laila M Hendawy¹,

HbA1c!5.7%, ii) prediabetes HbA1c 5.7-6.4%, and iii) T2D HbA1c R6.5%.

Mohamed O Taha² & Wessam A Ibrahim¹

The presence of other risk factors for CAD was recorded, while the extent of CAD

¹Ain Shams University Division of Endocrinology and Diabetes, Cairo,

was examined. Vessel disease (VD) was defined when stenosis was O70%.

Egypt;²Ain Shams University Division of Gynecology and Obstetrics,

Results

Cairo, Egypt.

From the total of 170 patients, 19.4% (33/170) presented normal HbA1c, 17.6%

(30/170) prediabetes and 63% (107/170) were diagnosed with T2D. Patients with

normal HbA1c were 60.5G16.7 years old, with BMI 29.1G5.2, 18.2% (6/33)

Background

were women, 48.5% (16/33) had hypertension, 36.4% (12/33) dyslipidemia,

Gestational diabetes mellitus is any degree of glucose intolerance with first

while 21.2% (7/33) had history of CAD. Of these, 33.3% (11/33) showed no VD,

diagnosis during pregnancy; it affects 3-10% of pregnancies. The presence of

33.3% (11/33) one VD 21.2% (7/33) two VD, 6% (2/33) three VD and 6% (2/33)

diabetes-related autoantibodies has shown to be able to predict the development

left main along with another one VD. Patients with prediabetes were 65.9G11

of type 1 diabetes before hyperglycemia arises.

years old, with BMI 29.6G5.1, 6.7% (2/30) were women, 63.3% (19/30) had

Aim of work

hypertension, 43.3% (13/30) dyslipidemia and 20% (6/30) had history of CAD.

To recognize the prevalence of islet cell antibodies among a sample of Egyptian

Of these, 30% (9/33) showed no VD, 30% (9/30) one VD, 6% (5/30) two VD and

females with gestational diabetes and its possible relation of development of Type

23.3% (7/33) three VD. Patients with T2D were 64.4G12 years old, with BMI

1 diabetes within 1 year.

23.8G2.6, 26.2% (28/107) were women, 69.2% (74/107) had hypertension,

Design and methodology

52.3% (56/107) dyslipidemia, while 24.3% (26/107) had history of CAD. Of

Our cross sectional study was conducted on 150 Egyptian pregnant females with

them, 42.1% (54/107) showed no VD, 27.1% (29/107) one VD, 17.8% (19/107)

gestational diabetes aged

19-39 years diagnosed by 75-g 2-h oral glucose

two VD, 11.2% (12/107) three VD and 1.9% (2/107) left main along with another

tolerance test. All females were subjected to full history, thorough clinical

one VD.

examination and laboratory measurement of anti-islet cell antibodies, those

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

females with positive antibodies were followed up 6 months and 1 year after

antidiabetic medications, insulin, herbal substances. However, in our history, we

delivery for their fasting insulin, fasting blood glucose and 2 h post prandial

learned that pregabalin and alfalipoic acid were given to the patient considering

levels.

neuropathic pain and proton pump inhibitors for dyspeptic complains. Physical

Results

exam revealed a healthy-appearing middle-aged male with BMI of 21.4. Initial

The prevalence of pregnant females with gestational diabetes having positive anti

tests showed low venous blood glucose

(44 mg/dl), high insulin levels

islet cell antibodies was (44%), the prevalence of females diagnosed to have

O1000 mIU/ml, C-peptide 15.6 ng/ml. To rule out pancreatic or extrapancreatic

diabetes mellitus was (37.88%) 6 months and (51.52%) 1 year postpartum.

insulinoma; abdominal ultrasound, abdominal computer tomography scan,

Conclusion

abdominal MRI and Ga-68 DOTATATE PET/CT was performed. The results

Gestational diabetes can be of type 1 diabetes due to islet cell antibodies and not

did not show an evidence of insulinoma. Intra-arterial calcium stimulation test

only type 2 diabetes due to increased insulin resistance

was also performed to rule out insulinoma but the results were inconclusive. Anti-

Keywords

insulin antibody test was performed for the differential diagnosis and it was

Pregnancy; Gestational diabetes; anti-islet cell antibodies; Type

1 diabetes;

positive. The symptoms associated with low glucose levels and high serum insulin

Type 2 diabetes; Insulin resistance

levels along with positive anti-insulin antibody lead us to the diagnosis of insulin

DOI: 10.1530/endoabs.49.EP425

autoimmune syndrome. According to the current literature suggesting the

relationship between insulin autoimmune syndrome and alpha lipoic acid and

proton pump inhibitors we discontinued that drugs and started alpha glucosidase

treatment and nutritional management. During the follow up the patient did not

report a hypoglisemic episode.

Conclusion

EP426

Insulin autoimmune hypoglycemia is a rare cause of endogenous hyperinsuli-

A retrospective analysis of the impact of new diagnostic criteria for

nemic hypoglycemia. It is a condition that should be kept in mind in patients who

gestational diabetes mellitus on the endocrinology service at a tertiary

have very high levels of insulin and who can not detect a specific focus through

hospital

imaging modalities.

Thaw Dar Htet¹, Alice Lam², Iouri Banakh², Rumes Sriamareswaran¹,

DOI: 10.1530/endoabs.49.EP427

Samuel Wu¹, Jasmina Felsinger¹, Kati Mattheisson³ & Elisabeth Nye¹

¹Department of Medicine, Peninsula Health, Melbourne, Australia;

²Department of Pharmacy, Peninsula Health, Melbourne, Australia;

³Department of Endocrinology, Peninsula Health, Melbourne, Australia.

EP428

Background

Incidence estimate of type 1 Diabetes in Youth in Dhaka

The prevalence of gestational diabetes mellitus (GDM) may increase with the

Ana Balsa¹, Bedowra Zabeen², Graham Ogle³, Samin Tayyeb² &

implementation of revised diagnostic criteria

(as recommended by the

Kishwar Azad⁴

International Association of the Diabetes and Pregnancy Study Groups) aimed

¹Serviço de Endocrinologia Centro Hospitalar Baixo Vouga, Aveiro,

at identifying pregnancies at increased risk of adverse perinatal outcomes. There

Portugal;²Department of Changing Diabetes in Children, Bangladesh

are clear implications for health-care services in terms of resources and the

Institute of Research and Rehabilitation of Diabetes, Endocrine and

associated cost-benefit relationship. Our study analysed the impact on clinic

Metabolic Disorders, Dhaka, Bangladesh;³International Diabetes

visits, the initiation of insulin treatment and fetal and maternal outcomes.

Federation Life for a Child Program, Sydney, Australia;⁴Bangladesh

Methods

Institute of Research and Rehabilitation in Diabetes, Dhaka, Bangladesh.

A retrospective cohort study was conducted. The medical records of patients with

GDM referred to Diabetes in Pregnancy Clinic were reviewed, comparing two

12-months periods: March 2012 to February 2013 (period 1) and March 2015 to

Introduction

February 2016 (period 2), before and after implementation of the new criteria.

Analysis of epidemiologic patterns in diabetes helps with understanding of

Maternal and fetal outcomes were analysed for six months of each period.

etiology, natural history and current and future needs. Bangladesh is a low-

Results

middle-income, densely populated country where there is limited information

165 GDM patients attended the clinic in period 1 vs 323 patients in period 2.

regarding incidence of childhood diabetes.

Insulin treatment increased significantly in period

2, from

34.2

53.1%

Aim

(PZ0.002). The mean number of Endocrinologist consultations (government

To assess the type of diabetes in children and young adults in Dhaka, Bangladesh,

billed) increased from 3.6 to 4.2 (PZ0.006) and with a Diabetic Educator from

from July 2011 until June 2016, and estimate minimum incidence of type 1

1.6 to 1.8 (PZ0.006). The rate of caesarean sections (CS) in patients with GDM

diabetes (T1D).

increased from 31.1% in period 1-47.0% in period 2 (PZ0.038). The number of

Methods

neonates grouped as “Small for Gestational Age” (SGA) increased in insulin-

Retrospective study using clinical records from Diabetic Association of

treated patients in period 2 vs period 1 (17 vs 0, P!0.001) but the number of

Bangladesh (BADAS) clinics in Dhaka and affiliated satellite centers in other

“Large for Gestational Age” neonates was similar (6 vs 5, PZ1).

districts. Subjects under

25 years

(y) diagnosed in the study period were

Conclusion

identified. Diabetes type was classified according to clinical evaluation.

The new GDM diagnostic criteria have impacted on existing health-care

Demographic information was obtained from the 2011 population census and

resources with a corresponding increase in costs with minimal evidence of

extrapolated using the estimated growth rate. Incidence was calculated for the

clinical benefits. Hospital systems will need to plan for the increased demands on

area surrounding the main clinics (Dhaka District) to minimize any ascertainment

pregnancy-related diabetes services.

bias.

DOI: 10.1530/endoabs.49.EP426

Results

Were identified 2347 subjects. Type of diabetes was more fully characterized for

those !18 years (1634 cases), and showed 1437 (87.9%) T1D, 151 (9.2%) type 2,

23 fibrocalculous pancreatic diabetes (1.4%), 5 (0.3%) neonatal, 18 (1.1%) other

types. For T1D incidence estimation a total of 526 subjects were ascertained. The

mean Dhaka district incidence rate for subjects !25 y was 1.24/100 000 per y

EP427

(males 0.92, females 1.71) and 0.96/100 000 for !15y (males 0.63, females 1.55)

Insulin autoimmune syndrome-a case report

. By age group, incidence/100 000 was 0.27 (0-4y), 0.60 (5-9y), 2.46 (10-14y),

Elif Sevil Alaguney, Belgin Efe, Goknur Yorulmaz, Berat Acu &

1.86

(15-19y), 1.44 (20-24y). No secondary ascertainment could be done, but

Insaf Durmus

ascertainment in Dhaka Division was estimated to be at least 95%.

Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey.

Discussion

The support to BADAS by the Changing Diabetes in Children and IDF Life for a

Child Programs have centralized care and permitted tracking of diabetes cases in

Introduction

young people in Bangladesh. T1D is commonest, but other forms occur which

Hypoglycemia is a medical emergency that can have many different causes in

could benefit from different management: further typology studies are warranted.

etiology. Autoimmune hypoglycemia in patients with very high insulin levels

T1D had a female preponderance. Peak T1D onset is at 10-14 y, as in developed

should also be considered in the differential diagnosis.

nations.

Case

A 50-year-old man was admitted to our clinic for investigation and treatment of

DOI: 10.1530/endoabs.49.EP428

hypoglycemic episodes. He did not have any evidence for the use of oral

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP429

EP431

Is thiol/disulfide homeostasis related to parity and gravidity in

Vascular dementia and type 2 diabetes: incidence and outcomes in

gestational diabetes?

elderly patients in a ten year study

Faruk Yildiz¹, Cemile Bicer², Mahmut Senyurt¹, Murat Alisik³

Nuria Mu

˜ oz-Rivas¹, Francisco Javier del Can˜ izo-Gómez1,

& Ayse Carlioglu¹

Manuel Méndez-Bailón², Ana López-de Andrés⁴, José María de

¹Regional Training and Research Hospital, Erzurum, Turkey;²Faculty of

Miguel-Yanes³, Valentín Hernández-Barrera⁴, Javier de Miguel-Díez³

Medicine, Yildirim Beyazit University, Ankara, Turkey;³Ataturk Training

& Rodrigo Jiménez-García⁴

and Research Hospital, Ankara, Turkey.

¹Hospital Universitario Infanta Leonor, Madrid, Spain;²Hospital Clinico

san Carlos, Madrid, Spain;³Hospital Universitario Gregorio Mara

˜ ón,

Madrid, Spain;⁴Universidad Rey Juan Carlos, Madrid, Spain.

Purpose

The purpose of this study was to evaluate the relation gestational diabetes mellitus

(GDM) and the thiol/disulfide balance, used as a marker of oxidative stress, by

Background

measuring that exchange using a novel technique.

To describe trends in the incidence and outcomes for vascular dementia in elderly

Material/Methods

patients with and without type 2 diabetes (T2DM) in Spain between 2004 and

Thirty one subjects diagnosed with GDM and 30 healthy pregnant women were

2013.

included in the study. Thiol/disulfide homeostasis concentrations were measured

Methods

by a newly developed method in this study. After native thiol, total thiol and

We used National Hospital Discharge Data to select all patients aged 70 years or

disulfide levels were determined; measures such as disulfide/ native thiol,

over discharged from hospital with a vascular dementia primary diagnosis.

disulfide/total thiol, and native thiol/total thiol were calculated.

Discharges were grouped by diabetes status (T2DM or non-diabetic). Incidence

Results

was calculated overall and stratified by diabetes status and age groups. We

Fasting blood glucose (FBG) levels (P!0.001), 50-g glucose load values (OGTT

analyzed diagnostic and therapeutic procedures, patient comorbidities, infectious

50)

(P!0.001), parity (0.002) and gravidity (PZ0.005) were significantly higher

complications, length of hospital stay and in-hospital mortality (IHM).

and native thiol (P!0.001) and total thiol levels (P!0.001) were significantly

Results

lower in patients with GDM compared to control subjects. We found negative

We identified a total of 170.607 admissions for vascular dementia (34.3% with

correlations between native and total thiols and FBG and OGTT 50. Parity and

T2DM). The adjusted incidence was higher among people with T2DM over the

gravidity had a significantly negative correlation between the disulfide, the

study period. We found a higher incidence in men than women in all years

disulfide/native thiol ratio, the disulfide/total thiol ratio, had a positive correlation

studied. T2DM was positively associated with vascular dementia hospitalization

between the native thiol/total thiol ratio. Low native thiol and total thiol levels in

(IRR 2.14, 95% CI). Mean age at admission was higher than 80 years for all

patients with GDM were found to be independent of age, gestational weeks and

groups and more than 70% has a Charlson Comorbidity Index (CCI) R2.

bmi in multivariate regression analyse.

Pneumonia was significantly associated with a higher mortality (OR: 2.59; 95%

Conclusion

CI 2.52-2.67). We found that percutaneous endoscopic gastrostomy (PEG) was

It can be concluded that oxidative stress is increased in patients with GDM, can

associated to lower IHM (OR: 0.37, 95% CI 0.31-0.45) while parenteral nutrition

play a pathophysiological role in the development of GDM and this increase is not

had the opposite effect

(OR: 1.29,

95% CI 1.18-1.41). Diabetes was not

associated age, gestational weeks and bmi. However, studies with larger sample

associated with a higher IHM (OR: 0.99, 95% CI 0.93-1.06). For the entire

sizes are needed in this area.

sample, time trend analyses showed a significant decrease in mortality in patients

DOI: 10.1530/endoabs.49.EP429

admitted for vascular dementia (OR: 0.98, 95% CI 0.97-0.99).

Conclusions

Incidence rates were higher in T2DM patients. Men have significant higher

incidence rates than women. Pneumonia and parenteral nutrition were associated

with mortality while PEG was associated to survival. The presence of diabetes is

not associated with a higher IHM during admission with vascular dementia.

DOI: 10.1530/endoabs.49.EP431

EP430

Endocrine factors associated with postprandial hypoglycaemia in

patients with cystic fibrosis: a pilot study

Yasir Elamin¹, Rachel Crowley^1,2, ED Mckone¹, Patrick Twomey^1,2,

Siobhan Hatton¹, Julie Martin-Grace¹ & S Kearns¹

EP432

¹St. Vincent’s University Hospital, Dublin, Ireland;²University College

Study of the glycemic control in the hospitalized patient

Dublin School of Medicine, Dublin, Ireland.

Lucía Vera Pacheco², Lorena Rentero Redondo¹, Carles Iniesta Navalón¹,

Amparo Meoro Avilés¹, María Teresa Gallego García¹,

Postprandial hypoglycaemia in patients with cystic fibrosis (PWCF) is frequently

Cristina Del Peso Gilsanz¹, María Amparo Egea Valera¹,

reported but poorly understood. The aim of this pilot study was to investigate the

Noelia Victoria García-Talavera Espín¹ & M. Bienvenida Gómez Sánchez¹

aetiology of postprandial hypoglycaemia in PWCF. Serum cortisol, insulin and

¹University Hospital Reina Sofía, Murcia, Spain;²University Hospital

C-Peptide were measured at the 2 hour timepoint of the annual glucose tolerance

Rafael Mendez, Lorca, Murcia, Spain.

test in 32 PWCF not known to have CF-related diabetes. Hypoglycaemia was

defined as glucose ! 3.3 mmol/l. Patients were classified as Normal glucose

Objective

tolerance (NGT; nZ17), Post prandial hypoglycaemia (PPH; 6) and Abnormal

To evaluate the degree of compliance of the glycemic objectives in non-critic-

glucose tolerance (AGT; 9-3 CF related diabetes, 4 impaired fasting glucose and

hospitalized patient and determinate the factors associated to the lack of

2 impaired glucose tolerance). There was a difference in insulin level at 2 hours

compliance of the aforesaid objectives.

between groups (PZ0.007, Wilcoxon); subanalysis showed a difference between

Material and method

AGT (mean 48.9 mu/l) and PPH groups (16.6 mu/l)(P 0.003) and between AGT

Retrospective observational study in hospitalized patients during 2014. Adult

and NGT groups (28.4 mu/l) (P 0.015). Of the PPH cases none had symptomatic

patient age

18 or older, who had at least two points of care de glucose

hypoglycaemia. Three PPH cases with cortisol ! 500 nmol/l underwent short

measurements

(capillary blood glucose) during their hospitalization, were

synacthen test (SST); 2 had a cortisol post-SST O 550 nmol/l. One patient

included. By the revising of the computerise-clinic-history, sociodemographic,

showed suboptimal response with a cortisol level at 416 nmol/l and is undergoing

clinic and administrative datum were obtained. The results of the glycaemia were

further investigation. There were no differences between groups in body mass

obtained from electronic devices.

index (median 22.1 kg/m²) or lung function. PPH occurred in 19% of the cohort

Results

and was associated with detectable insulin at the 2 hour OGTT timepoint,

2610 patients were included, 54.6% were men. The average age was 71.9G14.2

suggesting the possibility of dysregulated insulin release. AGT patients had

years old (73.7% older than 65 years old). The 73.5% of the patients were

higher insulin levels than NGT cases, suggesting relative rather than absolute

hospitalized in medical service. The main diagnoses when they were hospitalized

insulin deficiency in this cohort of PWCF.

were related with breathing system (20.1%), circulatory system (18.8%) and the

DOI: 10.1530/endoabs.49.EP430

central nervous system

(11.1%) diseases. The main chronic diseases were

diabetes

(60.9%), Chronic kidney disease

(18.9%), chronic obstructive

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

pulmonary disorder (COPD) (18.4%) and the congestive heart failure (CHF)

EP434

(17.6%). 49846 glycaemia were analysed (95.8% pre-prandial, 2.9% postprandial

The importance of islet antigen-2 and glutamic acid decarboxylase

and

1.3% night-time) with average values of

176.7G73.9 mg/dl,

250.2G

antibodies in proper diagnosis of diabetes mellitus at the age R30 and

108.2 mg/dl and 203.2G95.3 mg/dl respectively (P!0.001). The 66.7% fulfil

!70 years

at least one of both stablished criterion. 43.0% of patients had a pre-pandial

Aiste Kondrotiene¹, Evalda Danyte^2,3, Rimantas Zalinkevicius³ &

mean glycemic !140 mg/dl, 66.4% of patients had a random blood glucose

Rasa Verkauskiene^2,3

!180 mg/dl. No differences in hospital stay among patients with good and poor

¹Lithuanian University of Health Sciences, Medical Academy, Kaunas,

glycemic control (11.1G11.2 versus 10.34G9.4 days) (PZ0.081) were found.

Lithuania;²Department of Endocrinology, Kaunas clinics, Hospital of

The factors associated to the lack of compliance of the objectives were diabetes

Lithuanian University of Health Sciences, Kaunas, Lithuania;³Institute of

(OR:5,0[IC95%:

4.1-6.1]), the CHF

(OR: 1.5[IC95%:1.2-1.8]), the COPD

Endocrinology, Medical Academy, Lithuanian University of Health

(OR:1.3[IC95%:

1.0-1.6]) and the urgent hospitalization

(OR:2.1

[IC95%:

Sciences, Kaunas, Lithuania.

1.6-2.8]).

Conclusions

The glycemic control in hospitalized patients is far from adequate although we did

Objective

not find differences in hospital stay between patients with / without good glycemic

Misclassification of type 1 (T1DM) and type 2 diabetes mellitus (T2DM) is quite

control. We need to update the existent insulinization protocol because with the

common and crucial to choice of appropriate therapy. The aim of the study was to

current, the 33.3% of patients do not meet the goals.

evaluate the correspondence of islet antigen-2 (Anti IA2) and glutamic acid

DOI: 10.1530/endoabs.49.EP432

decarboxylase (Anti GAD65) antibodies with clinical diagnosis.

Methods

The Anti IA2 and Anti GAD65 were measured in 583 patients (337 males and 246

females) diagnosed with T1DM or T2DM with not typical manifestation at the

age R30 and !70 years. The data for analysis was collected from medical files.

Results

245

(42.02%) cases had primary diagnosis of T1DM, and 338 (57.98%) - T2DM.

One or both positive antibodies were found in 271 patients (group I), and all

negative in 312 (group II). The mean age at onset of diabetes mellitus was

42.55G9.29 yrs in group I vs. 41.83G8.53 yrs in group II; PZ0.33. One or both

antibodies were found in 141 patients with primary diagnosis of T1DM (odds

ratio (OR) 1.84 (95% CI 1.69-2.01, sensitivity 57.55%), 77 males (OR 0.92 (95%

CI 0.83-1.04, sensitivity 49.01%) and 27 females (OR 6.16 (95% CI 5.34-7.11,

EP433

sensitivity 71.28%). 208 patients with T2DM had negative antibodies (OR 2.56

(95% CI 2.38-2.77, sensitivity 61.54%), 63 males (OR 3.81 (95% CI 3.45-4.22,

Hypoglycaemia: Prevalence and factors associated in the

sensitivity 66.13%), and 67 females (OR 1.61 (95% CI 1.44K1.81, sensitivity

old-hospitalized patient

71.28%).

Lucía Vera Pacheco¹, Lorena Rentero Redondo², Carles Iniesta Navalón²,

Conclusion

María Teresa Gallego García², Amparo Meoro Avilés²,

The presence of antibodies corresponded to primary diagnosis in 49.01% to

Cristina Del Peso Gilsanz², María Amparo Egea Valera², Noelia Victoria

71.28% at the age R30 and !70 years.

García-Talavera Espín² & M^a Bienvenida Gómez Sánchez²

¹University Hospital Rafael Mendez, Lorca,Murcia, Spain;²University

DOI: 10.1530/endoabs.49.EP434

Hospital Reina Sofía, Murcia, Spain.

Objective

To determine the hypoglycaemia prevalence in an old-patient hospitalized and to

stablish the factors associated with its appearance and to study the association

between the hypoglycaemia with the stay in hospital and the mortality during the

hospitalization.

EP435

Material and method

The increase in unsaturated fatty acids is related with an

A retrospective study in which all patients, older than 65 years old that were

hospitalized during 2014 and at least two glycemic control have been realised,

anti-inflammatory profile in the hypothalamus of non-diabetic

were included. By the revising of the computerise-clinic-history, sociodemo-

IRS2-deficient mice

graphic, clinic and administrative data were obtained. The degree of comorbidity

Vicente Barrios¹, María Vinaixa², Laura M. Frago¹, Sandra Canelles¹,

(Charlson index) was calculated which classified it in three levels: absence,

Ángela M. Valverde³, Jesús Argente¹ & Óscar Yanes²

¹Department of Endocrinology, Hospital Infantil Universitario Nin˜o Jesús,

moderate and high. The results of the glycaemic were obtained from electronic

Instituto de Investigación La Princesa and CIBERobn, Instituto de Salud

devices.

Carlos III, Madrid, Spain;²Centre for Omic Sciences, Universitat Rovira i

Results

Virgili and CIBERdem, Instituto de Salud Carlos III, Tarragona, Spain;

1924 patients were included, 51,0% were men. The average age was 78,8G7,9

³Alberto Sols Biomedical Research Institute (CSIC/UAM), and CIBERdem,

years old. The 86,8% of the patients were urgent hospitalized and the 74,1% of the

Instituto de Salud Carlos III, Madrid, Spain.

patients were hospitalized in medical services. The main diagnoses when they

were hospitalized were related with breathing system (23,0%), circulatory system

(19,4%) and the central nervous system (11,2%) diseases. The Charlson index

Background

was 5,6G3,6, showing up the 98,4% a high comorbidity. The 8,7% of the patients

IRS2-deficient

(IRS2^-/-) mice are considered a good model to analyze the

presented at least one hypoglycaemia episode during the hospitalization, of which

development of diabetes as some of them present an increase in glycemia

the

26,3% presented more than two hypoglycaemia episodes during their

comparable to that observed in diabetes onset in humans, whereas a high

hospitalization.The factors associated to the appearance of any hypoglycaemia

proportion of these mice do not develop diabetes. Energy homeostasis regulation

episode were the hemiplegia (OR:1,7[IC95%:1,0-2,9]), and the chronic kidney

by the hypothalamus can be disturbed by an inflammatory environment, which

disease (OR:1,2[IC95%:1,0-1,4]. The patients hospitalised in medical services

predisposes an individual to the onset of diabetes. Saturated fatty acids induce

had also more hypoglycaemia risk than the ones hospitalized in surgery services.

hypothalamic dysfunction, whereas unsaturated fatty acids mediate several anti-

(OR:1,5[IC95%:1,1-1,4]. The median stay was 11,1 days (range: 3-107), without

inflammatory actions.

finding differences between patients with and without hypoglycaemia (12,1G

Objectives

10,9 versus 11,0G10,4 days; PZ0,181).As for overall mortality was 7.3%, and

Our aim was to determine the pattern of fatty acids in the hypothalamus of non-

no differences between the group of patients with / without hypoglycemia were

diabetic IRS2^-/- (ND) and diabetic IRS2^-/- (D) mice and its possible association

found (4.2% vs 7.6%; PZ0.108).

with hypothalamic inflammation.

Conclusions

Methods

The hypoglycaemia episodes in elderly patients were low comparing it to the

We studied 18 male mice including controls, ND and D mice. We analyzed

other studies and they were associated with chronic diseases such as the renal

enzymes involved in the generation of NADPH, fatty acid synthesis and

disease and the hemiplegia.Contrary to what you would expect, hypoglycemic

regulation of energy homeostasis by western blotting and pro- and anti-

episodes were not related to mortality or hospital stay.

inflammatory chemokines/cytokines by multiplexed bead immunoassay. Meta-

DOI: 10.1530/endoabs.49.EP433

bolomic studies were performed by proton nuclear magnetic resonance (H-NMR)

after extraction of hypothalamic metabolites in organic solvents.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

Introduction

Malic enzyme was increased in ND mice and fatty acid synthase in D and ND,

Gestational Diabetes Mellitus (GDM) has been associated with complications

with a greater increase in ND. Acetyl-CoA carboxylase was inhibited and AMPK

both in the neonate and in the mother; including increased risk of Type 2 Diabetes

activated in D mice, with no changes in ND mice. Among the studied

Mellitus (DM2), obesity, and cardiovascular disease. Fibroblast growth factor 21

chemokines/cytokines, monocyte chemoattractant protein-1, fractalkine and

(FGF21) is a key regulator of glucose and lipid metabolism. Recently, the

interleukin (IL)-2 were increased in D and IL-4 en ND mice. Metabolomic

relationship between FGF21 and metabolic component diseases such as diabetes

studies revealed an increase in the levels of u3-fatty acids, phosphatydil-

mellitus and obesity has been demonstrated. In addition, FGF21 mRNA and

ethanolamine, linolenic acid and MUFA plus PUFA in the hypothalamus of ND

protein levels, as well as soluble levels of this molecule, have been reported to be

mice with respect to controls. A negative correlation of the analyzed metabolites

increased in patients with GDM compared to normoglycemic pregnant women.

with fractalkine and a positive correlation with IL-4 was observed.

Objective

Conclusion

To associate FGF21 serum levels with metabolic profile of patients with GDM.

The favorable hypothalamic lipid profile suggests a beneficial role against

Material and methods

hypothalamic inflammation in non-diabetic IRS2^-/- mice.

Twenty patients with GDM and fifteen clinically healthy pregnant women were

DOI: 10.1530/endoabs.49.EP435

included; serum FGF21

levels were determined by ELISA, and glucose,

triglycerides, total cholesterol, HDL, LDL and VLDL values were measured.

Results

Our results shown that serum levels of FGF21 are significantly higher in the group

of patients with GDM compared to the control group (313.72G84.58 vs 116.46G

31.41 pg/mL, PZ0.013). The values of triglycerides, cholesterol and VLDL

EP436

showed a similar behavior between groups; while HDL levels were higher in the

Epidemiological indicators and prevalence of risk factors of diabetes

control group. Serum FGF21 levels positively correlated with triglyceride values

type 2 among the inhabitants of Almaty city and Almaty region of

(rZ0.344, P$0.05) and postprandial glucose (rZ0.356, P$0.05). There was no

Kazakhstan

correlation between total cholesterol, HDL, LDL and VLDL levels and FGF21

Laura Danyarova, Akmaral Tashmanova & Zhanmedet Shyman

levels in our study group.

Scientific-Research Institute of Cardiology and Internal Diseases, Almaty,

Conclusion

Kazakhstan.

The FGF21 molecule may play an important role in the GDM pathophysiology,

since it alters the metabolic profile, both glycemic and lipid, of these patients.

Relevance

DOI: 10.1530/endoabs.49.EP437

The main risk factors for developing diabetes type 2, such as obesity, overeating

and a sedentary lifestyle are common to a variety of chronic non-infectious

diseases.

Purpose of the study

Investigate the source of epidemiological indicators, risk factors for type

diabetes based on cross-sectional study of the population of Almaty city and

Almaty region of Kazakhstan.

Methodology

The material for the research were population at the age of 18-69 years living in

EP438

Almaty city and Almaty region. The study was conducted in three stages:

interviews with respondents, physical measurements and laboratory tests.

Site-specific cancer risk in people with type 2 diabetes: Nationwide

Results of the study

population-based cohort study in Korea

Analysis of the survey results on a national basis has revealed a significant

Du-Hyong Cho², Ju-Young Jang¹, Suk Kyeong Kim¹, Dong-Lim Kim¹

prevalence of diabetes among Russians (15.35%) compared with the Kazakhs

& Kee-Ho Song¹

(4.9% r$0.01), with other Asian ethnic groups (10.7%, r$0.05). But compare the

¹Konkuk University School of Medicine, Seoul, Republic of Korea;²School

results of Russians with other European nationality (8.3%) and Ukrainians (7.1%)

of Medicine, Eulji University, Daejeon, Republic of Korea.

have not showed significant differences (PO 0.05). The age has been proved as

a significant risk factor in the development of type 2 diabetes, and the ratio is 1:

Background

(OR Z9.266), ie in the age group over 45 years the risk of developing type

Many studies indicated an increased cancer incidence and cancer mortality in

2 diabetes increases by 9 times. Genetic inclination of diabetes refers to a group of

subjects with diabetes mellitus. But most of studies have been surveyed in western

the absolute risk of diabetes; the analysis showed that the 271 respondents pointed

countries and have problems in applying the results to Korean. We aimed to

to first-degree relatives with diabetes history, where diabetes occurred in 14.8%.

evaluate the site specific cancer risk of diabetic patients in Korea over 30 years,

The remaining 1304 people had no family history of diabetes, and diabetes among

and investigate causal relationship and temporal relationship by analyzing the

them was 5.8%. The ratio is almost 1: 3 (OR Z2.920). Risk factors, obesity, blood

organ-specific cancer risk in diabetics according to duration.

pressure, concomitant cardiovascular disease, glucose and cholesterol in the

Methods

blood plasma. Comparison of these factors in the groups of respondents with

Using a database provided by NHIS, we conducted a retrospective, population-

diabetes and without diabetes showed significant differences in body mass index

based cohort study for adults over 30 years from January 1, 2005 to December 31,

(BMI), blood pressure, both systolic (SBP) and diastolic (DBP). The values of all

2013. We calculated the hazard ratio (HR) for each cancer by using Cox

parameters in patients with diabetes were significantly higher than in those

regression. And we compared HR for each cancer according the duration of

without diabetes

(P!0.05). The survey revealed that people with diabetes

diabetes divided in to 6month, 6months to 3years and more than 3years to verify

compared with those without diabetes suffer the hypertension 2 times harder,

the possibility of detection bias or reverse causation.

ischemic heart disease - more than 3 times, myocardial infarction occurs 6 times,

Results

stroke - 4 times more often.

The incidence of total cancer per 1,000 Subjects with diabetes was higher than

Conclusion

with non-diabetes group. Hazard ratio(HR) for cancer of pancreas, liver, kidney,

Analysis of risk factors for type 2 diabetes of the population has confirmed the

bladder, colorectum, thyroid, lung, stomach and leukemia were significantly

impact of such factors as race, age and genetic inclination on the prevalence of

higher in diabetes group after adjusted. HR for cervix, endometrium and breast

diabetes.

cancer in female diabetes group were higher than those of non-diabetes group. HR

DOI: 10.1530/endoabs.49.EP436

for laryngeal cancer in male was higher in diabetes group. The total cancer risk

was higher in ! 6 months of diabetes duration (HR 2.03; 95% confidence interval

[95% CI]. 1.99-2.07), whereas the hazard ratio decreased with increasing

duration of diabetes, raging from 1.19 (95% CI, 1.18-1.21) between 6 months and

3 years to 1.12 (95% CI, 1.11 to 1.13) at over 3 years, but remained significantly

EP437

higher than the non-diabetic group. HR for pancreas, liver, colorectum, prostate

and endometrium were higher in diabetes group for entire duration of diabetes.

Association of FGF21 soluble levels with metabolic profile in

When excluding diabetes duration less than

6months, HR for stomach,

Gestational Diabetes patients

colorectum, liver, pancreas, kidney, bladder, thyroid, prostate, endometrium

Cristian A. Saucedo-Toral¹, María L. Lazo-de-la-Vega-Monroy¹,

and cervix showed similar pattern including diabetes duration less than 6 months.

Martha E. Fajardo-Araujo¹, Manuel A. Espinosa-Nava¹, Francisco J.

Conclusion

Anaya-Torres², Lorena del R. Ibarra-Reynoso¹ & Yeniley Ruiz-Noa¹

Cancer incidence risk increases in T2DM patients, and the phenomenon is more

¹Universidad de Guanajuato, León, Guanajuato, Mexico;²Clínica Médica

prominent in short durations, i.e. shortly after diagnosis of diabetes. As the

Campestre, León, Guanajuato, Mexico.

duration increases, incidence risk of cancer varies depending on the site of cancer

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

and patient’s gender. Thus, in diabetes patients, cancer screening should be

metformin during postpartum period were accepted as type 2 DM and were not

individualized regarding duration of diabetes, sex, and the site of cancer.

given OGTT. According to 75 g OGTT; with their basal average being (101.83G

DOI: 10.1530/endoabs.49.EP438

10.77 mg/dl) and 2nd hour glucose average being (124.66G39.53 mg/dl), 11

(34.3%) patients were not diagnosed with diabetes. Thirteen (36.11%) patients

were diagnosed with impaired fasting glucose, three (8.33%) with impaired

glucose tolerance, three (8.33%) with impaired fasting glucose and impaired

glucose tolerance, six (16.67%) with type 2 DM.

Discussion

Our study included pregnant women who had not been diagnosed with DM in the

beginning of their pregnancy who later on were diagnosed with GDM during

EP439

pregnancy. We followed them during their postpartum period. With these results,

Erosio interdigitalis blastomycetica- discrete and early sign for

it is found necessary to follow and evaluate the postpartum period of the patients

diabetes mellitus

diagnosed with GDM during pregrancy with regard to Type II DM progress.

Anca E. Chiriac & Doina Azoicai

DOI: 10.1530/endoabs.49.EP440

University of Medicine and Pharmacy, ‘Grigore T Popa’, Iasi, Romania.

Erosio interdigitalis blastomycetica is a special form candidiasis commonly

seen in the third web space of digits, but can spread to all web spaces.

Diagnosis is clinically suspected in the presence of maceration and

ulceration, erythema, sometimes associated with pain. The main predispos-

EP441

ing condition is chronic maceration (for example in launderers), irritant

Diabetic nephropathy in type 1 diabetes mellitus

chronic agents and prolonged moisture affect skin barrier with subsequent

Ines Barka, Nesrine Chikhrouhou, Amel Maaroufi, Maha Kacem,

colonization of Candida spp. Direct mycological examination and fungal

Molka Chaieb & Koussay Ach

culture certify the diagnosis and exclude similar clinical disorders, mostly

Department Endocrinology, Farhat Hached University Hospital, Sousse,

irritant contact dermatitis and psoriasis. Erosio interdigitalis blastomycetica

Tunisia.

is frequently diagnosed in daily practice especially in diabetes patients. We

present cases series of erosio interdigitalis blastomycetica as initial sign of

undiscovered diabetes mellitus. Suspicion of diabetes should be made in any

case of erosio interdigitalis blastomycetica. Screening for diabetes is

Nephropathy is a serious complication of Type 1 diabetes mellitus (T1DM)

mandatory in case of erosio interdigitalis blastomycetica.

with a grave prognosis after the onset of proteinuria. End stage of renal

DOI: 10.1530/endoabs.49.EP439

disease remains the major cause of excess morbidity and premature

mortality in patients with T1DM. The aims of the present study were to

investigate the prevalence of diabetic nephropathy and to evaluate risk

factors for its development among patients developing T1 DM. Seventy six

patients with T1DM history over 20 years were included in our study. We

analysed the occurrence and risk factors of diabetic nephropathy.

Microalbuminuria and macroalbuminuria were defined as urinary albumin

excretion 31-299 mg and 300 mg, respectively, per 24 h in at least two of

EP440

three consecutive samples, kidney failure was defined as a glomerular

Postpartum Tip 2 DM follow-up after gestational diabetes mellitus

filtration rate (GFR) !30 ml/min/1.73 m. The following risk factors were

Seda Sancak¹, Ali Ozdemir², Kerem Yi

˘it Abacar², Ayhan C¸ elik3,

considered: sexe, diabetic control

(HbA1c) and duration, hypertension,

Nalan Okurog˘ lu2, Ya¸ar Sertba¸2 & Hasan Aydin4

smoking. A total of 76 patients were enrolled: 43 men and 33 women, the

¹Fatih Sultan Mehmet Training and Educational Hospital, Division of

mean age and the mean diabetes duration was 39.9 years G9.5 (24-61

Endocrinology and Metabolism, Istanbul, Turkey;²Fatih Sultan Mehmet

years) and

28.18G5.9 years respectively. During follow-up, persistent

Training and Educational Hospital, Departmant of Internal Medicine,

microalbuminuria developed in four patients (5.3%); macroalbuminuria

Istanbul, Turkey;³Fatih Sultan Mehmet Training and Educational Hospital,

developed in seven patients

(9,2%) and kidney failure in

12 patients

Division of Obstetrics and Gynecology, Istanbul, Turkey;⁴Yeditepe

(15.8%). the risk of diabetic nephropathy was significantly higher in men

University Hospital, Division of Endocrinology and Metabolism, Istanbul,

than in women (PZ0.012). Our study suggests that several potentially

Turkey.

modifiable risk factors predict the development of nephropathy in type 1

diabetic patients.

Purpose

DOI: 10.1530/endoabs.49.EP441

GDM is defined as any degree of carbonhydrate intolerance that is first diagnosed

during pregnancy. Patients diagnosed with GDM are expected to have

complications such as Type II DM, obesity, hypertension in the long term.

Prevalence of GDM diagnosis during pregrancy changes between 2 and 10%. Our

purpose is to revaluate the OGTT of the patients diagnosed with GDM, with

regard to their postpartum Type II DM progress.

Materials and methods

EP442

450 pregnant women who were not diagnosed with diabetes in the beginning of

Diabetes and smoking: epidemiological study in two ethnic groups

their pregrancy were included to the study, who had consulted to our clinic

Georgios Papadakis¹, Thomas Zambelis², Kostas Konstantopoulos³

between 2012 and 2014. Seventy-two of those quitted the study willingly, 20 of

& Stylianos Chatzipanagiotou⁴

those quitted during follow-up, 12 of those quitted due to spontaneous abortion in

¹STEPS Stoffwechselzentrum, Biel/Bienne, Switzerland;²Department of

the first trimester. 346 remaining patients were included to the study. After 75 g

Neurology, Aeginition Hospital, Athens, Greece;³Department of Haema-

OGTT, GDM screening was made to those patients between 24th and 28th weeks

tology, Laikon University Hospital, Athens, Greece;⁴Department of

of their pregrancy. With 75 g OGTT, 61 patients were diagnosed with GDM.

Medical Biopathology, Aeginition Hospital, Athens, Greece.

They were reevaluated with regard to their postpartum Type II DM progress. But

36 of these 61 patients were made 75 g OGTT. Two of those became pregnant

again, two of those moved out of the city, 21 of those could not be reached; thus,

Objectives

they could not be reevaluated. Among the patients diagnosed with GDM, 29 of

Smoking tobacco is a risk factor for several diseases and has been increasing in

them were followed with diet, four of them with basal and short-acting insulin,

many developing countries. Smoking cessation counseling should be a routine

two of them only with basal insulin, one of them only with short-acting insulin.

component of diabetes care. The aim of the present study was to examine the

Three of those who were followed with diet and one of those who were followed

association between smoking status in two different groups of patients with

with basal and short-acting insulin were followed with metformin during

diabetes: Immigrants from Bangladesh who live in Greece and Greek-born

postpartum period. None of the patients used insulin during postpartum period.

subjects.

Results

Methods

Patients called postpartum in the mean month period 20.82G5.66. Mean age

A total of 166 immigrants with diabetes (122 with Type 2 and 44 with Type 1

average of the patients was 32G5. Postpartum BMI was 29.10G5.47 kg/m².

diabetes mellitus) from Bangladesh were compared with 123 Greek Caucasian

HbA1c average of the patients was 5.77G0.39%. Four patients who were using

patients (82 with Type 2 and 41 with type 1 diabetes mellitus). Patients from

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Bangladesh had a mean GS.D. duration of 10.34G6.2 years of living in Greece. A

Background

questionnaire was formulated and pilot-tested for the comprehensibility of

Low serum testosterone (LST) is associated with some chronic diseases, changes

questions by both ethnic groups. Interviews were conducted, a physical

in body composition and resistance to insulin. Diabetes is one condition that has

examination followed and blood samples for plasma glucose and HbA1c were

high prevalence of LST.

collected. Demographic characteristics and diabetes-related information was

Objetive

collected.

To determine the prevalence of LST in men with diabetes and its relationship with

Results

age, anthropometric and biochemical data.

A total of 40 (24.1%) patients from Bangladesh and 58 (47.2%) patients from

Material and methods

Greece were smokers, 18 (10.8%) patients from Bangladesh and 37 (30.1%)

A cross-sectional study of 65 men with type 1 and type 2 diabetes was conducted,

patients from Greece reported that they were ex-smokers at the time of

with age ranging from 25 to 73 years. Clinical data was obtained from clinical

examination and interview, whereas 108 (65.1%) patients from Bangladesh and

records, like disease duration, diary insulin dose, retinopathy, hypertension and

(22.8%) patients from Greece never smoked

(P!0.001). Patients from

medication. Biochemical parameters evaluated were: total testosterone (TT), free

Bangladesh reported less tobacco use than Greek patients

(5.61G11.91 vs

testosterone (FT), gonadotropins, prolactin, glycated haemoglobin (A1C), urinary

24.77G24.20 pack-years, P!0.001).

albumin/creatinine relation. LST was considered TT !3.0 ng/ml.

Conclusions

Results

Most immigrants reported less tobacco use than native Greeks. Higher education

Mean age was 51.9G19.9 years, 60% had type 2 and 40% type 1 diabetes and the

is associated with less smoking prevalence in both ethnic groups. Patients living

mean disease duration was 15.6G10.2 years. 76.9% had body mass index (BMI)

alone were more likely to smoke than those who live with families. Employed

R25 kg/m². Twenty-seven patients (41.5%) had LST, 6 (23.1%) in type 1 group

persons had a lower smoking prevalence than unemployed persons in both ethnic

and 21 (53.8%) in type 2. In patients under 40 years-old 5 (26.3%) had LST.

groups. Smoking is associated with higher glucose and HbA1c values in both

In multiple linear regression model TT was associated with BMI (b K0.355,

ethnic groups. From the literature tobacco smoking is related to insulin resistance,

PZ0.005) and age (b K0.255; PZ0.044) and no associations were found with

systemic inflammation, decreased b-cell function and pancreatic inflammation.

FT. However, patients with FT!15 pg/ml had a significantly higher A1C, 8.40G

Understanding some culturally relevant predictors of tobacco use among different

1.71% vs 7.54G1.38% (PZ0.029). BMI R25 kg/m² was associated an increased

ethnic population might assist health care providers in designing successful

risk of LST (odds ratio (OR): 6.50; 95% confidence interval (CI) 1.33-31.83),

smoking control programs, especially for patients with diabetes.

such as antiplatelet medication (OR: 5.83; CI: 1.40-24.23).

DOI: 10.1530/endoabs.49.EP442

Conclusion

In this sample we found a high prevalence of LST in men with diabetes, similar to

data described in other studies. Age and BMI were correlated with testosterone

levels such as in men without diabetes, and no association was observed with A1C

levels. Only FT! 15 pg/ml was associated with higher A1C. To clarify this

relation, more data is needed.

DOI: 10.1530/endoabs.49.EP444

EP443

Prevalence of hyperglycemia in patients hospitalized in the health area

of cuenca (Spain)

José Pérez-Rodríguez, Lidia Guerra-Navarro, Mubarak Alramadan,

Paula García-Notario, David Martín-Iglesias, Santiago Aranda-Regules

& Dulce Calderón-Vicente

Virgen de la Luz Hospital, Cuenca, Spain.

EP445

Vitamin D and testosterone in diabetes mellitus: cross-sectional

study results

Introduction and objectives

Nelson Cunha¹, Leonor Gomes^1,2, Diana Martins^1,2, Diana Oliveira^1,2,

Hyperglycemia is a common problem in hospitalized patients, that increases

Adriana Lages¹, Mara Ventura¹, Lúcia Fadiga¹, Diana Catarino¹ &

infections, mortality, costs and the hospital stay. The objective of this study is to

Francisco Carrilho¹

know the prevalence of hyperglycemia in our hospital.

¹Endocrinology, Diabetes and Metabolism Department, University Hospital

Methods

of Coimbra, Coimbra, Portugal;²Faculty of Medicine of University of

We designed a cross-sectional observational study. We included patients admitted

Coimbra, Coimbra, Portugal.

in the hospital every 3 days in 2 months. We excluded patients younger than

15 years, stays less than

3 days and those of the pediatric, gynecological,

emergency and intensive care services. We collected the data from these patients

Background

the third day of admission and at discharge. We defined hyperglycemia as two or

In the recent years, Vitamin D role has grown in cardiovascular and inflammatory

more capillary glucose values greater than 140 mg/dl.

diseases, and some relations were made with low serum testosterone (LST) levels.

Results

It is equally known that in patients with diabetes, the prevalence of LST is higher.

A total of 328 patients (173 females and 155 males) were included, with a median

Objetive

age of 73 years. The 75% were in medical services and 25% in surgical services.

To determine the prevalence of low levels of vitamin D and its relation with LST

The main reason for admission was infection (26%), followed by organ failure

in men with diabetes.

(12%). 33% (109) patients had hyperglycemia. Of these patients, 71.6% (78) were

Material and methods

known diabetics, while 28.4% (31) were not known diabetics. The median age of

A cross-sectional study of 65 men with type 1 and type 2 diabetes was conducted,

patients with hyperglycemia was 80 versus 68 years old in patients without

with age ranging from 25 to 73 years. Clinical data was obtained from clinical

hyperglycemia.

records, such as disease duration, diary insulin dose, retinopathy and

Conclusions

hypertension. Biochemical parameters were: 25-hydroxi-vitamin-D (25[OH]D),

The prevalence of hyperglycemia in our hospital is higher than another areas,

total testosterone (TT), free testosterone (FT), gonadotropins, prolactin, glycated

probably due to a higher mean age in our population. Almost one third of patients

haemoglobin (A1C). Low levels of 25(OH)D were considered when !30 ng/ml

with hyperglycemia were not diabetic. Therefore hospitalization is an opportunity

(insufficiency

20-29 ng/ml and deficiency!20 ng/ml) and LST when TT

to diagnose and treat adequately these patients.

!3.0 ng/ml.

DOI: 10.1530/endoabs.49.EP443

Results

Mean age was 51.9G19.9 years and the mean disease duration was 15.6G10.2

years, 60% had type 2 and 40% type 1 diabetes. 76.9% had BMI R 25 kg/m².

Forty-two patients

(64.6%) had low vitamin D levels (40% had 25(OH)D

20-29 ng/ml and 24.6% had 25(OH)D!20 ng/ml). In multiple linear regression

model, low levels of 25(OH)D were associated with triglycerides (b K0.314;

EP444

PZ0.011) and FT (b 0.273; PZ0.03) when adjusted for age, BMI and disease

Testosterone levels in men with diabetes mellitus. What relation?

duration. Men with low levels of vitamin D had significantly lower FT (15.82G

Nelson Cunha¹, Leonor Gomes^1,2, Diana Martins^1,2, Diana Oliveira^1,2,

9.53 vs 22.72G10.72 pg/ml; PZ0.013) and higher serum triglycerides (164.1G

Adriana Lages¹, Mara Ventura¹, Lúcia Fadiga¹, Diana Catarino¹ &

122.1 vs 104.9G45.2; PZ0.029). Mean A1C was 8.07G1.61% vs 7.48G1.40%,

Francisco Carrilho¹

respectively, but was not significantly different (PZ0.250).

¹Endocrinology, Diabetes and Metabolism Department, University Hospital

Conclusion

of Coimbra, Coimbra, Portugal;²Faculty of Medicine of University of

In this sample, the prevalence of low levels of vitamin D was similar to data

Coimbra, Coimbra, Portugal.

described in other studies (52-77%). When adjusted for age, BMI and disease

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

duration, these levels of vitamin D were associated with higher serum

Objectives

triglycerides and lower free testosterone, which may indicate the metabolic

T helper1 (Th1) cells were determined to have important roles in the development

effects of this vitamin in patients with diabetes.

of type 2 diabetes (T2D). We aimed to investigate relationship between Th1

DOI: 10.1530/endoabs.49.EP445

cytokines (IFN g, IL-2 and TNF-a) and T2D.

Material and methods

The study included 32 newly diagnosed type 2 diabetic patients (T2DPs) who had

not begun to take antidiabetic agents except from insulin and 30 healthy subjects

(CG) who did not have glucose intoerance (fasting or after glucose load). Serum

IFN-g, IL-2 and TNF-a levels were measured using ELISA method. Serum levels

of those ctokines in T2DPs were compared with those in controls.

Results

EP446

TNF-a levls of T2DPs were higher (P!0.05) than those in controls. There were

The relationship between serum uric acid and insulin resistance and

no differences between the IFN-g and IL-2 levels of T2DPs and controls

sensitivity parameters in Turkish type 2 diabetes mellitus patients

(PO0.05).

Betul Ekiz-Bilir¹, Bulent Bilir², Neslihan Soysal-Atile¹ & Gulsah Elbuken³

Conclusion

¹Tekirdag State Hospital, Endocrinology and Metabolic Diseases Division,

TNF-a levels increase in T2D. Decreased insulin action in T2D may be due to the

Tekirdag, Turkey;²Namik Kemal University, Medical Faculty, Internal

increased TNF-a levels, since TNF-a has been suggested to down regulate the

Medicine Department, Tekirdag, Turkey;³Namik Kemal University,

tyrosine kinase activity of the insulin receptor.

Medical Faculty, Internal Medicine Department, Endocrinology and

DOI: 10.1530/endoabs.49.EP447

Metabolic Diseases Division, Tekirdag, Turkey.

Summary

Hyperuricemia is associated with glucose metabolism disorders clinically. In this

study, we evaluated the relationship between serum uric acid concentrations and

some insulin resistance/sensitivity parameters in Turkish type 2 diabetes mellitus

patients.

EP448

Methods

Adipocytokines, incretins, insulin resistance and body composition

The anthropometric and laboratory data of 87 type 2 diabetes patients of both

coherence in women with previously diagnosed gestational diabetes

sexes

(35

male,

female) were evaluated retrospectively. HOMA-IR

mellitus

(homeostatic model of insulin resistance) and QUICKI (quantitative insulin

Migle Francaite-Daugeliene & Dzilda Velickiene

sensitivity check index) measurements were made by the formulae of [glucose

Lithuanian University of Health Sciences, Kaunas, Lithuania.

(mg/dl)

! insulin (mu/ml)]/405 and 1/[log ins (mu /ml)Clog glu (mg/dl)]

respectively.

Results

Introduction

The mean age of the patients were 54.4G11.2 (minimum 20, maximum 77) years.

Adipose tissue is a major source of adipocytokines. It plays an important role for

The serum uric acid values ranged from 1.7 to 9.6 with a mean of 4.82G1.39.

the development of insulin resistance (IR). Data implicate that incretins enhance

HOMA-IR values ranged from 0.51 to 25.99 with a median of 3.27G2.57.

insulin sensitivity. One aspect of the pathophysiology of gestational diabetes

QUICKI values ranged from 0.25 to 0.43 with a median of 0.32G0.04. There was

(GDM) is IR. The relationship between adipocytokines, incretins and GDM might

a positive and significant correlation between serum uric acid and insulin levels

be closely associated.

(rZ0.301; PZ0.005). There was a negative and significant correlation between

Aim

serum uric acid and A1c and glucose levels

(rZK0.372; PZ0.000 and

To evaluate the coherence of adipocytokines (adiponectin and leptin), incretins

rZK0.313; PZ0.003). The correlation of uric acid to age, diabetes duration and

(GLP-1, GIP), insulin resistance and BMI in women with previously diagnosed

body mass index did not reach statistical significance. Although the correlation of

GDM.

uric acid to HOMA-IR and QUICKI values did not reach statistical significance

Methods

(rZ0.128; PZ0.236 and rZK0.128; PZ0.236), HOMA-IR values increased

We examined 126 women with previously (16-43 years ago) diagnosed GDM.

but QUICKI values decreased with increasing uric acid levels.

BMI, incretins, adipocytokines were evaluated. IR was calculated with HOMA-

Conclusion

IR index. Data expressed as meanGS.D. for parametric data or median (min-max)

Although the correlations did not reach statistical significance, serum uric acid

for non-parametric data. ANOVA was used to compare data between groups of

levels are positively correlated to insulin resistance parameter (HOMA-IR) and

three or more variables. Non-parametric data correlation analysis was performed

negatively correlated to insulin sensitivity parameter (QUICKI) as expected. The

using the Spearman’s correlation coefficient. The results were considered

small sample size of our cohort might be responsible for this statistical

statistically significant at P!0.05.

insignificance. The negative correlation of serum uric acid to glucose and A1c

Results

might be related to increased renal excretion of uric acid together with glucose

Women’s average age was 53.52G8.34 years (39-77 years). The coherence

due to osmotic diuresis. These results must be confirmed with larger studies.

between adipocytokines, incretins and BMI was observed: increased BMI

DOI: 10.1530/endoabs.49.EP446

determined decreased adiponectin (rZK0.361, P!0.01), and increased leptin

(rZ0.838, P!0.01) either incretins concentrations (GIP rZ0.270, PZ0.01 and

GLP-1 rZ0.167, PZ0.21). HOMA-IR was higher in obese women (rZ0.641,

P!0.01). Data analysed in different BMI categories (normal weight/overweight/

obese): adiponectin (26.8(12.2-76.8)/21.4 (10.8-54.4)/17.9 (5.2-41.6), P!0.01),

leptin (5.9(0.2-16.1)/12.5(3.8-122.1)/24.7(11.1-74.9), P!0.01), GIP (0.8(0.2-

2.9)/0.97(0.2-5.2)/1.29(0.2-18.2), PZ0.145), GLP-1

(0.06(0.04-21.7)

/0.06(0.04-6.1)/0.06(0.04-18.2), PZ0.517), HOMA-IR

(2.2(0.5-4.7)/2.5(0.4-

EP447

6.4)/4.6(1.2-27.2), P!0.01). No significance between adiponectin and GIP,

Relationship with T helper 1 cytokines and type 2 diabetes

GLP-1 was defined (rZK0.152, PZ0.156/rZ0.02, PZ0.824). Women with

Havva Gonca Tamer¹, Ozge Telci Caklili², Ilkay Kartal³, Kagan Gungor⁴

lower adiponectin had higher HOMA-IR (rZK0.22, PZ0.03). The correlation

& Hasan Huseyin Mutlu⁵

between leptin and GIP, GLP-1, HOMA-IR

(rZ0.3, PZ0.05/rZ0.231,

¹Division of Endocrinology and Metabolism, Department of Internal

PZ0.03/rZ0.697, P!0.01) was observed. The positive correlation between

Medicine, Medeniyet University, Goztepe Training and Research Hospital,

GIP, GLP-1 and HOMA-IR (rZ0.388, P!0.01/rZ0.352, PZ0.001) was found.

Istanbul, Turkey;²Department of Internal Medicine, Medeniyet University,

Conclusion

Goztepe Training and Research Hospital, Istanbul, Turkey;³Division of

Adipocytokines and incretins are closely linked to the amount of fat tissue in the

Endocrinology and Metabolism, Department of Internal Medicine,

body: increased BMI correlates with decreased adiponectin and increased

Medeniyet University, Goztepe Training and Research Hospital, Istanbul,

leptin/incretins levels in women with previously diagnosed GDM. HOMA-IR

Turkey;⁴Division of Endocrinology and Metabolism, Department of

is closely associated with leptin and incretins.

Internal Medicine, Medeniyet University, Goztepe Training and Research

DOI: 10.1530/endoabs.49.EP448

Hospital, Istanbul, Turkey;⁵Department of Family Medicine, Medeniyet

University, Goztepe Training and Research Hospital, Istanbul, Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP449

assays: chromogranin at 10 times normal and Metanephrine at 3.33 times normal,

abdomino-pelvic ultrasound finds a supra-renal mass supplemented by pelvic CT

The coherence of carbohydrate metabolism and metabolic parameters

recovering an oval tissue formation measuring

46.8!36.5 mm Enhancing

(adipocytokines, incretins, insulin resistance) in women with previously

intensely after injection of contrast medium, evoke a pheochromocytoma

diagnosed gestational diabetes mellitus

confirmed by a MIBG scintigraphy which finds a focus of intense hyperfixation

Migle Francaite-Daugeliene & Dzilda Velickiene

of the tracer radio corresponding to a right adrenal neurectodermal tumor of

Lithuanian University of Health Sciences, Kaunas, Lithuania.

52!36 mm. In search of other pathologies coming within the framework of a

multiple endocrine neoplasia the assessment of extension is without anomaly.

Introduction

Patient is programmed in surgery for a management

There is growing evidence that gestational diabetes mellitus (GDM) significantly

Conclusion

increases the risk of adverse consequences, the most significant of which is a

In patients with pheochromocytoma

35% are diabetic, the diagnosis of

predisposition to the development of metabolic syndrome and diabetes mellitus

pheochromocytoma in the diabetic may be responsible for a glycemic imbalance

(DM). The reasons why some women develop DM, while the others not, are still

and this considerably alters the management.

studied. The relationship between various metabolic parameters and GDM might

DOI: 10.1530/endoabs.49.EP450

be closely associated.

Aim

To evaluate the coherence of carbohydrate metabolism and metabolic parameters

(adipocytokines, incretins, insulin resistance) in women with previously

diagnosed GDM.

Methods

We examined 126 women with previously (16-43 years ago) diagnosed GDM.

EP451

BMI was evaluated. Fasting plasma glucose (FPG) was examined for women with

Unacylated ghrelin does not seem to influence glucose homeostasis in

DM. OGTT was performed for carbohydrate metabolism testing for the rest.

obese women

Women assigned to different groups: NG - normal glucose, IFG-IGT - impaired

José Silva-Nunes^1,2, Miguel Brito², Carina Silva², Ana Oliveira² &

fasting glucose/impaired glucose tolerance and DM group. Incretins, adipocyto-

Luisa Veiga²

kines were evaluated. IR was calculated with HOMA-IR index. Data expressed as

¹Endocrinology Department - Curry Cabral Hospital, CHLC, Lisbon,

meanGSD for parametric data or median (min-max) for non-parametric data.

Portugal;²Research Group in Genetics and Metabolism - Lisbon School of

ANOVA was used to compare data between groups of three or more variables.

Health Technology, Lisbon, Portugal.

Non-parametric data correlation analysis was performed using the Spearman’s

correlation coefficient. The results were considered statistically significant at

P!0.05.

Background and Aim

Results

Unacylated ghrelin (UAG) is the major form of circulating ghrelin. Initially

Women’s average age was 53.52G8.34 years (39-77 years). Age differed in

considered as a non-functional peptide, soon after UAG has been associated to a

separate carbohydrate metabolism groups (PZ0.001). Carbohydrate metabolism

negative action on energy balance, suppression of hepatic glucose production and

was set for 58%: IFG-IGT for 16.7%, DM for 41.3% patients. The correlation

decrease in circulating levels of insulin. The aim of this study was to analyze the

between adipocytokines, incretins and FPG was evaluated: higher FPG was seen

association between the serum levels of UAG and glucose metabolism parameters

in women with lower adiponectin (rZK0.186, PZ0.037), higher leptin levels

in obese women, independently from the eventual interference of adiposity.

(rZ0.340 P!0.01) as well as incretins concentrations (GIP rZ0.368, P!0.01

Material and Methods

and GLP-1

rZ0.05, PZ0.004) and HOMA-IR (rZ0.656,P!0.01). Data

One hundred lean and 254 obese Caucasian women were studied. Each woman

analysed in different carbohydrate metabolism groups (NG/IFG-IGT/DM): BMI

was characterized for total body weight, body mass index (BMI), waist and hip

(26.7

(18.8-52.2)/27.9

(20.1-52.9)/34.8

(20.5-52.9), PZ0.001), adiponectin

circumferences, glucose at fasting and 2 hours after an oral glucose tolerance test

(21.6

(10.3-76.8)/18.7 (9.9-54.4)/17.7 (5.2-52.9), PZ0.07), leptin (14.7 (0.2-

(OGTT), fasting insulin, glycated hemoglobin

(HbA1c), and UAG. Insulin

74.9)/10.9 (2.2-48.6)/19.6 (1.6-66.3), PZ0.327), GIP (0.8(0.2-12.1)/0.8 (0.2-

resistance was assessed by the homeostasis model assessment (HOMA-IR).

5.2)/0.07 (0.05-21.7), PZ0.416), GLP-1 (0.06 (0.04-16.6)/0.07 (0.04-5.4)/0.07

Obese women were classified in three glycemic status subgroups (normogly-

(0.05-21.7), PZ0.044), HOMA-IR (2.3 (0.5-4.7)/2.4 (1.4-7.2)/4.5 (0.5-27.2),

cemia, prediabetes and diabetes) according to HbA1c and glucose values.

P!0.01).

Results

Conclusion

When compared with the lean group, significantly lower UAG levels were

Age, BMI, adipocytokines, incretins and IR are closely linked to the carbohydrate

observed in obese women when compared with the lean group (350.2G251.9 vs

metabolism: IFG-IGT and DM was more frequently seen in elder overweight/obese

219.2G149.7 pg/ml; P!0.001). However, no significant difference was observed

women, having lower adiponectin, higher GLP-1

concentration and higher

through obesity classes I to III. UAG levels were not significantly different among

HOMA-IR.

glycemic status subgroups and did not show any direct association with glucose,

DOI: 10.1530/endoabs.49.EP449

insulin, HOMA-IR, or HbA1c values.

Conclusions

Although the level of the unacylated form of ghrelin shows an association with

anthropometrics it seems not to be involved in glucose homeostasis.

DOI: 10.1530/endoabs.49.EP451

EP450

Instable diabetes revealing pheochromocytoma

Samir Ait Abderrahmane, Imad Boulmarka, Mounia Chenegreha,

Lila Brakni, Samia Ouldkablia & Brahim Oudjit

HCA, Kouba, Algeria.

EP452

Influence of a part of Korean red ginseng on blood glucose control and

complication markers of type 2 diabetic NSY rats

Introduction

Jung Hye Kim, Kahui Park, Sang Bae Lee, Ji Hong You, Yusik Kim,

Pheochromocytomas are secreting tumors, producing catecholamines (dopamine,

Jong Suk Park, Ji Sun Nam & Chul Woo Ahn

noradrenaline and adrenaline), responsible for arterial hypertension; Pheochro-

Gangnam Severance Hospital, Seoul, Republic of Korea.

mocytoma in the diabetic may be responsible for an unbalanced glycemic and this

considerably modifies the management. We present the case of a patient for whom

the diagnosis of pheochromocytoma was posed before a glycemic imbalance.

Objective

Clinical case

Ginsenoside or saponin, is considered as the major bioactive component

A 70-year-old patient is hospitalized for unexplained unstable diabetes mellitus

mediating the therapeutic properties of Korean red ginseng (KRG). However,

(Several episodes of severe hypo-hyperglycaemia per week with a 7.5% Hba1c. It

the exact physiological mechanism underlying anti-diabetic effects is still not

is diabetes mellitus evolving for 20 years, marked by instability of glycemic

fully Clarified. More than 30 different saponins together account for only about

figures For

3 years, during his hospitalization for management of severe

3-4% of KRG, thereby, it is assumed that non-saponin fraction of KRG also carry

hypertension was discovered associated with headache and slimming.Infectious

potential anti-diabetic effects; however, there is no study reporting the

and inflammatory balance without anomaly, no lipodystrophy, in search of

differentiated effects of saponin and non-saponin fractions of KRG on glycemic

endocrinopathy responsible for this hypertension and unstable diabetes Biological

indications and hyperglycemia-associated complication markers.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

adressin MAdCAM-1, chemokine receptors CXCR4 and CCR7. Sphingosine-1-

12-week-old male Nagoya-Shibata-Yasuda (NSY) mice were allocated into 4

phosphate receptors S1PR1 activate T-cell exit from MLN.

groups: control group given standard rodent diet (SRD) or treatment groups given

Methods

either Korean red ginseng extract (KRG), saponin fraction from KRG extract

We use RT-PCR method for investigating of mRNA expression levels of genes

(Spn) or non-saponin fraction from KRG extract (NSpn) admixed in SRD. The

MAdCAM-1, CXCR4, CCR7 and S1PR in MLN of the offspring of rats with

targeted administration doses of KRG, Spn and NSpn were all 200 mg/kg/day; all

experimental gestational diabetes. To determine the level of target genes was

mice were fed assigned regimens for 24 weeks. Parameters for glycemic control,

performed RT-PCR in real-time by thermocycler CFX96e Real-Time PCR

blood lipid profile, inflammation, oxidative stress, and anti-oxidant enzymatic

Detection Systems. The relative level of gene expression were studied with rat

activities were measured.

reference genes GAPDH by the method_DDCt. Statistical analysis were conducted

Results

using available software «Bio-Rad CFX Manager 3.1» (Bio-Rad, USA).

KRG had positive effects on glycemic control by attenuating the increase in FBG

Results

at 24-week and by increasing glucose clearance and insulin response during i.p.

Expression analysis of homing receptors in MLN revealed an expected significant

GTT as compared to control. KRG also attenuated increases in TNF-a, oxidized

increasing of CCR7 and MAdCAM-1 mRNA in offspring of animals with EGD,

LDL (oxLDL), advanced glycation end-products, and accumulation of

indicating the activation of the immune cells in the GALT, which is accompanied

malondialdehyde in skeletal muscle. Spn had a positive effect on insulin response

by intensification of lymphocytes homing and confirms the involvement of these

while NSpn attenuated oxLDL as compared to control.

receptors in the pathogenesis of diabetes. We were unable to detect changes in the

Conclusion

mRNA levels of another regulator - CXCR4 in MLN of the offspring of rats with

This study showed that anti-diabetic properties of KRG are not mainly mediated

EGD. Increased expression level of S1PR1 mRNA of MLN lymphocytes in the

by saponin, but the therapeutic potentials of KRG may be due to the orchestral

offspring of animals with diabetes confirms its important role in the progression of

effects of both saponin and non-saponin.

diabetes.

DOI: 10.1530/endoabs.49.EP452

Conclusions

Signals of chemokine receptors affect the activation of different Th cells subsets

and we may assume their pivotal role in the development of autoimmune diseases,

particularly diabetes mellitus. The revealed changes evidence of abuse of

formation of peripheral immunological tolerance and can trigger the development

of AID in the offspring of mothers with EHD.

DOI: 10.1530/endoabs.49.EP454

EP453

The prevalence of diabetic neuropathy, painful diabetic neuropathy and

the at risk diabetic foot in Qatar

Tarik Elhadd¹, Georgios Ponirakis², Khaled Ashawesh¹, Khaled Dukhan¹,

Adel Badie Abou Samra¹ & Rayaz Malik^1,2

¹Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar;

²Weil Cornell Medical College, Doha, Qatar.

EP455

Study of expression of genes mTOR, Foxp3, IL1b and IL17A in

Objective

parapancreatic adipose tissue of rats with streptozotocin-induced

To define the prevalence of Diabetic Peripheral Neuropathy (DPN), painful

diabetes and after metformin administrations

diabetic neuropathy (PDN) and the at risk diabetic foot in 2 out of the 3 National

Denis Putilin, Alex Kamyshny & Vita Kamyshna

Diabetes Centres in Qatar.

ZSMU, Zaporozhye, Ukraine.

Methods

712 people with Type-1 & Type-2 diabetes recruited from Alwakra Hospital and

Introduction

Hamad General Hospital underwent assessment for DPN & PDN using the

mTOR is not only a central regulator of lipid metabolism, controlling the

Neurothesiometer and the DN4 questionnaire, respectively.

processes of adipogenesis and lipolysis, but also a regulator of immunometabo-

Results

lism of immune cells infiltrating the adipose tissue. In its turn, the level of

The average age, duration of diabetes, systolic BP, BMI, HbA1c were: 52.2G

progression of diabetes is largely limited by Treg subpopulation, the complexity

0.49, 10.8G0.32 years, 132.6G1.26 mmHg, 32.2G0.52 kg/m2 and 8.3G0.11%,

and heterogeneity of which is confirmed by the detection of numerous tissue-

respectively. The prevalence of DPN and PDN were 31% and 36%, respectively.

specific Tregs, including the so-called VAT Tregs (visceral adipose tissue CD4C

However, 4 in 5 adults with DPN and 9 in 10 adults with PDN were undiagnosed.

Foxp3C regulatory T cells). Therefore, the purpose of the work was to find out

One in ten adults with diabetes were at high risk for diabetic foot ulceration (VPT

the level of expression of mRNA genes of mTOR, Foxp3, IL1b and IL17A in

O25) and had not been diagnosed. Patients with DPN were significantly older

parapancreatic adipose tissue of rats with experimental streptozotocin-induced

(57.1G0.73

v 49.8G0.62, P!0.0001), had a longer duration of diabetes

diabetes after introduction of metformin.

(14.34G0.57 v 9.1G0.36, P!0.0001), higher systolic blood pressure (139.8G

Methods

2.25 v 129.2G1.46, PZ0.001) and higher creatinine (118.6G16.76 v 70.9G2,

We use RT-PCR method for investigating of mRNA expression levels of genes

PZ0.007), but no difference in HbA1c (8.6G0.21 v 8.2G0.13), vitamin D

mTOR, Foxp3, IL1b and IL17A. To determine the level of target genes was

(23.7G1.7 v 23.3G0.9) or B12 (344.7G39.17 v 323G21.3).

performed RT-PCR in real-time by thermocycler CFX96e Real-Time PCR

Conclusion

Detection Systems. The relative level of gene expression were studied with rat

The overall prevalence of DPN, PDN and those at risk of foot ulceration in Qatar

reference genes GAPDH by the method_DDCt. Statistical analysis were conducted

are comparable to that reported in Europe and the US. However, an alarmingly

using available software «Bio-Rad CFX Manager 3.1» (Bio-Rad, USA).

low proportion of patients are diagnosed and treated for DPN and PDN. There is a

Results

need for a systematic screening for DPN and PDN in Qatar. Age, duration of

the development of diabetes causes the transcriptional activation of the gene of

diabetes, blood pressure and high creatinine are risk factors for DPN.

the protein kinase mTOR, does not affect the expression of mRNA of Foxp3,

DOI: 10.1530/endoabs.49.EP453

increases the level of expression of mRNA of proinflammatory cytokines IL1b

and IL17A. At the same the introduction of metformin in diabetic rats inhibits the

expression of mRNA of mTOR and increases the level of transcriptional activity

of the gene Foxp3 in parapancreatic adipose tissue.

DOI: 10.1530/endoabs.49.EP455

EP454

Changes in gene expression MADCAM1, S1PR1, CXCR4 and CCR7 in

offspring of rats with experimental gestational diabetes

EP456

Tanya Prozorova, Alex Kamyshny & Vita Kamyshna

Response to stroke in diabetic versus non-diabetic patients. Should

ZSMU, Zaporozhye, Ukraine.

Diabetes education systematically include advise on stroke symptoms

and the correct response to them?

Introduction

Paloma González-Lázaro¹, Julia Silva-Fernández¹, Rafael García-Ruiz²,

Mesenteric lymph nodes (MLN) is a major transition point for recirculating

Rosa García-Ruiz³, Francisco Javier Gómez-Alfonso¹, Florentino Del

lymphocytes of GALT. Homing of lymphocytes in MLN is regulated with

Val-Zaballos¹, Belvis Torres-Arroyo¹ & Carolina González-Pereira⁴

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Endocrinology Service. Mancha Centro Hospital, Alcázar de San Juan,

Conclusion

Spain;²Neurology Service. Manca Centro Hospital, Alcázar de San Juan,

This study showed no association between the rs1746661

and rs3480

Spain;³Internal Medicine, Marina Salud Hospital, Denia, Spain;⁴Unit Care

polymorphisms and GDM; however, the rs1746661T mutated allele seems to

Department, Hospital Universitario central de Asturias, Asturias, Spain.

be associated with increased SBP in pregnant women independently of GDM.

DOI: 10.1530/endoabs.49.EP457

Introduction

Stroke is the second cause of death in the world and the first cause of disability. It

is also the second cause of Diabetes-related death. The success of reperfusion

therapies is time-dependent, with most delays being patient-related. We

investigated the response to stroke in diabetic patients (DM), as their risk of

stroke is increased by 1,8-6 times.

Material and Methods

EP458

Consecutive patients with acute stroke or transient ischemic attack were

The relations of apelin with the carbohydrate metabolism in

prospectively included. Sociodemographic and clinical data, time from stroke

hypertensive patients with type 2 diabetes or without it

onset to decision to seek medical attention (Decision delay (DD)) and to hospital

Sergiy Koval, Kostiantyn Iushko & Tatyana Starchenko

arrival (Prehospital Delay (PD)) and first medical contact (FMC) were obtained.

L.T.Malaya Therapy National Institute of the NAMS of Ukraine, Kharkiv,

Decision to call the 112 Emergency Services (112-ES) within the first 15 min was

Ukraine.

considered the correct decision.

Results

Purpose

382 patients were included. 138 (36,1%) were diabetic. DD was ! 15 min in 41

The aim of the study was to evaluate the relationships of apelin with the

(29,7%) DM vs 57 (23,4%) non-diabetic patients (non-DM) (PZ0,17). FMC was

parameters of the carbohydrate metabolism in hypertensive patients with type 2

112-ES in 20 (14,5%) DM vs 50 (20,5%) non-DM (PZ0,14), and a correct

diabetes (T2D) and without T2D.

decision was made in 13 (9,4%) DM vs 32 (13,1%) non-DM (PZ0,28). PD was

Methods

!60 min in 14 DM vs 29 non-DM. No significant differences were found after

The study involved 93 patients with hypertension grades 2-3 combined with T2D

adjustment for potential confounders.

or without it (45 men and 48 women) in age from 43 to 70 years old. The

Conclusions

investigation complex included measuring levels of fasting blood glucose, fasting

Response to stroke symptoms in DM was not different to non-DM, while carrying

blood insulin with insulin resistance index calculation

(HOMA), glycated

a greater load of vascular risk factors and a higher risk of stroke. Even more,

hemoglobin (HbA1c). The blood level of apelin was tested using an Enzyme-

although not significant, the use of the 112-ES was quite lower in DM. We

linked immunosorbent assay. Two groups of patients were formed:

propose to systematically incorporate information on stroke risk, symptoms,

hypertensive patients with T2D (nZ63), 2. hypertensive patients without T2D

consequences and how to respond to stroke into DM education.

(nZ30). The control group consisted of 14 practically healthy volunteers.

DOI: 10.1530/endoabs.49.EP456

Results

The levels of apelin in both groups were significantly lower than in control group

0,882(0,788;0,924) ng/ml in hypertensive patients with T2D and

0,886(0,846;0,937) ng/ml in hypertensive patients without T2D versus

1,097(0,944;1,171) ng/ml in healthy volunteers

(P!0,001

and P!0,01

respectively). The significant difference in apelin levels between patients with

T2D and without T2D has been not found (PO0,05). The hypertension patients

with T2D had significant negative correlations of the apelin with HbA1c

(rZK0,45, P!0,05), insulin (rZK0,48, P!0,05) and HOMA (rZK0,47,

P!0,05). The patients without T2D had significant positive correlations of

the apelin with insulin (rZ0,71, P!0,001) and HOMA (rZ0,76, P!0,001). The

EP457

levels of apelin were significantly higher in the patients without T2D, but with the

The T allele of the rs1746661G/T polymorphism in FNDC5 (irisin) gene

insulin resistant

(HOMAO2,77), than in patients without T2D and normal

is associated with increased systolic blood pressure

HOMA - 0,937(0,916;1,112) ng/ml versus 0,851(0,839;0,884) ng/ml, P!0,001.

Leticia A. Brondani, Ana Paula Bouças, Tais S. Assmann, Angela

Conclusion

J. Reichelt, Sergio Martins-Costa, Leticia S. Weinert, Sandra P. Silveiro,

The presented data are confirmed the compensatory increasing of the antidiabetic

Bianca M. de Souza & Daisy Crispim

apelin factor in the initial manifestations of carbohydrate metabolism disorders

Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

and its subsequent decline is associated with the development of the T2D.

DOI: 10.1530/endoabs.49.EP458

Background

Gestational diabetes mellitus (GDM) is a risk factor for type 2 diabetes and both

conditions are characterized by insulin resistance (IR) and decreased insulin

production by pancreatic beta-cells. FNDC5 gene encodes a type I membrane

protein that is proteolytically processed to form a hormone secreted into the

blood, termed irisin. After induction by exercise, irisin activates profound

changes in the subcutaneous adipose tissue, stimulating browning and UCP1 gene

EP459

expression. This causes a significant increase in total body energy expenditure

Maturity-onset diabetes of the young type 5 (mody 5): a case report

and resistance to obesity-linked IR. Studies have shown that circulating irisin is

Carlos Silva Vaca, Elena García Fernandez, Juan Carlos Romero Rodriguez

decreased in women with GDM and the FNDC5 gene is also expressed in the

& Guillermo Martinez

human placenta. Thus, genetic variants in FNDC5 gene may be associated with

Hospital Universitario 12 de Octubre, Madrid, Spain.

DGM.

Objective

To evaluate if the polymorphisms rs3460A/G and rs1746661G/T in the FNDC5

Introduction

gene are associated with GDM and/or its clinical features.

MODY 5 is a rare type of dominantly inherited diabetes mellitus. It is asociated

Methods

with mutations of the hepatocyte nuclear factor-1beta (HNF-1beta) gene. They

We analyzed 132 pregnant women without GDM (controls) and 219 pregnant

are mostly missense mutations that produce truncated proteins with a variable

women with GDM (cases). Polymorphisms were genotyped by Real-Time PCR

clinical spectrum that encompasses among others: kidney, genital and pancreatic

using TaqMan MGB probes. Haplotypes constructed from the combination of

abnormalities.

rs1746661 and rs3480 polymorphisms were inferred using the Phase 2.1 program.

Case-report

Results

A 35 years-old man without relevant medical history, presented with acute

Genotype and allele frequencies of the rs1746661 and rs3480 polymorphisms did

hypergycemia (541 mg/dl) and ketosis but wihout metabolic acidosis. He had had

not differ significantly between cases and controls (PO0.05). The haplotype

cardinal symptoms for a 2-week period before presentation. Further investigation

frequencies also did not differ between the two groups (PZ0.913). Interestingly,

revealed a diagnosis of early onset diabetes in his mother, three siblings and a

patients carrying the T allele of the rs1746661 polymorphism had higher values of

niece who also had undergone nephrectomy due to polycystic kydney disease.

systolic blood pressure (SBP) than patients with the A/A genotype (127.2G18.7

Laboratory workout revealed acute renal injury

(MDRD4 57.2 ml/min per

vs 122.9G17.3 mm/Hg; PZ0.004), adjusting for the use of antihypertensive

1.73 m²) and elevated liver enzymes with a cholestatic pattern (Gamma-GT

medications.

74U/l; Alkaline Phosphatase 154 U/l; Bilirrubin 1.7 mg/dl), both resolved before

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

discharge. No other abnormalities were detected. Abdominal US was normal.

malnutrition and sarcopenia were different in diabetic patients compared with the

During hospitalization, the patient progressively achived adecuate glucose and he

group of non-diabetics.

was discharged with a basal-bolus insulin regimen, pending on the results of

Methods and material

pancreatic autoimmunity, and the performance of a magnetic cholangioreso-

A total of 312 institutionalized elderly people volunteers with a mean age of O65

nance. During follow-up the patient showed no evidence of islet-cell antibodies

years were selected, being

207 women and 105 men. They had preserved

nor glutamic acid decarboxylase autoantibodies (Anti GAD65 0.46 IU/ml, Anti

functional capacity and absence of cognitive impairment. Anthropometric

IA2 2.13 U/ml, anti insulin 0.51 U/ml), a C- peptide of 237 ng/ml and the

variables were measured, test of physical performance were carried out and

magnetic cholangioresonance that revealed aplasia of the dorsal pancreas. The

muscle mass was determined by bioelectrical impedance analysis (BIA). For the

diagnosis of MODY 5 diabetes was made after a genetic study for detecting HNF-

diagnosis of sarcopenia, the criteria recommended by the European Working

1beta gene mutations confirmed a missense mutation (M_000458.2:c.884GOA -

Group on Sarcopenia in Older People (EWGSOP) were used, which consist of

p.Arg295His-) in the DNA-binding homeodomain. The insulin was progressively

using the presence of both low muscle mass and low muscle function (strength or

withdrawn and metformin was introduced.

performance), and the method to evaluate if the patients had malnutrition was the

Conclusion

Mini Nutritional Assessment test.

MODY 5 encompasses a wide clinical spectrum. Analysis for mutations of HNF-

Results

1B is warranted in young patients with an AD pattern family history of diabetes

The prevalence of type 2 diabetes mellitus in this population was 21.15%, being

particularly when pancreatic atrophy, kidney or genital abnormalities are present.

57.6% of them women and 42.4% men (P 0.089). There were statistically

DOI: 10.1530/endoabs.49.EP459

significant differences in the variables age, weight, BMI, arm circumference,

tricipital skinfold and abdominal circumference, between diabetic and non

diabetic people, being all this variables higher in the diabetic group. According to

the results of the MNA test, the prevalence of malnutrition in the diabetic group

was of 52.2%, while in non diabetic people was 44% (P!0,05), and with regards

to the prevalence of sarcopenia, there were statistically significant differences

between the non diabetic group, in which the prevalence of sarcopenia was

27.3%, and diabetic people, with a higher prevalence (36.58%).

EP460

Conclusion

New-onset diabetes after transplantation (NODAT): an evaluation of

The prevalence of type 2 diabetes was 21.15%, which was higher in women than

risk factors in renal transplantation

in men, without statistically significant differences. Moreover, there were

Raquel Almeida, Andreia Campos, La Salete Martins & Jorge Dores

significant differences in the anthropometric parameters evaluated and the

Centro Hospitalar do Porto, Porto, Portugal.

prevalence of malnutrition and sarcopenia was higher in the diabetic group.

DOI: 10.1530/endoabs.49.EP461

Background

The identification of patients with high risk of diabetes mellitus (DM) after renal

transplantation in the pre-transplantation period is crucial for the prevention of

this pathology and reduction of the risk of cardiovascular morbidity and mortality.

With this study we intended to identify the risk factors for NODAT in renal

transplantation.

EP462

Methods

All patients submitted to renal transplantation at Centro Hospitalar do Porto

New onset diabetes after transplantation (NODAT): frequency and

between 01/01/2009 and 12/31/2013 were retrospectively evaluated. Patients with

characterization of patients in renal transplantation

history of DM, transplantation of more than one organ, younger than 18 years at

Raquel Almeida, Andreia Campos, La Salete Martins & Jorge Dores

transplantation, and patients with less than 6 months of follow-up were excluded.

Centro Hospitalar do Porto, Porto, Portugal.

DM was defined according to WHO criteria. To identify risk factors for DM, two

groups were formed: people with diabetes (DMC) and without diabetes (DMK).

Background

Results

The identification of patients with NODAT in renal transplantation is essential to

Of the 556 patients undergoing renal transplantation, 247 patients were excluded

establish adequate treatment and to reduce cardiovascular risk and graft failure.

and 309 patients were eligible for the analysis. A total of 68 patients (22%) with

With this study we intended to evaluate the frequency of NODAT and to

DM criteria were identified, with a mean time to onset of the disease of 8.9G15.3

characterize patients with NODAT in renal transplantation.

months posttransplant. Patients were followed for an average of 4.2G1.5 years

Methods

(DMC) and 4.2G1.8 years (DMK). DM C patients were significantly older at

All patients submitted to renal transplantation at Centro Hospitalar do Porto

the time of transplantation (54.1G11.5 vs 45.7G13 years, P!0.001), had higher

between 01/01/2009 and 12/31/2013 were retrospectively evaluated. Patients with

frequency of family history of DM (30.9% (P!0.001), higher obesity rate (17.6%

a history of DM, transplantation of more than one organ, younger than 18 years at

vs 4.6%, P!0.001) and higher deceased-donor rate (86.8% vs 75.5%, PZ0.048).

transplantation, and patients with less than 6 months of follow-up were excluded.

There was no statistically significant difference between groups in recipient sex

DM and intermediate hyperglycemia were defined according to WHO criteria.

distribution, donor age and sex, renal disease etiology, immunosuppressive

Patients with hyperglycemia in the postoperative period were considered diabetic

therapy used or HCV/CMV infection occurrence.

only if they maintained criteria 3 months after transplantation.

Discussion and conclusion

Results

The only modifiable pre-transplant risk factor found is obesity, whereby a healthy

Of the 556 patients undergoing renal transplantation, 247 patients were excluded

lifestyle and weight loss should be encouraged within the specific limitations of

and 309 patients were eligible for the analysis. DM screening was performed on

patients with end-stage renal disease. Since cardiovascular diseases are the main

all patients by assaying fasting blood glucose; No patient performed PTGO; 88

cause of morbidity and mortality in these patients, a tight control of all vascular

patients (28.5%) had no recorded HbA1c. The mean follow-up time was 4.2G1.7

risk factors is required.

years; 99 patients (32.4%) presented alterations in glucose metabolism: 68 (22%)

DOI: 10.1530/endoabs.49.EP460

DM criteria,

(5.5%) fasting glucose anomaly and

(4.5%) transient

postoperative hyperglycemia. The mean time to onset of DM was 8.9G15.3

months, with 73.5% of the diagnoses performed in the first 6 months after

transplantation. The diagnosis was established through fasting glycemia in 51

patients (75%), HbA1c in 13 (19%) and typical symptoms in 4 (5.9%). Of the 60

patients currently undergoing follow-up, 15 (25%) were without anti-diabetic

EP461

drugs, 22 (36.7%) with non-insulin anti-diabetics and 23 (38.3%) with insulin.

Malnutrition and sarcopenia in diabetic institutionalized older people:

The mean values of fasting blood glucose and HbA1c are 113G33 mg/dl and

are there differences with non diabetic people?

6.8G1.4%, respectively.

Beatriz Lardiés-Sánchez¹, Alejandro Sanz-París², Guayente Verdes-Sanz³

Discussion and conclusion

& Leticia Pérez-Fernández²

We believe that the prevalence of DM found is underestimated considering the

¹Royo Villanova Hospital, Zaragoza, Spain;²Miguel Servet Hospital,

use of fasting glycemia as a preferential screening method, which is not very

Zaragoza, Spain;³Obispo Polanco Hospital, Teruel, Spain.

sensitive to the diagnosis of DM in patients undergoing corticosteroid therapy.

PTGO would be a valuable complementary diagnostic test to increase diagnostic

Backgrounds and aims

sensitivity, especially in patients with fasting blood glucose anomalies or classic

The aims of the study were, on the one hand, to analize the prevalence of type 2

risk factors for DM.

diabetes mellitus in a population of institutionalized older people and, on the other

DOI: 10.1530/endoabs.49.EP462

hand, to evaluate if the anthropometric parameters and the prevalence of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP463

Conclusion

The evaluation of modified HOMA-IR and HOMA-islet indices before the start of

Incidence of diabetic ketosis and ketoacidosis in Caucasian adults with

intensive GC treatment and during OGCT may improve early detection of risk

type 2 diabetes mellitus: a population-based study

Petra

aći

´¹, Ivan Kruljac², Miroslav

aćic´2, Božidar Perić2,

groups for serious CMDs - IGT and DM.

Maja Filipovi

´-Grči

´², Gorana Miroševic´2 & Milan Vrkljan1,2

DOI: 10.1530/endoabs.49.EP464

¹University of Zagreb School of Medicine, Zagreb, Croatia;²University

Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia.

Aims

Diabetic ketosis (DK) and diabetic ketoacidosis (DKA) are known complications

of type 1 diabetes mellitus (T1DM). However, DK and DKA have been described

EP465

in T2DM. Referred to as ketosis-prone T2DM, this subtype of T2DM has been

described in Hispanics and Afro-Americans of sub-Saharan Africa, but the

Carbohydrate metabolism disorders associated with different

incidence and pathogenesis remains unknown. We aimed to analyze charac-

glucocorticoid therapy schemes

Guzel Nurrulina, Farida Valeeva & Kamilya Khasanova

teristics of patients with diabetic ketosis (DK) and diabetic ketoacidosis (DKA) in

Kazan Medical State University, Kazan, Russia.

Caucasian adults with T2DM.

Methods

Studied population included 261 749 adults. DK criteria included plasma glucose

Introduction

O13.9 mmol/l, and ketonuria O2; while in DKA bicarbonate !18 mEq/l or

Glucocorticoid therapy

(GCT) is one of the risk factors of carbohydrate

pH!7.30 was also required. Hyperglycemic crises without these criteria were

metabolism disorders (CMD) in patents with systemic inflammatory diseases.

defined as non-ketotic hyperglycemia (NKH).

CMD development is a concern not only with long-term therapy, but also during

Results

intensive short-term glucocorticoid

(GC) administration, which can lead to

During 5-year period, we observed 630 episodes of DK and 215 episodes of DKA.

different CMDs, including impaired glucose tolerance

(IGT) and diabetes

Only 8.6% of DK episodes and 34.4% of DKA were attributed to T1DM. Patients

mellitus (DM).

with T1DM were younger, leaner, majority had newly diagnosed disease, and

Aim

hyperglycemia was the main cause of admission. Stadardized incidence ratio for

To evaluate the prevalence of CMD after long-term and intensive GCT in patients

DK was 48.1 (95% CI 44.5-52.1) and 17.0 (95% CI 14.9-19.4) for DKA.

with systemic lupus erythematosus (SLE), systemic vasculitis (SV) and chronic

Incidence for both DK and DKA was increasing with age. Patients with T2DM

glomerulonephritis (CGN).

had a risk of 0.8% for developing DKA and 2.9% for DK over 5-year period.

Patients and methods

Conclusions

The study included 165 patients, among them with SLE - 53, SV - 35 and CGN -

Our study showed that DK and DKA are not uncommon in Caucasian adults and

67 patients. Ninety-eight patients received GC pulse-therapy (GCPT) (one series

the majority of episodes were contributed to T2DM. Further studies are needed to

of three sessions), and 67 - oral GCT (OGCT). All patients underwent standard

assess the impact of these clinical entities.

clinical and laboratory evaluation, oral glucose tolerance test (OGTT), evaluation

DOI: 10.1530/endoabs.49.EP463

of C-peptide, HOMA-IR and HOMA-islet indices.

Results

CMDs developed less often in patients receiving GCPT compared to long-term

OGCT (PZ0.035). In patients receiving OGCT the most prevalent CMDs were

IGT and DM - in 21 (31.1%) and 19 (28.4%) patients respectively, which was

significantly higher compared to patients in GCPT group (PZ0.038 and PZ

0.049). In both groups of patients with DM and IGT baseline C-peptide and

HOMA-IR before the treatment and OGTT was higher than in patients without

CMD or with IFG, which indicates the presence of insulin resistance in this

patient group. In DM patients a decrease of HOMA-islet index was observed in

the first group from 13.96 before OGTT to 11.8 after glucose load and in the

second group from 147 at baseline to 78.4 after the test.

EP464

Conclusion

HOMA-IR and HOMA-islet indices in the evaluation of different

GCT leads to IGT and DM in patients with increased insulin resistance both

carbohydrate metabolism disorders during glucocorticoid therapy

during GCPT and long-term OGCT. Long-term OGCT is associated with more

Guzel Nurrulina, Farida Valeeva & Kamilya Khasanova

CMDs compared to GCPT.

Kazan Medical State University, Kazan, Russia.

DOI: 10.1530/endoabs.49.EP465

Introduction

Diabetogenic effect limits the use of glucocorticoids (GC).

Aim

To evaluate the role of modified HOMA-IR and HOMA-islet indices in different

carbohydrate metabolism disorders (CMD) during oral (OGCT) and PULSE

(GCPT) glucocorticoid therapy (GCT).

EP466

Patients and methods

Type B insulin resistance syndrome in a patient with connective tissue

A study including 165 patients with systemic lupus erythematosus (nZ53),

disease

systemic vasculitis

(nZ45) and chronic glomerulonephritis

(nZ67) was

Agnieszka Lebkowska¹, Anna Krentowska¹, Agnieszka Adamska¹,

performed. 98 patients received GCPT (course dose - 1800-3000 mg) and 67 -

Beata Piasecka¹, Danuta Lipinska¹, Otylia Kowal-Bielecka²,

OGCT 15-30 mg/day.

Robert Semple³, Maria Gorska¹ & Irina Kowalska¹

Results

¹Department of Endocrinology, Diabetology and Internal Medicine,

GCPT was associated with less CMD compared to OGCT. Impaired fasting

Medical University of Bialystok, Bialystok, Poland;²Department of

glucose (IFG) was observed in 8 (8.2%) and 14 (20.9%), impaired glucose

Rheumatology and Internal Medicine, Medical University of Bialystok,

tolerance (IGT) - in 13 (13.3%) and 21 (31.3%) and diabetes mellitus (DM) - in

Bialystok, Poland;³The University of Cambridge Metabolic Research

(12.2%) and 19 (28.4%) patients receiving GCPT and OGCT, respectively.

Laboratories, Wellcome Trust-MRC Institute of Metabolic Science,

There was a significant decrease of HOMA-islet during glycemic peak in DM

Addenbrookes Treatment Centre, Cambridge, UK.

patients from 13.96 to 6.17 after GCPT (P!0.05), compared to insignificant

changes in other groups. After a course of GCPT HOMA-islet was significantly

lower in DM patients compared to patients with no CMD (11.8 vs. 15.4). No rapid

Introduction

decrease of b-cell function was observed in OGCT group, instead there was a

Type B insulin resistance syndrome is an autoimmune disorder characterized by

compensatory increase. Significant differences were observed in patients

the production of autoantibodies against the insulin receptor. It leads to glucose

receiving OGCT both at baseline and after OGTT on HOMA-IR (4.53 vs. 9.81

metabolism disorders, extreme insulin resistance, hyperandrogenism and is

in patients with IGT; 5.6 vs. 11.27 in patients with DM); no differences were

associated with other features of autoimmunity.

observed in patients without CMD (2.59 vs. 2.88) and with IFG (2.88 vs. 5.85). A

Case report

significant decrease of b-cell function was observed in DM patients, reflected by a

A 27-year-old man, with a 2-years history of psoriasis, was admitted to our

decrease of HOMA-islet after OGTT compared to baseline (147 vs. 78.4).

Department because of loss of weight (20 kg in 1 year) and fatigue. He also

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

reported Raynaud’s phenomenon. One year earlier the patient underwent careful

from the emergency department, during August 2017. Excluded patients who

haematological assessment because of peripheral lymphadenopathy and enlarged

were diabetic (phase 1). Non diabetic integrated a 3 phase study: phase 2 -

parotid glands, which showed changes characteristic for viral infection. Screening

Capillary glycemia evaluation 2 h after first meal; if O140 mg/dl, patient did

for cancer was negative. On admission, physical examination revealed

another evalution (fasting, 2 h after meal) (phase 3); if patient still hyperglicemic,

malnutrition

(BMI 16.4 kg/m²), acanthosis nigricans, sclerodactyly, psoriatic

the evaluated HbA1c and hemoglobine (phase 4).

lesions, enlarged parotid glands, palpable cervical and axillary lymph nodes,

Results

tachycardia. Laboratory analyses revealed anaemia, leucopaenia with lympho-

Evaluated 317 patients (121 diabetic, 196 non diabetics). Non diabetic group: 89

paenia, thrombocytopaenia, blood glucose concentration

361 mg/dl with

female, 107 male, age average 68.75G18.55 years, 75 patient from IM, 75 from

tendency to morning hypoglycaemia, HbA1c - 12.4% and glycosuria. Fasting

GS, 33 from OT and 13 from SU. 134 patients finished in phase 2, 47 in phase 3

C-peptide concentration was normal and increased adequately in glucagon

and 15 in phase 4. From patients that finished in phase 4, A1c average was 6.12G

stimulation test (0⁰ 2.87 ng/ml, 6⁰ 4.56 ng/ml). Fasting insulin concentration was

1.3% (four: A1c R6.5% and three: 5.7 !A1c ! 6.5%). In the previous group,

extremely high (O300 mIU/ml). In hyperinsulinaemic euglycaemic clamp insulin

only one patient had a hemoglobine

!12 g/dl and three were under

sensitivity index was decreased (M-2.1 mg/kg FFM/min). We confirmed the

corticosteroids. There was no statiscal signficance between glucose values and

presence of anti-insulin-receptor antibodies, indicating type B insulin resistance

the section of internament or days of hospital admission.

syndrome. Anti-GAD, IAA, IA2 antibodies were negative. Based on the clinical

Discussion

features, presence of antinuclear antibodies, anti-RNP/Sm antibodies, and

In the non diabetic group we calculated a 23.98% of ‘Stress Hyperglycemia’,

positive direct Coombs test diagnosis of mixed connective tissue disease/lupus

7.66% of the patients were at higher risk of developing diabetes, because they had

erythematosus was made. Tumour of blood cells was excluded. Firstly patient was

at least two hyperglycemic values and 2.04% were positive for Diabetes Mellitus

treated with insulin and metformin and then with metformin, prednisone and

(HbA1c R6.5%). The study identified a relevant percentage of people with a

chloroquine phosphate, which resulted in weight gain, normalization of blood

higher risk of developing diabetes, but a small percentage of people with diabetes;

glucose levels (HbA1c - 7.3%) and improvement of blood cell counts and skin

this might be explained by the efficiency of the national screening programmes.

lesions. Currently the patient is under metformin and hydroxychloroquine

DOI: 10.1530/endoabs.49.EP468

therapy.

Conclusion

We presented a case of severe type B insulin resistance syndrome, associated with

another autoimmune disease. Anti-insulin-receptor antibodies are crucial to

recognize the syndrome. The treatment is challenging and requires multi-

disciplinary approach.

DOI: 10.1530/endoabs.49.EP466

EP469

Evaluation of oral glucose tolerance test as a screening test detecting

glucose metabolism impairment in patients chronically treated with

glucocorticoids without previous history of diabetes

Karolina Nowak¹, Katarzyna Romanowska-Prochnicka^2,3,

EP467

Katarzyna Bornikowska¹, Wojciech Zgliczynski¹ & Lucyna Papierska¹

Parvovirus B19 infection may have a role in the etiopathogennesis of

¹Department of Endocrinology, Centre of Postgraduate Medical Education,

type 1 DM

Warsaw, Poland;²Department of General and Experimental Pathology,

Hasan Huseyin Gumuscu¹, Kevser Onbasi¹ & Nilgun Kasifoglu²

2nd Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland;

¹Dumlupinar University, Kutahya, Turkey;²Eskisehir Osmangazi

³Department of Systemic Connective Tissue Diseases, Eleonora Reicher

University, Eskisehir, Turkey.

National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw,

Poland.

Parvovirus

(Erythrovirus) B19

(EVB19) infection may trigger autoimmune

diseases like SLE, RA, and vasculitis. Parvovirus B19 belongs to the parvoviridae

Introduction

family and to the erythrovirus genus. The etiopathogenesis of autoimmune

One of the most common side effects of glucocorticoid treatment is glucose

diabetes mellitus could not been explained yet. The aim of our study was to

intolerance and diabetes. Although glucocorticoids cause mainly postprandial

investigate whether EVB19 may have a role in the etiopathogenesis of type 1 DM.

hyperglycaemia the International Diabetes Federation, American Diabetes

Therefore have we examined whether EVB19 is more frequent among type 1

Association and The European League Against Rheumatism recommend to

diabetics. 32 patients with type 1 diabetes and 30 control patients were included in

screen patients chronically treated with glucocorticoids by regularly determining

the study. 25 of the 32 type 1 diabetic patients had parvovirus B19 IgG positive

fasting plasma glucose. Such an approach can lead to false negative results. Since

sera. The seroprevalence of IgG parvovirus B19 among controls were in 16 of 30

pre-diabetes and diabetes lead to life-threatening conditions such as chronic renal

persons. This was statistically significant (p level was 0,039). 25-OH vitamin D

failure and myocardial infarction it is important to correctly diagnose these

levels were lower among Parvovirus B19 IgG seropositive patients than higher

conditions.

patients. This may be related to the fact that the immune status is impaired in

Objectives

vitamin D insufficiency. In conclusion, parvovirus B19 infection may play a role

The aim of the study was to evaluate if oral glucose tolerance test (OGTT) is a

in triggering type 1 diabetes and low vitamin D levels may increase susceptibility

better screening tool than plasma fasting glucose levels in diagnostics of diabetes

to parvovirus B 19 infection.

in patients chronically treated with glucocorticoids without previously diagnosed

DOI: 10.1530/endoabs.49.EP467

pre-diabetes or diabetes. The second objective was to determine the risk factors of

developing steroid-induced glucose metabolism impairment.

Material and methods

In 50 patients on GCS treatment diagnosed with connective tissue diseases OGTT

was performed. All participants underwent clinical and biochemical evaluation

(age, sex, time of treatment, current and cumulative dose and type of steroid,

EP468

family history of diabetes, BMI, WHR, HbA1c, HOMA-IR).

Hyperinter study: evaluation of glycemic values in acute inpatients

Results

from medical and surgical units. population without diabetes

13 patients (28%) had impaired glucose tolerance (three of them had coincide

Helena Santos Gonçalves, Anusca Lopes Paixao, Cristina Lameirao,

impaired fasting glucose). One patient (2%) diagnosed with diabetes had normal

Ana Rafael, Marta Gomes, Rita Silva, Rita Queiros, Natália Lopes,

levels of plasma fasting glucose. 36 patients had normal glucose metabolism.

Ana Filipa Rebelo & Paula Vaz Marques

Apart from age the statistical analysis showed no significant difference between

Vila Real Hospital, Centro Hospitalar Trás os Montes e Alto Douro,

groups in the rest of analyzed parameters thus the prediction of risk factors was

Vila Real, Portugal.

impossible.

Conclusions

Introduction

Only by performing OGTT 22% of patients could be correctly diagnosed with

Although inpatients hyperglycemia is a current uneasiness among the medical

pre-diabetes and diabetes. The oral glucose tolerance test is the only standardized

community, its prevalence in Portugal in unknown. We aim to identify ‘Stress

tool that is able to effectively detect the steroid-induced impairment in glucose

hyperglycemia’ and ‘New onset diabetes’ cases in inpatients in a district hospital.

metabolism. It should be performed in every patients chronically treated with

Methods

GCS even without other risk factors of diabetes.

We evaluated inpatients from Internal Medicine (IM), General Surgery (GS),

DOI: 10.1530/endoabs.49.EP469

Orthopedics and Traumatology (OT) and Stoke Unit (SU) departments, admitted

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP470

stressors to maintain metabolic homeostasis). Thus, it is essential to identify key

modifiers of phenotypic plasticity that define individual susceptibility to develop

Impact of exercise training on insulin sensitivity estimated by HOMA

T2D. Particularly, there is emerging evidence that alternative mRNA splicing is

model in elite athletes: association with body composition

dysregulated under adverse metabolic-conditions, such as T2D, in several tissues.

Marina Djelic¹, Sanja Mazic¹, Mirjana Sumarac Dumanovic²,

Therefore, we hypothesized that, as gene expression pattern in PBMCs commonly

Rada Jeremic¹, Ankica Vujovic¹, Tijana Durmic¹, Snezana Cvetkovic³ &

reflects disease-characteristic expression patterns, changes in spliceosome

Dragan Micic²

components of PBMCs may serve as early indicator of MetS/T2D development.

¹Institute of Physiology, School of Medicine, University of Belgrade,

To explore this, the expression of selected components of the major (nZ13) and

Belgrade, Serbia;²Clinic for Endocrinology, Diabetes and Metabolic

minor spliceosome (nZ4), and associated splicing factors (SFs; nZ28) was

Diseases, School of Medicine, University of Belgrade, Belgrade, Serbia;

evaluated in PBMCs of individuals with high risk to develop T2D due to a

³Institute of Forensic Medicine, University of Belgrade, Belgrade, Serbia;

previously occurred cardiovascular event (CORDIOPREV study). Specifically,

⁴Clinics for Pulmology, Clinical Center of Serbia, Belgrade, Serbia.

87 patients that developed T2D during the first 3-year follow-up (43 during the

first, 23 during the second and 21 during the third year) and 87 non-T2D matched

It has been shown that low values of insulin sensitivity have been related to

controls were selected. PBMCs were isolated from basal and post-prandial blood

metabolic diseases. Exercise prescription is crucial to prevent low insulin

at the inclusion in the study. Results revealed that the basal expression of certain

sensitivity in general population, and athletes are good physiological model. If

splicing-machinery components was altered in PBMCs from patients who

this assumption is correct, examine insulin sensitivity in elite athletes should

developed T2D (e.g. SRSF5, U2AF1) compared to controls, especially on those

reflect the positive effect of exercise on insulin sensitivity. The aim of this study

patients that developed T2D in a short-term (first year of study). The most

was to investigate the effects of regular exercise on insulin sensitivity estimated

remarkable changes were observed during the post-prandial response wherein

by HOMA model in elite athletes, as well as the possible relationship the insulin

expression of several SFs (e. g. PTB, Tra2beta) was drastically induced in T2D-

sensitivity with body composition. Sixteen low fat athletes (LFAG, BF!12%),

developing individuals compared to controls, which might suggest that the

15 high fat athletes (HFAG, BFR12%) and 15 sedentary subjects participated in

alteration of these SFs precedes the development of T2D. Taken together, our

study. The subjects underwent to an assessment of body composition. All subjects

results reveal the existence of pre-T2D development-associated spliceosome

were exposed to one bout exercise test on treadmill in order to examine acute

alterations, which could be related to the loss of phenotypic flexibility, and could

changes of insulin response. Blood samples were obtained at rest, immediately

help to predict development of T2D in high-risk patients.

after the exercise test and 30 minutes after recovery. Separated serum were used

DOI: 10.1530/endoabs.49.EP472

for insulin ELISA analysis and glucose levels. Insulin resistance index (HOMA-

IR) was calculated. At rest, LFAG had significantly lower insulin compared to

control group (P!0.05). Also, there were no statistically differences in basal

level of glycaemia and HOMA index between groups. In all three study groups

insulin levels were higher immediately after an acute bout of exercise compared

to baseline values (P!0.05), and remained equal (LFAG, P!0.05 compared to

baseline) or even higher (P!0.05, HFAG, P!0.05, controls) in recovery. There

is no significant correlation between the parameters of body composition and

HOMA-IR in all groups. In conclusion, our findings show that insulin respond to

acute exercise depends on body composition. Acute exercise elicited higher

insulin response in HFAG and controls. Also, these results suggest that chronic

exercise dose not altered insulin sensitivity estimated by HOMA model in elite

athletes.

EP473

DOI: 10.1530/endoabs.49.EP470

Abstract withdrawn.

EP471

Abstract withdrawn.

EP474

Debut diabetes characteristics

María Rosa Alhambra Expósito, Inmaculada Prior Sánchez,

Paloma Moreno Moreno & María Ángeles Gálvez Moreno

Hospital Universitario Reina Sofía, Córdoba, Spain.

Background

The diabetes type 1 (DM1) is a chronic autoimmune disease, it tends to appear in

childhood, its incidence continues to rise and the complications arising from

improper care poses serious health problems for those who suffer. LADA diabetes

is autoimmune diabetes which appear in adults.

Objetive

EP472

To describe the characteristics of the new diabetes debut in our environment.

Material and methods

Dysregulation of the splicing machinery could represent an early,

We included all patients who attended the Diabetes Day Hospital of our hospital

predictive event in the development of type 2 diabetes

for unknown type 1 or MODY diabetes from October 2015 to September 2016.

Emilia Alors-Pérez^1,2,3, Mercedes del Río-Moreno^1,2,3,

Results

Sergio Pedraza-Arévalo^1,2,3, Antonio Camargo⁴, Javier Delgado-Lista⁴,

A total of 43 patients were enrolled. With an average age of 36G13 years, 48.8%

José López-Miranda⁴, Manuel D Gahete^1,2,3, Justo P Castan˜o1,2,3 &

were men. The 34.9% were LADA type diabetics and the rest DM1. At diagnosis

Raúl M Luque^1,2,3

they had a mean BMI of 23G4 kg/m², with an abdominal perimeter of 86G12 cm,

¹Maimonides Institute of Biomedical Research of Cordoba (IMIBIC),

mean arterial tension 116G17/70G12 mmHg. An average glucose concentration

Cordoba, Spain;²Reina Sofia University Hospital (HURS), Cordoba, Spain;

238G106 mg/dl and an HbA1c of 11G3%, initial cholesterol of 173G

³Department of Cell Biology, Physiology and Immunology, University of

40 mg/dl, HDL 46G16 mg/dl, LDL 103G34 mg/Dl was noted. The level of

Cordoba (UCO); CIBER Physi, Cordoba, Spain;⁴Lipids and Athero-

peptide C at the diagnosis was 0.3G0.2 ng/dl (N up to 0.5 ng/dl). In DM-1, 72% of

sclerosis Unit, IMIBIC, HURS, UCO and CIBERobn, Cordoba, Spain.

patients had positive anti-GAD antibodies and 78% had anti-IA2 antibodies. In the

patients with diabetes type LADA 61% had positives only the Anti IA2, 24%

Metabolic syndrome (MetS) and type-2 diabetes (T2D) development is critically

antiGAD, the rest had positives both. Of the patients,

8% associated

affected by the loss of phenotypic flexibility (i.e. the difficulty to cope with

autoimmune thyroid disease. Without other autoimmune comorbidities.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

Results

The incidence of type 1 diabetes and MODY type diabetes is increasing in recent

The study concerned 16 type 2 diabetic patients. Females represent 66.7% and

years. In our setting, 78% of patients with DM-1 have positive antibodies. There

mean age was 55.8G14.73. The mean duration of diabetes was 5.06G4.02 years.

were few comorbidities al diagnosis.

The mean HbA1c was 7.52%. The means of Digit Span test were 5.26 before

DOI: 10.1530/endoabs.49.EP474

Ramadan, 5.80 during Ramadan, and 5.13 after Ramadan. The comparison by

repetitive measures did not show any difference between the three means.

Concerning the Cancellation task test, the comparison showed a significant

difference in the time response and the scores of the tests between the measures

during Ramadan (PZ0.029) and those after Ramadan (PZ0.015).

Discussion

These results show that fasting could impact the spatial recognition in type 2

diabetic patients. However, the evaluation of the short-term memory does not

show any difference between the three periods. We suggest that the difference in

the response time in our patients could be explained by the decrease in the

neuronal activity, secondary to the alteration of the carbohydrates intake cycle.

This suggests the importance of the regularity of the food intake in the

EP475

conservation of an appropriate cognitive functioning. However, this difference in

Effect of vitamin D supplementation on Glucose Tolerance, HOMA

results of the two tests shows the complexity of the neurocognitive processes.

indices and on the risk of GDM in pregnant women with vitamin D

Thus, they represent an interesting way to explore it.

deficiency - a prospective interventional study

Ramesh Jayanthy¹ & Naga Satya Vani Mudiganti²

DOI: 10.1530/endoabs.49.EP476

¹Sai’s Institute of Endocrinology, Hyderabad and Visakhapatnam, India;

²Osmania Medical College, Hyderabad, India.

Background

Vitamin D deficiency and GDM are highly prevalent with long term implications.

Prospective studies to analyse the effect of vitamin D supplementation on glucose

tolerance in pregnant women are limited.

Objectives

Objectives of the study are: 1) To determine the relation between vitamin D

deficiency and HOMA indices and glucose tolerance in the first trimester among

pregnant women. 2) To study the effect of vitamin D supplementation on HOMA

EP477

indices and on the occurrence of GDM in pregnant women with vitamin D deficiency.

Lack of postpartum reclassification test in gestational diabetes - factors

Methods

conditioning loss of follow-up

50 pregnant women in first trimester were enrolled. FPG, 2 hrPG, FPI, Plasma

Rita Bettencourt-Silva^1,2, Pedro Souteiro^1,2, Daniela Magalhães^1,2,

25(OH)D were done and HOMA IR and HOMA B were calculated at baseline and

Sandra Belo^1,3, Ana Oliveira^1,4, Davide Carvalho^1,2, Joana Queirós^1,3 &

at 28 weeks of gestation. Vitamin D deficient women were prescribed 2000 IU of

Diabetes and Pregnancy Study Group Portuguese Society of Diabetology³

vitamin D per day as per ACOG recommendations.

¹Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-

Results

talar São João, E.P.E., Porto, Portugal;²Faculty of Medicine, University of

There was no correlation between 25(OH)vitamin D and FPI, FPG, 2hrPG,

Porto, Porto, Portugal;³Diabetes and Pregnancy Study Group, Portuguese

HOMA IR and HOMA B in both vitamin D deficiency and sufficiency groups in

Society of Diabetology, Porto, Portugal;⁴Outpatient Clinic of Obstetrics and

the first trimester. At 28 weeks of gestation, in the vitamin D deficiency group,

Endocrinology, Centro Hospitalar São João, E.P.E., Porto, Portugal.

significant rise in FPG, 2hrPG, FPI and HOMA IR occurred despite correction of

vitamin D deficiency with supplementation. The risk of GDM was similar in both

Introduction

the groups.

Gestational diabetes mellitus

(GDM) is a risk factor for maternal-fetal

Conclusion

complications and development of diabetes or intermediate hyperglycemia after

There is no correlation between 25(OH)D and HOMA IR, HOMA B, FPG or

2hrPG in the first trimester of pregnancy. Vitamin D supplementation, in pregnant

pregnancy. The follow-up should be done by a multidisciplinary team. After

delivery, all women diagnosed with GDM should undergo an oral glucose

women with vitamin D deficiency, has no role in decreasing the risk of GDM at

tolerance test (OGTT) for reclassification

28 weeks follow up.

Aim

DOI: 10.1530/endoabs.49.EP475

To evaluate the non-adherence factors to reclassification OGTT after GDM.

Methods

A cohort of 5271 Portuguese women from the National Registry of GDM was

studied. Demographic, anthropometric and analytical data and maternal-fetal

outcomes were evaluated. The diagnosis of DGM was made according to WHO

criteria.

Results

In our sample, 1666 (31.5%) women with DGM did not undergo reclassification

OGTT. Of those who underwent OGTT, 92.2% had a normal test, 0.9% diabetes

EP476

and 6.9% intermediate hyperglycemia. The chance of follow-up loss was 46.5%

Rapid tests use in the evaluation of neurocognitive effects of Ramadan

higher in women below

year-old

(ORZ1.465, 95% CIZ1.294-1.660,

fasting in type 2 diabetic patients: Results of a pilot study

P!0.001) and 40.9% higher in those with R3

pregnancies

(ORZ1.409,

Ghizlane El Mghari, Loubna Oukit, Hanane Moata, Salwa Baki &

95%CIZ1.243-1.599, P!0.001). Women treated with insulin during pregnancy

Nawal El Ansari

had increased adherence to the reclassification test (ORZ1.377, 95% CIZ1.222-

Endocrinology Department, CHU Mohammed VI, Marrakesh, Morocco.

1.552, P!0.001), but those with worse glycemic control with HbA1cR5.7% in

Introduction

3rd trimester had 60% more chance of follow-up loss (ORZ1.608, 95% CIZ

Ramadan is the 9th month of the Muslim calendar, where people fast from the

1.318-1.962, P!0.001). The adherence to postpartum reclassification was also

sunrise to the sunset. Despite medical recommendations, 100 million Muslims in

significantly lower when there was fetal (ORZ5.085, 95% CIZ2.402-10.763,

the world with diabetes and 79% of patients with type 2 diabetes fast during

P!0.001) or neonatal (ORZ4.661, 95% CIZ1.365-16.055, PZ0.013) death.

Ramadan.

Age, number of pregnancies, HbA1c in the 3rd trimester and insulin treatment

The aim of our study is to determine the impact of fasting during Ramadan on the

remained statistically significant in the multivariate analysis.

cognitive performances for patients with type 2 diabetes using two fast tests.

Conclusion

Materials and methods

Younger women, with a higher number of pregnancies, worse glycemic control

Patients voluntarily accepted to participate to this study. The socio demographical

and fetal/neonatal mortality associated with pregnancy appear to be more likely to

and metabolical characteristics were collected. The evaluation of the neurocog-

lose the follow-up. Given the risk of diabetes after pregnancy, we should

nitive performances was obtained using two tests: Digit Span test which explores

emphasize the need for OGTT reclassification in the puerperium and define

the short-term memory and Cancellation test which explores the Visio spatial

strategies to promote their accomplishment.

component. Patients were explored before, during and after Ramadan. The results

DOI: 10.1530/endoabs.49.EP477

obtained were analyzed by ANOVA one factor.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP478

and gestation, among pregnant women with T1DM. Older than 26 years old

women has 7.4 times higher risk for negative birth outcome.

Gonarthrosis, Diabetes Mellitus (Type 1 or 2), Leptin, Nesfatin-1

Kadri Yildiz¹ & Kenan Cadirci²

DOI: 10.1530/endoabs.49.EP479

¹Erzurum Palandoken State Hospital, Erzurum, Turkey;²Erzurum Regional

and Educational Hospital, Erzurum, Turkey.

Gonarthrosis is a severe problem of movement system. It is a restrictive health

problem for modern human. And also; it is the other restrictive problem which

coexistence of diabetes mellitus

(DM) and gonarthrosis. Perhaps; an other

parameter that is deserved to research for this coexistence is metabolic syndrome.

Today, relationship between this clinical conditions are clear enough. And also

two lobotuary parameters as Leptin and Nesfatin-1 are an other headstone for

obesity and metabolic syndrome. Many studies established relationships between

obesity and Leptin, Nesfatin-1 separately. Leptin is a hormone that is made by

EP480

adipocytes and affects NeuroPeptid-Y levels. Its gene Ob is located in

The assessment of possible eating disorders among patients with type 2

Chromosome-7. Leptin regulates food intake and gain weight. Nesfatin-1 is a

diabetes mellitus using EAT-26 questionnaire

hormone that is released by hypothalamus. It regulates hungry and fat sorage. We

Veranika Labashova¹, Alla Shepelkevich² & Elena

aimed to evaluate the levels of these two hormones in diabetic patients that have

Brutskaya-Stempkovskaya²

gonarthrosis. 101 patients were measured clinically and laboratory by X-rays,

¹Republic Centre of Medical Rehabilitation and Balneotherapy, Minsk,

levels of insulin, Leptin and Nesfatin-1 on 2014-2016. 46 patients have Type 1

Belarus;²Belarusian State Medical University, Minsk, Belarus.

DM and 55 patients have Type 2 DM. All patients have gonarthrosis clinically

and radiologically. 31 of all patients have overweight (25-29.9), 43 patients have

obese (30-34.9), 20 patients have severely obese (35-39.9) and seven patients

Controversial data exist regarding the prevalence of eating disorders in

have morbidly obese (40 and up) accoding to BMI. In the Leptin results; there

individuals with diabetes. EAT-26 questionnaire is as a validated widely used

were high levels of 81 patients with insulin resistance. And these patients have

self-reported tool recommended in general population for assessing eating

increasing BMI. In the Nesfatin-1 results; there were significant lower in diabetic

disorder risk. The study aimed to determine the prevalence of abnormal eating

patients except in 11 patients. And also there were correlation between Nesfatin-1

behavior in patients with type 2 diabetes mellitus and a matched sample of

lowerity and overweighty. It seem like Leptin levels is related with BMI directly.

nondiabetic control subjects.

High insulin levels may increase Leptin levels. But; Nesfatin-1 is lower almost all

Research design and methods

patients with insulin resistance. Leptin and Nesfatin-1 has severe regulation on

A total 63 participants were randomly selected: 29 patients with type 2 diabetes

body energy storage. And they deserve more studies about diabetic population

mellitus and 34 nondiabetic control subjects. No significant differences existed

with gonarthrosis.

between cases and controls for age or ethnicity. Responses of diabetic patients to

DOI: 10.1530/endoabs.49.EP478

the EAT-26 were compared with those of a nondiabetic control group. The score

of 20 or higher defined as positive cut off, the mean values of each question in

both groups were taking into account.

Results

A total of 14.7% (nZ5) of the control subjects and 34.4% (nZ10) of the diabetic

subjects scored above the predetermined screening cut off. The majority among

screen positive participants were women: 100% in control group and 60% in

diabetes group. However, the assessment of the mean values on each item

revealed the statistically significant differences registered on 16, 17 question

concerning ‘eating dieting foods’ and ‘avoiding food with sugar’ (P!0.001). The

higher average scores were in group of patients with DM

2.03

and 1.58

accordingly vs 0.53 and 0.38 in control group. We suggest that these items could

EP479

reflect the total scores and distort the data.

Conclusions

A right time for pregnant women with type 1 diabetes mellitus

Recent research indicates the higher prevalence of possible eating disorders

Diana Simoniene^1,2, Rasa Mikalauskaite² & Neli Jakuboniene¹

among patients with type 2 diabetes mellitus on the total EAT-26, as compared to

¹Hospital of Lithuanian University of Health Sciences Kauno klinikos,

the control subjects (34.4% vs 14.7%). Moreover, further work is needed to

Kaunas, Lithuania;²Lithuanian University of Health Sciences, Kaunas,

establish the diagnostic validity of EAT-26 across diabetic subgroup.

Lithuania.

DOI: 10.1530/endoabs.49.EP480

Objective

Pregnancy in women with type I diabetes mellitus (T1DM) is associated with an

increased risk of various obstetric complications. The purpose of this study was to

evaluate relation of HbA1c, delivery age and various diabetes aspects on

pregnancy outcome and gestation in women with T1DM.

Methods

This was a cross-sectional study. A total of 48 women hospitalized to the Hospital

of Lithuanian University of Health Sciences Kauno klinikos Endocrinology

Department were included. Diabetes control was assessed by HbA1C according

to An Endocrine Society Clinical Practice Guidelines.

Results

EP481

In the 48 women with T1DM, the mean age was 28.7 years old (G6.1). Based on

Mediterranean diet and glycaemic control in a Mediterranean

the area under Receiver operating characteristic (ROC) curve (59.6, P!0.05) the

population with type 1 diabetes: a pilot study

optimal age mean for pregnancy and successful delivery was 25 years old. It was

Alexis Kyriacou^1,2, Josie M M Evans¹ & Angelos Kyriacou^2,3

found that only 27.1% of women in their first trimester of pregnancy with T1DM

¹School of Health Sciences, University of Stirling, Stirling, UK;²CEDM

had good glycaemic control (HbA1c %6.5% (48 mmol/mmol)) and 72.9% had

Centre of Endocrinology, Diabetes & Metabolism, Limassol, Cyprus;

poor glycaemic control (HbA1c O6.6% (O49 mmol/mmol)). Moreover, it was a

³Endocrinology and Diabetes, Salford Royal NHS Foundation Trust,

significantly increase of premature deliveries in women with poor glycemic

Salford, UK.

control (PZ0.002). To further explore pregnancy outcomes, we fit a logistic

regression model to predict the risk of adverse birth outcomes. We found out that

Background

pregnant women with T1DM and older than 26 years old had 7.4 times higher risk

The Mediterranean diet (MD) is the traditional diet of the people living in the

for negative birth outcomes than younger women fitting the same criteria

Mediterranean basin and has been linked with positive health outcomes e.g.

(PZ0.034 (95% PI 1.16-47.19).

reduced incidence of cardiovascular and neoplastic disease. No study has

Conclusion

investigated the relationship between the MD and glycaemic control in a

This short study showed that glycemic control during pregnancy is insufficient in

Mediterranean population with type 1 diabetes mellitus (T1DM). Furthermore,

women with T1DM. We found out that poor glycemic control causes premature

it is unknown how well controlled are such patients and whether they follow

delivery (P!0.002) and age is an important risk factor for pregnancy outcome

the MD.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

EP483

Patients known with T1DM were randomly conducted through the registry of the

Bone mineral density in male patients with type 2 diabetes mellitus, with

Cyprus Diabetes Association. Ethics: Received from the University of Stirling

and without hypogonadism

and the Cyprus National Bioethics Committee.

Agathi Vasileiou¹, Ioanna Karathanassi¹, Parthena Navrozidou²,

Results

Marianna Vlychou², Georgios Koukoulis¹ & Alexandra Bargiota¹

Twenty patients were conducted; eight patients fulfilled the inclusion criteria and

¹Department of Endocrinology and Metabolic Diseases, University of

completed antropometrics and the questionnaires; six had biochemistry. Age was

Thessaly, Larissa, Greece;²Department of Radiology, Faculty of Medicine,

34.6G10.7 years. All patients were classified as having moderate adherence to

University of Thessaly, Larissa, Greece.

the MD using the MedDietScore scoring system (28.9G5.2; max score 55).

Lowest score was seen for potatoes and non-refined cereals (1.4G0.7 and 1.4G

0.9; max score 5) and the highest for use of vegetables and olive oil in cooking

Introduction

(4.1G1.5 and 4.8G0.7; max score 5). All six patients with biochemical testing

Type 2 diabetes mellitus (T2DM) affects bone metabolism, but its relation with

had undetectable levels of fasting blood c-peptide. HbA1c was

63.5G

bone mineral density (BMD) remains controversial. It is also known that T2DM is

5.8 mmol/mol and fasting glucose levels 227.7G64.8 mg/dl; none had optimal

associated with hypogonadism in males. Male hypogonadism can also affect

diabetes control i.e. HbA1c%53 mmol/mol. MD score was unrelated to HbA1c

BMD. Thus the aim of this study was to evaluate BMD in male patients with

(rZK0.65; PZ0.16) or fasting glucose (rZK0.66; PZ0.15). Mean BMI was

T2DM with and without hypogonadism.

27.0G5.5; 67% were overweight or obese; BMI was marginally related to HbA1c

Methods/design

(rZ0.8117; PZ0.0499).

Hypogonadism was defined as serum free Testosterone (fT) value !5 ng/dl or 5-

Discussion

9 ng/dl C1 major sign suggestive of androgen deficiency and eugonadism was

Our results show a no association between the MD and glycaemic control

defined as fT value O9 ng/dl. We studied

119 patients with T2DM and

although a type 2 statistical error is plausible. Adherence to the MD diet was

hypogonadism (Group H) (age: 61.2G8.2 years) and 45 patients with T2DM

moderate in-line with our previous research that showed a moderate and reducing

without hypogonadism (Group NH) (age: 58.4G10.3 years) matched for age,

adherence in the general population in Cyprus. Furthermore, our results are

duration of diabetes, BMI and HbA1c. In both groups, we measured, lumbar spine

worrying regarding glycaemic control. A larger study is underway to further

(LS) BMD and total Tscore by Dual-energy X-ray absorptiometry (DEXA).

investigate these relationships.

Results

DOI: 10.1530/endoabs.49.EP481

Mean BMI (kg/m²) was similar in both groups (H: 30.9G5.0 vs NH: 29.6G5.9,

PZ0.17). Mean duration of diabetes was 9.4G8.5 years in Group H and 8.6G7.8

years in Group NH (PZ0.54) and mean HbA1c was 7.8G1.9% in Group H and in

Group NH 7.61G1.5%(PZ0.47). BMD at LS (g/cm²) and total T-score measured

by DEXA were lower in Group H compared to Group NH (0.53G0.08 vs 0.81G

0.07, PZ0.041) (K0.12G1.0 vs 0.78G0.72, P!0.001).

Conclusion

Male patients with T2DM and hypogonadism are found to have lower BMD

compared to T2DM males without hypogonadism. Thus, in male patients with

T2DM, hypogonadism is a risk factor for low BMD.

DOI: 10.1530/endoabs.49.EP483

EP482

Analysis of zinc status in type 2 diabetic patients and its correlation with

glycemic control

Emna Elfaleh¹, Mahdi Mrad², Ibtissem Oueslati¹, Afef Bahlous²,

Najla Bchir¹, Imen Horchani¹, Karima Khiari¹ & Néjib Ben Abdallah¹

¹Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia;

²Biochemistry Laboratory, Pasteur Institute, Tunis, Tunisia.

EP484

Pregnancy outcome in relation to a disorder of glucose tolerance during

Introduction

pregnancy

Recent studies have highlighted zinc’s dynamic role as a cellular second

Violeta Mladenovic^1,2, Jelena Nesic^1,2, Marija Andjelkovic^2,3,

messenger in the control of insulin signaling and glucose homeostasis. The aim of

Zoran Gluvic^4,6, Aleksandar Djukic^1,2 & Djuro Macut^5,6

our study was to assess the concentration of serum and urinary zinc levels in type

¹Center for Endocrinology, Diabetes and Metabolic Diseases, Clinical

2 diabetic patients and to investigate the correlation between this variable and

Center «Kragujevac», «Kragujevac», Serbia;²Faculty of Medical Sciences,

glycemic control.

Univeristy of «Kragujevac», «Kragujevac», Serbia;³Department of

Methods

Laboratory Diagnostics, Clinical Center «Kragujevac», «Kragujevac»,

Total 54 type 2 diabetic patients and 23 non diabetic healthy subjects (age

Serbia;⁴Division of Internal Medicine, Department of Endocrinology,

matched) were enrolled in a cross-sectional study. Patients with malabsorption

Zemun Clinical Hospital, Belgrade, Serbia;⁵Clinic for Endocrinology,

syndrome, chronic liver disease and chronic renal failure were excluded. Physical

Clinical Center Belgrade, Belgrade, Serbia;⁶School of Medicine,

examination and laboratory tests, including serum and urinary zinc measurements

University of Belgrade, Belgrade, Serbia.

were performed.

Results

The mean duration of diabetes was 4.32G7.95 years and mean HbA1c was 6.6G

Introduction

2.15%. Compared to control subjects, mean serum zinc level was significantly

Pregnancy as a state of insulin resistance can predict diabetes development in

lower in diabetic patients

(1.15G0.29

and

1.07G0.29 mg/l respectively,

some women, and is associated with increased risk for adverse outcome of

PZ0.02). However, urinary zinc level was significantly higher in diabetic

neonate and for mother.

patients than in control group

(1.04G1.06 mg/24 h and 0.57G0.4 mg/24 h,

Aim

respectively, PZ0.02). There were a negative correlation between serum zinc and

The aim of this study is to analyse pregnancy outcome in relation to a disorder of

HbA1c levels (rZ0.85, PZK0.01) and between serum zinc and fasting plasma

glucose tolerance during pregnancy.

glucose levels (rZ0.51, PZK0.01). However, a positive correlation between

Matherial and methods

urinary zinc and HbA1c levels (rZ0.23, PZ0.02) was observed.

The study included 77 healthy pregnant women in third trimester registered in

Conclusion

Center for endocrinology CC Kragujevac that were tested, according to conducted

In our study, patients with T2D had lower serum zinc concentration than non-

3 h OGTT with 100 g glucose (ADA criteria). As parameters of adverse outcomes

diabetic controls. This reduction could be associated with low zinc dietary intakes

we included: premature labor (before 37 gw., Low Apgar score (!8), neonatal

and increased urinary excretion relating to polyuria. Further studies were required

malformations, respiratory complications, hypoglycemia, birth body weight

to determine the role of zinc supplementation in improving glycemic control and

O4 000 g or !2 500 g, hyperbilirubinemia

preventing vascular complications in type 2 diabetic patients.

Results

DOI: 10.1530/endoabs.49.EP482

The mean age of patients was 30.8G4.7 years. The frequency of risk factors for

diabetes were: obesity (3.9%), hypertension (5.2%), previous gestational diabetes

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

mellitus (23.5%), smoking (23.4%), positive family history for diabetes (27.3%).

The first objective was to study the relationship between glucose, insulin and

From 77 patients, 18 was with GDM (23.3%). It has been shown that the number

C-peptide during a prolonged glucose load in two patients with active IAS. The

of risk factors significantly affect the outcome of pregnancy (P!0.005, c² test),

second was to study the variation of these parameters between the active and the

and that the degree of disorder of glucose tolerance during pregnancy affect the

recovery disease states.

outcome of pregnancy (rZ0.164, c² test). It has been shown that patients with

Methods

normal glucose tolerance usually have a favorable outcome of pregnancy, and a

Two patients with IAS and frequent hypoglycaemic episodes at the time of the

growing number of pregnancies with an adverse outcome.

first study underwent an extended oral glucose tolerance test with 75 g of glucose

Conclusion

(4 h). After apparent clinical and biochemical recovery, the procedure was

This study demonstrates that glucose intolerance during pregnancy predicts

repeated.

unfavorable adverse outcome

Results

Keywords: glicoregulation, pregnancy outcome

The data observed during the active and recovery states are shown in Table 1.

DOI: 10.1530/endoabs.49.EP484

Table 1

Hyperglycaemia phase

Hypoglycaemia phase

Glucose

Ins/c-pep

Glucose

Mean peak at

ratio

Mean peak at

State

1 h (mg/dl)

(uU/ng)

3-4 h (mg/dL)

(uU/ng)

Active

199

(range

7.0

(range

13.6

EP485

disease

187-210)

45-59)

Single standard labour tactic at 39-40 weeks in pregnancy with

Recovery

166

11.2

4.9

gestational diabetes - is it the best policy?

disease

Ofelia Bettikher & Irina Zazerskaya

Federal Almazov North-West Medical Research Centre, Saint Petersburg,

Russia.

Active disease state

The insulin/c-peptide ratio increased significantly from hyperglycaemia to

Objective

hypoglycaemia (PZ0.023) even after adjusting for the glucose levels (glycaemia

To assess labour outcomes in pregnancies with gestational diabetes

(GD)

to insulin/c-peptide ratio) (PZ0.027).

regarding different delivery tactics.

Recovery disease state

Design and methods

Patient showed a decrease in hyperglycaemia peak with a corresponding increase

The retro- and prospective study evaluating labour outcomes included 443 age

in the insulin/c-peptide ratio and a decreased insulin/c-peptide ratio during

matched patients with GD had given birth during 2014 (1st group - nZ251) and

hypoglycaemia phase.

2015

(2nd group - nZ192) according to the two clinical protocols, respectively.

Discussion

Expectant management in 2014 was supposed to use until 39-40 weeks of

During active disease, a lower insulin/c-peptide ratio during hyperglycaemia

gestation in the absence of any earlier delivery indications, in 2015 - until 40-41

and the paradoxical increase during hypoglycaemia seem to support the role of

weeks similarly. Statistical analysis was performed with SPSS 21.0 (SPSS Inc.)

insulin antibodies in the disease. During the recovery state, there is a reversal of

program. Statistical methods used: Student criteria for quantative analysis, c²

these ratios supporting an increase in bioavailable insulin with lower antibody

criteria for quality analysis; P!0.05.

titters.

Results

Labour induction rate was lower in the second group: 13.5% (26 of 192), than in

DOI: 10.1530/endoabs.49.EP486

the first: 17.1% (43 of 251), thus the rate of spontaneous labour raised (74.9%

(188 of 251) and 78.2% (150 of 192)). The rate of pre-arranged and urgent

caesarian section, macrosomia, diabetic embryopathy did not significantly differ

between groups, the same as dysthyroidism and fetal distress after induction

of labour: 7% (3 of 43) and 9.3% (4 of 43) - in the first, 7.7% (2 of 26) and 11.5%

(3 of 26) - in the second group, respectively. However, uterine inertia rate after

induction was twofold lower in the second group comparing to the first one: 7%

(3 of 43) and 15.4% (4 of 26), respectively.

Conclusion

Expectant management until 40-41 weeks in patients with GD in the absence of

earlier delivery indications has led to the labour complications rate fall and

spontaneous labour rate rise. Probably, single standard tactic for labour at 38-40

weeks in all patients with GD is not one of choice. Such management is preferable

EP487

for high risk antenatal fetal death pregnancies: fetal distress, macrosomia, diabetic

Lipoprotein particle size in women with type 1 diabetes mellitus and its

fetopathy or severe maternal conditions, first of all, preeclampsia.

relationship to carotid intima-media thickness

DOI: 10.1530/endoabs.49.EP485

Anjuli Gunness¹, Mohamed Ahmed¹, Agnieska Pazderska¹, Niamh Phelan¹,

Kevin Moore¹, Gerard Boran², Lucy-Ann Behan¹, Mark Sherlock¹ &

James Gibney¹

Department of Endocrinology, Adelaide and Meath Hospital, Tallaght,

Dublin 24, Ireland;²Department of Clinical Chemistry, Adelaide and Meath

Hospital, Tallaght, Dublin 24, Ireland.

EP486

Although cardiovascular disease (CVD) is greatly increased in type 1 diabetes

mellitus (T1DM), patients typically have apparently healthy lipid profiles. Simple

Insulin autoimmune syndrome: the relationship between insulin,

measurement of plasma lipids however does not provide information regarding

c-peptide and glucose in active and recovering disease states

lipoprotein particle size which in the nondiabetic population is independently

Tiago Nunes da Silva¹, Ana Gonçalves Ferreira¹, Isabel Manita¹,

predictive of CVD. Plasma lipids and lipoprotein subclasses (using polyacryl-

Ana Catarina Matos¹, Isabel Carvalho², Paula Font³, Susana Prazeres³

amide gel-tube electrophoresis) were studied in reproductive age women with

& Jorge Portugal¹

T1DM and compared to a matched control group. Outcomes were correlated with

¹Endocrinology Department Hospital Garcia de Orta, Almada, Portugal;

carotid intima-media thickeness (CIMT), a validated marker of atherosclerosis.

²Clinical Chemistry Department Hospital Garcia de Orta, Almada, Portugal;

Compared to nondiabetic women, T1DM women were younger (29 vs 34 years)

³Endocrinology Laboratory IPO Francisco Gentil, Lisboa, Portugal.

and of lower BMI (24.7 vs 31.3 kg/m²), with all data reported as median. Total

(TC) and LDL-cholesterol (LDL-C) did not differ between groups. Triglyceride

Insulin autoimmune syndrome (IAS) is a very rare cause of hypoglycaemia in

(TG) levels were lower (0.76 vs 0.91 mmol/l, PZ0.0331) and HDL-cholesterol

western countries. One proposed mechanism is anti-insulin antibody capture of

(HDL-C) greater (1.65 vs 1.49 mmol/l, PZ0.00331) in T1DM. T1DM women

prandial insulin followed by the dissociation of insulin from anti-insulin antibody.

had a greater proportion (46% vs 5%, P!0.0001) of small LDL-C particles,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

lower mean LDL particle size

(269

272 A

˚, P!0.0001) and a greater

Methods

percentage of small-dense-LDL particles (%SDLDL; 3 vs 0%, P!0.0001).

A total of 65 patients (32 men and 33 women, mean age 51.6G5.2 years); 31-

CIMT correlated positively in T1DM with %SDLDL (r 0.2983, PZ0.0098) and

with type 2 diabetes and hypertension (group 1), 34 - with isolated arterial

negatively with LDL size (rK0.3118, PZ0.0068), but did not correlate with TC,

hypertension (group 2). Control group 20 healthy volunteers. We evaluated data

HDL-C, LDL-C or TG. Despite apparently healthy lipid profiles, women with

transthoracic echocardiography and ultrasound thickness of the intima-media

T1DM have a greater proportion than nondiabetic women of atherogenic small

complex of the common carotid artery (IMC CCA). Omentin level in blood serum

LDL particles. The likelihood that this is clinically relevant is strengthened by the

were determined by ELISA kit.

observed correlation of CIMT with particle size and lack of correlation with

Results

standard lipid profile. Further studies are needed to explore the mechanisms

Left ventricular hypertrophy (LVH) was diagnosed in 67.5% of patients in group

underlying these abnormalities.

1 and 34.2% of patients in group 2 (P!0.05). IMC CCA patients of group 1 was

DOI: 10.1530/endoabs.49.EP487

significantly higher than in the comparison group (P!0.001). Omentin level in

group 1 was reduced in comparison with the 2 - nd group and the control

(262.24G10.46, ng/ml versus 296.43G12.72, ng/ml and 379.46G6.22 ng/ml,

respectively, P!0.001). There was a negative correlation relationship between

the content omentin plasma and left ventricular hypertrophy

(rZK0.54;

P!0.05) and IMC CCA (rZK0.46, P!0.05).

Conclusions

It was found that patients with type 2 diabetes and hypertension observed the

progression of LVH and remodelling of the vascular wall, which are related to an

imbalance omentin serum. Thus omentin reduction level can be considered as a

EP488

biomarker of cardiovascular complications in these patients.

The upper limb infection in diabetic patients (about 32 cases)

DOI: 10.1530/endoabs.49.EP489

El Ansari Nawal, Habra Bahia & El Mghari Ghizlane

Service of Endocrinology Diabetology and Metabolic Diseases CHU

Mohammed VI, Faculty of Medicine and Pharmacy, Marrakech, Morocco.

Introduction

The diabetic patient is vulnerable to infection compared to the general population.

This is due to the deleterious effect of hyperglycemia on the basis of chemotaxis,

phagocytosis and bactericide neutrophils / What weakens the defenses of the

diabetic person to infections. Infections of the upper limb in diabetics are not

EP490

uncommon, and are often characterized by severity and often unfavorable

developments. The objective of this work: determine the prevalence, clinical and

Casuistic from Endocrinology Medical Consultation at

therapeutic characteristics of the infection of the upper limb in diabetics.

Clinica Girassol 2015

Matériels et méthodes

Domingos LIRA, Anselmo Castela, Gertrudes Béu & Francisca Silva

Study including

patients seen in the emergency. The parameters:

Clinica Girassol, Luanda, Angola.

epidemiological characteristics âge, sex, weight, size, marital status, housing

environment, origin, nature of the work, the pets, Characteristics of the diabetes:

Introduction

type, age of the beginning, evolution, treatment, glycemic balance, the follow-up.

There are few studies either hospital bases or population based in Africa and in

Characteristics of the lesions: type, Seat, the mechanisms, bacteriological sample.

Angola we also have the same situation regarding endocrinology data. With this

Deadline between the consultation and the appearance of the lesions. Manage-

paper, the Angolan Society of Endocrinology Diabetes and Metabolism

ment emergency: medical treatement, surgical care.

(SAEDM), wants to contribute to the systematic and continued study of

Discussion

endocrine pathology in Angola.

At our patients, the hurts were grave and spread, this can give some explanation

Objective

by the delay of the consultation been understandable by the educational lack and

Study of the casuistic of endocrine pathology in ambulatory setting regarding the

by the particularly vulnerable fragile ground to the infections seen the diabetes.

year 2015.

The diabetes was discovered on the occasion of the lesions of the upper limb in

Methods

18% of the cases, during the evolution, in spite of the institution of a local

Compilation of data obtained from medical notes files from the ambulatory

treatment and an antibiotic treatment, a locol extension regional and sometimes

appointments available in digital and physical support. Files with incomplete data

general of the infection drove to make an amputation in 25% of the cases for

or without prove or clinical-laboratory correlation have been discarded. We

saving of the patient.

designed the distribution of patients according to the pathology, or group of

DOI: 10.1530/endoabs.49.EP488

pathologies at the respective frequencies as per sex and age group. Diabetes

Mellitus and Obesity have been considered as specific pathologies. Thyroid

diseases have been included in the same entity considered as Thyroid Pathologies

and the others in a group classified as Other Endocrine Pathologies. Diabetes

Mellitus and Obesity (including overweight) were profiled according to the WHO

criteria; Disturbances of Thyroid have been established obeying to the

ultrasonography criteria or to functional anomalies.

Results

We worked with a pool of 1630 processes (files) related to patients that had

endocrine pathology. Ninety one (5.58%) were incomplete. Therefore were

EP489

excluded because had not confirmation data of endocrine disease. The validated

The peculiarities of structural and functional state of the myocardium

files (1539 files) could be distributed as follows: 1159 (75.3%) corresponding to

and blood vessels in patients with type 2 diabetes mellitus and arterial

Diabetes Mellitus, 156 (10.1%) corresponding to Pathologies of Thyroid, 85

hypertension depending on the dynamics of adipokines

(5.5%) corresponding to Obesity and 139 (9.0%) classified as Other Pathologies.

Olena Al-Trawneh, Oleksandr Bilovol & Lesya Bobronnikova

Distribution per sex: 794 (51.6%) were women and 745 (48.4%) men. The

Kharkiv National Medical University, Kharkiv, Ukraine.

distribution of pathologies per sex: Diabetes Mellitus: 533(45.9%) women and

626

(54.1%) men; for Obesity: 56 (65.9%) women and 29 (34.1%) men and for

Purpose

Pathology of Thyroid we found 132 (84.6%) women and 24(15.4%) men.

To study the features the structural and functional state of the myocardium and

DOI: 10.1530/endoabs.49.EP490

blood vessels in patients with diabetes mellitus and arterial hypertension

depending on omentin level.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP491

type

1 diabetes is more prevalent among women is in accordance to the

international data. It is important to highlight that significant number (63%) of the

Depression and quality of life in patients with type 2 diabetes mellitus

patients have been diagnosed in the status of diabetes ketoacidosis.

Andreja Maric, Dunja Molnar, Tea Premosa, Sonja Novak, Jurica Vidovic

& Maja Mikolaj Kiric

DOI: 10.1530/endoabs.49.EP492

County Hospital Cakovec, Cakovec, Croatia.

Introduction

Depression is the leading cause of disability worldwide, and is a major contributor

to the overall global burden of disease. People with DM have 2.4-4.3 times

greater risk of depression than people without DM as well as patients (pts) treated

EP493

with insulin. Women experience depression more often than men. Symptoms of

depression can make it more difficult to successfully manage diabetes and prevent

Bronze diabetes - a rare secondary cause of diabetes

diabetes-related complications.

Pedro Souteiro^1,2, João Sérgio Neves^1,2, Sofia Castro Oliveira^1,2,

Materials and methods

Sandra Belo^1,2, Celestino Neves^1,2, Paula Freitas^1,2 & Davide Carvalho^1,2

¹Department of Endocrinology, Diabetes and Metabolism, Centro

A total of 138 subjects (74 males, 64 females; aged 18-80 years) with T2DM

Hospitalar Sa˜o João, Porto, Portugal;2Faculty of Medicine of University

participated in cross-sectional study. Two questionnaires: BDI (Beck depression

of Porto, Porto, Portugal.

inventory) and SF-36 (Short-Form-36 Health Survey) were used. Using BDI the

severity of depression was detected; SF-36 was used for measuring self-reported

physical and mental health status.

Introduction

Results

Secondary causes of diabetes refer to a category in which diabetes is associated

The prevalence of depression was higher in females with diabetes (45.3%)

with other diseases. They are thought to constitute less than 2% of the total cases

compared to males (35.1%). Women with depression (29/64 of pts) were aged 39-

of diabetes.

76 yrs, BMI 22.3-44.6 kg/m², HbA1c O7% was observed in 17/29 of depressive

Case report

women, duration of DM2 was 2-192 months. Men with depression (26/74 of pts):

A 56 year-old caucasian man, with no relevant medical history, presented to the

age 35-79, BMI 23.2-43.2 kg/m², HbA1c O7% in 13/26 of depressive men,

Emergency Department with fatigue, polyuria, polydipsia, polyphagia and

duration of DM2 was 6-360 months. According to BDI questionnaire scores, mild

involuntary weight loss (6 kg in two weeks). He was hemodynamically stable

depression was reported in 17 male and 15 female pts, moderate depression was

and exhibited a glycaemia of 445 mg/dl without acidosis. Insulin perfusion was

found in 6 males and 9 females and severe depression in 3 male and 5 female pts.

initiated and the patient was hospitalized with the diagnosis of new-onset

Mean scores of SF-36 questionnaire were compared between diabetics with and

diabetes. Physical examination revealed a greyish skin tone, body mass index

without depression, and correlated to BDI scores. Depressive pts had statistically

of 19 kg/m² and hepatomegaly. Blood analysis showed a haemoglobin A1c of

lower scores than non depressive (both sexes) in Physical functioning, Emotional

13.4%, negative anti-GAD and anti-insulin antibodies, transferrin saturation of

role functioning, Mental health, Bodily pain (just males) and General health

98% and high ferritin levels

(4533 ng/ml). This clinical picture raised the

perceptions.

suspicion of diabetes secondary to hemochromatosis. Abdominal ultrasound

Conclusion

showed an enlarged liver (19.5 cm) with bright echostructure and the hepatic

T2DM is associated with an increased risk of depression. In order to prevent

magnetic resonance imaging described signs of iron overload. Liver biopsy was

negative consequences of non recognized and untreated depression, evaluation of

then performed showing accentuated iron deposits in the hepatocytes, sinusoidal

psychological status in patients with T2DM is recommended.

lining cells and bile ducts epithelia. Genetic study identified a HFE gene mutation

DOI: 10.1530/endoabs.49.EP491

(C282Y homozygote). Due to possible iron accumulation in the pituitary gland

and the patient complaints of erectile dysfunction, pituitary function was

evaluated revealing hypogonadotropic hypogonadism

(total testosterone

0.59 ng/ml; FSH 3.40 mUI/ml; LH 2.78 mUI/ml) with no other axis affected.

Patient was discharged from hospital with a basal-bolus insulin regimen and a

250 mg testosterone monthly enanthate injection. He maintains follow-up with an

A1c of 7.3% and undergoing periodic phlebotomies.

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Conclusions

In hemochromatosis iron accumulation in the skin and pancreas can lead to

Diabetes Mellitus type 1: characterization of patients at the endo-

hyperpigmentation and impair insulin production causing the so called ‘bronze

crinology ambulatory follow up during the year 2015

diabetes’. This case alerts clinicians not to overlook secondary causes of diabetes

Anselmo Castela, Gertrudes Béu, Francisca Silva & Domingos Lira

that can be precociously suspected based on a careful physical examination.

Clinica Girassol, Luanda, Angola.

DOI: 10.1530/endoabs.49.EP493

Introduction

Diabetes Mellitus is a chronic disease that has serious effects on the morbi-

mortality. Diabetes type 1 is less prevalent, representing 5-10% of the total cases.

Data collected in Africa are scarce, and prevalence and incidence at sub - Saharan

Africa are about 3-12/100,000 and 1.1-2.1/100,000 people, respectively. The

Angolan reality is not known.

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Objective

To show the casuistic of diabetes type

obtained from the ambulatory

The epidemiology of type 2 diabetes mellitus and its complications in

consultation of Endocrinology for the year 2015.

South Korea

Methods

Ryungwoo Kang & Deborah Chee

We performed a retrospective study of the available clinical files in digital and

Korea National Enterprise For Clinical Trials, Seoul, Republic of Korea.

physical support. The diagnosis of type 1 diabetes was according to the diagnostic

criteria defined by the WHO. Parameters that have been studied: sex, age, A1c,

Background

clinical onset, duration of the disease.

The prevalence of diabetes in South Korea has drastically increased, and 8.6-

Results

11.0% of Korean adults aged R30 years were suffering for the disease in the early

In the year

2015, 1630 patients have been observed at the Endocrinology

2000s, according to the Korea National Health and Nutrition Examination

Ambulatory Service. Only 1539 process were considered for analysis. Among

Survey.

these patients, 1159 (75.3%) were diabetic, being 19 of them (1.63%) type 1

Objective

diabetics. The distribution by sex was: 9 (47.4%) men and 10 (52.6%) women.

The present study was performed to estimate the incidence and prevalence of type

The age spread from 4 to 40 years with a mean of 23 years. Diabetic ketoacidosis

2 diabetes mellitus (T2DM) and its complications in South Korea using the Health

(63.11%) was the clinic presentation found at the time of the diagnosis. The time

Insurance Review and Assessment (HIRA) database from 2010-2015, which

of evolution of the disease varied from 6 months to 15 years of age with an

covers 96.3% of the claim data of the Korean population.

average of 4.6 years. The average glycosylated hemoglobin (HA1c) was 8.86%.

Methods

Conclusion

T2DM, coronary artery disease (CAD), cerebrovascular disease (CVD), and

The epidemiology of diabetes is not known, and we cannot advance conclusions

peripheral artery disease

(PAD) were defined as underlying disease and its

from the data collected by our team. Most of the patients observed in

complications of T2DM. We used the Healthcare Common Procedure Coding

endocrinology (75.3%) had the diagnostic of Diabetes Mellitus. The fact that

System codes provided by HIRA to identify associated procedures or surgeries.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

A Poisson distribution was assumed when calculating 95% confidence intervals

sensitivity, patients are often misdiagnosed with type 1 or type 2 DM. Correct

for prevalence and incidence rates.

classification of this type of diabetes becomes essential for proper management of

Results

the disease. Our objective was to describe clinical features of patients with

After age standardization, the prevalence of T2DM in Korean adults aged more

MODY diagnosed at our institution.

than 30 years, was 6.3-7.5% and the annual incidence rates of T2DM ranged from

Methods

9.0-11.0/1,000 person-year during the six year. The incidence rates of T2DM in

We collected clinical data from patients with clinical characteristics and genetic

men and women aged more than 30 years significantly decreased from 2013 to

confirmation of MODY.

2015

(P%0.001). On the other hand, the incidence in women aged more than 65

Results

years significantly increased from 2013 to 2015 (P%0.001). The incidence rates

We included 30 patients (15 females). All patients but one had diagnosis of DM

of CAD and CVD with T2DM patients were 21.4 and 13.6/1,000 person-year.

(one female had gestational diabetes, but currently has no criteria for diabetes).

Conclusion

Mean age at diagnosis of DM and MODY was 27.5C/K10.8 and 46.3C/K13.2

This study estimated the incidences and prevalence of T2DM in most of Korean

years, respectively. Genetic testing was positive for mutation in the Glucokinase

population which is the great concern for public health. We also confirmed the

(GCK) gene in 3 patients, the ATP-binding cassette transporter sub-family C

relatively higher risk of as the complications with the T2DM patients compared to

member 8 (ABCC8) gene in 1 patient and the hepatocyte nuclear factor-1

the general population in Korea.

homeobox A (HNF1A) gene in 26 patients. Currently, 9 patients are exclusively

DOI: 10.1530/endoabs.49.EP494

treated with oral antidiabetic agents and 3 patients have no pharmacological

treatment. Last mean HbA1c was 7.5C/K 1.3%. Peripheral neuropathy was

diagnosed in 11 patients (36.7%), autonomic neuropathy in 5 patients (16.7%),

diabetic retinopathy in 16 patients (53.3%), diabetic kidney disease in 11 patients

(36.7%), ischemic cardiac disease in 2 patients (6.7%), vascular cerebral disease

in 3 patients (10%) and peripheral arterial disease in 4 patients (13.3%).

Conclusions

There is a relevant delay in MODY diagnosis and clinicians should be alert for

EP495

this type of diabetes. The most frequent mutation identified in our population was

Prevalence of obesity and diabetes among in a developing country

in the HNF1A gene. This study confirms the clinical heterogeneity of MODY

(Albania)

patients.

Dorina Ylli¹, Tomi Thomo², Violeta Hoxha¹, Marjeta Kermaj¹,

DOI: 10.1530/endoabs.49.EP496

Gerond Husi¹, Thanas Fureraj¹ & Agron Ylli¹

¹“Mother Teresa” Univeristy Hospital Center, Univerity of Medicine

Tirana, Faculty of Medicine, Tirana, Albania;²Ministry of Health, Tirana,

Albania.

It is well known nowadays the positive effect that early detection of prediabetes

has in preventing and postponing the diabetes onset. The aim of our study is to

EP497

explore the diabetes prevalence in Albania and to identify and stratify the

The relationship between Serum Vaspin and atherogenic risk factors in

population at risk for developing diabetes.

T2DM

Material and methods

Magda Shokry Mohamed, Manal Mohaned Abushady, Mona

A large scale multicentre screening was performed in Albania as part of a

Mohamed Abdelsalam, Maram Mohamed Maher, Lila Mahmoud Hendawy

National Campaign. 15744 patients were consecutively recluted. The following

& Rana Hashem Ibrahim

data were obtained: age, weight, height, BMI, waist circumference, glicemia, total

Ain Shams University, Cairo, Egypt.

cholesterol, LDL, Triglycerides, HDL. The subject were suddivided according

gender and age group.

Results

Introduction

In 15744 subjects, 62% females, 38% males, 49% was aged between 40-49 years

Increased visceral adiposity is usually associated with a clustering of atherogenic

old, 46% between 50-59 years old and 20% between 60-65 years old. 6.3% were

risk factors, such as insulin resistance, hypertension, dyslipidemia, alterations in

already diagnosed with diabetes mellitus (5.5% female and 7.4% male of the

coagulation and inflammatory cytokine profiles. Visceral adipose tissue derived

explored population). 15% of the patients who declared not having diabetes had a

serpin (Vaspin) is an adipokine with insulin sensitizing effect which is markedly

fasting glycaemia O 100 mg/dl. Of these 15%, 24% had a glycaemic value above

elevated in high body mass index (BMI) people.

126 mg/dl and 75.6% have glicemic value between 100-126 mg/dl (impaired

Aim

fasting glucose (IFG) or pre-diabetes. In the population with IFG 39.8% have a

To evaluate serum Vaspin level in relation to atherogenic risk factors such as

BMI between 25-30 and 44.8% kg/m² a BMI O 30 kg/m^2. 89.5% of females have

insulin resistance, dyslipidemia, hypertension, inflammation in obese subjects

a WC (Waist circumference) O 80 cm and 74% of males a WC O92 cm.

with T2DM and obese subjects without T2DM.

Conclusions

Method

Albania is a developing country who went trough important socio-economical

80 subjects participated, with BMI ranging from 27-39 selected from outpatient

changes in the last decade. We find a high diabetes mellitus prevalence which

clinic of Endocrinology of Ain Shams University Hospital. They were divided

could be higher because of the not yet diagnosed diabetes. An important role have

into 2 groups 40 obese subjects with T2DM (group I) and 40 obese subjects

the pre-diabetes population where a high prevalence of overweight and obesity is

without T2DM (group II). History, clinical examination, FBS, 2-PP, HBA_1C,

observed. Campaign to rise diabetes and pre-diabetes awareness and encourage

Total cholesterol, Triglycerides, HDL and LDL, HOMA/IR, Serum Vaspin level

lifestyle modification are very important to prevent and postpone the diabetes

(by ELISA) and CRP were done.

onset in the prediabetes population.

Results

DOI: 10.1530/endoabs.49.EP495

Serum Vaspin was higher in group II than group I (P%0.01). HOMA-IR was

higher in group I than group II (esp. females) with P%0.01. Regarding hs-CRP

there was no significant difference. In Group I serum vaspin had a negative

correlation with age

(PZ0.010), diabetes duration

(PZ0.015), a positive

correlation with Waist/Hip ratio (PZ0.047), and LDL (PZ0.034). There were

no correlation with BMI, systolic blood pressure, diastolic blood pressure, HA1c,

fasting blood glucose, 2 HPP, total cholesterol, triglycerides, HDL, hs-CRP and

EP496

HOMA-IR (PO0.05). In group II, serum vaspin had no correlation with any of the

Maturity onset diabetes of the young - clinical characteristics of a

variants (P-valueO0.05). Vaspin level was found to be independently correlated

portuguese cohort

with male gender and younger age with (PZ0.031).

Ana Amado, Raquel Almeida, André Carvalho, Cláudia Amaral,

Conclusion

Cláudia Freitas, Conceiça˜o Bacelar, Joana Vilaverde, Maria

Obese subjects with T2DM have more atherogenic risk profile and lower Vaspin

Helena Cardoso, Sofia Teixeira & Fátima Borges

level than obese subjects without T2DM. It was inversely correlated with age and

Endocrinology Department, Centro Hospitalar e Universitário do Porto,

diabetes duration and positively correlated with Waist/Hip ratio, LDL. Male

Porto, Portugal.

gender and age are strong independent predictors of serum vaspin level. Vaspin

may be an important adepokine that may play an important protective role against

metabolic disturbance and cardiovascular risk in obese subjects with T2DM.

Introduction

DOI: 10.1530/endoabs.49.EP497

Maturity onset diabetes of the young (MODY) accounts for 1-2% of all forms of

diabetes mellitus (DM). As classic criteria that lead to its suspicion have low

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Diabetes Complications

EP500

EP498

Overweight and obesity in pregnant with diabetes mellitus type 1

Paloma Moreno-Moreno, Ángel Rebollo-Román, Rafael Palomares-Ortega,

Prevalence of diabetic neuropathy and nephropathy in different ethnic

Concepción Mun˜oz-Jimenez, María Rosa Alhambra-Expósito & María

minorities

Ángeles Gálvez-Moreno

Rajab Khan

Management Unit of Clinical Endocrinology and Nutrition, University

University of Manchester, Manchester, UK.

Hospital Reina Sofía, Córdoba, Andalucía, Spain.

Introduction

Objectives

The focus on diabetic complications has increased over the years yet it is only

Pregnant women who are overweight or obese have an increased risk of

recently that research has identified a link between ethnicity and the development

complications during pregnancy, as do pregnant women with type 1 diabetes

of diabetic complications.

mellitus (DM1). The objective of this study is to describe the prevalence of

Aims

overweight/obesity in pregnant women with DM1, and associated complications.

To establish the relationship between ethnic group and the prevalence of either

Patients and methods

diabetic nephropathy or neuropathy.

Retrospective descriptive study of pregnant women with DM1 (2004-2014).

Method

Variables analyzed: age, initial body mass index (BMI), HbA1c, abortions, type

A retrospective note review was undertaken for all diabetic patients who had a

of delivery and fetal malformations. Statistical analysis: comparing proportions

status of ‘current’ in the database. This returned 6608 patients, however, only

with the chi-squared and comparing means with Student’s test.

1838 patients met the inclusion criteria. The notes were reviewed, analysed and

Results

compared with the current literature on ethnicity and diabetic microvascular

156 pregnancies in women with DM1. Age 31.41G4.51 years. At the beginning

complications.

of pregnancy, 50.4% were normal weight, 36.2% were overweight (12.4% grade 1

Results

and 23.8% grade 2) and obesity was 10.5% (7.6% grade 1, 1.9% grade 2, 1%

Of the 1838 patients: 56.9% were Caucasian, 13.9% Afro-Caribbean, 23.0%

grade 3). 3% women had BMI !18.5 kg/m². Normal weight vs overweight/-

South Asian and 6.3% Other. Afro-Caribbean’s had a higher mean systolic blood

obesity: unplanned pregnancies 70.4 vs 66.7% (PZ0.85); HbA1c (%) previous

pressure (139.03 mmHg) compared to other ethnicities with Caucasians having

gestation 7.4G1.4 vs 7.4G1.2 (PZ0.98), first trimester 7.4G1.7 vs 7.1G1.3

the lowest mean at 132.91 mmHg. Afro-Caribbean’s were found to have poorer

(PZ0.88), second trimester 6.3G0.8 vs 6.5G0.8 (PZ0.31), third trimester 6.5G

glycaemic control (69.5 mmol/mol) compared to the remaining ethnic groups.

0.8

6.5G0.8 (PZ0.88); newborn weight 3516.1G735.22 vs 3617.07G

Nephropathy was found to be most common in Afro-Caribbean’s (14.3%)

693.10 g

(PZ0.42); newborn size

50.9G2.4

50.8G2.5 cm

(PZ0.76).

followed by South Asians (13.1%). Caucasians and Other groups had lower rates

Maternal and neonatal complications (%) normal weight vs overweight/obesity:

at 7.8% and 8.6%, respectively. Neuropathy was most common in Caucasians

maternal hypoglycemia 3.7 vs 6.7 (PZ0.7); gestational hypertension 5.7 vs 12.2

(24.4%) and lowest in Afro-Caribbean’s (14.7%); the other two ethnic groups,

(PZ0.3); abortions 3.8 vs 9.5 (PZ0.33); induced childbirth 58 vs 61 (PZ0.92);

South Asians and Other, had similar levels at 17.4% and 16.4% respectively.

caesarean section

38 vs 55 (PZ0.12); macrosomia 29.4 vs 24 (PZ0.71);

Conclusion

congenital malformations 8 vs 7.1 (PZ0.78); newborn hypoglycemia 6 vs 5

The link between ethnicity and complications was found to be statistically

(PZ0.93).

significant (P!0.01). Future research and epidemiological studies must focus on

Conclusions

why these differences occur and if they are independent of socio-demographic,

In our series, the prevalence of overweight/obesity in pregnant women with DM1

anthropometric and clinical characteristics.

is high, occurring in almost half of pregnancies. There were no differences in

DOI: 10.1530/endoabs.49.EP498

glycemic control during gestation or in the occurrence of maternal or neonatal

complications associated with overweight/obesity.

DOI: 10.1530/endoabs.49.EP500

EP499

Correlation of homocysteine with macro and microvascular

complication in patients with diabetes mellitus type 2

Marija Krstevska¹ & Ksenija Bogoeva Kostovska²

¹Department of Medical and Experimental Biochemistry, School of

Medicine, University Ss. Cyril and Methodius, Skopje, Center, Macedonia,

EP501

²Doctor’s Practices Prof. Dr Bogoev, Skopje, Center, Macedonia.

Does empowerment from an ‘ABC approach’ and ‘Telemedicine’

improve outcomes in a nurse-led diabetes kidney clinic?

Susan Irwin & Parijat De

In recent years, plasma homocysteine (Hcy) level, has been reported to be

Sandwell & West Birmingham Hospital NHS Trust, Birmingham, UK.

associated with the vascular complications of diabetes mellitus type 2 (DM2). In

patients with DM2, elevated Hcy levels were associated with insulin resistance

and nephropathy. The aim of this study was to investigate the association of

Aims

hyperhomocysteinaemia with micro and macrovascular complications, increased

Implementation of a protocol-driven, nurse-led clinic to see influence on

levels of HbA1c and lipid parameters in patients with DM2 in a Macedonian

cardiovascular risk and renal disease progression using a simple ‘ABC’ approach

population. 80 DM2 patients were enrolled for the study and were classified into

- target HbA1c !7%, BP !125/75 mm Hg and Cholesterol !4 mmol.

two groups: 30 patients with no associated complications, control, and 50 patients

Method

with complications. Homocysteine levels and the other conventional parameters

Weekly Diabetes Specialist Nurse (DSN) clinic with emphasis on ABC approach

(HbA1c, lipid profile, and microalbuminuria) for identifying complications of

and guided FLORENCE Telehealth free texting technology for medication

DM2 were measured. The Hcy levels were significantly higher in DM2 patients

reminders and self-monitoring of BP (machines provided).

(16.05G6.12 vs 10.44G3.33 micromol/l) compared with control. Significantly

Results

elevated homocysteine levels were found in DM2 patients with CAD (P!0.001),

May 2008 - Apr 2009 (12 months) - Cohort A 41 patients. May 2010 - June 2014

neuropathy (P!0.000), retinopathy (P!0.05), high blood pressure (PZ0.02)

(24 months) - Cohort B 133 patients. Mean age 64 years, 78-90% patients

and microalbuminiria (P!0.000) as compared to control subjects. There was a

Asians/Afro Caribbean. Excellent patient satisfaction scores, significant

positive correlation between elevated HbA1c (rZ0.475) levels and serum LDL-

reductions in HbA1c in Cohort A and B by 0.7% (7.62 vs 8.32%) and 1.5%

cholesterol (rZ0.871) with Hcy concentration in DM2 patients with compli-

(9.1

vs 7.6%) respectively, SBP (12-16 mmHg) and DBP (3-6 mmHg) and

cation. The results of this study have shown that homocysteine levels were

Cholesterol in all cohorts were achieved. Urine ACR decreased significantly in

significantly higher in DM2

patients with developed micro-/macro-vascular

both cohorts

(by mean

17-39 mg/mmol). Number of BP medications

(3)

complications and highly positive correlated with HbA1c and serum LDL-

increased in all cohorts. 95 and 85% patients respectively in both cohorts were

cholesterol, also. Results have shown that hiperhomocysteinemia is risk factor in

prescribed ACE, ARB or both.

etiology of vascular complications in DM2 patients.

Conclusions

DOI: 10.1530/endoabs.49.EP499

Outcomes suggest that our nurse-led clinic is highly effective in DN patients. The

‘ABC approach’ and simple information sharing strategy

(Telehealth

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

FLORENCE) were effectively used to inform strategic decision making/intensi-

Additional investigations were performed: kidney ultrasound, which revealed

fication of therapy through patient empowerment, up-skilling of knowledge and

shrunken kidneys, Urea- 64.21 (N 15.0-45.0), Phosphorus-1.98 (N 0.48-2.19),

improved medication compliance - 3 key processes in any chronic disease

Parathyroid hormone-273.76

9.0-79.5),Vitamin D-7

30.0-100.0);

management.

Potassium-5.59 (N3, 5-5), pH-7.26 (N 7.32-7.72) Hemoglobin-10.2 (N 12-16).

DOI: 10.1530/endoabs.49.EP501

The patient had no diabetic specific complications. When DM was diagnosed the

patient has already got dipstick proteinuria 0.3 g/l and it was considered as the

result of diabetes. Therefore no further investigations were performed to find out

the cause of proteinuria. We have not performed renal biopsy to diagnose the real

cause of proteinuria, we just started to treat CKD.

Conclusion

Often proteinuria is revelaed when DM is diagnosed, that’s why, no further

investigations are performed to precise the real cause of it. Yes, hyperglycemia

EP502

can cause various damages of kidney, but not in all cases. So, we always have to

Causes of diabetic ketoacidosis: type 1 diabetes versus type 2 diabetes

remember that in diabetic patients the cause of proteinuria may be due to other

Marwa Omri, Rayene Ben Mohamed, Imen Rezgani, Sana Mhidhi,

reasons. We always have to pay attention to other diabetic specific complications

Aroua Temessek & Faika Ben Mami

and always ask about detail clinical history, for correct diagnosis, better

National Institute of Nutrition, Tunis, Tunisia.

management and prevention of progression of renal disease.

DOI: 10.1530/endoabs.49.EP504

Aim

The aim of our study was to compare the clinical profile of type 1 and type 2

diabetic patients who are hospitalized in our service for diabetic ketoacidosis.

Methodology

This was a descriptive study involving 121 diabetic patients hospitalized for

diabetic ketoacidosis in the C department of diabetology of the national institute

of nutrition of Tunis.

Results

EP505

Of the 121 subjects studied, 57.85% are type 2 diabetic patients and 42.15% are

A Review of the literature: What are the impacts of hypoglycaemia in

type1. Type 2 diabetic patients are older, have a higher glycated hemoglobin level

insulin-dependent diabetic adults?

and a higher BMI compared to the type 1 diabetic patients. For both type of

Charles O’Donovan¹ & Olivia O’Donovan²

diabetes, the principal causes of ketoacidosis are infectious diseases represented

¹University of Leeds, Leeds, UK;²Bradford Teaching Hospitals, Bradford,

mainly by urinary tract infection. For type

2 diabetic patients cessation of

UK.

treatement, inaugural diabetes, insulinopenia and lipodystrophy are observed

respectively in 22.7, 12.3, 11.9 and 10.1% of patients presenting ketoacidosis. For

type 1 diabetic patients cessation of treatment, inaugural diabetes, pregnancy and

Background

lipodistrophy are observed respectively in 18.4, 14.6, 8.9 and 7.1% of patients

The prevalence of diabetes has reached epidemic proportions and according to the

hospitalized for ketoacidosis.

World Health Organisation (WHO) more than 220 million people worldwide have

Conclusion

diabetes. The main complication in insulin-dependent diabetes mellitus (IDDM)

The main causes of diabetic ketoacidosis are infectious diseases and cessation of

patients is hypoglycaemia, with approximately 90% of all IDDM patients having

treatment, in type 2 diabetic patients as well as in type 1 diabetic patients. So that,

experienced a hypoglycaemic episode. Hypoglycaemia has a substantial clinical

education remains the best way to prepare diabetic patients to face situations of

impact in terms of mortality, morbidity and quality of life.

stress and to have a good therapeutic compliance.

Methods

DOI: 10.1530/endoabs.49.EP502

A systematic search of MEDINE and EMBASE was performed for all relevant

published articles. Reference lists of all included studies were also searched.

Studies were included assessing fear of hypoglycaemia, recognition of symptoms,

health-seeking behaviour and impact on overall wellbeing. One reviewer

screened abstracts of all identified citations, selected potentially eligible studies

and assessed their full-text versions using the STROBE

(Strengthening the

EP503

reporting of observational studies in epidemiology) checklist for cohort, case-

control and cross-sectional studies (combined.) Findings from the studies were

then narratively synthesized.

Abstract withdrawn.

Results

Eight studies were included in this review. After hypoglycaemia, IDDM patients

have significantly (o!0.01) raised fears of future hypoglycaemia, more fatigue,

reduced alertness and a negative impact on health-related quality of life (HRQL.)

Conclusion

Hypoglycaemia has a wide range of negative emotional, social and behavioural

consequences on IDDM patients. These impacts, hence are a major barrier to

IDDM patients achieving optimal glycaemic control. There remains a need for a

large multi-country study that incorporates mixed-methods data collection,

including a qualitative aspect to provide more in-depth views of the effects of

hypoglycaemia.

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DOI: 10.1530/endoabs.49.EP505

Is proteinuria always associated with diabetes mellitus?! Do we always

make right diagnosis?!

Natia Katamadze & Anna Shamanadze

V.Iverieli Endocrinology, Metabology, Dietology Center ‘ENMEDIC’,

Tbilisi, Georgia.

EP506

Introduction

A protective effect of lobeglitazone on renal fibrosis in unilateral

Proteinuria is a condition in which urine contains an abnormal amount of protein.

ureteral obstruction mice model

Proteinuria is a sign of chronic kidney disease (CKD), which can result from

Hye-Soon Kim¹, Kwi Hyun Bae¹, Gwon Soo Jung¹, Hye Jin Ham¹,

diabetes, high blood pressure and other diseases that cause inflammation in the

Bo Yoon Park¹, Yeon Kyung Choi¹, hyun Ae Seo², Jung Beom Seo¹ &

kidneys. If CKD progresses, it can lead to end-stage renal disease, when the

Keun Gyu Park¹

kidneys fail completely.

¹Kyungpook National University Hospital, Dae Gu City, Republic of Korea;

Case presentation

²Fatima Hospital, Dae Gu City, Republic of Korea.

Sixty-three years old female patient attended our clinic as her glycaemia was poor

controlled. She is diagnosed with diabetes mellitus (DM) type 2 during 9 years.

Laboratory studies were performed: HbA1c- 9.4%, elevated plasma creatinine

Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly

176.32

(N53, 0-97.2) and proteinuria in urine with dipstick 1.01 g/l was observed.

all cause types of chronic kidney disease. Although classic peroxisome

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

proliferator-activated receptor-gamma (PPARg) agonists have a protective effect

Results

on diabetic nephropathy, much less is known about their direct effects in renal

A significant among-group difference was found in adiponectin (ApN) (DM1 vs

fibrosis. This study aimed to investigate possible beneficial effects of

DM2 vs DM3Z15.23G11.54 vs 7.93G5.75 vs 4.47G2.14; ANOVA: FZ11.56,

lobeglitazone, a novel PPARg agonist, on renal fibrosis in mice with unilateral

dfZ2, P!0.0001), C-reactive protein (CRP) (DM1 vs DM-OH vs DM-INS Z

ureteral obstruction (UUO). Through hematoxylin/eosin and Sirius red staining,

2.14G2.42 vs 4.15G5.13 vs 2.16G2.32; FZ7.27, dfZ2, PZ0.026), high

we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy

density lipoprotein (HDL) (DM1 vs DM-OH vs DM-INS Z1.71G0.21 vs 1.37G

and fibrosis. Immunohistochemical analysis in conjunction with quantitative

0.35 vs 1.52G0.31; FZ14.01, dfZ2, P!0.001), uric acid (UA) (DM1 vs

RT-PCR and western blot analysis revealed that lobeglitazone treatment inhibited

DM-OH vs DM-INS Z249.12G71.3 vs 351.4G88.1 vs 321.9G137.13; FZ

UUO-induced upregulation of renal Smad-3

phosphorylation, alpha-smooth

14.23, dfZ2, P!0.001) and body mass index (BMI) (DM1 vs DM-OH vs

muscle actin, plasminogen activator inhibitor-1, and type 1 collagen. In vitro

DM-INS Z24.35G4.01 vs 30.45G7.17 vs 28.51G5.17; FZ12.01, dfZ2,

experiments with rat mesangial cells and NRK-49F renal fibroblast cells

P!0.0001), between tested groups. Tukey post hoc test showed a significant

suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are

difference (P!0.05) in ApN between DM1 and DM-OH, DM1 and DM-INS, and

mediated by inhibition of the TGF-b/Smad signaling pathway. In conclusion, the

DM-OH and DM-INS, but not in BMI (PZ0.12), CRP (PZ0.21), UA (PZ0.41)

present study demonstrates that lobeglitazone has a protective effect on UUO-

and HDL (PZ0.89) between DM-OH and DM-INS. In DM-INS the best model

induced renal fibrosis, suggesting that its clinical applications could extend to the

(R²Z0.942) for ApN included HDL (R²Z0.66, PZ0.002) and UA (R²Z0.35,

treatment of non-diabetic origin renal disease.

PZ0.007). In DM-INS ApN correlated significantly (P!0.05) with HDL (rZ

DOI: 10.1530/endoabs.49.EP506

0.55), FPG (rZ0.42), CRP (rZ0.49), and fibrinogen (FIB) (rZ0.69). Duration of

insulin therapy did not correlate with ApN in DM-INS (PZ0.82).

Conclusions

ApN was decreased in DM-INS compared to DM-OH, which could be explained

with an effect of insulin on adipocytes and C-peptide, consequently on ApN level.

Decreased ApN suggests increased risk of vascular disease in insulin treated

patients. HDL was among the main predictors of ApN. In DM-INS HDL was not

decreased, while CRP was not increased, which could be beneficial in CVD

EP507

protection.

Using the plastic closure techniques of wound defecting treatment of

DOI: 10.1530/endoabs.49.EP508

patients with diabetic foot syndrome

Maksym Prystupiuk, Iuliia Onofriichuk, Liudmyla Naumova,

Lev Prystupiuk & Marianna Naumova

Bogomolets National Medical University, Kyiv, Ukraine.

Purpose

To improve methods of plastic closure of wound defects in patients with diabetic

foot syndrome using skin flaps on vascular pedicle of the perforating vessels.

Methods

EP509

The study involved patients with diabetes type 2 complicated with diabetic foot

syndrome neuroischemic form. The study included 31 patients, 15 people in the

Prayer marks in immigrants from Bangladesh with diabetes mellitus

study group and 16 people - the control group. Area wounds ranged from 3.8 to

who live in Greece

21 cm². Cleansing the wounds was performed by ultrasonic cavitation. On the

Georgios Papadakis¹, Thomas Zambelis², Kostas Konstantopoulos³ &

wound bandage with sorption-based antimicrobial composition of nanosized

Stylianos Chatzipanagiotou⁴

silica. Thus, the wound was purified for 2-3 days. On the third day, the wound

¹STEPS Stoffwechselzentrum, Biel/Bienne, Switzerland;²Department of

was applied vacuum-assisted closure with a standard negative pressure of

Neurology, Aeginition Hospital, Athens, Greece;³Department of Haema-

125 mm Hg. The device was applied for 3-6 days. The number of colony-forming

tology, Laikon University Hospital, Athens, Greece;⁴Department of

units for the success of the operation should be less than 10. Formed flap, which

Medical Biopathology, Aeginition Hospital, Athens, Greece.

corresponds to the size and configuration of the defect on the foot.

Results

Introduction

In the study group noted engraftment graft in 14 patients. Time of full engraftment

Prayer marks (PMs) have been reported in the literature among Muslim prayers.

and the healing of the wound defect in patients of the main group was 14G3 days

PMs are found most often on the forehead, knees, ankles and dorsa of the feet. The

in the control group healing ulcers - 51G10 days.

most common changes consist of thickening, lichenification and hyperpigmenta-

Conclusions

tion of the skin, the causative factors being repeated pressure and friction during

Improved techniques in the treatment of wound autodermoplastic defects in

pray.

patients from diabetic foot syndrome, which is preparation wounds using an

Objectives

ultrasonic cavitation, vacuum bandage hardware. Using a split skin flap can

Immigrant populations are disproportionately affected by diabetes and its

effectively cover the bandage wounds, supporting the ability to save limbs and

complications. Moreover, diabetic foot ulcer is a major complication of diabetes

improve the quality of life.

mellitus, and probably the major component of the diabetic foot. PMs are foot

DOI: 10.1530/endoabs.49.EP507

lesions that can ulcerate. In our study we focused on the frequency of PMs among

Bangladeshi immigrants who live in Athens, Greece and have diabetes.

Methods

A total of 166 immigrants from Bangladesh (150 men and 16 women) with

diabetes mellitus and 65 (58 males and eight females) normal subjects from

Bangladesh were recruited. Characteristic pictures of PMs are taken and

provided.

EP508

Results

Insulin therapy with an impact on inflammation can change the risk for

The mean duration of living in Greece was 10.34G6.2 years. The mean age was

cardiovascvular diseases in type 2 diabetes

44.05G8.1 years old and the reported duration of diabetes 4.86G4.5 years. The

Spomenka Ljubic^1,2, Anamarija Jazbec², Martina Tomic¹, Ivana Antal¹ &

mean A1C was 7.74G1.6% and the mean Glucose values 190.3G72 mg/dl. A

Lea Smircic-Duvnjak^1,2

total of 28 patients with diabetes (16.9%) (one patient with type 1 DM, and 27

¹Vuk Vrhovac University Clinic, Merkur University Hospital, 10000

patients with type 2 DM) and one subject in control group (1.5%) had PMs and all

Zagreb, Croatia;²University of Zagreb, 10000 Zagreb, Croatia.

of them where males. Diabetic patients with PMs and diabetic patients without

PMs had similar and not statistical significant BMI (23.67G2.89 vs 24.30G

3.42 kg/m², PZ0.187), age

(44.04G7.3

44.06G8.35

years, PZ0.488),

Introduction

disease duration (3.86G3.0 vs 5.07G4.74, PZ0.080), and A1C values (7.4G

Patients with diabetes (DM) are at increased risk for cardiovacular disease (CVD).

1.3 vs 7.8G1.6%, PZ0.408). None of the PMs had infection, ulceration or

Possible effects of insulin therapy on development of atherosclerosis and CVD

bleeding at the time of examination. The marks were not itchy or painful and they

were studied.

were observed on the dorsal aspect of the left foot.

Patients and methods

Conclusions

Relevant metabolic parameters were determined in 348 patients assigned into

PMs can often provide clinicians with helpful information for the patient’s

groups with DM2 on oral hypoglycemic drugs (DM2-OH) and insulin (DM2-INS),

cultural background. PMs could ulcerate and our study emphasizes the need for

and with DM1.

clinical awareness of PMs, especially for patients with diabetes. Moreover, people

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

come from different ethnic groups and ethnicity can have important effects on

Objective

health and on the management and treatment of diabetes.

A diabetic state is causally related to heart failure (HF) which is a leading cause of

DOI: 10.1530/endoabs.49.EP509

mortality. Early detection of high-risk individuals is imperative for primary

prevention. The aim of this study was to investigate the role of N-terminal pro-B-

type Natriuretic Peptide (NT-proBNP) in patients with diabetes type 2 (DT2).

Methods

We investigated 86 patients both sexes with DT2 aged 65.54G11.37 years (from

50 to 65 years) without clinical cardiovascular disease at baseline. Plasma levels

of NT-proBNP and other biochemical data were measured. Control group

included 34 healthy subjects the same age.

EP510

Results

Therapy of hormonal disorders in women with acne

NT-proBNP level increased with age in both the diabetic and control group but

Liudmyla Naumova, Lev Prystupiuk, Maksym Prystupiuk,

patients with DT2 had higher NT-proBNP levels (P!0.05). NT-proBNP was

Marianna Naumova & Iuliia Onofriichuk

significantly correlated with HbA1c

(rZ0.53, P!0.001), serum creatinine

Bogomolets National Medical University, Kyiv, Ukraine.

(rZ0.62, P!0.001), serum cystatin C (rZ0.48, P!0.001), and age (rZ0.31,

P!0.001). Multivariate linear regression analysis of the significant variables

Introduction and objectives

showed that age (PZ0.011), male gender (PZ0.012), triglyceride (P!0.001),

About 9% of world population suffer from acne, which occupies the 8th place

systolic blood pressure

(P!0.001), and cystatin C

(P!0.001) were the

among all human diseases, and the 3d place among dermatological disorders.

independent predictors of fasting serum log-NT-proBNP levels in diabetic

Acne is diagnosed in 54% of 18 year aged women. Acne manifests mostly in 12-

patients.

14 year age and regresses after 20 year age, even though more and more women

Conclusions

have recently addressed their doctors for acne problem developing after 20 year

We showed the role of risk factors to heart failure in patients with DT2. In these

age. Location of this dermatosis in open areas of skin leads to depression and

patients, the presence of dyslipidemia, hypertension, and renal impairments were

social disadaptation, which underlines the actuality of this problem. It is well

predictors of fasting serum log-NT-proBNP levels. Thus adjustments for the age,

known that a leading role in the development of adult acne is played by

sex and renal function are necessary for determining cardiac risk based on

hyperandrogenism, which is often caused by polycystic ovarien syndrome

NT-proBNP level.

(PCOS). Well known also is that combined oral contraceptives are used for the

DOI: 10.1530/endoabs.49.EP511

treatment of female acne caused by hyperandrogenism syndrome. However, not

all patients benefit from this kind of treatment. Therefore, the aim of our study

was to better investigate endocrine system status and establish disorders

stimulating the appearance and development of acne in adult women and then

prescribe the proper therapy.

Material and methods

Our study involved 126 women with acne, of 18-37 year age. It included the

EP512

performance of Sonography of thyroid gland and pelvic organs as well as the

Metabolic risk factors in adolescent girls with type 1 diabetes

determination of levels of the following hormones: Prolactin, TSH, FSH, LH,

Marta Isabel Pinheiro¹, Juliana Oliveira¹, Rita Santos Silva^2,3,

17-Hydroxyprogesterone, DHEAS, Free testosterone, Oestradiol, Progesterone,

Cíntia Castro Correia^2,3 & Manuel Fontoura^2,3

Anti-Mullerian hormone.

¹Department of Pediatrics. Hospital Pediátrico Integrado, Centro Hospitalar

Results

de Sa˜o João, Porto, Portugal;2Pediatric Endocrinology and Diabetology

The investigation confirmed high androgenic hormones level in 86.5% of women

Unit, Hospital Pediátrico Integrado, Centro Hospitalar de São João, Porto,

with acne, although clinical manifestations of hyperandrogenism syndrome were

Portugal;³Faculdade de Medicina da Universidade do Porto, Porto,

found only in 45% of these women. i) PCOS was found in 20.2% of women with

Portugal.

acne. ii) Hyperprolactinemia - in 34.9%. iii) Atypical (late) form of congenital

adrenal dysfunction - in 44.9%. So, it was established that, other than PCOS,

Hyperprolactinemia and Atypical (late) form of congenital adrenal dysfunction

Background

are also main causes of hyperandrogenism in women, which can lead to acne.

Adolescent girls with type

1 diabetes

(T1DM) have a higher incidence of

Depending on the endocrine pathology of patients, appropriate treatment was

metabolic risk factors like hypertension, dyslipidemia, non-alcoholic hepatic

prescribed: i) Oral contraceptives for PCOS. ii) Dopamine agonists for

steatosis (NASH), abdominal adiposity and polycystic ovarian syndrome (PCOS)

Hyperprolactinemia. iii) Synthetic glucocorticoids for Atypical (late) form of

when compared with their non-diabetic peers. Moreover, metabolic risk factors

congenital adrenal dysfunction. Also, regardless of the type of hormonal

seem to appear even in T1DM girls without overweight or obesity. We aimed to

disorders, all women received proper topical therapy in accordance with the

determine the prevalence of several metabolic risk factors in adolescent T1DM

severity of acne.

females, according to their nutritional status.

Conclusions

Methods

As a result, we got to the following conclusions: i) On the background of the

Girls older than 14 with T1DM for a period longer than 2 years were included.

proposed differentiated combined therapy within 6 months, positive effects were

They were divided into two groups according to their body mass index (BMI

achieved in 85% of women with significant reduction of the eruption and without

above or below the 85th percentile). The two groups were compared in what

its recurrent appearance. ii) The condition of skin and acne eruptions was clearly

regards the presence of abdominal adiposity, hypertension, lipid profile

dependent on hormone levels in the blood. iii) In order to achieve efficient

abnormalities, NASH and PCOS.

treatment of female acne, combined therapy should be based on the correction of

Results

hormonal disorders.

44 adolescents were included: 25 with normal weight and 16 (39%) with obesity

DOI: 10.1530/endoabs.49.EP510

or overweight. No difference was found between age (17G1.8 for girls with

normal weight vs 17G1.7 for obese and overweight girls; PZ0.49) or mean A1c

among groups (8.5G1.4 vs 8.5G1.1; PZ0.98). Girls with normal weight had a

longer duration of T1DM (9G4 vs 7G4; PZ0.03). In what regards overweight or

obese girls, 23% had abdominal adiposity, 14% hypertension, 21% lipid profile

abnormalities, 23% NASH, 23% PCOS and 20% metabolic syndrome. Among

normal weight diabetic girls, 6% had abdominal adiposity, 19% hypertension, 5%

lipid profile abnormalities, 6% NASH and 6% PCOS. No statistical significant

differences were found between the two groups.

Discussion

EP511

The prevalence of metabolic risk factors, including NASH and PCOS, was similar

N-Terminal pro-B-type natriuretic peptide level in type 2 diabetic

of that reported in the published data concerning diabetic young women, although

patients

there are few studies in the pediatric population. Even though metabolic

Volha Vasilkova^1,3, Tatiana Mokhort², Elena Naumenko³ &

syndrome and its components were more prevalent among overweight and obese

Margarita Zmailik³

T1DM girls, they were also present among normal weight diabetic individuals.

¹Gomel State Medical University, Gomel, Belarus;²Belarusian State

DOI: 10.1530/endoabs.49.EP512

Medical University, Minsk, Belarus;³The Republican Research Center for

Radiation Medicine and Human Ecology, Gomel, Belarus.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP513

both increased NF-kB p65-Ser⁵³⁶ phosphorylation and decreased GSK3b-Ser⁹

phosphorylation in the aortas from high-fat fed mice were reversed by treating

Transcultural prevalence of depression in type 2 diabetic patients in

with telmisartan. Taken together, our findings demonstrate that telmisartan

Egypt and Yemen

ameliorates hyperglycemia-exacerbated vascular inflammation at least in part by

M. M. Aboshady¹, M. R. Halawa¹, A. A. Elewa¹, G. El-Khouly² &

increasing GSK3b-Ser⁹ phosphorylation, which mediates a decreased VCAM-1

A. S. Bin-Nabhan³

expression in a PPARg-independent manner. Telmisartan may be useful for the

¹Endocrinology Unit and Internal Medicine Department, Faculty of

treatment of DM-associated vascular inflammation and cardiovascular diseases.

Medicine, Ain Shams University, Cairo, Egypt;²Neuropsychatry Depart-

ment Ain Shams University, Cairo, Egypt;³Endocrinology Unit and Internal

DOI: 10.1530/endoabs.49.EP514

Medicine Department, Hadhramout University, Sanaa, Yemen.

Background and aims

Depression is a common co-morbidity among people with diabetes that reduces

quality of life and is associated with morbidity, mortality, and health care costs.

We aimed to assess the prevalence of depression among patients with type 2

EP515

diabetes in two Arabic nations, Egypt and Yemen and to examine its relationship

Continuous glucose monitoring system in the value of diabetes mellitus

with socio-demographic data and diabetes complications.

type 1 control

Methods

Tatiana Mokhort², Elena Makhlina¹, Marina Kapliyeva¹, Yana Navmenova³

We conducted a cross-sectional analysis on 200 subjects with type 2 diabetes,

& Irina Savosteeva

divided into two groups: 100 Egyptian and 100 Yemeni subjects. All selected

¹Gomel State Medical University, Gomel, Belarus;²Minsk State Medical

subjects were subjected to full medical history and clinical examination.

University, Minsk, Belarus;³Republican Scientific and Practical Center for

Laboratory tests included fasting plasma glucose and HbA1C. MADRS scale

Radiation Medicine and Human Ecology, Gomel, Belarus.

was used for diagnosis of depression.

Results

Both groups were age and sex matched. The prevalence of depression was 39% in

Purpose

Egyptian and

34% of Yemeni patients, with no statistical significance. In

Estimation of the continuous glucose monitoring system (CGMS) in the value of

Egyptian diabetics, depression was significantly associated with female gender,

diabetes mellitus type 1 (DM1) control.

duration of diabetes, poor glycemic control, higher number of children, low and

Materials and methods

very low socioeconomic levels, high mean number of cigarette smoking, lower

162 DM1 patients have been divided on 2 groups: 1st group with adequate control

mean number of years of education and presence of diabetes complications.

DM1 - glycated hemoglobin (HbA1C) %7.5% (nZ38) and 2nd group with

However, in Yemeni diabetics, depression was significantly associated with

inadequate control - HbA1CO7.5% (nZ124). All patients carried out CGMS

female gender, birth order, poor glycemic control, Low and very low

with glycemia symmetrization scales and an estimation of probability of a

socioeconomic levels, lower mean number of years of education, diuretic usage

dysglycemia, hypo- and hyperglycemias risks with calculation of indexes of risk

for medical co-morbidities. The most important predictors of depression were

(InR). High risk of a hypoglycaemia at InR more than 4.5; low - less than 2.5.

female sex, higher number of children, divorce, Low and very low socioeconomic

The high risk of a hyperglycaemia at InR is more 9.0, low risk - less than 4.5.

levels and lower mean number of years of education.

InR dysglycemias - a difference of InR hyper- and hypoglycemias.

Conclusion

Results

High prevalence of depression among Egyptian and Yemeni type 2 diabetic

HbA1C level in the 1st group of patients was 6.75% (6.40; 7.25) - adequate

patients. Depression associated with poor glycemic control.

control DM1, and in 2nd - 9.40% (8.30; 11.10) - inadequate control. InR in group

Keywords: Diabetes mellitus; depression; Egyptian; Yamani.

1 was less (8.25 (4.80; 14.70)), than in the 2nd group - 16.24 (10.45; 20.60) (P!

DOI: 10.1530/endoabs.49.EP513

0.001). In the group with inadequate control of DM1 InR of a hyperglycaemia has

been raised at 85% of patients, in comparison to 48% of patients in the 1st group.

Low InR of a hyperglycaemia in 2nd group was at 2% vs 1st group - 23% (P!

0.001). InR hypoglycemias has made 5.60 (3.00; 10.50) in 1st group and 5.00

(1.60; 9.20) - in 2nd group. In the absence of differences between groups in InR

hypoglycemias, InR of a dysglycemia significantly differed: 2.40 (3.00; 8.20) vs

9.85

(2.80; 18.55), (P!0.001). Hypoglycaemia InR exceeded 4.5 independently

EP514

of adequacy of control DM1 (high risk of hypoglycemias) at 53% of patients of

1st group and at 62% of patients 2nd group. Low InR of a hypoglycaemia in 2nd

Telmisartan attenuates hyperglycemia-aggravated VCAM-1 expression

group was at 19% that is significantly less (P!0.001), than in 1st group - 31%.

and monocytes adhesion in TNFa-stimulated endothelial cells by

Conclusions

increasing GSK3b-Ser⁹ phosphorylation

Inadequate control of HbA1C level among the patients with DM1 was observed

Du-Hyong Cho¹, Sun-Ju Bae¹ & Kee-Ho Song²

three times more often than adequate. By results of CGMS the insulin therapy

¹Eulji University School of Medicine, Daejeon, Republic of Korea;

scheme has been optimizated according to a daily nutrition that allowed to reach

²Konkuk University School of Medicine, Seoul, Republic of Korea.

improvements of control DM1.

DOI: 10.1530/endoabs.49.EP515

Uncontrolled hyperglycemia accelerates endothelial damage and vascular

inflammation caused by proinflammatory cytokines including tumor necrosis

factor a

(TNFa), which leads to arteriosclerotic cardiovascular diseases.

Glycogen synthase kinase 3b (GSK3b) is reported to mediate TNFa-stimulated

nuclear factor-kB

(NF-kB) activation and expression of vascular adhesion

molecules. Although a few clinical trials have suggested that telmisartan, an

angiotensin II type

receptor blocker

(ARB), decreases cardiovascular

EP516

complications in diabetic patients, the underlying molecular mechanisms for

the beneficial effects have not been fully elucidated. Here, we investigated a

Chronic kidney disease in elderly patients with type 2 diabetes: 6 years

of follow-up study

molecular mechanism mediating the telmisartan’s beneficial effects on vascular

Soo-Kyung Kim, Kyung-Soo Kim, Seok Won Park & Yong-Wook Cho

inflammation in hyperglycemia-treated endothelial cells. Telmisartan dose-

CHA Bundang Medical Center, CHA University, Seongnam,

dependently attenuated the hyperglycemia-aggravated vascular cell adhesion

Republic of Korea.

molecule-1

(VCAM-1) expression and THP-1

monocytes adhesion, which

accompanied an increased GSK3b-Ser⁹ phosphorylation and a decreased NF-

kB p65-Ser⁵³⁶ phosphorylation. Among ARBs, including losartan and fimasartan,

Objective

only telmisartan induced GSK3b-Ser⁹ phosphorylation and showed the inhibitory

To evaluate prevalence of chronic kidney disease (CKD) and risk factors for

effects on expression of VCAM-1 and phosphorylation of NF-kB p65-Ser⁵³⁶. The

decline of renal function in elderly patients with type 2 diabetes (T2DM) after

telmisartan’s beneficial effects were not changed by pretreatment with GW9662, a

6 years of follow-up.

specific and irreversible peroxisome proliferator-activated receptor g (PPARg)

Methods

antagonist, although GW9662

clearly inhibited rosiglitazone-induced CD36

A cohort of 208 elderly patients (65 years or older) with T2DM participated in an

expression. Ectopic expression of GSK3b-S9A, a constitutively active mutant of

examination during 2005, a 6-years follow-up examination during 2011. An

GSK3b, significantly restored the telmisartan-attenuated VCAM-1 expression,

estimated glomerular filtration rate (eGFR) was calculated using the modification

NF-kB p65-Ser⁵³⁶ phosphorylation, and THP-1 monocytes adhesion. Finally,

of diet in renal disease equation. CKD was defined as eGFR !60 ml/min per

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

1.73 m² and worsening nephropathy was defined as eGFR !45 ml/min per

calculated by Cockcroft-Gault formula. Anemia was defined according to World

1.73 m².

Health Organization criteria

(2008). In addition to routine clinical tests we

Results

measured serum levels of EPO and TNF alpha using immunoassay. Correlations

Among the 208 elderly patients with T2DM, 95 patients (45.7%) had CKD at

were assessed by Spearmen’s correlation coefficient

(rs). We found EPO

baseline. Obesity, longer diabetes duration, and usage of ACEI or ARB were

deficiency in 46.3% and decreased serum ferritin levels in 11.6% patients. Serum

independent factors related to the presence of CKD. Mean follow-up duration was

level of TNF alpha correlated negatively with hemoglobin level (rsZK0.311,

54.9 months. On multivariate Cox analysis, elderly patients with diabetes duration

PZ0.003). It had no significant interrelations with age, serum creatinine, ferritin,

R10 years had a 2.85-fold increased risk for worsening nephropathy compared

cholesterol, glomerular filtration rate and urinary albumin excretion. In patients

with those with diabetes duration !5 years (95% CI 1.29-6.30; PZ0.010).

without EPO deficiency TNF alpha level correlated with mean cell hemoglobin

Compared with HbA_1c !8.0%, HbA_1c R9.0% had a 2.82-fold increased risk for

content (rsZK0.700, PZ0.003), serum EPO (rsZ0.375, PZ0.017) and urea

worsening nephropathy (95% CI 1.40-5.69; PZ0.004). Elderly patients with

concentrations (rsZ0.433, PZ0.011). In EPO-deficient patients it correlated with

obesity showed worse renal prognosis than those without obesity (HR 1.89; 95%

serum urea (rsZ0.393, PZ0.032) but not with mean cell hemoglobin content

CI 1.01-3.53; PZ0.045).

(PZ0.950) and EPO level (PZ0.247). The results of the study suggest that

Conclusions

anemia in patients with early DN is multifactorial. EPO-deficient and EPO-

Since CKD was commonly accompanied in elderly patients with T2DM, it is

sufficient anemic patients with DN are characterized by different clinical

important to monitor and manage renal function in those patients, especially who

correlates of serum TNF alpha level. Further larger studies are needed to elucidate

had diabetes duration R10 years or HbA_1c R9.0% or obesity.

clinical implications of these findings.

DOI: 10.1530/endoabs.49.EP516

DOI: 10.1530/endoabs.49.EP518

EP517

EP519

Association of metabolic risk factors with hyperfiltration and urine

Non-alcoholic steatohepatitis and diabetes mellitus: a case report

albumin creation ratio in represent Korean population (Korea National

Sara Castelo Branco¹, Miguel Vasques², Lurdes G. Matos², Edite Filipe² &

Health and Nutrition Examination Survey 2011-2014) without chronic

Adelaide Milheiro²

kidney disease

¹Santa Marta Hospital, Lisbon, Portugal;²Curry Cabral Hospital, Lisbon,

Eun-Gyoung Hong, Sangmo Hong & Yun Mi Choi

Portugal.

Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si

Gyeonggi-do, Republic of Korea.

Non-alcoholic steatohepatitis (NASH) is a clinical entity characterized by the

infiltration of fat into the liver associated with hepatic inflammation. The etiology

The development of glomerular hyperfiltration precede the diagnosis of diabetes,

is unknown, however its most frequently observed in patients with type 2 diabetes

but most study had undertaken with diabetes or obesity patients. In this study, we

mellitus (DM 2), obesity or insulin resistance. DM 2 is an independent risk factor

determine the association between glomerular hyperfiltration and other metabolic

for the progression of NASH. Usually there are no symptoms, so it is not possible

risk factors which associated diabetes in represent Korean population without

to estimate its prevalence. The treatment focuses on the control of associated

chronic kidney disease. We analyzed 19 244 subjects with a estimated glomerular

diseases such as DM 2 and obesity. A 65-year-old woman without alcohol or

filtration rate(eGFR) above 60 ml/min per 1.73 m² and urine albumin creation

toxicophilic abuse, without obesity (BMI of 22.7) and with clinical history of

ratio (ACR) below 30 mg/g from the 5th (V-2,3, 2011-20012) and 6th (VI-1,2,

immune thrombocytopenic purpura, DM 2 (controlled under diet), hypertension

2013-2014) Korea National Health and Nutrition Examination Survey

and cystic lesion of the pancreas (5 years before biopsy compatible with mucinous

(KNHANES). The estimated glomerular filtration rate was calculated on the

lesion). Due to the increasing of the pancreatic lesion, with dilatation of the

basis of the CKD-EPI equation. Hyperfiltration was defined as eGFR above the

wirsung canal, the patient was submitted to body-caudal pancreatic resection.

age- and sex-specific 95th percentile for healthy subjects. According to glucose

During the intraoperative period, the liver presented with a cirrhotic pattern, and

tolerance, the prevalence of hyperfiltration were increased 4.7% in normal, 4.9%

liver biopsy was performed. Histology showed steatohepatitis, with fibrosis grade

in prediabetes, and 5.4% in diabetes (P for trend !0.001). After adjusting age,

5/6 and focal balloonization of hepatocytes. Additional study: ANA 1/160,

sex, body weight, hyperfiltration associated with higher body mass index

remaining autoimmunity (AMA, SMA, LKM and antibodies anti-liver antigens)

(P!0.001), waist circumference (P!0.001), systolic blood pressure (PZ0.003),

and viral serologies (HIV, hepatitis B and C) negative. After the surgery, insulin

HbA1c (PZ0.039), fasting plasma glucose (PZ0.005), triglyceride (PZ0.001),

therapy was initiated with good metabolic control. The patient did not present

energy intake

(PZ0.001), protein intake

(PZ0.034), and sodium intake

micro or macrovascular complications. The present case describes a diabetic

(PZ0.002). Hyperfiltration was independently associated with ACR

(BZ

patient with an incidental diagnosed cirrhotic liver caused by NASH. The

0.053, P!0.001) in multiple regression analysis with above mentioned factors.

association of NASH and DM2 is present in more than 75% of the diabetics and in

Higher waist circumference (P!0.001), systolic blood pressure (P!0.001),

this case other related conditions (as obesity, hyperlipidemia, insulin resistance,

HbA1c (P!0.001), fasting plasma glucose

(P!0.001), and triglyceride

and drugs) were excluded. The early intervention in DM 2 is crucial, in order to

(PZ0.001) were also independently associated with ACR. In Korean general

reduce related pathologies and their progression especially in this case with silent

population, both hyperfiltration and ACR were associated with similar metabolic

steatohepatitis and cirrhotic liver.

risk factor and each were independently associated. Longitudinal studies are

DOI: 10.1530/endoabs.49.EP519

needed to explore the risk for hyperfiltration and microalbuminuria.

DOI: 10.1530/endoabs.49.EP517

EP520

A novel lipid tetrad index as predictor of premature coronary artery

EP518

disease in diabetic patients

Clinical correlates of TNF alpha levels in anemic patients with early

Saswati Das & S. K. Gupta

diabetic nephropathy

Maulana Azad Medical College, Delhi, India.

Ivan Pchelin & Alexander Shishkin

Saint Petersburg State University, Saint Petersburg, Russia.

Background

The aim of this study was to explore if evaluation of lipid risk factors like

Anemia occurs early and predicts high risk of cardiovascular events and death in

Lipoprotein(a) (Lp(a)) and conventional lipid profile parameters can be a efficient

patients with diabetic nephropathy (DN). It results from various factors including

predictor of the cardiovascular risk in the patients of Diabetes.

erythropoietin (EPO) deficiency and inflammation. The aim of this study was to

Methods

evaluate clinical correlates of TNF alpha levels in anemic patients with early

Sixty individuals with angiographically proven premature CAD and 30 healthy

diabetic nephropathy. We investigated 95 anemic patients with type 2 diabetes

individuals matched for age and sex were studied a tertiary health care centre,

mellitus and chronic kidney disease (stages 1-3). Glomerular filtration rate was

New Delhi, India, over a period of 18 months. CAD patients were divided into

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

two groups based on presence (nZ30) (group I) and absence (nZ30) (group II) of

EP522

type 2 diabetes mellitus (DM). The serum levels of Lipoprotein (a) were measured

by ELISA and routine lipid profile (serum triglyceride, total cholesterol, HDL-C

and LDL-C) was measured by automated analyzer. Angiographic clinical vessel

Abstract withdrawn.

scoring was also done for all the patients.

Results

Lipoprotein (a) levels for Group I was 40.26G8.23 mg/dl, Group II was 40.81G

11.16 mg/dl respectively which was significantly (i.e. P!0.01) higher than the

levels in healthy controls (Lp(a)Z16.39G5.71 mg/dl). We found a significant

increase in mean levels of Total cholesterol (TC), Low Density Lipoprotein-

Cholesterol (LDL-C) and Triglyceride (TG) in cases than controls (P!0.01). In

contrast High Density Lipoprotein-Cholesterol (HDL-C) values decreased. Non

HDL-C was calculated using the equationZ(Total Cholesterol[TC]KLDL-C).

Lipid Tetrad Index (LTI) and Atherogenic Index were also calculated for all

patients. The Modified Lipid Tetrad Index that we propose was calculated using

the equation MLTIZ(non HDL-C!triglycerides!lipoprotein(a)/HDL-C). On

analyzing by cumulative probability plot the new modified Lipid Tetrad Index

defined by us is able to discriminate case and control populations more precisely

EP523

than the existing LTI and Atherogenic Index. The Modified Lipid Tetrad Index

The prevalence of common risk factors for depression development in

has a better sensitivity and specificity than the existing LTI and also has a better

diabetes mellitus of the type 1

correlation with the angiographic vessel score in all patients.

Yana Navmenova¹, Eelena Mahlina¹ & Tatyana Mohort^1,2

Conclusion

¹The Republican Research Center for Radiation Medicine and Human

The new proposed Modified Lipid Tetrad Index is a better marker and predictor of

Ecology, Gomel, Belarus;²Gomel State Medical University, Gomel,

severity of premature CAD diabetic patients from India, than the existing Lipid

Belarus;³Belarusian State Medical University, Minsk, Belarus.

Tetrad Index and Atherogenic Index.

DOI: 10.1530/endoabs.49.EP520

Objective

To evaluate the frequency of common risk factors for depression development in

patients with the diabetes mellitus of the type 1 (DM1).

Materials and methods

163 patients with DM1 at the age of 18-65 years old, period of DM is 11.18 (4.28;

22.33) years. The evaluation of the anxiety and depression level was carried out

with the use of the Hospital anxiety and depression scale (HADS); a questionnaire

was carried out with the use of specially developed form to reveal common risk

factors for depression development. A study group was divided into two

EP521

subgroups depending on the level of depression in accordance with the HADS:

Assessing the impact of ‘nephrogenic’ risk factors on the development

group 1 included patients with DM1 and depression (nZ46) and group 2 included

of cardiac pathology in patients with long duration diabetes type 1

patients with DM1 without depression (nZ117).

Margarita Arutyunova, Alexandra Glazunova, Inna Klephortova,

Results and conclusion

Sergey Martynov, Oxana Manchenko, Irina Ulianova, Alexandr Ilyin,

i) There are more patients that live alone (23.9% in comparison with 9.4%

Minara Shamkhalova & Marina Shestakova

consequently, rZ0.04) and person with disability status (69.6% in comparison

Endocrinology Research Centre, Moscow, Russia.

with 47.9% consequently, rZ0.03), among patients with DM1 and depression,

than among patients with DM1 without depression. ii) The disability status is

Aim

associated with the risk for depression development in DM1

(ORZ2.41;

The aim of study is to investigate the effects of renal pathology on the

PZ0.01; 95% CI 1.16-4.19).

cardiovascular system in patients with T1D, the detection of the most important

DOI: 10.1530/endoabs.49.EP523

cardiovascular risk factors associated with CKD.

Methods

The study includes 156 patients with a long duration of T1D (more than 20 years):

24 patients without CKD, 82 patients with 1-4 stages of CKD, 29 patients on

hemodialysis, 21 patients after kidney transplantation. In addition to the routine

methods of survey assessed indicators of phosphorus-calcium metabolism

(calcium, phosphorus, parathyroid hormone (PTH), vitamin D, fibroblast growth

factor 23 (FGF-23)), the markers of: cardiac disease - atrial natriuretic peptide

(NT-proBNP), endothelial dysfunction - asymmetric dimethylarginine (ADMA),

systemic inflammation (C-reactive protein, fibrinogen). All patients underwent

EP524

ambulatory blood pressure monitoring, echocardiography, had a multi spiral

Comorbilities and morbimortality of patients with hospital

computed tomography of heart with Agatston index definition.

hyperglycemia in the health area of Cuenca (Spain)

Results

José Pérez-Rodríguez, Dulce Calderón-Vicente, Santiago Aranda-Regules,

Decrease of glomerular filtration rate (GFR) was associated with: increased

Lidia Guerra-Navarro, Paula García-Notario, Mubarak Alramadan &

systolic blood pressure

(SBP) (rZK0.209762; P!0.05), mass index myo-

David Martín-Iglesias

cardium of left ventricular

(LVMI) (rZK0.221375; P!0.05), the level of

Virgen de la Luz Hospital, Cuenca, Spain.

NT-proBNP (rZK0.465808; P!0.05), ADMA (rZK0.355866; P!0.05),

C-reactive protein

(rZK0.204248; P!0.05), fibrinogen

(rZK0.224840;

Introduction and objectives

P!0.05), triglycerides (rZK0.287844; P!0.05), a decrease of HDL-C (rZ

Hyperglycemia (HG) is a common problem in hospitalized patients that increases

0.179257; P!0.05)/Albuminuria is positive correlated with hypertriglyceridemia

infections, mortality, costs and the hospital stay. The objective of this study is to

(rZ0.335853; P!0.05), SBP (rZ0.262411; P!0.05), NT-proBNP level (rZ

know the association of the HG with cardiovascular risk factors (CVRF), stress

0.218696; P!0.05). The mineral and bones disorders of CKD (CKD-MBD) such

factors, hospital stay and mortality.

as secondary hyperparathyroidism (SHPT), deficiency of vitamin D, calcification

Methods

of the coronary arteries was the most relevance factors among the nephrogenic

We designed a cross-sectional observational study. We included patients admitted

risk factors of cardiac disease.

in the hospital every three days in two months. We excluded patients younger than

Conclusion

15 years, stays less than three days and those of the pediatric, gynecological,

CKD and conditions accompanying it for, especially MBD-CKD, are powerful

emergency and intensive care services. We collected the data from these patients

predictors of cardiovascular disease. The reason of such a close relation is caused

the third day of admission and at discharge. We defined HG as two or more

not only by the negative impact of nephrogenic risk factors, but also by worsening

capillary glucose values greater than 140 mg/dl. We consider stress factors as

conditions such as dyslipidemia, systemic inflammation, endothelial dysfunction,

infection/sepsis, surgery and corticosteroids treatment.

as demonstrated in our study.

Results

DOI: 10.1530/endoabs.49.EP521

A total of 328 patients were included 109 of patients had HG. Regarding CVRF,

the hyperglycemic patients had hypertension in 67%, dyslipidemia in 45.9% and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

both disorders in 38.5%; compared to 42.9%, 24.7% and 17.8%, respectively in

Methods

non-hyperglycemic patients. The HG group had two stress factors in 33.7% vs

A comparative observational study of 60 patients, male and female (1:1) aged 60-

8.4% in non-HG group; and three stress factors in 10.6% vs 3.6% respectively.

85 years. Enrolment criteria - known diabetics, HbA1c 7-9 and DPN of 1-5

Hyperglycemic patients were treated with corticosteroids in 36.7% vs 15.6% in

years. Patients were randomized into 2 treatment groups G1 and G2. The study

non-hyperglycemic patients. The mean hospital stay was 9.17 days in HG group

period was 4 weeks (w) with results assessed at baseline and bi-weekly follow-ups

compared with 7.53 days in non-HG group (P!0.52). Longer stays were

using diabetic neuropathy symptom (DNS) score. G1: 30 patients with an

observed in HG group. Finally, the rate of mortality in hyperglucemic patients

established DPN were treated with PEMF therapy - frequency of 10 Hz, thru two

was of 3.7%, vs 0.5% of the non-hyperglycemic patients (P!0.044).

emitters of 20 mTesla and 6 mTesla, keeping north polarity was towards the body.

Conclusions

A total of 15 sitting of 20 (10C10) min - one per day. G2: 30 patients with an

Patients with hospital HG are more likely to have other CVRF associated. Stress

established DPN were continued on oral symptomatic treatment options like -

factors such as surgery, corticosteroids treatment and infection/sepsis increase the

amitriptyline, duloxetine, gabapentin, pregabalin and tramadol. Patients in both

risk of HG. Finally HG is associated with a longer hospital stay and higher

the groups were on Vitamin B 12C Alpha Liponic Acid which were continued.

mortality.

Results

DOI: 10.1530/endoabs.49.EP524

In G1 application of LF-PEMF therapy significantly facilitated the regression of

the main clinical symptoms of DPN. Patient scores were more differentiated on

DNS score. Complete relief in the symptoms of DPN was achieved in four

patients at 2 w which sustained at four patients at 4 w. DNS score of 1 was

achieved in ten patients. DNS score of 2 was achieved in 18 patients at 2 w which

was sustained at 4 w. Overall 32 patients had a relief of main clinical symptoms

on the DNS score. In G2 there was a mild regression of the main clinical

symptoms of DPN. Complete relief in the symptoms of DPN on DNS score was

achieved in 0 patients at 2 w and in one patient at 4 w. DNS score of 1 was

achieved in two patients at 2 w which increased to three patients at 4 w. DNS

EP525

score of 2 was achieved in seven patients at 2 w which was increased to 11

Diabetes and mental health disorders: not a good combination

patients at 4 w. Overall 14 patients had a relief of main clinical symptoms on the

Rahat Tauni^1,2, Nida Ali², Ravina Tanna², Debbie Charles-Obi²,

DNS score.

Jyotsna Bhudia² & Ritwik Banerjee²

Conclusion

¹Cambridge University Hospitals, Cambridge, UK;²Luton and Dunstable

The present study provides convincing data regarding the effectiveness of

University Hospital, Luton, UK.

LF-PEMF therapy, on patients with DPN symptoms. The usage of oral

symptomatic drugs is limited due to the high frequency of adverse events, lack

of evidence of long term efficacy and concern about dependence. Considering the

A 49 year old lady presented to the hospital unconscious with severe

benefits and safety, in comparison to oral symptomatic drugs, LF-PEMF can be

hypoglycaemia. She had type 1 diabetes for 24 years and coeliac disease. She

used as an adjacent in the management of diabetic neuropathy cases. A bigger

was hypo-unaware and had multiple admissions with DKA and hypoglycaemia

study is warranted to determine whether DPN can be modulated with LF-PEMF

over the years. She did not engage in the self-management of diabetes, therefore,

and how it can influence nerve regeneration. Limitations of this study include

insulin was being injected by the carers in the community and by nurses in the

small sample size, short duration of treatment and non-availability of follow-up

hospital. Her erratic and unpredictable glycaemic control was attributed to non-

data.

compliance. She admitted to eating gluten diet, and recent upper GI endoscopy

Keywords: LF-PEMF - low frequency pulsed electro magnetic field, DPN -

showed mark villous atrophy. Her meal size and pattern were variable at home.

diabetic polyneuropathy, DNS - diabetic neuropathy symptom, w - weeks.

During admission, she was found to be self-injecting her own insulin without a

DOI: 10.1530/endoabs.49.EP526

clinical indication. She was assessed by a psychiatrist and was diagnosed to have

a personality disorder. She was deemed to have full mental capacity and insight

into her condition and the harm that can occur with her behaviour. She was seen

by a psychologist and admitted to self-injecting insulin without a clinical

indication. It transpired that this was due to an ongoing court battle with her

children, and the secondary gain was to get the attention of her children. Diabetes

can contribute to the pathogenesis of psychiatric disorders, and some psychiatric

disorders are significant risk factors for the development of diabetes. Up to 45%

of mental disorders and severe psychological distress goes undetected in people

being treated for diabetes. Psychiatric disorders co-existing with diabetes include

EP527

delirium, mood disorders, substance abuse, anxiety, eating disorders and

Correlation of NGAL and thyroid function in patients with type 1

psychosis. There could also be some overlap between physical features of

diabetes

diabetes especially hypoglycaemia and symptoms of psychiatric disorders.

Alena Sazonava^1,2, Tatiana Mokhort¹, Volha Shyshko¹, Alena Mokhort¹ &

Physicians and endocrinologists should actively seek these issues especially in

Natalia Karlovich^1,2

people with ‘brittle’ diabetes as early recognition and treatment of psychiatric and

¹Belarusian State Medical University, Minsk, Belarus;²City Endocrinolo-

behavioural problems may lead to satisfactory diabetes control and avoid hospital

gical Dispensary, Minsk, Belarus.

admissions.

DOI: 10.1530/endoabs.49.EP525

Neutrophil gelatinase-associated lipocalin (NGAL) was shown to be highly useful

in assessing kidney injury in patients with diabetic nephropathy. Taking into

account recent data that dysthyroidism may have reversible effects on GFR the

purpose of the study was to investigate potential relationship between serum

NGAL levels, thyroid status and ultrasound thyroid characteristics in patients

with type 1 diabetes (T1D) with CKD.

Materials and methods

We recruited 118 patients (43m; 75f; age 40.78G12.241 years; BMI 25.50G

4.956 kg/m²; duration of T1D 22.86G9.737 years) with CKD. Hypertension was

observed in 76 (64.41%) patients, 56 (47.46%) took ACE inhibitors. Lipid profile

EP526

changes were found in 87 (73.73%) patients, and only 30 (25.42%) of them

received statins. GFR was estimated by CKD-EPI formula. All patients were

Management of diabetic peripheral neuropathy (DPN) using low

divided into two groups: group 1 comprised 95 patients with GFRO45 ml/min,

frequency pulsed electro magnetic field (LF-PEMF)

group 2 - 23 patients with GFR!45 ml/min. Biochemical parameters, NGAL,

Satish Chander Wasoori¹, Deepak G. Pande², Chetan Bhardwaj¹ &

thyroid hormones levels were measured. USG of thyroid gland was performed.

Manoj Naik¹

Nonparametric statistical methods were used. A P-value !0.05 was considered

¹Park Hospital, Gurgaon, Haryana, India;²G D Diabetes Center, Delhi,

significant.

India.

Results

Groups were matched by age, gender, HbA1c, TSH, fT4, ATPO levels, thyroid

Objective

gland volume (VolThG). Comparative analysis of patients in the subgroups

To evaluate the effectiveness of low frequency pulsed electro magnetic field (LF-

according to GFR revealed reliable differences in fT3 (PZ0.028) and NGAL

PEMF) in the management of diabetic peripheral neuropathy (DPN) symptoms.

levels (PZ0.0003). Low-fT3 was occurred significantly more often in group 2 -

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

34.78% vs 16.84% (c²Z4.5, PZ0.034). Mean NGAL levels in patients with

Aim and objective

GFR!45 ml/min (1.98 [0.91; 3.29]) were higher than those in group with GFRO

Mucormycosis is a rare life-threatening fungal infection. Immunocompromised

45 ml/min (0.88 [0.48; 1.30]). Presence of nodal pathology observed more

patients are often affected. We report a rare diabetic patient with pancreatic

frequently in group 2 - 39.13% vs 16.84% (c²Z5.5, PZ0.019), despite the fact

adenocarcinoma who was presented diabetic ketoacidosis and rhino-orbito-

that there were no differences in presence of hypoechoic nodes O1 cm.

cerebral mucormycosis.

Correlation of VolThG and NGAL (rZK0.288) and serum creatinine levels

Case presentation

was revealed (rZ0.222).

A 66 years old man with pancreatic adenocarcinoma and type 2 diabetes mellitus

Conclusion

was presented diabetic ketoacidosis and severe infection of the facial sinuses,

Decline of GFR leads to deviation from the normal structure of thyroid gland and

orbita, and soft palate in the right half of the face. It was learned that the infection

developing of local nodal pathology in group of patients with T1D and is

developed after tooth extraction. Diabetic ketoacidosis improved after fluid and

accompanied by an increase of NGAL levels and low-fT3.

electrolyte replacement and insulin treatment. Non-septate hyphae structures

DOI: 10.1530/endoabs.49.EP527

were shown in biopsy sample from affected tissues. Brain MRI showed that this

infection was extended to the brain. Amphotericin B therapy was started

immediately due to delay rapid progression and recommended surgical

debridement. Surgical debridement is the main therapy for mucormycosis but

patient and his relatives did not accept surgical treatment. Amphotericin B

therapy was continued but he dead within the following 2 months.

Conclusion

In diabetic patients with impaired immunity, procedures such as tooth extraction

can cause rare serious infections like mucormycosis.

DOI: 10.1530/endoabs.49.EP529

EP528

Impaired awareness of hypoglycemia in adults with type 1 diabetes is

not associated with peripheral neuropathy

Damianos Tsitlakidis, Milena Djordjevic, Nicolle Muller, Ulrich Muller &

Christof Kloos

University of Jena, Jena, Germany.

Objective

The impaired awareness of hypoglycemia (IAH) affects people with type 1

diabetes and is a risk factor for severe hypoglycemia. This study aims to evaluate

EP530

the association between the impaired awareness of Hypoglycemia by diabetes

Renal function preservation with Manidipine vs Amlodipine in type 2

type 1 and the peripheral neuropathy (PNP).

diabetic hypertensive patients with persistent microalbuminuria

Methods

Sara Quintana-Arroyo¹, Carmen Acosta-Calero¹, Claudia Arnás-León¹,

276 adults with type 1 diabetes, 135 men and 141 women, were studied from Mai

Ana Delia Santana-Suárez¹, Agnieszka Kuzior¹, Margarita Sáiz-Sátjes²,

2015 to January 2016 to the outpatient department of University hospital of Jena.

Manuel Nivelo-Rivadeneira¹ & Francisco Javier Martinez-Martin¹

A cross sectional study was performed, using the Gold Score for assessing

¹Servicio de Endocrinología y Nutrición, Hospital Dr. Negrín de Gran

hypoglycemia awareness and the peripheral neuropathy was evaluated with the

Canaria, Las Palmas de Gran Canaria, Spain;²CAP Rambla Terrassa,

Neuropathy Symptoms Score (NSS) and the Neuropathy disability Score (NDS)

HUMT, Barcelona, Spain.

from Young and Boulton.

Results

The median age of the group was 51G16 years with 23G13 years diabetes

Objectives

duration. The BMI score was 27G5 kg/m² and the DDCT adjusted HbA1c was

The AMANDHA randomized study (PROBE design) showed that the addition of

7.27%G1.1. 85 patients had PNP and 80 had IAH. 27.6% of patients without PNP

Manidipine 20 mg vs Amlodipine 10 mg for 2 years in 91 hypertensive type 2

and 38.8% of patients with PNP had IAH (PZ0.067). The HbA1c did not show

diabetic patients with persistent microalbuminuria, uncontrolled with a renin-

any difference between the adults with and without IAH (7.1 vs 7.3%; PZ0.121).

angiotensin system inhibitor (given full-dose for at least the 6 previous months)

The duration of diabetes was longer for the adults with IAH (31.34 vs 26.95 years;

was more effective in reducing albuminuria in spite of similar blood pressure

PZ0.001). In the regression analysis, a significant association of the IAH to the

control. Patients with significant renal impairment (PlCr O1.4 mg/dl in women

diabetes duration (Exp(B)Z1.031; PZ0.007), but not to PNP (Exp(B)Z1.387;

and O1.5 in men) had been excluded. However, no data were published on the

PZ0.284) or HbA1c (Exp(B)Z0.801; PZ0.115), is shown.

progression of renal dysfunction, with only PlCr values reported, which were not

Conclusions

significantly different. We undertook to establish if there were differences in

This study revealed in adults with diabetes type 1 association between the

glomerular filtration rate (GFR) progression.

diabetes duration and the IAH but not with the presence of PNP.

Methods

DOI: 10.1530/endoabs.49.EP528

Post-hoc analysis of AMANDHA. GFR was estimated by the MDRD-4 equation

for each individual measurement. Point-to-point GFR were compared by unpaired

t-test and progression was compared by the Kruskal-Wallis test. (non-parametric

ANOVA). Values are given as mean (G standard error).

Results

Baseline GFR were

67.3

(G5.2) and

70.2

(G5.0) ml/min/1.73 m²

with

Manidipine and Amlodipine, respectively; at 6 months they were 68.6 (G5.6)

and 69.5 (G5.3), and at 2 years 66.9 (G4.7) and 65.5 (G5.0). During follow-up,

patients treated with Manidipine lost 0.4 (G3.9) ml/min/1.73 m² of FGR vs 4.7

(G5.2) with Amlodipine. Point-to-point GFR were not significantly different

between the groups, but GFR loss after 2 years was lower with Manidipine

EP529

(PZ0.032).

A rare presentation of diabetic ketoacidosis: Rhino-orbito-cerebral

Conclusions

mucormycosis

The previously published data of AMANDHA showed a markedly greater

Askin Gungunes¹, Senay Arikan Durmaz¹, Selim Yalcin², Aydin Cifci³,

albuminuria reduction (about 40% more) with Manidipine vs Amlodipine, which

Veysel Burulday⁴ & Ayse Carlioglu⁵

was attributed to efferential arteriole dilatation. The present post-hoc analysis also

¹Department of Endocrinology and Metabolism, School of Medicine,

shows a better preservation of renal function with Manidipine. These results

Kirikkale University, Kirikkale, Turkey;²Department of Oncology, School

strengthens the case for combined treatment with Manidipine and a renin-

of Medicine, Kirikkale University, Kirikkale, Turkey,³Department of

angiotensin system blocker in hypertensive type 2 diabetic patients with persistent

Internal Medicine, School of Medicine, Kirikkale University, Kirikkale,

microalbuminuria.

Turkey;⁴Department of Radiology, School of Medicine, Kirikkale

DOI: 10.1530/endoabs.49.EP530

University, Kirikkale, Turkey;⁵Department of Internal Medicine, Erzurum

Regional Training and Research Hospital, Erzurum, Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP531

control. Apart from the slow-down of neuropathic symptoms some patients from

the main group demonstrated growth of hair on legs

(12.5%) which was

Significance of hemorheological approach for screening diabetic

considered as a positive potentiating effect of phosphocreatine on the background

nephropathy in the type II diabetes mellitus

therapy of diabetic neuropathy.

Sangbae Lee, Kahui Park, Jung Hye Kim, Ji Hong You, Yusik Kim,

Conclusions

Ji sun Nam, Jong Suk Park & Chul Woo Ahn

1. The ITT-analysis in the primary end point after the combined therapy with

Gangnam Severance Hospital, Seoul, Republic of Korea.

application of phosphocreatine showed the decrease of NSS score by 42.1%, and

NDA score by 13.3%.

Objective

2. Use of phosphocreatine as a cytoprotective agent in the combined DN therapy

Hemorheologic alterations or changes in blood viscosity have been suggested to

is pathogenetically substantiated and allows to expand the opportunities of drug

play a role in the pathogenesis of diabetic microvascular complications. We

therapy for patients suffering from DN.

measured various hemorheologic parameters in type 2 diabetes patients and

3. Results of the conducted trials demonstrate a potential for further study of

assessed their possible role as a diagnostic tool for diabetic nephropathy.

administration of this medicine in a larger long-term randomized and controlled

Methods

trial.

Four hundred-seventy patients with type 2 diabetes were included in this study.

DOI: 10.1530/endoabs.49.EP532

Hemorheologic parameters, including erythrocyte deformability, elongation

index (EI), critical shear stress (CSS), and aggregation index (AI) were measured

using microfluidic hemorheometer. Various metabolic parameters were assessed

from fasting blood samples and urinary albumin to creatinine ratio was used to

assess diabetic nephropathy.

Results

There were significant differences in Elongation index at 3 Pascal (EI at 3Pa),

Fibrinogen/EI, and shear stress among patients in different stages of chronic

kidney disease

(all P!0.05), EI at

3 Pa, Fibrinogen/EI, and shear stress

significantly differed among the groups. Fibrinogen/EI differed between normal

or CKD 1 and CKD 2 patients. In multiple regression analysis, Fibrinogen/EI at

3Pa was an independent predictor of albumin to creatinine ratio independent of

EP533

age, ESR, hematocrit, HbA1c, and body mass index (ßZ0.101, P!0.05). Also,

The effect of different antihypertensive treatment protocoles on

critical time, critical stress, fibrinogen/EI at

3Pa, CSS/EI et

3Pa, ad

glycemic control and lipid profile in type 2 diabetic patients with

fibrinogen/CSS at 3Pa were significantly different among patients at different

microalbuminuria and stage 1 hypertension

stages of diabetic nephropathy (all P! 0.05). Among the variables, Fibrinogen/EI

Muge Erek¹, Alparslan Ersoy¹ & Canan Ersoy²

at 3Pa showed area under the ROC curve of 0.721, suggesting 860 mg/dl% as a

¹Department of Nephrology, Uludag University Medical Faculty, Bursa,

cut off point for diabetic nephropathy with the sensitivity of 74% and specificity

Turkey;²Department of Endocrinology and Metabolism, Uludag University

of 62%.

Medical Faculty, Bursa, Turkey.

Conclusion

Fibrinogen/EI is a sensitive parameter measured via point-of-care testing for

screening diabetic nephropathy in patients with type 2 diabetes.

In hypertensive diabetic patients, renal angiotensin system blockers are first

DOI: 10.1530/endoabs.49.EP531

preferred due to their antihypertensive and antiproteinuric activities. Carvedilol, a

third generation beta blocker, may provide additional benefits in diabetic patients.

We aimed to compare the short-term efficacy of losartan treatment alone and in

combination with cilazapril or carvedilol on blood pressure, glycemic control and

lipid profile in microalbuminuric type 2 diabetic patients.

Methods

The study conducted in 30 consecutive patients with type 2 diabetes mellitus and

stage 1 hypertension. After 2 weeks follow-up period (Period 1), all patients

received losartan 50 mg/day as a single dose for 6 weeks (Period 2). Then,

patients were randomized into 3 groups at the end of 6th week. Losartan dose was

increased to

100 mg/day in the first group

(Group

1, n:10). Carvedilol

EP532

(25 mg/day) in the second group (Group 2, n:10) and cilazapril (5 mg/day) in

New features of pathogenetic treatment of diabetic neuropathy (DN)

the third group (Group 3, n:10) was added to losartan 50 mg/day treatment for

at on early stage

another 6 weeks (Period 3).

Kulshara Yerdesova & Aknur Myrzabaeva

Results

Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.

In all three groups, effective blood pressure control was provided during losartan

50 mg administration and post-randomization treatment period. Body mass index

in Group 1 significantly decreased during the losartan dose-increasing period.

Goal of research

When the losartan dose was increased in Group 1, fasting glucose values were

To evaluate the clinical efficacy of phosphocreatine in the combined metabolic

significantly decreased, but not in other groups. There was no significant

therapy of diabetic neuropathy at an early stage.

difference in measurements of post-prandial glucose, and serum fasting insulin,

Materials and methods

fructose, lipid and apolipoprotein levels between the three groups. A1c values in

A pilot study was carried out with participation of 36 patients suffering from DM

the losartan group significantly decreased from baseline 8G1.2% to 7.8G1.0 at

2. Using the method of randomization the patients were divided into two groups.

6th week and 7.5G0.9% at 12th week. The reductions in A1c values of losartan

Apart from the standard therapy the main group (nZ24) received phosphocrea-

plus carvedilol and losartan plus cilazapril groups were not significant (PO0.05).

tine

(intravenous infusion dose

2 g per 100.0 of saline solution). DN was

Conclusion

evaluated using the Neuropathic Symptomatic Score (NSS) by means of filling in

As a result, the use of high-dose losartan in hypertensive microalbuminuric type 2

a questionnaire used for analysis of the presence and strength of neuropathic

diabetic patients provided short-term more effective glycemic control when

symptoms. As well as using the Neuropathic Dysfunctional Account (NDA), at

compared to carvedilol or cilazapril treatments with low-dose losartan.

that vibration, tactile, temperature, pain sensitivities of lower limbs. The main

Significant decreases in the high dose losartan group in terms of body mass

parameters of efficacy were NSS score after 6 weeks of treatment and NDA score

index, fasting blood glucose and A1c levels, it could explained by diet compliance

after 6 weeks of therapy.

and better weight control when compared with other groups.

Results, discussion

DOI: 10.1530/endoabs.49.EP533

A faster clinical effect was noted in the main group during analysis of the score,

relief of neuropathic symptoms occurred even without changes in the metabolic

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP534

Conclusions

SMCG showed preprandial hyperglycemia, mainly before breakfast and dinner.

Impact of skin bundle implementation on hospital aquired pressure foot

Few hypoglycemias were detected but before lunch and night. Maternal and

ulcers and lenght of stay in inpatients with diabetes

neonatal outcomes were similar to other studies.

Khaled Ashawesh¹, Asma Elyousfi², Masoud Alam¹, Lynda Bloomer¹ &

Abdul Wajid Safi¹

DOI: 10.1530/endoabs.49.EP535

¹Dudley Group of Hospitals Foundation Trust, Dudley, UK;²University of

Leicester, Leicester, UK.

Objective

To assess the impact of launching SKIN (Surface, Keep moving, Incontinence,

Nutrition) bundle on development of pressure foot ulcers among in-patients with

EP536

diabetes.

Methods

The analysis of interrelation of filtrational ability of kidneys and

SKIN Bundle was launched at Dudley Group of Hospitals Foundation Trust in

indicators of the androgenic state at patients with diabetes

mellitus type 1

mid- February 2011. Data on pressure foot ulcers were collected among patients

Elena Vaschenko¹ & Tatjana Mokhort²

with and without diabetes admitted during February 2010- February 2011 and

¹The republican Research Centre for Radiation Medicine and Human

then from February 2011-March 2012, from pressure ulcer database.

Ecology, Gomel, Belarus;²Belarusian State Medical University, Minsk,

Results

Belarus.

Between 14/02/2010 and 13/02/2011, number of admissions to adults’ wards was

64,000. Of these, 5,452 had diabetes. Out of the latter, 72 patients were identified

to have foot ulcers, of them 23 patients developed the foot ulcers during their

Objective

hospital stay, giving rise a 0.42% rate of development of hospital acquired foot

To analyze correlation between the duration of diabetes mellitus (DM), renal

ulcers among in-patients with diabetes. During the thirteen and a half month

function and androgenic state indicators in patients with DM type 1.

period following SKIN bundle launch (14/02/2011 - 31/03/2012), there were 13

Material and methods

patients who developed hospital acquired foot ulcers out of 6,232 in-patients with

191 males with DM 1 type in the age of 18-55 years. The control group included

diabetes admitted during the same period, giving rise to a lower rate (0.21%) of

25 almost healthy males in the age 21-41 years. The compensation of DM was

development of foot ulcers in the hospital among patients with diabetes. The

estimated by the level of glycosylated hemoglobin. Also, the indicators of lipid

development of hospital acquired foot ulcers among patients with diabetes,

profile, glomerular filtration rate MDRD, total testosterone, luteinizing

therefore, dropped significantly by 51% P value of 0.04 (P!0.05) after the

hormone/follicle-stimulating hormone

(LH/FSH), prolactin, sex hormone-

launching SKIN bundle. The average length of hospital stay (LOS) among

binding globulin.

patients with diabetes who had foot ulcers was significantly shorter by an average

Results

of 3.55 days, P value of 0.044 (P!0.05), after this SKIN bundle implementation.

It was defined that diabetes duration significantly it is above at patients with GFR

Conclusion

!60 ml/min/1.73 m². In the group with GFR

!60 ml/min/1.73 m² in the

SKIN bundle resulted in more than 50% reduction in pressure foot ulcers, with

absence of compensation (Hb A1c O7.5%) more than LH, FSH, LH/FSH high

significant decrease in LOS among those who developed ulcers. SKIN Bundle can

levels and significantly lower levels of the general and free testosterone were

therefore be considered as a tool to reduce inpatient pressure Ulcers.

noted significantly. At patients with GFR MDRD O60 ml/min/1.73 m²

DOI: 10.1530/endoabs.49.EP534

significant distinctions on the level of testosterone and gonadotrophins at various

compensation of SD haven’t been revealed.

Conclusion

The revealed changes are important risk factors for development and progression

of vascular complications and require appropriate arrangements.

DOI: 10.1530/endoabs.49.EP536

EP535

Continuous glucose monitoring system in patients with gestational

diabetes mellitus: a prospective study

Rosa Marquez-Pardo, Isabel Torres-Barea, Mgloria Baena-Nieto,

Concepcion Cruzado-Begines, Manuel Cayon-Blanco, Rosario

EP537

Lopez-Velasco & Lourdes Garcia-Garcia-Doncel

PDE5i preserves renal function in models of Diabetic Nephropathy:

Jerez Hospital, Jerez de La Frontera, Cádiz, Spain.

from bench to bedside

Riccardo Pofi¹, Daniela Fiore¹, Tiziana Feola¹, Elisa Giannetta¹, Giulia

Le Grazie¹, Carla Di Dato¹, Daniele Gianfrilli¹, Biagio Barbano²,

Introduction

Mary A. Venneri¹, Andrea Lenzi¹ & Andrea M. Isidori¹

Gestational diabetes mellitus (GDM) is associated with an increase of maternal-

¹Department of Experimental Medicine, Sapienza University of Rome,

fetal complications. Continuous glucose monitoring system (CGMS) detects

Rome, Italy;²Department of Clinical Medicine, Sapienza University of

postprandial hyperglycemia and hypoglycemia during 24 h.

Rome, Rome, Italy.

Methods

Women with GDM in gestational weeks 26-32 were allocated a CGMS (Ipro^TM2)

after diagnosis in an observational prospective study. It was analysed:

One third of diabetic patients suffer from Diabetic Nephropathy (DN) that leads to

- CGMS: Mean glucose and standard deviation, area under the curve (AUC) with

end-stage renal disease

(ESRD). The molecular pathways involved remain

glucose O140 and !70. Percentage of glucose above or below the limit of

underexplored. We showed that chronic phosphodiesterase-5 inhibition (PDE5i)

normality before and after breakfast, lunch, dinner and night. (Target ranges:

improve vascular inflammation [1] and tissue remodelling, reducing proteinuria

before meals 70-95, after meal 70-140 and night 70-120 (expressed: mg/dl)).

[2] in murine diabetes. Our aim was to investigate the effect of PDE5i on animal

- Maternal and neonatal outcomes.

and human models of DN.

Results

Materials and methods

nZ32. Maternal age 33 years (O35 years Z43.8%), family history of diabetes

16 mice were randomly assigned to four groups: control (CTRL), sildenafil

47%, personal history of diabetes

34.4%, prepregnancy BMI

25.9 kg/m²

(SILD), streptozotocin (STZ), STZCSILD. Renal Doppler ultrasound (RDU)

(O30 kg/m² Z21.8%), weigh gain 7.7 kg, HbA1c 4.9%, insulin treatment

was performed at baseline and after 6 weeks. Renal resistive index-RRI, GFR

28%. CGMS: Glucose before breakfast 90G7.5, after breakfast 120G20, before

(ml/min), mean Blood Pressure-MBP (mmHg) were recorded. FITC-dextran

lunch 86G9.9, after lunch 112G19.6, before dinner 93G12.3 and after dinner

(2 mg/kg) was used to assess permeability and integrity of renal endothelium. 30

110G17.8. AUC O140Z0.81 and !70Z0.59. Percentage of glucose above or

type 2 diabetic (T2DM) patients were randomly assigned to placebo (PLC) or

below targets: before breakfast O95Z33.6% and !70Z5.4%, after breakfast O

tadalafil (TAD) 20 mg/die. RDU was performed at baseline and after 5 months.

140Z24.6% and !70Z0.6%, before lunch O95Z20.8% and !70Z11.9%,

Results

after lunch O140Z14.5% and !70Z2.2%, before dinner O95Z37.6% and !

All STZ-treated animal developed diabetes. Compared to the STZ, STZCSILD

70Z6.3%, after dinner O140Z8.1% and !70Z2.9%, night O120Z8.4% and

preserved renal function. Specifically, SILD treatment prevented: (a) the ESRD-

!70Z8.9%. Maternal and neonatal outcomes: Caesarean 25%, gestational age

related hypertension

(MBP, mean change from baseline: STZ 28.72G3.76,

at delivery 39 week, macrosomia 12.5%, large for gestational age 25%, small for

STZCSILD K9.46G4.84, PZ0.002); (b) the fall in GFR (STZ K15.24G3.67,

gestational age 6.3%, neonatal hypoglycaemia 21.9%, need for supplemental

STZCSILD 17.79G3.67; PZ0.005); (c) the rise in RRI (STZ 0.10G0.03,

oxygen in the neonatal 6.3%.

STZCSILD K0.07G0.03; PZ0.026); (d) the reduction in FITC-perfuse vessels

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

(microvascular density mean change STZ -2.45G0.48, STZCSILD 2.1G0.49,

Materials

PZ0.005); (e) pericytes detachment from endothelial cell coverage (STZ 10%,

Patients who had a diagnosis of DKA.

STZCSILD 60%, P!0.01). TAD treated T2DM patients: (a) improved renal

Methods

microcirculation (RRI: PLC 0.01G0.04, TAD K0.04G0.03; PZ0.014); (b)

Survey about the character of nutrition, alcohol drinking and other risk factors.

decreased diastolic pressure (PLC 0.71G9.00, TAD K6.00G9.11; PZ0.012).

Design

Conclusions

All patients were divided into two groups according to their age. The first group-

PDE5i treatment reversed ESRD in a hyperglycemic mouse model targeting renal

12 patients younger then 65 y.o.-Nutritional Risk Screening survey, the second

pericytes and restoring intrarenal haemodynamics. In humans, PDE5i improved

group - 3 patients (65-90 y.o)-Mini Nutritional Assessment survey. ‘Alcoholic

renal microcirculation slowing worsening of renal function in course of DN.

agnosia’ survey for identification of alcohol addiction.

PDE5i could disclose novel treatment strategies for DN.

Results

References

Fifteen patients - 11 men and 4 women. Average age - 36G0.93 y.o. According

1. Venneri MA Chronic inhibition of PDE5 limits pro-inflammatory monocyte-

to diabetes types: 11 patients of type 1, 4 patients of type 2. From 15 members of

macrophage polarization in streptozotocin-induced diabetic mice. Plos One 2015.

the nutrition

members (66.66%) had nutrition problems. Five patients

2. Sonneveld R Sildenafil prevents podocyte injury via PPAR-g-mediated TRPC6

(33.33%) were closed to the nutrition risk questions. According to ‘Alcohol

inhibition. J Am Soc Nephrol. 2016.

agnosia’ survey: five patients had alcohol problems(33.33%), three of them (60%)

DOI: 10.1530/endoabs.49.EP537

realized this problem, two (40%) were indifferent. Ten patients did not have

(66.66%) alcohol addiction. The risk factors DKA: inadequate insulin therapy - 7

patients (46.66%), 5 of them (71.42%) had alcohol problems, 2 of them (13.33%)

had sober life style. Two patients took drugs (13.33%) and alcohol problems.

Exacerbation of concomitant diseases - 6 patients (40%), 4 of them had problems

with alcohol (66.66%).

Conclusion

The most significant risk factors for DKA developing were inadequate insulin

EP538

therapy, exacerbation of concomitant diseases (40%), alcohol drinking (33.33%),

Relationship between microvascular complications of Diabetes Mellitus

taking drugs (13.33%). 66.66% had nutrition problems but this state is rather

and trace element levels

result then cause of DKA.

Zeliha Temurer Af¸ar, Yasemin Tutuncu, Berçem Ayçi

¸ek,

DOI: 10.1530/endoabs.49.EP539

Engin Sennarog˘ lu, Dilek Berker & Serdar Guler

Ankara Numune Training and Education Hospital, Ankara, Turkey.

Objective

To determine whether relationship between trace element levels and micro-

vascular complications of type 2 Diabetes Mellitus (T2DM).

EP540

Methods

One hundred eighteen patients with type 2 DM (mean age: 56G6.2 years) and 40

Somnological parameters for patients with type 1 diabetes and

control subjects (mean age: 40.0G8.8 years) were included in the study. Group 1

nocturnal hypoglycemia

(nZ40 patients) was composed of patients with no had microvascular

Ina Darashkevich¹, Tatiana Mokhort², Lola Nikanava¹, Ludmila Smirnova¹

complications and it divided into two subgroup, first subgroup (nZ20) included

& Serhej Tishkovsky¹

patients with glysemic regulation, the second subgroup (nZ20) with not glysemic

¹Grodno State Medical University, Grodno, Belarus,²Belarus State Medical

regulation. Group 2 included 38 patients with diabetic retinopathy (19 patients

University, Minsk, Belarus.

had proliferative retinopathy,

19 patients had nonproliferative retinopathy).

Group 3 included 40 patients with both diabetic retinopathy and nephropathy (20

Objective

patients had microalbuminuri, 20 patients had macroalbuminuri). Patients with

To determine the effects of hypoglycemia while sleeping on somnological

type 2 DM who had liver disease, renal disease, malabsorbtive disease and who

parameters for patients with type 1 DM.

had been taken any diuretic drugs were excluded. Trace elements including Crom

Materials and methods

(Cr)(mg/l), Copper (Cu)(mg/l), Zinc (Zn)(mg/l) were measured by Inductively

The study included 57 person with type 1 DM (Group 1 - patients with blood

Coupled Plasma-Mass spectrophotometry (ICP-MS). And, Iron (Fe)(mg/dl) was

glucose levels (BGL) during sleep !3.9 mmol/l; Group 2 - Patients with BGL -

measured by ELISA.

from 3.9 to 10.0 mmol/l. The examination included: daily monitoring of blood

Results

glucose by ‘CGMSGold’ (‘MedtronikMINIMED’ (USA)), polysomnography

Difference of age was only found between control subject and all patients with

«SOMNOlab2 (PSG) Polysomnography (R & K)», the definition of HbA1c.

DM (P!0.001). Mean age were found not difference between in Group 1,2,3

Results

(PZ0.24, PZ0.22, PZ0.26). Magnesium, Fe, Zn, Cr levels were lower in all

Table

diabetic patients than control healthy subjects (P!0.001, PZ0.039, PZ0.001,

P!0.001). Crom levels were found lower in patients with both only diabetic

retinopathy and only diabetic nephropathy than patients with not any

microvascular complications (P!0.01, for both). Also, Cr levels were found

Group 1 nZ14

Group 2 nZ43

lesser in patients with only diabetic nephropathy than in only with diabetic

Indicator

Me [25;75]

retinopathy (P!0.01).

BGL during sleeptime

2.35[2.00;3.10]*

6.10[4.10;7.50]

Conclusions

(mmol/l)0

The study indicated that an association between low Crom levels and existence of

Hypoglycemia «before

7.00[3.00;27.00]*

5.23[0.00;5.00]

microvascular complications of DM when trace element levels were measured by

sleep» (%)

ICP-MS.

HBA1c (%)

7.00[6.00;8.10]

7.67[6.40;9.00]

DOI: 10.1530/endoabs.49.EP538

Total sleep time (TST) (h)

6.24[5.40;7.10]*

5.30[4.51;6.20]

REM (%)

39.50[26.00;48.00]*

29.70[23.00;45.80]

N1(%)

14.11[10.60;23.00]*

8.80[4.70;14.30]

N2(%)

38.8[35.20;61.40]

48.20[34.00;53.30]

N3(%)

3.00[1.20;6.10]

3.44[2.30;6.30]

N4(%)

1.45[0.00;2.89]*

3.00[1.00;8.40]

EP539

^*P!0.05.

The frequency of different risk factors for diabetic ketoacidosis in real

clinical practice in Russia

Discussion and conclusions

Irina Dzherieva, Natalia Volkova, Pavel Anchutin & Valerya Nechayeva

For patients of Group 2 marked shortening of TST - 5.30 [4.51; 6.20] hours vs 6.24

Rostov State Medical University, Rostov, Russia.

[5.40; 7.10] hours (PZ0.0219). Night hypoglycemia extend REM-sleep (39.50

[26.00; 48.00]% vs 29.70 [23.00; 45.80]% in the comparison group (PZ0.0479),

The purpose

N1 sleep stage (14.11 [10.60; 23.00]% vs8.80 [4.70; 14.30]% (PZ0.0110), as well

To estimate the frequency of appearance of different risk factors for the DKA

as reduce the N4 stage of sleep (1.45 [0.00; 2.89]% vs 23.00 [1.00; 8.40]%).

(diabetic ketoacidosis) developing in a real clinical practice in Rostov-on-Don.

The share of hypoglycemia ‘before sleep’ extends N1 (rZ0.5442); an increase

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

in the length of N1 leads to a reduction in the duration of the deep stages of slow-

The aim

wave sleep N3 (rZK0.6835), N4 (rZK0.5673); an increase in the duration of

Of the study was to determine the relationship between depression and anxiety

REM reduces N3 (rZK0.5887).

symptoms and chronic diabetes complications, disease duration, glycaemic

Conclusion

control in type 1 diabetic patients.

Hypoglycemia during sleep lengthens REM-sleep, REM sleep so reduces

Methods

glycemia, providing interactive effects relative to each other, helping to increase

18-54 year old 215 patients with T1DM were enrolled in the study. Participants

the N1 and reduction of deep sleep stage (N3 and N4).

filled questionnaires about DM, disease duration, complications and Beck’s

depression (DB) and anxiety (BA) inventory. All patients were evaluated for

DOI: 10.1530/endoabs.49.EP540

microvascular complications. Laboratory tests: HbA1c, creatinine, albumin in

24 h urine sample were performed.

Results

124 females (57.67%) and 91 males (42.33%) participated in the study. Cohort

consisted of 66 participants with DN (mean age 32.44G6.5 years) and 149

without DN (mean age 31.53G9.99). The group without DN consisted of 53

EP541

patients without any complications (mean age 29.49G9.25) and 96 patients with

The value of blood glucose levels for the parameters of nocturnal sleep

DP and/or DR (mean age 31.07G9.11). The emotional state of females was worse

for patients with type 1 diabetes

than males (BD: female 9.78G9.07; male 7.51G7.11; P!0.05; BN: female

Ina Darashkevich¹, Tatiana Mochort², Lola Niconova¹ &

13.86G9.99; male 8.86G7.79; P!0.01). There was no statistically significant

Serhey Tishkovsky¹

difference between BD among patients with or without complications (PO0.05).

¹Grodno State Medical University, Grodno, Belarus;²Belarus State Medical

There was a statistically significant difference (PZ0.04) between BA scores

University, Minsk, Belarus.

among patients without any complications (NZ53, female 31/male 22) (BA

9.42G8.1) and those with DN (NZ66, female 36/male 30) (BA 12.05G8.84).

The emotional state of patients with longer disease duration (O30 years) (BD

Objective

13.59G11.49; BN 15.61G9.79) was worse than patients with shorter one (!10

To establish the differences in terms of sleep for patients with type 1 diabetes,

years)

(BD 8.14G8.55; BN 10.86G9.67)

(P!0.05). There was nofound

depending on the level of blood glucose levels (BGL) during the night.

statistically significant differencebetween the emotional state and glycaemic

Materials and methods

control in T1DM patients.

The study included 43 participants with type 1 diabetes (Group A - patients with

Conclusions

BGL during sleep from 3.9 to 7.4 mmol/l, Group B - 7.5-10.0 mmol/l. Patients

The emotional state of females’ with type 1 diabetes mellitus is worse than males’.

had daily monitoring of BGL ‘CGMSGold’ by ‘MedtronikMINIMED’ (USA),

Patients with chronic diabetes complications have more anxiety symptoms than

polysomnography

«SOMNOlab2 (PSG) Polysomnography (R & K)», the

those without any complications. Emotional state is worse in diabetics whose

definition of HbA1c.

disease duration is longer.

Results

DOI: 10.1530/endoabs.49.EP542

See Table.

Group A nZ25

Group B nZ18

Indicator

Me [25;75]

BGL during sleep time

4.50[4.00; 5.60] &

8.20[7.50; 9.50]

(mmol/l)

BGL “after sleep” (mmol/l)

7.90[7.40; 9.20]&

9.65[8.50;11.30]

HBA1c (%)

7.00[6.00;8.50]&

8.95[7.50; 9.30]

EP543

Total sleep time (TST) (h)

5.59 [4.80; 6.53]&

4.90[4.23; 5.39]

REM (%)

29.40[22.50;43.00]&

39.90[24.70;41.40]

The trigger off severe vomiting and hypertension during pregnancy in

N1 (%)

11.05[5.00; 18.30]

7.00[4.70;14.00]

type 1 diabetic patient: case report

N2 (%)

48.50[38.00;53.10]

41.29[25.70;53.90]

Egle Kreivaitiene¹, Ruta Kriksciuniene^1,2 & Evalda Danyte^1,2

N3 (%)

4.00[2.70; 7.80]&

2.65[0.00; 5.25]

Department of Endocrinology, Hospital of Lithuanian University of Health

N4 (%)

3.50[1.90;13.50]&

1.30[0.00; 7.50]

Sciences (HLUHS), Kaunas, Lithuania;²Lithuanian University of Health

Sciences (LUHS), Institute of Endocrinology, Kaunas, Lithuania.

^&P!0.05

TST is longer in the group with BGL 4.50 mmol/L. REM sleep 10.5%

increase in Group B. The shares represented a deep sleep are larger in

Diabetic mothers have an increased risk for pregnancy (early pregnancy

Group A. In Group A the increase of TST decreases BGL during sleep (rZ

loss, polyhydramnios, pre-eclampsia, premature labor) and progression of

0.4098) and N2 sleep stage (rZ0.4246). Decrease in N2 share decreases

diabetic complications. We present a case of the progression of diabetic-

BGL during sleep (rZ0.4997) and reduces N4 (rZ0.5182), and has a

related complications including autonomic neuropathy (AN) which caused

negative coefficient with a value of REM sleep (rZK0.4330). In group B,

severe vomiting during pregnancy. A 27-year-old type 1 diabetic woman

REM sleep phase is inversely correlated with BGL “after sleep” (rZK

with pregnancy of 8 weeks gestational age (GW) was admitted to our

0.5056), N3 (rZK0.8371), N4 (rZK0.7594).

hospital for glycemia and diabetic-related complications control. She has

had diabetes for 13 years. The control of diabetes was poor (HbA1c 9.13%).

She was already diagnosed with multiple diabetes-related complications

Conclusion

(nonproliferative diabetic retinopathy and maculopathy, polyneuropathy,

BGL 4.5 mmol/l during sleep increases the duration of sleep by increasing the N2,

nephropathy). An insulin-pump therapy was started to achieve a better

N4 and extending reduce REM sleep.

glycemia control during pregnancy. The minor progression of albuminuria

was noticed during first hospitalization. Around 11 GW she was hospitalized

DOI: 10.1530/endoabs.49.EP541

for the second time because of the sudden blood pressure (BP) elevation

(160/110 mmHg), nausea, vomiting, headache, glycemia variability. The

progression of diabetic nephropathy was observed, antihypertensive (AH)

drugs for the treatment of secondary hypertension were started. Despite the

better glycemia control which was achieved (HbA1c 6.1%) in few months,

the patient was hospitalized for the other nine times during the pregnancy.

EP542

The main complains were severe nausea, vomiting, BP elevation and

Emotional state association with microvascular complications, disease

ketonemia. The progression of all diabetes-related complications was

duration and glycaemic control in type 1 diabetic patients

observed. The maximum doses of AH drugs were required for management

Edita Prakapiene², Karolis Zukas¹, Lina Radzeviciene^2,3 &

of BP. Albuminuria progressed to nephrotic level, hypoalbuminemia and

Rasa Verkauskiene^2,3

hypoproteinemia occured. Diabetic retinopathy developed to proliferative.

¹Lithuanian University of Health Sciences (LUHS), Faculty of Medicine,

Severe vomiting led to electrolytes dis-balance. Nausea and vomiting was

Kaunas, Lithuania;²Department of Endocrinology, Lithuanian University of

considered to be caused by the progression of AN, when other possible

Health Sciences (LUHS), Kaunas, Lithuania;³Lithuanian University of

causes were excluded. At 36 GW during planned C-section a healthy girl

Health Sciences (LUHS), Institute of Endocrinology, Kaunas, Lithuania.

was born (Abgar 8/8). Poor control of diabetes may lead to the severe

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

progression of the diabetes-related complications. The progression of

his mother, uncle, aunt and all six brothers were diagnosed as diabetes

diabetic autonomic neuropathy remains forgotten in many cases during

mellitus. His uncle, aunt and aunts children were using oral antidiabetics.

pregnancy.

His system query showed that he had pollakuria and nocturiafor the last 3

DOI: 10.1530/endoabs.49.EP543

months. His physical examination was normal except diminished skin turgor

tonus. His laboratory was normal except blood glucose of 564 mg/dl, HbA1c

8.2%, urea 50 mg/dl, creatinin od 1.34 mg/dl, urine ketone bodies were

CCC, urine glucose 500 mg/dl. He was treated with i.v. saline, and

insulin. On the follow up basal-bolus regimen was initiated. He had

hypoglycemias due to four units bolus insulin and 14 units basal insulin

glargine so bolus insulin was stopped and vildagliptine-metformin and

insulin glargine was added. He had hypoglycemias as well and insulin

glargine was stooped and gliclazide MR 60 mg was started and discharged.

After 2 weeks his HbA1c was 6.9%, fasting plasma glucose was 122 mg/dl

EP544

so vildagliptine-metformin was stopped and gliclazide was tapered to

Predictor factors of hypertension induced in pregnancy in patients with

30 mg/day. After 3 months his fasting blood glucose was 98 mg/dl and

gestacional diabetes mellitus

HA1c was 5.1%. His peripheral blood analysis was consistent with HNF1A

Begon˜a Sanchez-Lechuga1, Cristina Lopez-Tinoco1, Antonio

gene and diagnosed as MODY 3. Transcription factor defects are the most

Campos Caro², Raquel De la Varga Martín², Isabel Mateo Gavira¹,

common reasons of the MODY. Insulin secretion is decreased up to 85% but

Francisco Javier Vilchez Lopez¹ & Manuel Aguilar Diosdado¹

is sensitive to sulfonylureas. Low dose sulfonylureas generally control

¹Endocrinology and Nutrition Department, Puerta del Mar University

glycemia very well. But diabetic ketoasidosis is a very rare complication for

Hospital, Cadiz, Spain;²Investigation Unit Department, Puerta del Mar

MODY 3.

University Hospital, Cadiz, Spain.

DOI: 10.1530/endoabs.49.EP545

Gestational diabetes mellitus (GDM) is associated with an increased risk of

pregnancy-induced hypertension (PIH). Ambulatory blood pressure moni-

toring (ABPM) has been used to screen for PIH and preeclampsia. To date,

there are no data regarding ABPM in women with GDM. Currently, little is

known in GDM about the role of inflammatory biomarkers in PIH

development and their impact on perinatal morbility and the risk of future

complications. With this study we aim to identify, in women with GDM, at

an early stage inflammatory markers and BP profiles (detected by ABPM)

that could define a population at higher risk of developing PIH and

EP546

preeclampsia. We prospectively studied 113 normotensive women with

GDM consecutively recruited at 28-32 weeks of pregnancy. ABPM was

Screening for macrovascular complications in diabetic patients in

carried out for one 24-h period on each patient, using the SPACELABS

Korça, Albania

90207 ABP monitor. Serum biomarkers (PAI-1, IL-6, IL-8, leptin, IL1-b,

Ema Lumi¹, Dorina Ylli² & Agron Ylli²

TNF-a, adiponectin, resistin, NGF, HGF and MCP1) were determinated in

¹Department of Internal Medicine, Regional Hospital, Korce, Albania;

61 patients by MILLIPLEX kit. Clinical and metabolic data, obstetric and

²Department of Endocrinology, UHC Mother Teresa, Tirana, Albania.

perinatal outcomes were analysed. The mean age was 34.4G4.2 years and

BMI was 27.5G5.3 kg/m². Fifty-six percent of the patients had non-dipper

Background

pattern. In this group, BMI was significantly higher (P!0.05) and the levels

Diabetes mellitus (DM) is a common metabolic disorder and is associated with

of night-time systolic (105.3 vs 98.8 mmHg) and diastolic BP (63.1 vs

development of chronic macrovascular complications leading to significant

57.2 mmHg), and furthermore, higher levels of PAI-1 (296.99G161.3 vs

morbidity and mortality. The aim of the study was to evaluate the prevalence and

162.07G117.52 pg/ml) and resistin

(175.69G92.17

101.74G

clinical profile of macrovascular complications in diabetic patients in Korca,

64.34 pg/ml) were observed. Seventy-eight women delivered to date, 3%

Albania.

had preeclampsia and 7% PIH. Higher levels of adiponectin (125 992.7G

Material and methods

94 472.4 vs 39 850G31 136 pg/ml) were observed in patients who not

A total of 456 cases with type 2 DM attending Department of Endocrine

develop PIH. We concluded that a higher rate of non-dippers pattern and

(outpatient/inpatient), from January 2012 to March 2016 (4 years), were recruited

night-time systolic/diastolic BP were observed. The non-dipper group had

in this study. Ages (15C) cases were screened for macrovascular complications.

higher BMI and levels of PAI-1 and resistin, which could be a useful

Demographic, clinical and laboratory parameters were included in analyses. A

predictor of PIH. Adiponectin was significantly lower in patients with PIH

thorough cardiovascular and cerebrovascular history as documented by previous

and then could point at a protective mechanism in PIH. Further studies will

medical records (including medical and hospital records) was collected for all of

be needed to determine the relationships between BP alterations and

the patients. Standardised electrocardiogram and a careful examination of the

inflammatory markers, and obstetrics and perinatal outcomes.

lower extremities was made for all patients.

DOI: 10.1530/endoabs.49.EP544

Results

During the 4 years study 456 patients were evaluated. The mean age of the study

population was 63.78G10.02 S.D., with female:male ratio 270/186; duration of

diabetes 7.32G7.0 S.D. Of those 82 cases (18%) were newly diagnosed with DM.

Mean HbA1c was 8.5G1.5 DS. Mean BMI was 28.06kg/m² G4.37 DS (range

17.6-45.9). 47% of the patients were overweight and 27.5% were obese.77.4% of

the patients had hypertension.

13.4% of patients were tabacco users. The

prevalence of macrovascular diseases in total was 25.7%. The prevalence of

cardiovascular disease, cerebrovascular disease (stroke), diabetic foot wounds

and amputacion of an extremity were 16.9, 4.16, 4.37 and 0.21% respectively.

EP545

The prevalence of cardiovascular disease was three times more often in males

Patient first admitted as diabetic ketoacidosis and diagnosed as

than females. There was significant positive correlation

(P!0.05) between

MODY 3

macrovascular complication and the duration of diabetes, age of the patients, BMI

Ahmet Kaya, Mustafa Kulaksizoglu & Ilker Cordan

and hypertension respectively.

Necmettin Erbakan University, Meram Medical Faculty, Division of

Conclusion

Endocrinology and Metabolism, Konya, Turkey.

There was high prevalence of macrovascular disease, especially cardiovascular

disease in Korc¸a population with DM. Screening for chronic macrovascular

complications of diabetes is recommended in order to prevent and treat them,

reducing morbidity and mortality from diabetes.

A male patient aged 63 years old was admitted to the emergency department

Keywords: Type 2 Diabetes Mellitus;macrovascular diseases, cardiovascular

with the complaints of polydipsia, polyurea and dizziness. He had

disease, cerebrovascular disease, diabetic foot wounds, amputation.

hypertension which was on a calcium channel blocker and his hypertension

was in control. His plasma glucose was measured as

564 mg/dl and

DOI: 10.1530/endoabs.49.EP546

hospitalized due to his new onset diabetes. His family history showed that,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP547

decompensation factor (50%), followed by therapeutic failure (40%). Add

Osteoprotegerin as a cardiovascular risk marker in diabetic patients

that, 21% of patients required ventilatory support, 19% needed vasopressor

Anna Dabrowska¹, Beata Wojtysiak-Duma², Dariusz Duma³, Anna

support and only 2.3% of the patients were dialyzed. This review shows that

Torun-Jurkowska⁴, Anna Mieszkowska¹, Beata Matyjaszek-Matuszek¹ &

despite all the teachings and warnings about the disease and its severity,

Jerzy Tarach¹

many patients maintain a poor understanding of it, and it continues to be

¹Department of Endocrinology, Medical University of Lublin, Lublin,

necessary to develop strategies to improve adherence to therapy and to

Poland;²Department of Biochemical Diagnostics, Chair of Laboratory

achieve a better metabolic control.

Diagnostics, Medical University of Lublin, Lublin, Poland;³Department of

DOI: 10.1530/endoabs.49.EP548

Laboratory Diagnostics, Medical University of Lublin, Lublin, Poland;

⁴Department of Mathematics and Medical Biostatistics, Medical University

of Lublin, Lublin, Poland.

Introduction

It’s known that type 2 diabetes is an independent risk factor for cardiovascular

disease. Osteoprotegerin (OPG), a glycoprotein secreted mainly by osteoblasts, is

also produced by heart muscle and vessels. Its role in the pathogenesis of

atherosclerosis and future cardiovascular events is still discussed.

EP549

Material and methods

Prognostic factors and all-cause mortality in patients with type 2

The study was conducted in 113 patients (48 F, 65 M) with type 2 diabetes

diabetes presenting with diabetic ketoacidosis: a population based,

mellitus (DM2) and coronary heart disease (CHD), aged mean 68.22G9.56. The

case-control study

studied group was divided into subgroups: 61 subjects with acute coronary

Petra

´ a

´ić¹, Miroslav

aći

´², Ivan Kruljac², Bo

ˇidar Peri

´²,

syndrome (ACS) and 52 subjects with stable angina (SA). Among patients with

Maja Filipović-Grčić², Gorana Mirošević² & Milan Vrkljan^1,2

ACS two groups were separated: with myocardial infarction (MI) and with

¹University of Zagreb School of medicine, Zagreb, Croatia;²Department of

unstable angina (UA). The control group was composed of 46 well-balanced

Endocrinology, Diabetes and Metabolic Diseases ‘Mladen Sekso’,

patients (33 F, 13 M) without DM2 and CHD. Determinations of serum OPG

University Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia.

levels with the use of MicroVue OPG-EIA (an assay sensitivity of 0.4 pmol/l)

were performed. Statistica

10.0

StatSoft was used for data analysis. OPG

concentrations were shown as medians.

Introduction

Results

Little is known about diabetic ketoacidosis (DKA) in type 2 diabetes mellitus

Patients with DM2

and ACS as well as subjects with DM2 and SA had

(T2DM). Moreover, the clinical impact of diabetic ketosis (DK) in T2DM is

significantly higher OPG levels than patients in control group (6.5 pmol/l and

elusive. The aim of this study was to analyze characteristics and mortality of

5.64 pmol/l vs 3.48 pmol/l) (HZ62.258; PZ0.000) (P!0.001). The tendency of

patients with DKA and DK and to identify possible prognostic factors.

higher OPG concentrations in subjects with ACS compared to patients with SA

Methods

was observed (PO0.05). Higher OPG levels were noted in patients with MI

This was a population-based, cross-sectional study that included all patients with

(7.36 pmol/l) than in those with UA (4.72 pmol/l)

(P!0.05). Patients with

T2DM presenting to emergency department with DKA, over the 5-year period.

complications in the course of ACS such as: cardiac arrhythmias, pulmonary

We analyzed all first admissions of 137 patients with DKA and 137 age- and

oedema, cardiac tamponade had statistically significantly higher OPG concen-

gender-matched patients with non-ketotic hyperglycemia (NKH) and DK.

trations (8.40 pmol/l) compared to subjects with uncomplicated course of ACS

Results

(5.86 pmol/l) (P!0.05). Higher OPG levels were also found in patients with

During a median follow-up of 35.0 months, 55 (39.9%) patients in the NKH

transmural MI

- with Q-wave MI

(8.37 pmol/l) than in patients with

group, 32 (23.2%) patients in the DK group and 61 (44.2%) patients in the DKA

subendocardial MI - with non-Q wave MI (6.44 pmol/l) (P!0.05).

group died. Patients with DKA had significantly higher mortality rates when

Conclusions

compared with DK (HR 2.55, 95% CI 1.65-3.92, P!0.001) and NKH (HR 1.27,

OPG may be a marker of cardiovascular disease and ischemia’s severity in

95% CI 1.05-1.53, PZ0.012). In patients with DKA, age, serum urea and

diabetic patients.

sodium, the use of calcium channel antagonists, ASA and insulin therapy

correlated positively with mortality, while weight loss and increased body

DOI: 10.1530/endoabs.49.EP547

temperature prior to the DKA episode, smoking and alcohol consumption were

associated with decreased mortality. A nomogram derived from these variables

predicted mortality with a sensitivity of 69.7%, specificity of 90.0% (AUCZ

0.866).

Conclusion

DK and DKA represent two distinct subgroups of patients with T2DM. A

nomogram derived from independent prognostic factors may have important

clinical role in selecting high risk patients with DKA.

DOI: 10.1530/endoabs.49.EP549

EP548

Diabetic ketoacidosis in an intensive care unit - review

Joana Oliveira, Rodolfo Gomes, Bárbara Picado, Fernando Gonçalves &

José Araújo

Hospital Beatriz Ângelo, Lisboa, Portugal.

Diabetic ketoacidosis (DK) is one of the most serious complications of

diabetes mellitus

(DM). We performed a case review of DK patients

EP550

admitted to the intensive care unit (ICU) of our Hospital between 1 June

Can the most frequent DRB1* gene’s alleles be associated with

2012 and 30 June 2016. A demographic analysis was made, time of DM

cardiovascular autonomic neuropathy among patients with type 1

evolution, the therapy and the factors that led to its decompensation. Thus, a

diabetes mellitus? A case - control pilot study

total of 42 DK patients were admitted to the ICU in the referred period, mean

Dovile Razanskaite-Virbickiene¹, Vilma Vezbaviciene¹,

age was 45 years, a clear predominance of female patients (67%) and

Erika Skrodeniene² & Rimantas Zalinkevicius³

Caucasian patients (76.7%). The majority of the patients were type 1

¹Department of Endocrinology, Medical Academy, Lithuanian University of

diabetics (57%), 40% were diabetic type 2 and 3% had a diagnosis of

Health Sciences, Kaunas, Lithuania;²Department of Laboratory Medicine,

diabetes secondary to corticosteroids. The mean duration of the disease was

Medical Academy, Lithuanian University of Health Sciences, Kaunas,

12 years, and diabetes was previously unknown in 12% of the patients,

Lithuania;³Institute of Endocrinology, Medical Academy, Lithuanian

where appears as an inaugural diagnosis. The mean HbA1c value of these

University of Health Sciences, Kaunas, Lithuania.

patients was 12.6%. Regarding the treatment, 64% of the patients were

exclusively treated with insulin, 21% only with oral antidiabetics and 12%

did not do any type of therapy, considering that the disease was not known.

Background and aim

Half of the patients presented nausea and vomiting, and prostration was the

HLA alleles are associated with type 1 diabetes (T1D) and a spectrum of risk can

second most frequent presentation (33%). Infection was the most common

be from increased to neutral or to protective. We aimed to evaluate the association

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

of cardiovascular autonomic neuropathy (CAN) with DRB1* gene’s alleles

Table 1. Baseline Characteristics.

among T1D.

Methods

NDMCNCVD

NDMCCVD

The case - control pilot study included 70 patients with T1D at the age 18-54

years. 36 patients with CAN were assigned to the case group and 34 patients

without CAN - to the control group. The groups were homogeneous according to

Age, years

62.86G6.15

65.57G8.40

the duration of diabetes, mean age at diabetes presentation and gender. The

*BMI, kg/m2

24.05G1.52

26.53G3.36

diagnosis of CAN was confirmed when 2 or more pathological standartized

Sex (M/F)

3/10

cardiovascular tests were present. HLA alleles identification was determined for

Age at Diagnosis

41.5G6.52

44.6G8.55

all participants by using the polymerase chain reaction with sequence specific

Duration T2D

primers.

*Fasting glucose, mmol/l

8.65G3.73

10.12G2.71

Results

HbAlc, %

8.63G2.25

8.9G0.98

70 patients with T1D were included in the study: 26 males and 44 females.

Cholesterol, mmol/l

4.54G0.57

5.29G1.09

Patients mean age was 30.48G11.22 years, mean duration of diabetes - 17.52G

Triglyceride, mmol/l

1.17G0.45

1.21G0.89

6.96 years, mean HbA1c 9.26G1.74%. The frequency distribution of DRB1

gene‘s alleles among case group showed, that the most frequent alleles were: *04

Means G SD *: P!0.05

allele - 18 (25.00%), *03 - 12 (16.66%), *01 - 11 (15.27%), *07 - 8 (11.11%),

*08 - 6 (8.33%), and among control group - *04 allele - 22 (32.35%), *01 - 14

(20.58%), *03 - 8 (11.76%), *13 - 6 (8.82%). We confirmed the 3.20 (pZ0.018)

Conclusion

increased relative risk for CAN in T1D with DRB1 gene‘s *08 allele, also *11

Our results provide evidence that diabetic CVD is associated with methylation

(OR 1.67), *07 (OR 1.66) and *03 (OR 1.63) alleles were associated with

changes in metabolic pathway alterations in blood leukocyte DNA. These

increased risk. The highest probability was to find heterozygotes of *08/*X (OR

differences in methylation are worthy of further validation using larger cases of

3.20), *03/*04 (OR 3.20), *07/*X (OR 2.07), *03/*X (OR 1.79) genotypes among

diabetic patients with and without cardiovascular disease.

T1D with diagnosed CAN.

Conclusion

DOI: 10.1530/endoabs.49.EP551

DRB1 gene’s *08 allele and *08/*X, *03/*04, *07/*X, *03/*X genotypes are

associated with increased risk for CAN among patient with T1D.

DOI: 10.1530/endoabs.49.EP550

EP552

Prevalence of eye complications and its correlation with kidney

function: clinical practice data of diabetes patients

Kalpana Dash, Sunil Kumar Ch, Aftab Ahmed, Sambit Das,

EP551

Balaji Jaganmohan, Surekha Tippisetty, Vamsi Krishna Kolukula

Genome-wide DNA methylation analysis for type 2 diabetes mellitus

& Krishna G. Seshadri

and cardiovascular disease: from a 23-year follow-up in the Da Qing

Apollo Sugar Clinics, Hyderabad, India.

diabetes prevention study

Xiaonan Dong, Yanyan Chen & Guangwei Li

Department of Endocrinology, FuWai Hospital, National Center for

Background

Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking

Type 2 Diabetes Mellitus (T2D) patients are at very high risk to have eye

Union Medical College, Beijing, China.

complications. Purpose of the study was to determine the prevalence of diabetes

eye complications (DEC) and its correlation with glomerular filtration rate (GFR)

in diabetes population attending community clinics across India.

Background

Methods

Cardiovascular disease (CVD) is a serious complication of diabetes mellitus

A total of 1547 T2D patients (935 males and 612 females) EMR records were

(DM) and is associated with considerable morbidity and high mortality. There is

retrospectively analyzed. For DEC correlation with GFR, patients were grouped

increasing evidence to suggest that dysregulation of the epigenome is involved in

into GFR %60 and GFR O60 mg/ml/1.73m². Statistical analysis was done using

diabetes and CVD.

SPSS version 20, with significance P %0.05.

Objective

Results

To assessed the alteration of DNA methylation in patients with/without diabetes

In 1547 T2D patients, 204(13.1%) had DEC, mean (SD) age 56.7(10.0) years;

but developed CVD in a cohort study of Chinese patients.

122(59.8%) males and 82(40.2%) females. Of these, GFR calculated for 443

Methods

patients had mean GFR of 91.2 mg/ml/1.73 m²; 388(87.5%) and 55(12.5%)

40 patients were randomizely selected from diabetics/nondiabetics with/without

patients had GFR O60 and %60, respectively. DEC was observed in 79(17.8%)

CVD after 23 years follow-up, including 20 DM without CVD, 20 DM with CVD.

patients, mean (SD) age 55.5(13.8) years; among them 49(62%) males and

Then a genome wide methylation analysis was conducted using the recently

30(38%) females. GFR was significantly lower in patients with DEC compared to

developed Illumina Infiniumw Methylation EPIC BeadChip, and focusing on

patients without DEC (79.4 vs. 93.8 mg/ml/1.73m²; PZ0.000). Prevalence of

individual cytosines at CpG loci throughout the promoter regions.

DEC in patients with GFR %60 was higher compared to patients with GFR O

Results

60(38% vs.

15%; PZ0.000). However, there was no specific gender

DNA methylation data was analyzed with RnBeads software, and we observed

preponderance.

CpG sites in promoter area of CPT1C, CREB5, ACACB, OLR1, CXCL11

Conclusion

showing higher methylation levels and HADHB showing lower methylation

Our study is one of the few studies from India that reports the prevalence of DEC

levels in DM with CVD patients after enrolling top 500 regions among combined

from a community based clinics based on fundus photographs and correlating

rank (combined P value !0.05, respectively). Singular Value Decomposition

with GFR, thus diabetes kidney disease (DKD). The correlation of DEC with low

(SVD) analysis indicated that significant bvalue of DNA methylation correlated

GFR can suggest presence of DKD in a community, thus, reiterating the

with patient BMI, fasting glucose, cholesterol, triglyceride. After adjusting for

significance of EC screening in community diabetes practices. Implementing

confounding factors, these CpG sites were correlated with fasting glucose. These

these findings into clinical decision pathways may improve the quality of health

genes were then clustered in Fatty acid degradation, Glucagon signaling pathway,

care delivery.

Adipocytokine signaling pathway and PPAR signaling pathway according to

DOI: 10.1530/endoabs.49.EP552

KEGG analysis, which play a role in the synthesis of key enzyme in lipid

metabolism.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP553

was no association between pancreatic steatosis and diabetic retinopathy observed

in the obese group.

Atherosclerotic cardiovascular risk assessment score in diabetes

Conclusion

patients: a retrospective analysis of clinical data

In this study, pancreatic steatosisis was strongly associated with diabetic

Sanjiv Shah, Jayaprakashsai Jana, Balaji Jaganmohan, Raja Selvarajan,

retinopathy in non-obese subjects with T2DM. This result suggests that pancreatic

SG Moazam, Vamsi Krishna Kolukula, Surekha Tippisetty &

steatosis might affect the prevalence of microvascular complication in patients

Shashank R Joshi

with T2DM. However, we still need more studies to define the relationship

Apollo Sugar Clinics, Hyderabad, India.

between pancreatic steatosis and microvascular complication of diabetes mellitus

in details.

Background

DOI: 10.1530/endoabs.49.EP554

The study aimed to minimize the risk causing factors and evaluate new

atherosclerotic cardiovascular disease (ASCVD) risk score using Million Hearts^w

Longitudinal ASCVD risk assessment tool among type 2 diabetes mellitus (T2D)

patients.

Methods

A non-interventional retrospective analysis of electronic medical records of

Apollo Sugar Clinics, India. A total of 365 patient’s data was collected, and were

EP555

categorized into normotensive (!120-129/80, mmHg), prehypertensive (130-

Dyslipidaemia and diabetes: a real world clinical evidence in Indian

139/80-89, mmHg), and hypertensive (O140/90, mmHg) based on their blood

scenario

pressure (BP). ASCVD risk score of each patient was calculated using Million

Shantharam Duvvuru, Sambit Das, Moazam SG, N Rajendiran,

Hearts^w Longitudinal ASCVD Risk Assessment Tool, as per ACC/AHA 2016

S Venkataraman, NK Narayanan, AV Bhanu Keerthi,

guidelines. Statistical analysis was done by using SPSS version

20, with

Vamsi Krishna Kolukula & Shashank Joshi

significance set at 2 tailed P %0.05.

Apollo Sugar Clinics, Hyderabad, India.

Results

Total 365 patients were analysed, their mean (SD) age was 52.6 (11.9) years,

63.6% were males and 36.4% were females. Of these patients 45.8%, 24.4%, and

Background

29.9% were normotensive, prehypertensive, and hypertensive, respectively. The

Dyslipidaemia, a major risk factor for cardiovascular disease

(CVD) is

indicators of ASCVD risk, age, BMI, and total cholesterol (each P!0.05) were

considerably increasing in patients with diabetes. The purpose of the study was

significantly different among three groups. Of the 365 patients only 161 patients

to evaluate the lipid profiles of diabetes patients attending Apollo Sugar Clinics

who met the ASCVD risk assessment criteria the score was calculated. The

across India.

10-year baseline risk score was 16.8% and expected risk would reduce to 12.5% if

Methods

statin therapy is initiated. A significant difference in risk score was observed

The current study was a retrospective analysis of electronic medical records of

among three groups at baseline (14.4%; 15.6%; 19.4%, PZ0.05), and expected

1487 type 2 diabetes (T2DM) patients who registered at (Dec 2014 to Oct 2016)

10-year risk (10.8%; 11.6%; 14.4%, PZ0.07) if statin therapy initiated.

Apollo Sugar Clinics, across India. Patients with diabetes were diagnosed as per

Conclusion

the ADA guidelines, and the data was collected from the patients after signing

Treatment of cholesterol level by moderate or high intensity statins should be an

informed consent. Statistical analysis was done by using SPSS version 20, and a

essential component of multifactorial intervention for primary prevention of CV

2-tailed P %0.05 was set to be significant.

disease in diabetes patients.

Results

DOI: 10.1530/endoabs.49.EP553

In total (NZ1487) T2DM patients, males and females were 64.9% and 35.1%,

respectively and had mean (SD) age 53.0 (10.6) years. Of these patients analysed,

54.8% had high low density lipoprotein (LDL; O100 mg/dl), 86.1% had low high

density lipoprotein

(HDL; !50 mg/dl),

40.7% had hypercholesterolemia

(O180 mg/dl) and 76.3% had hypertriglyceridemia (O100 mg/dl). In low HDL

group of 86.1%, 54.3% had high LDL and 79% had high TG. Further, mean

concentrations of LDL (111.1 vs 105.6; PZ0.01), HDL (43.3 vs 38.9; P!0.001),

and TC (177.9 vs 169.2; P!0.001) were significantly higher in females compared

EP554

to males (P %0.01). However, of these patients 45.2% and 59.3% are at LDL and

The association between pancreatic steatosis and diabetic retinopathy in

TC targets, respectively.

patients with non-obese type 2 diabetes mellitus

Conclusions

Jee Sun Jeong¹, Mee Kyung Kim¹, Kyung do Han², Ki-Hyun Baek¹,

The prevalence of dyslipidaemia was observed to be high in diabetes patients than

Ki-Ho Song¹, Dong Jin Chung³ & Hyuk-Sang Kwon¹

reported in normal population. The pattern of dyslipidaemia is different in India

¹Department of Internal Medicine of The Catholic University of Korea,

which is termed as ‘atherogenic dyslipidaemia’ where, in addition to low HDL,

Seoul, Republic of Korea;²Department of Medical Statistics of The

there were elevated levels of both TG and LDL. This increases morbidity of non-

Catholic University of Korea, Seoul, Republic of Korea;³Department of

communicable disease and needs multifactorial intervention for primary

Radiology of The Catholic University of Korea, Seoul, Republic of Korea.

prevention of CVD in diabetes.

DOI: 10.1530/endoabs.49.EP555

Background

In the previous study, it was demonstrated that pancreatic steatosis was

significantly associated with subclinical atherosclerosis in patients with non-

obese T2DM. As the result, it was suggested that pancreatic steatosis might be

related to macrovascular complication of T2DM. However, the association of

pancreatic steatosis on microvascular complication of T2DM has been unknown.

Objective

EP556

This study aimed to investigate the relation between pancreatic steatosis and

Markers of nonalcoholic fatty liver disease in patients with diabetes

diabetic retinopathy in T2DM subjects.

Irina Savasteeva¹, Maria Rusalenko¹, Yulia Yarets¹, Veronika Selkina¹,

Method

Yana Navmenova¹, Marina Kaplieva², Alena Makhlina²,

Attenuations of pancreas and spleen of 168 patients with T2DM were measured

Tamara Yeudachkova¹, Elena Vaschenko¹ & Tamara Moskvicheva¹

by using non-enhance computed tomography (CT) imaging. Then the difference

¹Republican Scientific and Practical Center for Radiation Medicine and

of attenuation between pancreas and spleen

(P-S) and attenuation ratio of

Human Ecology, Gomel, Belarus;²Gomel State Medical University, Gomel,

pancreatic-to-spleen (P/S) values were calculated for evaluation of pancreatic

Belarus.

steatosis. Obesity was defined when subjects had BMI O25 k/m² according to the

Asian-specific BMI cut-offs. The presence of diabetic retinopathy was assessed

by an expert ophthalmologist using dilated fundoscopy.

Given the significant correlation between the indices of lipid metabolism, liver

Results

dimensions, glycated hemoglobin and indicators cytolysis of hepatocytes

The attenuation values of P-S and P/S were significantly related to diabetic

identified a number of predictors that have had a significant influence on the

retinopathy in patients with non-obese T2DM. In the non-obese group, compared

formation of NAFLD. At a BMI above 26.5 kg/m², the relative risk (RR) for BMI

with those without, P-S odds ratio (OR) of patients with pancreatic steatosis was

was 20.02 and was statistically significant (8.25O48.61). When VLDL level

0.192

(95% CI 0.051, 0.727) and P/S OR was 0.12 (95% CI 0.028, 0.515) for

above 0.6 mmol/l relative risk for NAFLD also was statistically significant

diabetic retinopathy, after adjusting for age, gender, and BMI. However, there

(RRZ28.50; 11.18O72.65). With increasing levels of triglycerides above

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

1.43 mmol/l relative risk for NAFLD was 34.69 and was statistically significant

Results

(12.68O94.91). In the course of the factor analysis, we analyzed the contribution

82 patients were seen in total. 64 patients had full medicines management review

of isolated predictors in the development of NAFLD patients with diabetes. So

whilst the pharmacist individually reviewed 34 patients. Complete data for this

with type 2 diabetes have made the contribution to such predictors as a BMI

audit was available in in 48/82 patients. 30/48 (62%) were males. Ethnicity

(65.4%), and increase level of triglycerides (16.85%), while type 1 diabetes - BMI

distribution was - Asian 17, Afro-Caribbean 16, Caucasian 12, others 3. A mean

(65.4%) and the level of VLDL (81.0%). In type 2 diabetes the leading influence

reduction in HbA1c from 75 to 70 mmol/mol (PZ0.01) was achieved. Systolic

obesity and atherogenic focus lipogenesis. Patients with type 1 diabetes on the

blood pressure reduced from 136.8 to 137.2 mmHg (NS). No significant change in

development of obesity affects both NAFLD and associated levels of atherogenic

diastolic blood pressure was seen either

(71.5

71.0). Significant urinary

lipids, and the degree of compensation of carbohydrate metabolism and

albumin:creatinine ratio

(ACR) improvement was observed: 49 down to 40

associated level of glycation of proteins.

mg/mmol (P!0.01). 28/64 (43%) patients were not on an antiplatelet agent.

DOI: 10.1530/endoabs.49.EP556

60/64 (94%) were on a lipid-lowering agent. 47/64 (73%) patients received an

ACE inhibitor, ARB or both. 9/48 (19%) patients were either referred to renal

physicians or discussed in the renal-diabetes MDT. 11/48 (23%) patients used

Telemedicine and patient held records to improve self - management skills (FLO

Telemedicine-8, Patient Knows Best PKB-3).

Conclusion

These results suggests that the nurse-led clinic is effective in reducing HbA1c and

urine ACR levels in this high CV risk patients and should help improve

EP557

cardiovascular and renal outcomes in future. Pharmacist presence helps improve

Meal composition affects risk markers for kidney disease differently in

medication knowledge and adherence - most patients received lipid-lowering

type 2 diabetes and healthy subjects

agents and majority were on ACE/ARBs, whilst aspirin prescription remained

Camilla Olofsson^1,2, Agneta Hilding¹, Nicola Orsini¹,

low. We hope to further improve results as the clinic progresses to its full

Inga-Lena Andersson², Ole Torffvit³, Kerstin Brismar^1,2 &

potential in future.

Neda Rajamand Ekberg^1,2

DOI: 10.1530/endoabs.49.EP558

¹Karolinska Institutet, Stockholm, Sweden;²Karolinska University

Hospital, Stockholm, Sweden;³Lund University Hospital, Lund, Sweden.

Background/aims

Oxidative stress and inflammation play a role in development of diabetic kidney

disease. Postprandial hyperglycemia and hyperlipidemia are speculated to be

associated with increased oxidative stress and inflammation. The aim was to

examine the effect of meal composition on post-prandial risk markers for kidney

disease among those with type 2 diabetes (T2D) and healthy subjects (HS).

Material/methods

EP559

On four occasions 21 patients with T2D and 21 HS ingested an isocaloric lunch

Inhibin B levels and bone health in male adult patients with Type 1

(600 kcal) with different compositions of carbohydrate (CH) (54%), CH & fibers

Diabetes Mellitus

(15 g), fat (50%) and protein (40%). Blood samples were taken and urine samples

Eleftheria Barmpa¹, Spyros Karamagiolis², Stelios Tigas³,

collected before and up to four hour after the meal. B-glucose, insulin,

Parthena Navrozidou⁴, Marianna Vlychou⁴, Ioannis Fezoulidis⁴,

triglycerides, CRP, IL-6, IL-18, and urine IgG2, IgG4 and ACR were analyzed.

Georgios N. Koukoulis¹ & Alexandra Bargiota¹

Statistical method: repeated measure ANOVA and area under the curve.

¹Department of Endocrinology and Metabolic Diseases, University of

Results

Thessaly, Larissa, Greece;²General Hospital of Larissa, Larissa, Greece;

T2D had a mean age (GSD) of 63 (4) years while HS had a mean age of 52 (16),

³Department of Endocrinology, University of Ioannina, Ioannina, Greece;

PZ0.004, and T2D had higher BMI (29 vs 24 kg/m², P!0.001). There were

⁴Department of Radiology, University of Thessaly, Larissa, Greece.

postprandial differences between the meals for glucose, insulin and triglycerides

for both groups, all P!0.05. High CH meals resulted in higher peaks of glucose

and insulin, while high fat meal gave higher peaks of triglycerides. Both groups

Introduction

had an overall increase in IL-6 for all meals. IL-18 decreased after CH meal only

Existing data suggest that Type 1 Diabetes Mellitus (T1DM) can affect both

in HS, PZ0.003. Urine IgG2 and IgG4 responses were different between the

hypothalamic-pituitary-testis axis and bone health. The mechanisms by which sex

groups after CH-meal (PZ0.02). CRP, urine ACR, urine IgG2 & IgG4 was not

steroids influence bone remodeling remain incompletely understood. Data linking

affected by meal composition within the groups.

gonadal function and bone turnover in male patients with T1DM are lacking. The

Conclusion

purpose of this study was to examine any possible association between sex

CH meal showed higher glucose and fat rich meal higher triglyceride levels

steroids levels and parameters of bone assessment in male adult patients with

suggesting risk for oxidative stress in T2D. However, CRP, IL-6, IL-18, urine

T1DM.

albumin excretion, IgG2 & IgG4 were not significantly modulated by meal

Methods/design

composition in this population.

We studied 53 male patients with T1DM (Group-D) and 42 healthy controls

DOI: 10.1530/endoabs.49.EP557

(Group-C) matched for age, sex and BMI. In both groups HbA1c, Inhibin B

(InhB), total testosterone (TT), SHBG, LH, FSH, b-crosslaps, type 1 procollagen

total N-terminal propeptide (TP1NP) and BMD at lumbar spine (LS), femoral

neck (FN) and total hip (TH) by dual energy X-ray absorptiometry (DXA) were

measured.

Results

Mean age (years) (D: 34.9C10.6 vs C: 34.1C9.9, PZ0.41) and BMI (kg/m²) (D:

23.7C8.1 vs C: 24.5C7.7, PZ0.38) were similar in both groups. In Group-D,

mean duration of DM was 14.4C8.5 years and mean HbA1c was 7.8C1.3%.

EP558

Higher levels of FSH (PZ0.043) and SHBG (PZ0.041), and a trend towards

Audit of a nurse-led and pharmacist assisted diabetes renal out-patient

lower InhB (PZ0.049) and TT (PZ0.051) concentrations, were observed in

clinic - does it help improve medicines management and clinical

Group-D compare to controls. LH was similar in both groups (PZ0.069). Total

outcomes?

BMD (tBMD, g/cm²) and z-scores were lower in Group-D at all three sites ((LS:

Susan Irwin, Gurpreet Kaur, Caroline Lacy & Parijat De

PZ0.031 and PZ0.036), (FN: PZ0.042 and PZ0.039), (TH: PZ0.046 and

Sandwell & West Birmingham NHS Trust, Birmingham, UK.

PZ0.044)). No significant difference in b-crosslaps (PZ0.080) and TP1NP

(PZ0.086) was found between the two groups. Regression analysis showed: a

negative association between InhB and HbA1c (PZ0.038), InhB and tBMD at LS

Aim

(PZ0.041) and a positive association between InhB and b-crosslaps (PZ0.044)

To audit clinical outcomes and adherence to prescription recommendations in a

and InhB and TP1NP (PZ0.047).

diabetes renal clinic.

Conclusion

Method

These data suggest that InhB might contribute to bone turnover changes observed

Baseline data was compared to the final clinic visit within a 12 month period,

in T1DM. Further studies are needed.

using information from clinic letters and electronic records of patients attending

our hospital diabetes renal clinic in 2016 (1st January - 31st December). Patients

DOI: 10.1530/endoabs.49.EP559

with at least 1 follow-up within a 12 month period were included.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP560

(88.7;142.2) compared with euglycemia

97.0

(83.2;107.0), PZ0.046

and

hyperglycemia 96.0 (79.2;110.2), PZ0.028. protein S level was significantly

Cardiovascular disease and risk factors in patients with type 1

increased during hypoglycemia 93.6 (79.2;103.4) compared with euglycemia 77.6

diabetes mellitus

(52.6;90.2), PZ0.046 and hyperglycemia 76.3 (61.0;84.5), PZ0.046. Protein C

Irina Tenu¹, Cornelia Bala², Silvia Iancu², Gabriela Roman² &

level, AT-III, vWf, IAT induced by arachidonic acid (PZ0.069) and adenosine-

Ioan Veresiu²

diphosphate (PZ0.058) did not differ between groups.

¹Department of Endocrinology, Cluj County Clinic Emergency Hospital,

Conclusions

Cluj-Napoca, Romania;²Department of Diabetes, Nutrition and Metabolic

Acute insulin-induced hypoglycemia causes platelet hyperactivity, which may

Disease, Cluj County Clinic Emergency Hospital, Cluj-Napoca, Romania.

increase the risk of adverse cardiovascular and cerebrovascular events.

Hypoglycemia leads to increased free protein S level, which, is probably, due

Objective

to activation of the endothelium in patients with DM1 without microvascular

The occurrence of cardiovascular disease (CVD) in patients suffering from type 2

complications.

diabetes is a widely discussed issue, less so in those with type 1 (T1DM). The

DOI: 10.1530/endoabs.49.EP561

purpose of this study was to evaluate the frequency of these complications as well

as certain risk factors that they are associated with.

Material and methods

We conducted a retrospective observational study by analyzing data from the

observation charts of 106 patients evaluated in our clinic between January 2015

and December 2016. All patients had a history of T1DM of more than 20 years.

We assessed the occurrence of hypertension

(HT), stroke, acute coronary

EP562

syndrome (ACS) and peripheral artery disease (PAD), as well as certain risk

Biomarkers status and their relation with the presence of type 2

factors. One patient was excluded due to insufficient information.

diabetes with and without angiopathy

Results

Ana Valente^1,2, Manuel Bicho^3,4, Rui Duarte⁵, João Raposo⁵ &

We included 105 patients (46% women), with a mean age of 51.46G12.58 years,

Helena Soares Costa^1,6

mean disease duration of 30.16G8.69 years and the mean age at diagnosis of

¹Unidade de Investiga

¸a˜o e Desenvolvimento, Departamento de

21.31G11.82 years. The frequency of chronic diabetes complications was: 87%

Alimenta

¸a˜o e Nutrição, Instituto Nacional de Saúde Doutor Ricardo Jorge,

retinopathy, 89% neuropathy, 42% nephropathy and 12% amputations, and for

I.P., Lisboa, Portugal;²Atlântica University Higher Institution, Barcarena,

CVD: 60% HT, 10% ACS, PAD 19 and 5% stroke. There was a statistically

Portugal;³Laboratório de Genética, Instituto de Saúde Ambiental,

significant higher risk in patients diagnosed with CVD in regard to the mean age,

Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal;

mean duration of disease and mean age at diagnosis of T1DM. There was a

⁴Instituto de Investiga

¸a˜o Científica Bento da Rocha Cabral, Lisboa,

statistically significant correlation for the presence of peripheral neuropathy and

Portugal;⁵Associac¸ão Protectora dos Diabéticos de Portugal, Lisboa,

nephropathy in patients with HT (P-value 0.0205 and 0.0001 respectively).

Portugal;⁶REQUIMTE-LAQV/Faculdade de Farmácia da Universidade do

Patients suffering from PAD had a worse glycemic control (HbA1C 9.4 vs 8.80%,

Porto, Porto, Portugal.

P-valueZ0.033) and lower HDL-cholesterol levels

(54.04

63.30 mg/dl,

P-valueZ0.040) than those without. Patients who had suffered a stroke had better

cholesterol and LDL-cholesterol levels

(158.8

189.04 mg/dl, P-valueZ

Introduction

0.000196 and 81.8 vs 106.33 mg/dl, P-valueZ0.029 respectively).

A useful tool for disease clinical characterization and treatment of type 2 diabetes

Conclusion

is the knowledge on the status of several biomarkers. The aim of this study was to

More attention should be awarded in the screening for CVD in patients with a

evaluate the levels of cardiovascular, oxidative stress and nutritional biomarkers

long history of T1DM.

and their relationship with the presence of type 2 diabetes and angiopathy.

Methods

DOI: 10.1530/endoabs.49.EP560

A population-based case-control study in 150 Portuguese type 2 diabetic patients

was performed. Group I - 75 diabetics with angiopathy, group II - 75 diabetics

without angiopathy and group III - non-diabetic controls. Plasma levels of

homocysteine, cysteine, malondialdehyde (MAD), vitamins B₆, C, A and E and

carotenoids were measured by HPLC methods. Vitamin B₁₂ and folate serum

levels were achieved by an electrochemiluminescence method.

Results

EP561

The hyperhomocysteinemia prevalence was 20% (group I), 8.7% (group II) and

0.71% (group III). Group I showed the higher prevalence of hypercysteinemia

Platelet aggregation and physiological anticoagulants in acute

(17%). The MAD serum levels were above the reference value for all groups. The

insulin-induced hypoglycemia in patients with type 1 diabetes (DM1)

Karina Sarkisova^1,2, Ivona Renata Jarek-Martynowa², Marina Shestakova^1,2

percentage of subjects with ascorbic acid low plasma levels were statistically

& Ekaterina Koksharova²

different in diabetic (I: 55%; II: 47%) compared to non-diabetic subjects (III:

¹I.M. Sechenov First Moscow State Medical University, Moscow, Russia;

22%). The prevalence of hypovitaminosis B₆ deficiency was at least 30% for all

²Endocrinology Research Centre, Moscow, Russia.

groups. In group I, the probability to have hyperhomocysteinemia was around

three times higher

(PZ0.04) in comparison with group II and

times

(PZ0.0006) with group III. The combined effect of type

2 diabetes and

Background and aims

angiopathy is associated with high MAD (OR: 5.33; PZ0.002) serum levels

Hypoglycemia can be a risk factor for adverse cardiovascular and cerebrovascular

compared to group III. Type 2 diabetes predisposes to hypovitaminosis C (OR:

events. However, changes in platelets and coagulation hemostasis during

3.10; PZ0.0002).

hypoglycemia have not been extensively studied. The aim of this study was to

Conclusion

assess the impact of insulin-induced hypoglycemia on the platelet activity,

The prevalence of hypovitaminosis C and B₆ were relevant. The presence of type

endothelial dysfunction and the physiological anticoagulant level in patients with

2 diabetes increases the risk of hyperhomocysteinemia, oxidative stress and

DM1.

hypovitaminosis C. The isolated effect of angiopathy increases the probability to

Research design and methods

have hyperhomocysteinemia.

We studied seven patients with DM1 (four male and three female, age 26.5G5.8,

DOI: 10.1530/endoabs.49.EP562

A1C 8.4G1.8%) without microvascular complications during hyperinsulinemic

(1 mU/kg per min) hypoglycemic clamp protocol. Induced platelet aggregation

(IAT) in whole blood using thrombin receptor activating peptide 6 (tRaP-6),

collagen, arachidonic acid, adenosine-diphosphate was measured during

hypoglycemia (plasma glucose

2.3G0.1 mmol/l), normoglycemia (pg 4.4G

0.4 mmol/l), and hyperglycemia (pg R12 mmol/l) by multiple electrode platelet

EP563

aggregometry (Multiplate). Physiological anticoagulants (Protein S, Protein C,

Severe hypoglycaemias in patients with unnoticed hypoglycaemias:

AT-III), von Willebrand factor (vWf) was determined by ELISA. Statistical

a two-year follow up

analysis was performed with SPSS 22.0 for Windows, P!0.05.

Eyvee Arturo Cuellar Lloclla, Guillermo Martínez de Pinillos Gordillo,

Results

Carmen Carretero Marín, Fernando García Pérez, José Álvaro

Collagen-induced platelet aggregation was significantly increased during 20-min

Romero Porcel, Ignacio Fernández Pen˜ a, Juan Manuel García de

of hypoglycemia 34.0 (25.2;51.7) compared with euglycemia 26.5 (18.0;35.0),

Quirós Mun˜ oz, Ignacio Fernández López, Mariana Tomé Fernández-

PZ0.027 and hyperglycemia 23.5 (20.0;23.5), PZ0.028. Thrombin-induced

Ladreda & María Victoria Cózar León

platelet aggregation was significantly increased during hypoglycemia

104.0

Hospital de Valme, Sevilla, Spain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction and objectives

Conclusion

Having frequent hypoglycaemias can enable the appareance of severe and

In our sample, the prevalence of SGA was 3.5 times higher compared to LGA.

unnoticed hypoglycaemias, as well as favouring vascular damage in these

Women without previous GDM or macrosomia, with lower BMI before

patients. Our objective is to evaluate de incidende of severe hypoglycaemias (SH)

pregnancy, insufficient weight gain during pregnancy, lower HbA1c in 3rd

in patients with Diabetes Mellitus type

1 and the reduction of perceived

trimester and twin pregnancies had significantly more SGA. Monitoring fetal

hypoglycaemias.

intrauterine growth, assessing risk-benefits of therapeutic and an individualized

Material and methods

approach is required.

A prospective study was conducted. Patients attending to their Endocrinology

DOI: 10.1530/endoabs.49.EP564

appointments between September 2013 and January 2014 were surveyed to

evaluate their capacity to perceive hypoglycaemias (Clark’s test). Patients with a

test result compatible with a diminished capacity to sense hypoglycaemia were

tracked 2 years later. The data was analysed using a Chi-squared test (IC 95%)

with SPSS 21.0.

EP565

Results

104 patients were surveyed, out of which 41 had a diminished capacity to perceive

A case of pulmonary tuberculosis presented with recurrent diabetic

ketoacidosis

hypoglycaemia (mean age 36.6G11.6 years, 61% women, HbA1c, 26%G1.04%

Nalan Okuroglu, Sabiha Komoglu, Rojda Usta, Berrak Tas, Meltem Sertbas

and 58.5% had O20 years diabetes evolution). After 2 years, 43.9% referred

& Ali Ozdemir

having had severe hypoglycaemias, out of those 55.6% had had more than 3

Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey.

episodes and 33.3% had had a loss of consciousness. 19.5% had an insulin pump

(21.4% in patients with severe hypoglycaemia). We found a statistically

significance between Clark’s test results and severe hypoglycaemias

(P!0.002).

People with diabetes are at increased risk for developing tuberculosis than

Conclusions

non-diabetics. We presented a patient with recurrent diabetic ketoacidosis

A pathological Clark’s test may be able to identify patients at risk for severe

who was later diagnosed with pulmonary tuberculosis.

hypoglycaemia, which makes it a useful tool to detect this group of patients. If a

Case

high incidence of severe hypoglycaemia is observed, measured should be taken to

A 22 year old male with type 1 diabetes for nine years was admitted to the

educate this patients to be able to recognize and interpret the symptoms of low

emergency service due to nausea and vomiting. Detecting high anion gap with

blood glucose as well as developing therapeutic strategies to avoid them, all of

metabolic acidosis in his blood gas), and ketones in urine analysis,the patient was

which would improve their quality of life.

hospitalized for diabetic ketoacidosis (DKA). Additional analysis of urine, liver,

DOI: 10.1530/endoabs.49.EP563

kidney tests, abdominal ultrasound, chest X-ray were within normal limits.

Lumbosacral MR imaging based on the low back pain did not reveal any

pathology. Serological tests of celiac disease was negative. After receiving

intravenous insulin, DKA resolved and he was discharged. 1 week later, the

patient admitted to our hospital because of high anion gap metabolic acidosis and

hyperglycemia. The cortisol and anterior hypophysis hormones made for the

etiology of DKA were within normal range. Recommending outpatient clinic

control the patient was discharged. For the third time, after another nausea,

vomiting and abdominal pain, the patient was referred to another health center

EP564

with diabetes ketaoacidosis; gastroscopy was performed and esophageal lineer

Small for gestational age and gestational diabetes - Should we be more

ulcers were detected. Pathology was compatible with non-specific inflammation.

permissive?

After being discharged, the patient was presented again to our emergency

Rita Bettencourt-Silva^1,2, Pedro Souteiro^1,2, Daniela Magalha˜es1,2,

department suffering from chest pain, retrosternal burning and weight loss. Again

Sandra Belo^1,3, Ana Oliveira^1,4, Davide Carvalho^1,2, Joana Queirós^1,3 &

ketoacidosis was detected and hospitalized. During his admission, chest X-ray

Diabetes and Pregnancy Study Group Portuguese Society of Diabetology³

revealed right upper lobe cavitary lung lesion. With positive sputum acid-fast

¹Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-

bacilli(AFB) stains he was diagnosed and treated for pulmonary tuberculosis.

talar São João, E.P.E., Porto, Portugal;²Faculty of Medicine, University of

Discussion

Porto, Porto, Portugal;³Diabetes and Pregnancy Study Group, Portuguese

The tuberculosis incidence in diabetes is four times higher than general

Society of Diabetology, Portugal;⁴Outpatient Clinic of Obstetrics and

population. Especially in the developing countries like Turkey where the

Endocrinology, Centro Hospitalar Sa˜o João, E.P.E., Porto, Portugal.

prevalence of type 2 DM is increasing, tuberculosis is an important health

problem and patients with diabetes should be screened for tuberculosis.

Introduction

Gestational diabetes mellitus (GDM) is a risk factor for large for gestational age

(LGA) newborns. The optimization of glycemic control and weight gain

restriction during pregnancy according to BMI has contributed to decrease

LGA but may increase the risk of small for gestational age (SGA).

Aim

To evaluate the predictors of SGA in women with DGM.

Methods

A cohort of 5271 Portuguese women from the National Registry of GDM was

studied. Demographic, anthropometric and analytical data and maternal-fetal

outcomes were evaluated.

Results

Women presented a mean age of 33.14G5.4 years, mean BMI of 26.99G

5.81 kg/m² and mean weight gain during pregnancy of 9.63G5.78 kg. The

newborn’s growth was evaluated according to Fenton curves in 4727 cases. We

identified 3898 (82.5%) newborns appropriate for gestational age (AGA), 180

(3.8%) LGA and 649 (13.7%) SGA. Women with SGA had a significant lower

DOI: 10.1530/endoabs.49.EP565

pre-pregnancy weight

(66.95G15.20 vs 71.01G16.04, P!0.001) and BMI

(26.07G5.75 vs 27.06G5.77; P!0.001). The prevalence of SGA was lower in

women with previous GDM (ORZ0.592, 95%CIZ0.466-0.805, P!0.001) or

macrosomia (ORZ0.274, 95%CIZ0.145-0.520, P!0.001) and greater number

of pregnancies

(ORZ0.798, 95%CIZ0.737-0.863, P!0.001) and two-fold

higher in twin pregnancies

(ORZ2.059, 95%CIZ1.313-3.229, PZ0.001).

Insufficient weight gain during pregnancy increased the possibility of SGA by

EP566

35% (ORZ1.346, 95%CIZ1.127-1.609, P!0.001). A lower value of HbA1c in

Which one is much more cause in osteoarthritis? Diabetes mellitus

3rd trimester was presented in pregnancies with SGA (5.18G0.38 vs 5.25G0.44,

Type 1 or 2?

ORZ0.662, 95%CIZ0.516-0.849, PZ0.001). No significant differences were

Kadri Yildiz¹ & Kenan Cadirci²

found regarding age, week of diagnosis and treatment with insulin or oral

¹Erzurum Palandoken State Hospital, Erzurum, Turkey;²Erzurum Regional

antidiabetic agents.

and Educational Hospital, Erzurum, Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Osteoarthritis is a great public health problem indiscriminately; ie

Background and aims

goanrthritis, coxarthritis or dejenerative spine diseases. Osteoarthritis is

To evaluate the level of tubular and glomerular biomarkers of kidney injury as

focude sixth decades in elderly people, espicially in women. Many studies

potential nephroprorotective effects of GLP-1R agonist (liraglutide) addition in

assingned the efficiancy of Diabetes Mellitus in the etiology of

type 1 diabetic patients compared to standard insulin therapy.

Osteoarthritis. Correlations between bone-destructive characteristics and

Materials and methods

carbohydrate metabolism errors is now quite accused in this clinical views.

12 T1DM patients with normo-(AER !20 mg/l, nZ7) and microalbuminuria

A comparing between Diabetes Mellitus Type 1 and 2 is aimed in this study

(AER!199 mg/l, nZ5) with liraglutide 1.2 mg as add on to insulin for 6 month

which one cause in much more osteoarthritis. 167 (69 gonarthroisis, 57

and

12 patients with normo-(AER

!20 mg/l, nZ8) and microalbuminur-

coxarthritis and 41 dejenerative spine diseases) patients is joined to this

ia(AER!199 mg/l, nZ4) on standard insulin therapy. Biomarkers of kidney

trials for

4 years. All patients were evaluated by endocrinologists and

damage (collagen i.v., nephrin, podocin, cystatin C, kidney injury molecule-1

orthopaedists. According to results; there were more counts of Type 2

(KIM-1), neutrophil gelatinase-associated lipocalin

(NGAL), uromodulin,

patients in all groups (51 Type 2 and 18 Type 1 in gonarthrosis; 46 Type 2

osteopontin) were measured by enzyme-linked immunosorbent assay ELISA in

and 11 Type 1 in coxarthritis, 32 Type 2 and 9 Type 1 in dejenerative spine

the morning urine and fasting plasma; overnight AER by immunoturbidimetry

diseases). Statistical difference is significiant

(P!0.05). Many recently

assay; glomerular filtration rate (GFR) by CKD-EPI formula were measured

clincal and laboratory studies assigned a correlations between Diabetes

before and after 6-month treatment. Concomitant RAAS blockage-drugs given in

Mellitus and all rheumatoid diseas. Carbohydrate metabolism is a headstone

stable doses. Differences were examined for statistical significanse (P!0.05)

of all metabolic systems. All defects and errors in carbohydrate metabolism

using Wilcoxon Signed-Rank Test.

can affect other metabolic systems and bone-soft tissue systems by the

Results

metabolits, especially sorbitol. And also presdisposition of Type

2 to

Initially the groups were similar by average age, HbA1c, plazma glucose, BP,

Metabolic Syndrome can mark pathophyisology of Osteoarthritis as

lipids, uric acid, C-reactive protein, creatinine, eGFR. HbA1c before and after

difference proportions of these types.

6 month treatment. There were no significant differences in BP, albuminuria,

creatinine, eGFR, HbA1c in 6 month. BMI decreased from 29 (22;38) to 26.8

DOI: 10.1530/endoabs.49.EP566

(21;34.7) kg/m², PZ0.01 in GLP1 group. Urinary levels of podocin, KIM-1 and

collagen did not changed before and after therapy. In GLP1 group observed

significant reduction in the urinary levels of NGAL/creatinine 1.48(0.81;2.29) vs

0.65(0.34;0.74) ng/mmol, PZ0.015; KIM-1/creatinine

115(35;328) vs

47(21;116) ng/mmol, PZ0.02; cystatin C

881(464;1579) vs

136(91;205)

EP567

ng/mmol, PZ0.01; nephrin 0.1(0.09;0.15) vs 0.004(0.01;0.1), uromodulicreati-

Prevalence of distal symmetric polyneuropathy in diabetic patients in

nine rised from 175(82;278) to 458 (235;754); and plazma levels of cystatin and

general medicine wards

osteopontin after treatment: 1264 (877;1472) vs 722 (672;848) ng/ml, PZ0.007;

Ana Lopes¹, Helena Gonçalves², Liliana Fonseca¹, Catarina

126.8

(45;161) vs 65 (45;74), PZ0.02, respectively compared to the stable levels

Castelo Branco¹, João Gonçalves¹, Luisa Sousa¹, Margarida Calejo¹,

of markers in the standard insulin treatment group.

Sara Martins¹, João Neves¹ & Sofia Teixeira¹

Conclusion

¹Centro Hospitalar do Porto, Porto, Portugal;²Centro Hospitalar

The present data suggest that GLP-1R adding to standard insulin therapy might be

Trás-os-Montes e Alto-Douro, Vila Real, Portugal.

effective for the weight reduction and as potential nephroprotective strategy for

attenuating the chronic kidney injury in T1DM.

DOI: 10.1530/endoabs.49.EP568

Background

Distal symmetric polyneuropathy (DSPN) is one of the most prevalent chronic

complications of diabetes and the most common cause in the pathway to diabetic

foot ulceration. Screening for DSPN enables early intervention and prevention of

complications. The Semmes-Weinstein Monofilament Examination (SWME) is

currently the method of choice to screen DSPN, but ideally two neurologic tests

should be used. The Michigan Neuropathy Screening Instrument (MNSI), which

evaluates vibratory sensation and ankle reflex, has been proposed as a useful

screening test of DSPN. The objective of this study was to determine the

prevalence of DSPN in diabetic patients in general medicine wards.

Methods

EP569

Diabetic patients admitted within a 5 months period were evaluated with the

MNSI and the SWME after exclusion of other causes of polyneuropathy. A score

Diabetic choroidopathy and renal function

O2 in the clinical examination of MNSI and %7 positive answers in a total of 10

Antonio Manuel Garrido Hermosilla^1,2, Mariola Méndez Muros³, Cristóbal

in SWME were considered positive.

Morales Portillo³, Tomás Martín Hernández³, Natividad González Rivera³,

Results

María Jesús Díaz Granda^1,2, Enrique Rodríguez de la Rúa Franch^1,2 &

Twenty-three patients were included (75.6G13.7 years; 56.5% male; 9.9G6.1

Estanislao Gutiérrez Sánchez^1,2

years of disease duration). Only 2 (8.7%) had previously been diagnosed with

¹Ophthalmology Department, Virgin Macarena University Hospital, Seville,

DSPN. The SWME was positive in only one of these patients while the MNSI was

Spain;²OftaRed - RETICS Ocular Pathology, Institute of Health Carlos III,

positive in both. In the remaining undiagnosed 21 patients, 12 patients (57.1%)

Madrid, Spain;³Endocrinology Department, Virgin Macarena University

were positive for the MNSI, while 14 (66.7%) were positive for the SWME. Both

Hospital, Seville, Spain.

MNSI and SWME were positive in 10 out of 23 patients (43.5%) and 19 out of 23

(82.6%) had at least one screening test positive.

Objectives

Conclusion

Examine the relationship between choroidal thickness (CT) and renal function

In this study, more than half of the diabetic patients without a previous diagnosis

tests.

were screened positive for either the MNSI or SWME test. Data indicates that

Methods

using both MNSI and SWME increases the detection of DSPN. This study

Cross-sectional study with 42 eyes of 21 ocular treatment-naïve diabetic patients.

confirms that DSPN is a prevalent complication of diabetes and that

Demographic and ocular data were analyzed as well as the following renal

hospitalization is an excellent opportunity to screen for DSPN.

function tests: microalbuminuria, microalbumin/creatinine ratio and glomerular

DOI: 10.1530/endoabs.49.EP567

filtration rate (CKD-EPI and MDRD-4). Choroidal thickness was measured by

swept-source ocular coherence tomography (SS OCT).

Results

The mean age was 49.76G17.61 years old (18-74), with a sex ratio of

approximately 1:1. 66.7% suffered from type 2 diabetes mellitus, with a mean

time of evolution of 12.14G10.08 years. 51.2% of patients didn’t present diabetic

EP568

retinopathy. Among renal function tests, only microalbuminuria positively

Tubular and glomerular biomarkers of kidney injury on glucagon-like

correlated with CT (P!0.05).

peptide-1 (GLP-1) therapy in type 1 diabetic patients

Conclusions

Zamira Zuraeva², Olga Vikulova^1,2, Olga Mikhaleva²,

The analysis of CT with SS OCT could be a prediction tool of renal function in

Marina Shestakova^1,2, Aleksandr Ilyin¹, Minara Shamkhalova^1,2 &

diabetic patients.

Ivan Dedov¹

¹Endocrinology Research Center, Moscow, Russia;²I.M. Sechenov First

DOI: 10.1530/endoabs.49.EP569

Moscow State Medical University, Moscow, Russia.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP570

Chronic kidney disease (CKD) is an important complication of diabetes and

Risk factors of diabetic foot complications

determinant of mortality. Albuminuria represents early diabetic nephropathy, and

Radhouane Gharbi, Melika Chihaoui, Ons Rejeb, Meriem Yazidi,

also indicates generalised vascular dysfunction. Understanding the epidemiology

Ibtissem Oueslati, Fatma Chaker & Hedia Slimane

of CKD and albuminuria helps inform health planning and identify opportunities

University of Tunis El Manar, Faculty of Medicine of Tunis, La Rabta

to prevent or delay progression of diabetic kidney disease. The last available

Hospital, Department of Endocrinology, Tunis, Tunisia.

serum creatinine and urine albumin/creatinine ratio (UACR) in patients with Type

(T1DM) or Type 2 (T2DM) diabetes recorded on the DIAMOND database were

used for analysis. Patients were divided into tertiles of age. CKD was defined

Introduction

as eGFR!90 ml/min; microalbuminuria as UACRO2.5 mg/mmol

(male),

Diabetic foot disease is a major health problem. The identification of its risk

O3.5 mg/mmol (female); macroalbuminuria as UACRO20 mg/mmol. NA-

factors should guide preventive measures. The aim of this study was to determine

normal albumin excretion; MA-microalbuminuria; A-macroalbuminuria;

the factors associated with diabetic foot complications.

ND-not done CKD was common and increased with age. Microalbuminuria

Patients and methods

also increased with age and was similar in patients with and without CKD.

It is a retrospective study including 47 patients admitted at the department of

Macroalbuminuria was uncommon. In summary, CKD is common in hospital-

Endocrinology in La Rabta hospital for diabetic foot complications during the

based diabetic patients. The low prevalence of macroalbuminuria indicates that

years 2015 and 2016. Clinical and para-clinical data were collected.

this mostly does not reflect classical diabetic nephropathy.

Results

The mean age was 51 years (27 to 78). There were 39 men (83%). It was a type 2

diabetes in 85% of patients. The mean duration of the disease was 13 years (0 to

30 years). Patients were illiterate or had a primary school level in

73%.

T2DM, No

Hypertension was present in

23% of the patients, smoking in

61% and

T1DM, CKD

T1DM, No CKD

T2DM, CKD

CKD

dyslipidemia in 29%. Diabetes was complicated with peripheral neuropathy in

Number/ %

81% of the patients, retinopathy in 54% and nephropathy in 53%. Coronary artery

(%NA/MA/A/ND)

(% NA/MA/A/ND)

(%NA/MA/A/ND)

(%NA/MA/ND)

disease was present in 15%, stroke in 6% and peripheral artery disease in 46%.

Age 18-58

271/ 27%

732/ 73%

721/ 42%

978/ 58%

Conclusions

(nZ2702)

(60/ 13/ 6/ 21)

(51/ 10/ 1/ 38)

(56/ 14/ 4/ 26)

(60/ 13/ 6/ 21)

Diabetes foot problems occur more often in men with a long duration of diabetes,

Age 58-71

106/ 75%

36/ 25%

1736/ 67%

826/ 33%

peripheral neuropathy and peripheral artery disease.

(nZ2704)

(56/ 19/ 5/ 20)

(45/ 23/ 6/ 26)

(50/ 17/ 5/ 28)

DOI: 10.1530/endoabs.49.EP570

Age 71-107

54/ 85%

9/ 15%

2244/ 84%

397/ 16%

(nZ2704)

(20/ 31/ 6/ 43)

(44/ 22/ 11/ 23)

(40/ 28/ 6/ 26)

(47/ 20/ 5/ 28)

DOI: 10.1530/endoabs.49.EP572

EP571

Diabetes mellitus as an important comorbidity in patient with sepsis

Entela Puca¹, Edmond Puca², Agron Ylli² & Pellumb Pipero²

¹American Hospital 2, Tirana, Albania;²UHC Mother Teresa, Tirana,

Albania.

Sepsis represents the host’s systemic inflammatory response to a severe infection.

It is a common condition in hospital settings and is associated with high rates of

EP573

morbidity and mortality. Since1992 the knowledge about sepsis epidemiology has

Two case reports of diabetic ketoacidosis: as lethal as avoidable

clearly improved. There are differences in epidemiologic data about sepsis

Rodolfo Gomes, Joana Oliveira, Bárbara Picado, Fernando Gonçalves &

identification in different countries. The aim of our study is to make a panoramic

José Araújo

view of sepsis at the service of Infectious Diseases, University Hospital Center,

Hospital Beatriz Ângelo, Loures, Portugal.

‘Mother Teresa’, Tirane, Albania during January 2009 to December 2013 and to

highlight its accompanying diseases.

Diabetic ketoacidosis (DKA) is one of the most serious complications of diabetes

Material and methods

mellitus (DM). We describe 2 cases of type-2 diabetic patients admitted by a

In our study we included patient over O14 years old, since we are a service for

surgical reason/trauma in which DM control was neglected. We present a

adult patients only. Our study was a retrospective one. A septic patient was

defined based on the 2001 sepsis conference definition. Study period was from

74-year-old patient with poor metabolic control (HbA1c 7,6%) treated with

January 2009 to December 2013.

metphormin, sitagliptin and glibenclamide, admitted for orthopaedic surgery.

Results

During hospitalization, there were noted several episodes of disorientation with

During our study time from 2009-2013 we had 707 patients with sepsis. The

hyperglycaemia about 300-350 mg/dl. At day 6, the patient was prostrated and

mean age was 50.3879 years old and SDEV resulted G19.59 years old. The most

with a glucose over 500 mg/dl and metabolic acidosis (pH 7,34; pCO₂ 29 mmHg;

affected age resulted 55-75 years old. Comorbidities in patients with sepsis were

pO₂ 89 mmHg; HCO₃ 15,6 mmol/l; lactate 8 mg/dl). Because of DKA, the patient

as below: Diabetes mellitus 5.2%, HIV/AIDS 4.5%, malignancies 1.6%, alcoholic

was transferred to an Intermediate Care Unit (IntCU), where it was begun fluids

cirrhosis 1.2%, autoimmune diseases 0.99%, post-transplant patients 0.84%, and

and insulin perfusion, with great response. Simultaneously, we present a case of a

homeopathies 0.7%.

70-year-old patient, already with diabetic retinopathy, treated with insulin,

Conclusions

metphormin and sitagliptin, that was admitted because of a pneumothorax and 3

In nowadays sepsis definition is modified. However its concept remains the same.

broken ribs after a fall. She was admitted in Pneumology ward, maintaining

hyperglycemias, nauseas and vomiting. At day 8, she was found prostrated,

The sepsis cases are increasing. The age and other comorbidities are risk factors

frankly dehydrated and with a hyperglycaemia over 500 mg/dl. After diagnosing

that play an important role in the increasing of morbidity and mortality. Diabetes

DKA with a serious metabolic acidosis

(pH

6,97; pCO₂

8 mmHg; pO₂

mellitus resulted as a major comorbidity in patient with sepsis.

106 mmHg; HCO₃ 3 mmol/l; lactates 31 mg/dl), she was transferred to IntCU,

DOI: 10.1530/endoabs.49.EP571

where she was treated with fluids and insulin, with good posterior metabolic

control. In both cases, the patients presented had the DM diagnosis, being treated

accordingly at home. Although, after being admitted for an unrelated reason, it

was neglected all DM control as well as the symptoms that came from its

decompensation, ending in an extremely serious state. This reinforces the need of

EP572

approaching each patient with all its conditions, reassuring the essential role of

The prevalence of chronic kidney disease and albuminuria in patients

Internal Medicine in management and orientation of these patients since their

with Type 1 and Type 2 diabetes attending a single centre

admission.

MS Majeed, G Boran, LA Behan, M Sherlock & J Gibney

DOI: 10.1530/endoabs.49.EP573

Departments of Endocrinology1, and Chemical Pathology 2, The Adelaide

and Meath Hospital, Incorporating the National Children’s Hospital,

Tallaght, Dublin 24, Dublin, Ireland.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP574

deplete and often have minimal symptoms. Cautious administration of fluid

boluses with monitoring is recommended in the presence of intravascular volume

Characteristics of patients with cystic fibrosis and hydrocarbon

depletion. Rarely, DKA can cause pulmonary oedema in these patients due to

alteration in an adult unit

interstitial hypertonicity from hyperglycaemia, which often responds to insulin

Elena Fernández González, Nerea Aguirre Moreno, Layla Diab Cáceres,

treatment alone. If there is inadequate response to maximal medical therapy,

Carmen Acosta Gutiérrez, Ana Ramos-Leví, Miguel Sampedro Nu

˜ ez,

earlier haemodialysis is warranted.

Isabel Huguet Moreno, Mónica Marazuela Azpiroz, Rosa María

Conclusion

Girón Moreno & Alfonso Arranz Martín

Aggressive intravenous fluid resuscitation is a key treatment for DKA. However,

Hospital Universitario La Princesa, Madrid, Spain.

cautious fluid administration should be considered in dialysis-dependent patients.

DOI: 10.1530/endoabs.49.EP575

Introduction

Hydrocarbon Alteration (HA) is considered as the most common complication in

Cystic Fibrosis (CF) and is related to a further deterioration of the lung function

and the nutritional status.

Objective

Analyze the prevalence of HA in patients with CF in an adult unit and its

relationship with pulmonary complications.

EP576

Material and methods

Severe diabetic gastroparesis - two cases of challenging treatment

We conducted a retrospective study with 71 patients of our CF unit (age 30C/K9

Pedro Souteiro^1,2, Sofia Castro Oliveira^1,2, Joa˜o Sérgio Neves1,2,

years, 50.5% women, BMI 22.2C/K3.8 kg/m² and CF evolution 22C/K9 years).

João Santos-Antunes², Rita Bettencourt-Silva^1,2, Sandra Belo^1,2,

Patients were classified, according to the glycaemic response to oral glucose

Celestino Neves^1,2, Paula Freitas^1,2, Joana Queirós¹, César Esteves^1,2 &

overload, in 3 categories: normal glucose tolerance (NGT, 31%), pre-diabetes

Davide Carvalho^1,2

(preDM, 29.6%) and diabetes (CFRD, 39.4%). The analysis included the variables:

¹Department of Endocrinology, Diabetes and Metabolism, Porto, Portugal;

age, sex, BMI, lung function, chronic bronchial infection, pulmonary exacer-

²Faculty of Medicine of University of Porto, Porto, Portugal.

bations and its degree of severity.

32.4% of the patients received some

hypoglycaemic treatment (78.6% of them were CFDR): 32% were under bolo-

basal insulin, 28% basal insulin, 16% oral drugs and 24% other treatments.

Introduction

Statistical analysis was performed with STATAv12.0.

Gastroparesis is defined by a delayed gastric emptying without mechanical

Results

obstruction. It can be a debilitating complication of diabetes that is poorly

Lower BMI was observed when comparing patients with CFRD (20.65C/K

understood and has limited therapeutic options.

0.6 kg/m²) and preDM (23.72C/K0.7 kg/m²) (PZ0.005); and a tendency was

Case reports

noticed between CFRD and NTG

(22.64C/K0.6 kg/m²)

(PZ0.1). CFRD

1st case - We report the case of a 34-year-old woman with type 1 diabetes mellitus

patients showed greater frequency of severe pulmonary exacerbations than

(T1DM) with diabetic nephropathy and gastroparesis, and a reasonable glycaemic

preDM (PZ0.016). Higher colonization prevalence by Staphylococcus aureus

control (haemoglobin A1c 6.9%) on insulin-pump regimen. Gastric emptying

meticilin-resistant

(MRSA) (NTG 4.54%, preDM 9.5%, CRFQ 17.86%) and

scan revealed 100% contrast retention 2 hours after its ingestion, confirming

Achromobacter xylosoxidans (NTG 4.54%, 19.05% preDM, DRFQ 21.43%) was

severe gastroparesis. Repeated vomiting, refractory to oral anti-emetics, led to her

observed. This trend was not noticed for Staphylococcus multisensible aureus,

hospitalization 8 times in one year in a total of 109 days. She also underwent a

Pseudomonas aeruginosa, and Haemophilus influenzae.

medical pregnancy interruption due to hyperemesis gravidarum. Due to difficult

Conclusions

management of vomits the patient underwent a gastric peroral endoscopic

HA is frequent among our CF patients. Lower BMI is associated with higher

pyloromyotomy (G-POEM). After the procedure she had pronounced sympto-

degree of HA. CFRD patients show more frequent severe pulmonary

matic improvement and reduced need of hospitalization (only 10 days in the

exacerbations and higher prevalence of infections by MRSA and Achromobacter

6 months of follow-up). The post-procedure scan showed a near-normal gastric

xylosoxidans. This reinforces the importance of adequate nutritional and

emptying (52% contrast retention at 2 hours).

endocrine control as well as the need to a multidisciplinary approach for the

2nd case - A 23-year-old woman with T1DM with diabetic gastroparesis with no

treatment of CF patients.

other end-organ damage. She presented a poor glycaemic control with a

DOI: 10.1530/endoabs.49.EP574

haemoglobin A1c of 10.3%. Gastric scan revealed severe retention with a half-

emptying time of 862.6 minutes (normal time of 80G20). She was severely

disabled by vomit episodes that required frequent and prolonged hospitalization

periods. She also underwent G-POEM with fair symptomatic improvement and

reduced need of hospitalization during her follow-up despite post-procedure

gastric scanning still showed a delayed gastric emptying (93% retention at

2 hours).

Conclusions

EP575

Diabetic gastroparesis presents a challenging treatment since medical therapy has

Management of diabetic ketoacidosis in haemodialysis patient

disappointing results in some patients. In those cases, endoscopic procedures can

Heidy Hendra, Hannah Stacey & Sumith Abeygunasekara

lead to symptomatic relief and enhanced quality of life obviating the need of more

Broomfield Hospital, Chelmsford, UK.

aggressive alternatives like gastrectomy.

DOI: 10.1530/endoabs.49.EP576

Introduction

Diabetes mellitus is the commonest cause of chronic kidney disease leading to

end-stage renal failure (ESRF). Fluid replacement is one of the cornerstone

treatments of DKA, however anuric dialysis patients are at risk of fluid overload.

Information for managing DKA in haemodialysis patients is relatively sparse.

Case report

A 76-year-old gentleman with type 1 diabetes was admitted with drowsiness. He

EP577

has twice weekly dialysis and on 700 ml/day fluid restriction. Due to recurrent

Predictors of in-hospital mortality in diabetic patients - analysis of

episodes of hypoglycaemia, his insulin dose was reduced. On examination he had

958305 hospitalizations

dry mucous membranes, cool peripheries and erythematous left below knee

Magdalena Walicka¹, Monika Puzianowska-Kuznicka^2,3, Marcin Chlebus⁴,

amputation stump. Blood pressure was 92/50 mmHg. Blood gas showed pH 7.17,

Andrzej Sliwczynski⁵, Melania Brzozowska⁵, Daniel Rutjowski⁵,

HCO_- 13.2, glucose level 35 and ketones of 6 mmol/l. He was diagnosed with

Lidia Kania^1,2, Marcin Czech⁶, Andrzej Jacyna⁵ & Edward Franek^1,2

DKA precipitated by inadequate insulin administration and stump infection. He

¹Department of Internal Diseases, Endocrinology and Diabetology, Central

was commenced on fixed rate insulin infusion (FRII) and antibiotics. In total he

Clinical Hospital of the Ministry of the Interior and Administration,

received 1 litre of fluid. He continued his scheduled haemodialysis sessions.

Warsaw, Poland;²Department of Human Epigenetics, Mossakowski

Discussion

Medical Research Centre, Warsaw, Poland;³Department of Geriatrics and

Currently there are no studies available which assess the treatment of DKA in

Gerontology, Medical Centre of Postgraduate Education, Warsaw, Poland;

dialysis-dependent patients. DKA is uncommon in these patients as ESRF leads to

⁴Department of Quantitative Finance, Faculty of Economic Sciences,

improved glycaemic control due to reduced kidney gluconeogenesis, less insulin

University of Warsaw, Warsaw, Poland;⁵National Health Found, Warsaw,

clearance and improved insulin sensitivity. Anuric dialysis patients do not have

Poland;⁶Warsaw University of Technology, Business School, Warsaw,

glycosuria and osmotic diuresis, therefore they are less likely to be volume

Poland.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

Diabetes Therapy

Diabetes mellitus is a lifelong chronic disease with higher risk of mortality and

EP579

morbidity

A modelling approach for cost-savings in the elderly ontarian

Objective

population with type 2 diabetes due to reduction in mild hypoglycemia

To study the risk factors of death in hospitalized diabetic patients

events for SGLT-2 inhibitor versus sulfonylurea (SU) initiation after

Methods

metformin

Data obtained from the database of the National Health Fund (NHF), a public

Pendar Farahani

organization financing medical procedures in Poland regarded

958305

McMaster University, Hamilton, Ontario, Canada.

hospitalizations of adult (R18 years old) patients with diabetes in 2014 year.

Logistic regression models were performed to identity independent predictors of

in-hospital mortality.

Background

Results

Mild hypoglycemia in elderly is associated with significant chronic consequences

There were 573719 hospitalizations in non-surgical wards and 384586 in surgical

leading to physical and cognitive dysfunction and eventually frailty and

wards. The mean in-hospital mortality rate was 3,20% (4,52% in non-surgical and

disability. Mild hypoglycemia appears to be under-recognized in real-world

1,23% in surgical wards). In non-surgical wards, odds ratio for in-hospital death

clinical settings in the elderly and can lead to significant costs for patients.

increased with patients age, being 52-fold higher in the R95 years old group

Objective

compared to the 18-24 years age group; male gender, emergency admission,

To calculate cost-savings due to mild hypoglycemia reduction for SGLT-2

admission on weekend or other non-working day, hospitalization in county/town,

inhibitor versus SU initiation after metformin for elderly Ontarians with type 2

private or regional hospital (vs teaching hospital), were factors associated with

diabetes.

greater mortality. In surgical wards odds ratio for in-hospital death started to

Methods

increase after 75th year of life, being 13-fold higher in the R95 years old group

An economic model was calculated incorporating data from RCTs on SGLT2I for

compared to the 18-24 years age group; female gender, emergency admission,

mild hypoglycemia. Data on prevalence of type 2 diabetes and SU utilization for

admission on weekend or other non-working day, hospitalization in county/town

elderly in Ontario were obtained from published data from Institute for Clinical

or regional hospital (vs teaching hospital), were factors associated with greater

Evaluative Sciences

(ICES). Costs per event for mild hypoglycemia were

mortality.

obtained from published studies.

Conclusions

Results

Predictors of in-hospital mortality in patients with diabetes are age, sex, type of

With assumption of only one mild hypoglycemia during the first year of SU

hospital admission, admission on non-working day and type of hospital.

versus SGLT2 inhibitor initiation as add-on to metformin for the elderly Ontarian

DOI: 10.1530/endoabs.49.EP577

population with type 2 diabetes, the total cost from the patients’ perspective

would lead to an annual cost-savings of CDN $2 066 224 due to less cost for mild

hypoglycemia episodes treatment. Sensitivity analysis resulted in a minimum

annual cost-savings of CDN $691 048 and a maximum annual cost-savings of

CDN $8 402 373 for SGLT-2 inhibitor versus SU initiation after metformin due

to mild hypoglycemia reduction for the Canadian population with type 2 diabetes.

Conclusion

This study illustrates that reduction in mild hypoglycemia episodes (which mostly

are not reported in real-world clinical settings) due to SGLT2I utilization instead

of SU in elderly Ontarian with type 2 diabetes can lead to a significant cost-

savings from patients’ perspective.

EP578

DOI: 10.1530/endoabs.49.EP579

Gestacional diabetes mellitus: 4 years study case at a tertiary level

maternity hospital

Francisco Evora, Marta Pinto & Céu Almeida

Bissaya Barreto Maternity - CHUC, Coimbra, Portugal.

Introduction

EP580

Gestational diabetes mellitus (GDM) is a carbohydrate intolerance with onset or

recognition during pregnancy. Timely screening and proper management of this

Do adding B vitamins and folate to metformin has beneficial effect on

condition is essencial to maximize pregnancy and neonatal outcomes.

renal function and lipids in type 2 diabetic patients

Methods

Marina Shargorodsky & Elena Omelchenko

Retrospective analysis of all cases of GDM, and the respective new-borns,

Wolfson Medical Center and Tel Aviv university, Holon, Israel.

followed in our obstetrics unit between 2012 and 2015. Clinical and workup

parameters were evaluated.

Introduction

Results

Metformin is effective in reducing cardiovascular mortality, however may

From a total of 644 cases of GDM, median age was 33, median BMI was 27

decrease vitamin B12 and folate levels, and increase levels of homocysteine.

(overweight/pre-obese) and the most common academic qualifications was a

Hyperhomocysteinemia is associated with adverse impact on lipid parameters and

licentiate degree (13 years of school). In terms of risk factors, 51% had a family

renal function. The present study was designed to determine the effect of

history of DM and a personal history of: GDM (11%), macrossomia (4%),

homocysteine lowering therapy by using group B vitamins and folate

hydramnios (3%), fetal malformations (5%) and fetal death (0.3%). With respect

supplementations on lipid metabolism especially HDL cholesterol as well as

to pregnancy and maternal complications we verified that 7% had hypertension

kidney function assessed by serum creatinine, urine microalbumin (MA), albumin

diagnosis during pregnancy, 4% had one or more urinary tract infection and 11%

creatinin ratio (MaCR) and GFR in diabetic patients treated with high doses of

had preterm birth. The labour was induced in 36% of the times, and we had a 37%

metformin.

caesarean rate, 20% of dystocic deliveries and an eutocic delivery in 43%.

Methods

Neonatal outcomes consisted of a morbidity rate of 22% and 0.5% mortality rate

In a randomized, placebo-controlled study, 60 diabetic patients treated with a high

(3 cases). Pharmacological management was necessary in 38% (35% insulin vs

dose of metformin were randomly assigned to receive daily oral supplementation

3% metformin).

with folate (1000 mcg), vitamins B12 (400 mcg) and B6 (10 mg) (Group 1) or

Conclusions

placebo (Group 2). Metabolic parameters were measured at baseline and after

There is no denying that GDM is increasing worldwide. From an obstetric

4 months folow-up.

perspective this is probably related with the increased mother weight (obesity

Results

epidemic) and the delayed age for the first pregnancy (social motives), which are

The two groups were similar at baseline in terms of metabolic parameters. After

represent at our casuistic. Not long ago, GDM management was a dichotomy that

4-months, HDL cholesterol was significantly greater in patients who received

consisted of lifestyle changes (diet and physical exercise) or insulin therapy.

vitamin supplementation than patients in the placebo group (P!0.0001). Post-

Nowadays, for selective cases we can also add to our therapeutic arsenal

treatment vitamin B12 and folic acid levels were greater in group 1 vs group 2

metformin, which was contraindicated in the past. At our maternity the metformin

(PZ0.007 and P!0.0001, respectively). Hcy level decreased significantly in the

therapy was implemented in 17 cases on 2014 and 2015, translating this new

treatment group from 10.0G4.4 to 7.6G2.5 mol/l, PZ0.002 and did not change

tendency.

in the placebo group

(PZ0.964). In GLM model, group was significant

DOI: 10.1530/endoabs.49.EP578

independent predictor of endpoint HDL choleserol

(PZ0.018), while post-

treatment LDL cholesterol did not differ by group after controlling for the other

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

variables in the model (PZ0.158). Posttreatment GFR was significantly greater in

EP583

patients who received vitamin supplementation than patients in the placebo group

Hypoglycemia, weight changes and health related quality of life

(P!0.003). Plasma creatinine, urine protein and urine microalbumin did not

(HRQoL) instruments for diabetes care

differ significantly by treatment group at baseline at the end of the study.

Carolyn Akladious¹ & Pendar Farahani²

Nevertheless, within the vitamin -treated group, MaCR dcreased from baseline

¹St. George’s University of London, London, UK;²McMaster Univerity,

(P!0.036) and did not change in the placebo group.

Hamilton, Ontario, Canada.

Conclusion

Adding B vitamins and folate supplementations to metformin was associated with

beneficial effects on HDL cholesterol and renal function in diabetic patients.

Background

DOI: 10.1530/endoabs.49.EP580

Diabetes is a chronic disease with significant negative impact on quality of life.

Hypoglycemia and weight gain are two important variables that can impact

HRQoL negatively in patients with diabetes under treatment with medication.

Objective

The objective of this study was to evaluate HRQoL tools and questionnaires and

to explore if the HRQoL instruments address issues related to hypoglycemia and

weight gain, which impact HRQoL along other domains.

Methods

EP581

A systematic review was conducted utilizing databases on PubMed, Google and

The role of sodium-glucose co-transporter 2 inhibitors as add-on

Google Scholar to find HRQoL tools that have been utilized in diabetes care. The

therapy in type 2 diabetes

tools in English language were selected. The construct of the HRQoL tools were

Maria Hayon Ponce¹, David Blánquez Martínez², Maria Jose

analysed by the domains.

Jiménez Jiménez¹, Rossana Sofía Manzanares Cordova¹, Maria del Carmen

Results

Serrano Laguna¹, Miguel Quesada Charneco¹ & Martin Lopez de la

In general, three types of HRQoL tools and questionnaires have been utilized in

Torre Casares¹

diabetes care (total NZ84): diabetes specific (NZ27), domain specific (NZ33)

¹UGG Endocrinología y Nutrición, Complejo Hospitalario Universitario de

and general HRQoL (NZ24). 9.5% (NZ8) and 2.5% (NZ2) of tools had domains

Granada, Granada, Spain;²Farmacia Hospitalaria, Complejo Hospitalario

for hypoglycemia or weight changes, respectively. None of the tools had both

Universitario de Granada, Granada, Spain.

domains, simultaneously. 88% (NZ74) of tools had no domain for hypoglycemia

or weight changes.

Objective

Conclusion

SGLT2 inhibitors, have been shown to improve glycaemic control, stabilize

This study illustrated that few HRQoL instruments incorporated domains related

insulin dosing and mitigate insulin-associated weight gain in patients whose type

to hypoglycemia and weight gain. This calls for developing more comprehensive

2 diabetes mellitus (T2DM) was inadequately controlled. The objective is to

HRQoL instruments to measure the impact of hypoglycemia and weight gain on

evaluate the real-world efficacy and safety of adding iSGLT-2

therapy in

quality of life of patient with diabetes on pharmacotherapy. Addressing such an

inadequately controlled patients with oral antidiabetic drugs and with or without

issue is very timely, in light of recent utilization of newer classes of medications

insulin therapy.

in diabetes care such as SGLT2I and GLP1A which have safer glycemic profile

and cause weight loss.

Materials and methods

This observational study assessed the efficacy and safety of SGLT-2 inhibitors

DOI: 10.1530/endoabs.49.EP583

used as add-on therapy in a group of 45 T2DM patients from a community

endocrinology practice from January 2015 to April 2016. Primary endpoint was

HbA1c mean change from baseline at 15 months. Secondary endpoints included

change in body weight,other glycaemic parameters,and percentage of patients

reporting adverse effects of therapy.

Results

A total of 45 patients met all the study criteria. 60% with oral antidiabetic drugs,

EP584

11.1% with oral antidiabetic drugs and basal insulin regimens, 11.11% with basal-

Use of an innovative Technology Enabled Care service (TECS)

bolus insulin therapy and 17.8% with oral antidiabetic drugs and basal-bolus

‘Florence’ to empower patients and enhance adherence to BP

insulin therapy.Baseline patient characteristics were as follows: average age,

treatments in diabetes

60.2G9.7 years; mean duration of T2DM, 11.3G8.3 years; 80% male; baseline

Susan Irwin & Parijat De

body mass index (BMI), 32.76G4.96 kg/m²; mean baseline HbA1c, 9.17G

Sandwell & West Birmingham NHS Trust, Birmingham, UK.

2.02%;systolic BP 143.67G15.46 mmHg and diastolic BP 80.44G10.16 mmHg.

Mean duration of SGLT2 inhibitors 7.42G4.22 months. HbA1c and weight were

significantly reduced by 1.36G1.79%, P ! 0.000 and 3.21G3.52 kg, P ! 0.000,

Background

respectively; systolic BP (12.91G10.57 mmHg, P !0.000), diastolic BP (6.39G

Social deprivation is high within our large ethnic and diabetes prevalent

7.34 mmHg P! 0.000) and triglycerides (45.58G115.65 mg/dl, P ! 0.011).

population. Compliance is a major stumbling block in the achievement of Blood

Genital- and urinary tract infections were reported by 6.7% patients.Any diabetic

Pressure (BP) targets. Given the above, we took the opportunity to enrol with

ketoacidosis case was reported.

West Midlands Academic Health Science Network (WMAHSN) Florence (Flo)

Conclusion

Exemplar project mobile phone texting service. Flo sends advice and collects

SGLT-2 Inhibitors added to other oral antidiabetic drugs or insulin in patients

patient information which clinicians can access through any device connected to

with uncontrolled T2DM significantly improved glycemic control, reduced

the internet.

weight, blood pressure and triglycerides,and was generally well tolerated.In

Aims

conclusion, SGLT-2

inhibitors,appears to be an important addition to the

Our aims were to improve adherence to BP treatment via engaging and motivating

therapeutic options for the management of type 2 diabetes, particularly when used

patients and determine the clinical and cost effectiveness of this simple

as add-on therapy.

Telemedicine model.

DOI: 10.1530/endoabs.49.EP581

Method and results

Of the 100 patients enrolled for BP management (April 2015-2016) from diabetes

renal clinics:

† BP medications adjusted in 27/100 (27%).

† 46/100 (46%) patients were discharged with good BP control following

medication adjustment.

Total outpatient attendances prevented: 107

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† 45 (for those we continue to follow up)

† 62 (for those discharged)

This has saved £11 663 (national average £109 per OP attendance) simply from

Abstract withdrawn.

non-face to face BP management against a total cost of £2329 assuming 75% of

the 107 patients have used the WMAHSN Hypertension CKD/diabetes protocol

for the full 12 weeks (364 texts/patient, cost per patient £29.12 for the service).

Conclusion

Flo’s use continues to grow and 5 new teams are ready to join in our Trust. Thus,

this clinically and cost effective model of care delivery

(with high patient

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

satisfaction) utilises manpower resources and healthcare professional time

Aim

effectively to improve outcomes and can be easily replicated in any NHS Trust

To analyze the effects of inositol administration on parameters related to glucose

or CCG.

homeostasis.

DOI: 10.1530/endoabs.49.EP584

Material and methods

Systematic review and meta-analysis of articles published in Medline or Web of

Science Until February 1, 2016. We included studies that met the following

criteria: i) Randomized controlled clinical trials of inositol/inositol isomer

supplementation against placebo in parallel design, ii) performed in humans, iii)

with information about glycemic control parameters and iv) published as full

article. The following parameters were considered: Fasting plasma glucose (FPG),

blood glucose at 2 h after an oral glucose tolerance test (OGTT), impaired oral

glucose tolerance, need for insulin treatment, body mass index

(BMI),

insulinemia, HOMA-IR and HbA1c. For the meta-analysis, Revman 5.1 software

EP585

with a random effects model was used.

The decreased adiponectin level after the treatment with glibenclamide

Results

is associated with deterioration of left ventricular function

The search retrieved 476 publications, of which 22 articles were finally included,

Merita Emini¹, Edmond Haliti², Nikica Car³, Luljeta Begolli⁴,

with a total of 1533 individuals. Treatment time ranged from 28 days to 12

Artan Ahmeti² & Gani Bajraktari²

months. Significant differences were observed in all parameters evaluated except

¹Clinic of Endocrinology, University Clinical Center of Kosovo, Prishtina,

in BMI, HbA1c and % of patients who needed treatment with insulin. Treatment

Kosovo;²Clinic of Cardiology, University Clinical Center of Kosovo,

with inositol decreased FPG (mean difference K0.44 mmol/l (K0.65, K0.23)),

Prishtina, Kosovo;³University Clinic of Diabetes, Endocrinology and

glycemia at 2 h of OGTT (mean difference K0.69 mmol/l (K1.14, K0.23)), % of

Metabolism ‘Vuk Vrhovac’, University Hospital ‘Merkur’, Zagreb, Croatia;

patients with impaired glucose tolerance

(relative risk

0.28

(0.12,

0.66)),

⁴Institut of Biochemistry, University Clinical Center of Kosovo, Prishtina,

insulinemia (mean difference K38.49 pmol/l (K52.63, K24.36)) and HOMA-IR

Kosovo.

(mean difference K1.96 mIU/l!mmol/L (K2.62, 1.30)). No relevant side effects

were observed in patients treated with inositol.

Conclusions

Background and aim

Inositol treatment improves glucose tolerance and insulin resistance by a

Hyperglycemia is an important pathogenetic factor, which causes abnormalities at

mechanism independent of body mass index.

the cardiac myocyte level, leading to structural and functional abnormalities and

diabetic cardiomyopathy (DCM). It has been proposed that DCM could also occur

DOI: 10.1530/endoabs.49.EP586

as a consequence of other metabolic alterations. Adiponectin concentration is

negatively associated with obesity, insulin resistance (IR), oxidative stress and

endothelial dysfunction. It can be considered as a predictive biomarker of IR and

cardiovascular risk. Treatment of diabetic patients with conventional sulfonylurea

such as glibenclamide has been reported to be associated with adverse

cardiovascular effects and a higher incidence of cardiovascular death. The aim

of this study was to assess the effect of glibenclamide on adiponectine level and its

impact on left ventricular function in type 2 diabetic patients.

Methods

This single-blind, prospective, randomized controlled study consists of 32 weeks

EP587

screening period and a 24-weeks treatment period with glibenclamide. From the

A rare pediatric presentation of type 1 diabetes mellitus with duchenne

167 patients screened, most of whom were treated for hypertension or with

muscular dystrophy - what to expect in the future?

metformin, 40 type 2 diabetic patients, were divided in two groups (glimepiride vs

Pascu-Gabara Elena-Iuliana¹, Arhire Amalia Ioana¹, Ioacara Sorin^1,2 &

glibenclamide) with a body mass index (BMI) O25 treated with glibenclamide

Fica Simona^1,2

for more than

months before screening were included in the study.

¹Elias University Emergency Hospital, Bucharest, Romania;²Carol Davila

Anthropometric, biochemical and echocardiographic measurements were

university of medicine and pharmacy, Bucharest, Romania.

performed before and at the end of treatment.

Results

In the glibenclamide group significant differences were observed in HbA1C

Introduction

which was decreased from 8.8%G1.4 to 8.3%G1.1% (P!0.001), and in the

Duchenne muscular dystrophy (DMD) is a genetic condition caused by mutations

other hand adiponectin was significanty decreased (from 34.3G22.6 to 20.3G

in the X-linked dystrophin-gene leading to muscle degeneration and early death in

11.3 ng/ml, PZ0.011). From echocardiographic measurements early diastolic

males.Since DMD is characterized by aggressive inflammation it is recommended

(e’) and systolic (s’) myocardial wall velocity of the septum (from 6.7G1.4 cm/s

the use of pharmacological treatment with corticosteroids (CS). Type-1 diabetes

to 5.6G1.5 cm/s, PZ0.04, and from 7.0G1.2 cm/s to 6.1G1.2 cm/s, PZ0.03,

mellitus (T1DM) is one of the most common chronic diseases in childhood and is

respectively); as well as right e’ and s’ (from 11.7G2.7 cm/s to 7.9G3.8 cm/s,

caused by insulin deficiency resulting from the autoimmune destruction of insulin

PZ0.01, and from 12.5G4.3 cm/s to 8.4G3.2 cm/s, PZ0.01, respectively) were

producing beta-cells of the pancreas.

decreased from baseline to the

24 weeks treatment. While DcT time was

Case presentation

significantly increased in the group of Glibenclamide, which can explain

We present the case of a 3-years-old male patient who was admitted in our clinic

worsening of diastolic dysfunction in diabetic patients treated with this drug.

for episodes of symptomatic hypoglycemia alternating with hyperglycemia. He

Conclusions

was diagnosed with T1DM and DMD 1-year prior his admission and had been on

The decreased adiponectine level after the treatment with glibenclamide is

Humulin-N and Humulin-R combination and Deflazacort 12mg/daily treatment

strongly associated with deterioration LV diastolic and systolic function, in type 2

ever since.His medical history includes upper respiratory tract infection remitted

diabetic patients. This finding highlights the need of further investigations of the

after bronchodilator and expectorant medication in the last month.Clinical

impact of metabolic disorders on cardiac function in diabetic patients, beyond

examination revealed short stature and overweight patient:heightZ90.9 cm

hyperglicemia.

(K2.71 SDS),

(5-th percentile); weightZ14 kg

(25-th percentile); BMIZ

DOI: 10.1530/endoabs.49.EP585

17.28 kg/m², (88-th percentile); pubertal stage-1 according to Tanner; hypotonic

muscular system, hypokinetic, normal thyroid palpation, language deficiency.

Lab tests revealed glycemic control with HbA1cZ7.8% (in target for age),

hepatic cytolysis

(ASTZ244 IU/l, ALTZ583 IU/l), euthyroidism

(TSHZ

3.95 uIU/ml). Funduscopic examination and thyroid ultrasound were normal.

During admission the patient is switched from multiple-dose-injection therapy

(MDI) to cutaneous-insulin-infusion therapy (CSII) with aspart, well tolerated;

basal rates, the correction factor and carbohydrates-ratio are set, followed by

glycemic profile evolving favorably. Considering the risks of untreated DMD and

EP586

the metabolic pathology association, the patient continues treatment with

Effects of inositol on glucose homeostasis: systematic review and

Deflazacort 12 mg/daily under multidisciplinary surveillance. Parents received

meta-analysis of randomized controlled trials

nutritional counseling.

Inka Min˜ ambres1, Gemma Cuixart1, Ana Gonçalves2 & Rosa Corcoy1

Conclusion

¹Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;²Centro Hospitalar

Possible endocrine complications of DMD with chronic CS treatment

Do Algarve, Algarve, Portugal.

consequences regarding growth failure, pubertal disorder due to hypogonadism,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

excessive weight gain, diabetes, especially in pediatric patients, and bone health

control by increasing the renal excretion of glucose. Vulvovaginal candidiasis

have not been explored in depth. Treating children can be challenging when

(VVC) is the infection of the vaginal vestibuler area. We present a case of VVC

having such rare presentation because there is a need for better comprehension of

accompanied by use of dapagliflozin.

metabolic and endocrine implications for DMD with the purpose of developing

Case

improved clinical treatments and/or quality of life.

A-48-year-old woman who had T2DM since 8 years was admitted to the

DOI: 10.1530/endoabs.49.EP587

endocrinology clinic. Her past medical history was remarkable for atopic

. She had been using metformin

dermatitis. Her body mass index was 33.7 kg/m²

and sulfonylurea. Her initial laboratory results were; fasting plasma glucose:

131 mg/dl, hemoglobin A1c: 7.8%. Dapagliflozin 10 mg daily therapy added to

her therapy. On the 12th day of dapagliflozin therapy she noted vulvovaginal

pruritus. Three days later she complained the severity of symptoms. Physical

examination revealed wide erythema on vulvar, vaginal and perineal regions of

genitourinary area. Positive vaginal culture for Candida albicans was detected.

She was diagnosed with VVC. The treatment of VVC was made through topical

clotrimazole. Three days later the clinical manifestations become worsened and

EP588

dapagliflozin was discontinued. Signs and symptoms of VV were regressed two

Significant effect of a group education program on glycemic control and

days later.

incidence of hypoglycemia in patients with diabetes mellitus type 1:

Summary

A case-controlled study

Vulvovaginitis is a frequently encountered acute and recurrent complication of

Zadalla Mouslech¹, Maria Somali², Sarantis Livadas⁵, Christos Daramilas²,

diabetes mellitus; tend to be worsened by poor glycemic control. Appropriate

Alexandra Chatzi³, Maria Papagianni³, George Mastorakos⁴,

diagnosis and management is essential to confirm optimal genital and metabolic

Christos Savopoulos¹ & Apostolos I. Hatzitolios¹

health. We consider that this case will be mostly useful among atopic patients who

¹1st Medical Propedeutic Department of Internal Medicine, AHEPA

have potential risk for VVC and drug withdrawal may be considered in such of

University Hospital, Aristotle University of Tessaloniki, Thessaloniki,

these patients.

Greece;²Endocrinology, Metabolism and Diabetes Unit, Euromedica

DOI: 10.1530/endoabs.49.EP589

General Clinic, Thessaloniki, Greece;³Endocrine Unit, 3rd Pediatric

Department, Aristotle University, Hippokration Hospital, Thessaloniki,

Greece;⁴Department of Endocrinology, Metabolism and Diabetes, Aretaeio

Hospital, School of Medicine, National and Kapodistrian University Athens,

Athens, Greece;⁵Endocrine Unit, Metropolitan Hospital, Athens, Greece.

DM1 constitutes a real challenge in everyday practice for both physicians

and patients. Due to the complexity of the disease and its unpredictable

nature, structured education and training programs are nowadays

EP590

implemented that ensure active patient involvement and self-care behaviors

to achieve adequate glycemic control, prevent diabetic complications and

Efficacy of body weight reduction on SGLT-2 inhibitor in people with

improve the quality of life of patients. These programs provide patients with

type 2 diabetes mellitus

the necessary knowledge and skills to self-monitor and self-manage the

Chong Hwa Kim¹, Hyun A Cho¹, Su Jin Jung¹, Ki Young Lee² &

disease and its associated metabolic conditions.

Sung Rae Kim³

Aims

¹Sejong General Hospital, Bucheon, Kyunggido, Republic of Korea;

To evaluate the effect of a structured 12-month education program that motivated

²Gacheon University Gil Hospital, Incheon, Republic of Korea;³The

patients to follow a healthy Mediterranean diet and exercise regularly as well as to

Catholic University of Korea Bucheon St. Mary’s Hospital, Bucheon,

adjust carbohydrate intake and insulin dose according to their needs.

Kyunggido, Republic of Korea.

Methods

The education group (EG) was comprised of 62 patients (45 males) with type 1

Objective

DM, mean age 36G4.2 years and BMI: 24.2G3.1 kg/m². An age- and BMI-

Dapagliflozin, sodium-glucose cotransporter-2

(SGLT-2) inhibitor, reduces

matched control group (CG, nZ25, mean age 41G6.4 years, BMI: 25.7G

hyperglycemia and body weight by inhibiting renal glucose reabsorption.

4.2 kg/m²) was composed of patients referred but not enrolled in the project.

However, only a few studies have shown the efficacy of dapagliflozin in type 2

Results

diabetic patients. We evaluated the efficacy and safety of body weight reduction

At the end of this program, HbA1C levels were significantly decreased (8.5G

of dapagliflozin in real practice with type 2 diabetes in Korea.

2.1%vs 7.08G0.79%, P!0.0001) as was also the incidence of hypoglycemic

Methods

episodes (P!0.05). Regarding daily glucose fluctuations, significant improve-

This is a retrospective, observational study, data from 61 patients with 12 months

ment (P!0.05) was observed, as reflected in low, high and daily median glucose

of dapagliflozin (10 mg once-daily) therapy were analyzed, visited medical center

values. On the other hand, the above parameters remained stable in the CG.

from January 2015 to July 2016. We had divided into three treatment groups: first

Conclusions

group taking combination of dapagliflozin and metformin (Group 1); second

These results strongly support the need for long-lasting structured education

group taking triple combination of dapagliflozin and metformin with sulfonylurea

group courses in adult diabetic patients keen to change their habits in order to

or dipeptidyl-peptidase IV (DPP-4) inhibitors (Group 2); third group taking

achieve self-management of the disease.

quadriple combination of dapagliflozin, metformin and sulfonylurea with DPP-4

DOI: 10.1530/endoabs.49.EP588

inhibitors (Group 3).

Results

After 12 months, mean change from baseline body weight was K3.4G2.6 kg

(P!0.001) for total, K3.4G3.1 kg (P!0.001) for group 1, K2.7G2.0 kg

(PZ0.008) for group 2, K4.0G2.3 kg (P!0.001) for group 3. In total, mean

change from baseline SBP and DBP were K6.0G14 mmHg (PZ0.001) and

K3.4G7.7 mmHg (PZ0.002) respectively. Patients who achieved body weight

reduction of R5% after 12 months were classified in the responder group and!

5% non-responder group. There were baseline fasting C-peptide level was higher

EP589

in responder group than non-responder group (3.25G1.07 ng/ml vs. 2.62G

Dapagliflozin induced vulvovaginitis in an atopic patient with type 2

1.02 ng/ml, PZ0.023). In total, reductions in HbA1c and PP2 glucose levels were

diabetes mellitus

K0.61G0.82% (P!0.001) and K35.4G62 mg/dl (P!0.001) respectively.

Narin Nasiroglu Imga, Merve Catak & Dilek Berker

There were no serious adverse event including hypoglycemia in dapagliflozin

Ankara Numune Education and Research Hospital Department of

group.

Endocrinology and Metabolism, Ankara, Turkey.

Conclusions

In patients with type 2 diabetes, SGLT-2 inhibitor improved glycemic control and

Introduction

reduced body weight reduction with safety of dapagliflozin.

Dapagliflozin is sodium-glucose co-transporter receptor 2 (SGLT2) inhibitor that

DOI: 10.1530/endoabs.49.EP590

is recently discovered an oral antidiabetic (OAD) agent that improves glycemic

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP591

Results

107 of approximately 215 (49.7%) women completed the questionnaire. 83%

Modification of lifestyle and influence on leptin and insulin resistance to

were aware of risks related to DM in pregnancy. However, the majority of women

prevent type 2 diabetes mellitus

(74%) had not received preconception counselling. The main source of

Shishko Elena & Mokhort Elena

information regarding contraception was the general practitioner (70%). Most

Belarusian State Medical University, Minsk, Belarus.

women (78%) believed combined oral contraceptive pills (COCPs) were safe in

DM. 63% of women were uncertain of the safety of intra-uterine devices (IUDs)

The aim of the present study was to determine the change of fasting serum leptin

in DM and 44% were uncertain of contraceptive implant (CI) safety. The main

and insulin levels and insulin resistance in patients with risk factors of diabetes

forms of contraception ever used were condoms (87%) and COCPs (74%), with

mellitus of type 2 (DM 2) including impaired glucose tolerance/impaired fasting

34% using long-acting reversible contraception (LARC) of IUDs and CIs. 29% of

glucose (IGT/IFG), obese and first-degree relatives of patients with diabetes after

sexually active women were not using any contraception or planning pregnancy.

lifestyle modification.

Amongst 110 pregnancies in 47 women there were 78 (71%) live births, 4 (4%)

Material and methods

stillbirths,

(15%) miscarriages, 2 (2%) ectopic pregnancies and 10 (9%)

The study included 100 patients (32 men, 68 female) 25-65 years old at risk

terminations.

factors of DM 2. All patients received recommendations on a balanced diet and

Conclusion

physical activity. The average fasting plasma glucose (FPG), 2-h plasma glucose

Despite knowledge of pregnancy risks, preconception counselling is lacking and

concentrations (2-h PG) following a 75-g oral glucose tolerance test, HbA1c,

pregnancy outcomes poor. There was uncertainty regarding safety of LARC, the

index HOMA-IR. Fasting serum leptin and insulin levels were detected by

most reliable contraceptive methods and over a quarter of women used no

sensitive ELISA.

contraception. Better education of women with DM regarding contraception and

Results

preconception planning is needed.

During 18 months our study 56 patients carried out this recommendations

DOI: 10.1530/endoabs.49.EP592

(research group) and 44 patients did not (control group). Patients of the research

group demonstrated mean reduction of body mass index (K2.6G0.4 kg/m²) and

waist-to-hip ratio (K0.2G0.01) (P!0.01) and persons of the control group had

significant increase of these parameters (P!0.05). Among subjects with IGT/IFG

at baseline, glucose levels normalized in 56.0% of patients from the research

group and 4.5% in control group (P!0.001). Fasting serum insulin and HOMA-

IR in research group decreased from 11.9G4.3 to 9.6G4.5 mU/ml and from 3.6G

1.1 to 2.7G1.4 accordingly (P!0.05). In control group the specified parameters

had increased significantly (P!0.01). The main novel finding was that serum

leptin median in research group was decreased from 34.7 to 26.4 ng/ml (K23.9%,

P!0.001) and increased in control group from 37.9 to 44.7 ng/ml (C17.9%,

P!0.01). The risk reduction of DM 2 development among patients of the

EP593

research group was 48.0% compared to the control group.

Management and control of hospital hyperglycemia in the health area of

Conclusion

Thereby, lifestyle modification can prevent the development of type 2 diabetes in

cuenca (Spain)

subjects with risk factors by reduction leptin and insulin resistance.

José Pérez-Rodríguez, Paula García-Notario, David Martín-Iglesias,

Lidia Guerra-Navarro, Mubarak Alramadan, Santiago Aranda-Regules &

DOI: 10.1530/endoabs.49.EP591

Dulce Calderón-Vicente

Virgen de la Luz Hospital, Cuenca, Spain.

Introduction and objectives

Hyperglycemia is a common problem in hospitalized patients that increases

infections, mortality, costs and the hospital stay. The objective of this study is to

know the management and control of hyperglycemia in our hospital.

Methods

We designed a cross-sectional observational study. We included patients admitted

in the hospital every three days in two months. We excluded patients younger than

15 years, stays less than three days and those of the pediatric, gynecological,

EP592

emergency and intensive care services. We collected the data from these patients

Australian women with diabetes survey of contraceptive use and beliefs

the third day of admission and at discharge. We defined hyperglycemia as two or

about safety of contraceptive options

more capillary glucose values greater than 140 mg/dl.

Santhi Chalasani¹, Pinar Kozan^4,5, Rickie Myszka², Kirsten Black^1,3,

Results

Kris Park² & Emily Hibbert^1,2

A total of 328 patients were included. 109 patients had hyperglycemia and 85

¹University of Sydney- Sydney Medical School Nepean and Central,

were known diabetics. Diabetic patients had the next previous treatments: only

Sydney, Australia;²Nepean Hospital, Kingswood, Australia;³Royal Prince

oral antidiabetic agents (55.3%), insulin (38.8%), and without treatment (5.9%).

Alfred Hospital, Sydney, Australia;⁴Garvan Institute of Medical Research,

During admission 48.5% were treated with insulin sliding scales, 19.2% with

Sydney, Australia;⁵University of New South Wales- St Vincent’s Clinical

insulin bolus-basal regimen, 12.1% with basal insulin, 7.1% with premixed

School, Sydney, Australia.

insulin,

2% with only antidiabetic agents and 11.1% without treatment. The

glycemic control during admission was considered good in 25% (mean glycemia

!140 mg/dl), regular in 45% (140-200 mg/dl) and bad in 29% (O200 mg/dl).

Introduction

Hypoglycemia was diagnosed in 12.5% (2.1% severe). Only 23% patients had a

Women with diabetes mellitus (DM) are at increased risk of adverse maternal and

recent HbA1c, with a mean HbA1c of 7.37G1.4%. When the patients discharge

foetal outcomes. Preconception planning is required to minimize risks, including

from hospital, the antidiabetic treatment for home was not adequately adjusted in

good understanding of contraceptive options.

47.4%.

Objectives

Conclusions

To determine in Australian women with DM beliefs regarding safety of various

A high percentage of diabetic patients are still treated with insulin sliding scales

contraceptive methods in DM, information sources regarding contraception,

during hospitalization. Few patients have a good glycemic control. Most of

recent and previous contraceptive use, knowledge of pregnancy risks, access to

patients hadn’t a recent HbA1c. Finally, treatment is not adequately adjusted at

preconception planning and pregnancy history.

discharge in almost half of patients. That’s why, we believe it’s necessary to

Methods

create a multidisciplinary protocol to improve the management of the hospital

We conducted a cross-sectional 22 item structured questionnaire-based study of

hyperglycemia.

Australian women with DM (Type 1 or 2) aged 16-49 years attending Nepean

Hospital, a tertiary referral centre. Women were recruited via mail, at scheduled

DOI: 10.1530/endoabs.49.EP593

appointments or hospital admission.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP594

combined AG and AA genotype) of the COMT Val108/158Met achieved

significantly better HbA1c values compared to patients carrying GG genotype.

Impact of the insulin pump therapy on quality of life children and

Conclusions

adolescents with diabetes mellitus type 1

Our results showed that the presence of one or two A allele of the COMT

Nataliia Nikolaeva

Val108/158Met was associated with improved glycemic response, and with a

Saratov Medical Univesity, Saratov, Russia.

better response to insulin detemir therapy in T2DM patients.

DOI: 10.1530/endoabs.49.EP595

Objectives

To investigate the changes parameters of quality of life (QoL) in children and

adolescents with diabetes mellitus type 1 (T1DM), using different regimes insulin

therapy.

Research design and methods

Thirty patients with diabetes mellitus type 1, aged 5-18 years (mean 13.3G3.04

yr), with disease duration from 1 to 10 years (mean 5.4G3.4 yr) took part in

EP596

paired study. QoL was assessed with the PedsQL (Generic Core Scales and

A dramatic improvement in metabolic parameters and cutaneous

Diabetes Module, Russian version) at two time points: 1^st - during multiple daily

manifestations of insulin-resistance in a type 2 diabetic patient with

insulin injection (MDI); 2^d - after initiation continuous subcutaneous insulin

Congenital Generalized Lipodystrophy (Berardinelli-Seip Syndrome)

infusion (CSII). Data were analyzed in subgroups aged 5-7 yr, 8-12 yr, 13-18 yr.

treated with pioglitazone

Results

Carolina Chaves, Catarina Moniz, Bernardo Dias Pereira, Isabel Sousa,

Nevertheless, analysis demonstrated positive dynamic of QoL in patients after

João Anselmo & Rui César

initiation CSII. Treatment barriers decreased due to reduction of a number of

Hospital do Divino Espírito Santo, Ponta Delgada, Portugal.

injections (75.3 vs. 90.0 P!0.05) in preschool-age children. Patients at the age of

8-12 evaluated higher physical function (74.2 vs. 94.0, P!0.05) after initiation

CSII. In adolescent’s group social activity indicates improved (85.0 vs. 95.0,

Background

P!0.05). Further, they were less worried about long-term complications

Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a autosomal recessive

(70.0 vs. 85.0, P!0.05).

disorder with only up to 500 reported cases. It is characterized by generalized

Conclusions

absence of fat since birth and severe metabolic derangements such as insulin

Using of insulin pump therapy in children with T1DM allows to improve of

resistance, hyperglycemia and dyslipidemia. Diabetes mellitus generally

quality of life. Preschoolers get used to the necessary of insulin therapy easier,

develops during the second or third decade of life. This is a rare clinical

schoolchildren and adolescents have opportunity to increase the level of their

condition, with worldwide prevalence of 1 in 10 million people and incidence of

physical and social activity.

1:500.000 newborns/year in Portugal.

DOI: 10.1530/endoabs.49.EP594

Patient and methods

11-year-old caucasian boy was referred to the Pediatric Endocrinology

consultation because of fasting hyperglycemia detected during routine blood

tests. There was no history of polyuria, thirst or weight loss. He was medicated

with antihypertensive medication since

6-years-old. Physical examination

revealed a thin patient with acromegaloid features and severe acanthosis

nigricans involving the posterior cervical region, axillary and periumbilical

areas. Subcutaneous tissue atrophy was notoriously evident in the face, trunk and

EP595

limbs. Secondary sexual characteristics were compatible with stage V of

Efficacy of insulin detemir treatment in type 2 diabetes mellitus is

TANNER scale. Blood tests revealed hyperglycemia with hyperinsulinemia,

associated with a allele od the catechol o-methyltransferase

dyslipidemia, low leptin, HOMA_IR index indicating insulin resistance, alterations

polymorphism

in hepatic function suggesting fatty liver and all autoantibodies searched were

Tomislav Bozek¹, Antonela Blazekovic², Matea Nikolac Perkovic³,

negatives. Thyroid function, IGF-1 and Growth Hormone (GH) were within the

Kristina Gotovac², Lea Smircic-Duvnjak¹, Nela Pivac³ & Fran Borovecki³

normal range for age and sex. Abdominal ultrasounds revealed a hepatospleno-

¹Vuk Vrhovac University Clinic, Merkur University Hospital, Zagreb,

megaly.

Croatia;²Department for Functional Genomics, Center for Translational and

Results

Clinical Research, University of Zagreb School of Medicine, Zagreb,

The presumptive diagnosis of BSCL was admitted and the patient was started on

Croatia;³Division of Molecular Medicine, Rudjer Boskovic Institute,

metformin 1000 mg twice daily. Pioglitazone, 30 mg/day in two divided doses

Zagreb, Croatia.

was added three months later. After

18 months of treatment, glucose and

triglycerides levels were near normal, hepatic enzymes, liver echographic

features and cutaneous manifestation of insulin-resistance were improved. Leptin

Introduction

remained undetectable.

Growing evidence suggests that nutrients and hormonal signals converge and

Conclusion

directly act on brain centers, leading to changes in energy metabolism and stable

Early introduction of pioglitazone in diabetic patients with BSCL may

body weight over time. Catechol O-methyltransferase (COMT) is one of the

dramatically improve insulin resistance without relevant side effects.

major enzymes involved in catecholamine and estrogen degradation. There is a

Keywords: Lypodystrophty, Berardinelli-Seip Syndrome, Insulin-resistance

well-established association between the COMT Val108/158Met polymorphism

DOI: 10.1530/endoabs.49.EP596

and abdominal obesity, blood pressure increase and T2DM. Basal insulin detemir

besides a low pharmacodynamic coefficient of variability, exhibits anorexigenic

features, probably through a complex interplay of its effects on the CNS and on

the finely tuned efferent and afferent signals between muscle, brain, liver, renal

and adipose tissues.

Aims

To investigate the association of COMT Val108/158Met polymorphisms with

EP597

effectiveness of insulin detemir in achieving glucose control and body weight

Comparison of neonatal outcome in women with gestational diabetes on

control.

different pharmacoglogical agents dilevered at term

Methods

Tarik Elhadd¹, Sindu Jacob², Vincent Boama^2,3, Khaled Ashawesh¹,

Observational study included 185 T2DM patients inadequately controled with

Khaled Dukhan¹, Stephen Beer¹ & Hiba Satti²

premix insulin analogues, which were replaced with three doses of insulin aspart

¹Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar;

at mealtime and insulin detemir at bedtime that were followed for 52 weeks. After

²Department of Obstetrics, Alwakra Hospital, Hamad Medical Corporation,

DNA isolation from blood samples, genotyping of COMT Val108/158Met

Doha, Qatar;³Sidra Hospital and Research Centre, Doha, Qatar.

polymorphism (rs4680) was performed.

Results

The mean age of participants was 67.1G8.01 years, with a mean duration of

Objective

diabetes 16.1G5.9 years. HbA1c and fasting plasma glucose were significantly

Though many studies have looked at the neonatal outcomes in patients with

decreased after

weeks

(8.58% vs

7.78%,

11.7 mmol/l vs

8.7 mmol/l,

gestational diabetes on different medications, there is no consensus on the

respectively, P! 0.001). At the end of the follow up period, 28.1% of patients

preferred drug for initiation of therapy. We aim to compare the neonatal outcome

achieved HbA1c!7.0%. Insulin detemir had a significant weight sparing effect in

in a cohort of patients attending our service, to determine if one modality is

overweight patients. The most prominent finding was that A carriers

(the

superior to the other.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

Conclusion

This study is a prospective observational study from 1-07-2015 to 31-04-2016.

A 20 mg/day and its combination with Eslidine showed a good hypolipidemic

The data of all gestational diabetic patients referred to the Joint Diabetic Clinic, in

efficacy and tolerability in hyperlipidemic pts with CVD and type 2 DM. Addition

a local secondary Hospital, who required pharmacological intervention were

of Eslidine to statin therapy resulted in a more reduction in LDL-Ch and TG levels

entered into an excel spreadsheet. This included their antenatal, intrapartum and

and noticeably improved hepatic functional activity.

postnatal details. P values calculated with Student’s t-test. Statistical significance

DOI: 10.1530/endoabs.49.EP598

if P! 0.05.

Results

The total number of patients studied was 107. There were 58 patients (54%) who

were treated with Metformin only, their BMI at booking was 30 kg/m², average

HbA1c 5.69%. The average birth weight of the neonates of this group was

3287.78 g and there were 9 (15.51%) Neonatal ICU admissions. 17 patients were

commenced on insulin, thier HbA1c was 5.78% and their booking BMI was 32.

EP599

The average birth weight in this subgroup was 3409.24 g with 2 (11.76%) NICU

admissions. 32 (29.90%) of our patients required Metformin and insulin. Their

Pancreas transplantation: experience in a central hospital

Ana Cláudia Martins¹, Miguel Vasques¹, Paula Bogalho¹, Inês Aires²,

average weight at booking was 35, and thier HbA1c was 5.8%. In this subgroup,

Aníbal Ferreira², Francisco Remédio², Jorge Paulino³, Fernando Nolasco²,

the average birth weight was

3494.56 g with

5(15.62%) requiring NICU

Américo Martins³ & Ana Agapito¹

admission. The least birth weight was observed in the subgroup with Metformin

¹Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,

alone (54% of our patients), P!0.4. The subgroups with insulin showed a higher

Portugal;²Department of Nephrology, Centro Hospitalar Lisboa Central,

neonatal birth weight. The least NICU admissions were in the insulin only group.

Lisbon, Portugal;³Department of Surgery, Centro Hospitalar Lisboa

Discussion

Central, Lisbon, Portugal.

The least birth weight was observed in the subgroup with Metformin alone (54%

of our patients), with the subgroups with insulin showed a higher neonatal birth

weight. However, the least NICU admissions were seen in the insulin only group.

Introduction

Conclusion

Pancreas transplantation is an established treatment for selected patients with type

Whether the increase in birth weight seen in patients on insulin, is indicative of

1 diabetes mellitus (T1DM) and severe chronic kidney disease (CKD), reducing

uncontrolled blood sugars or due to the direct effect of insulin as shown in some

mortality and morbidity.

studies, requires further evaluation. Further analysis of the ongoing cohort is

Methods

needed before we can recommend any one mode of treatment as the preferred

We retrospectively reviewed the cases of pancreas transplantation performed at

choice in our setting.

our centre from 1-January-2011 to 30-June-2016.

DOI: 10.1530/endoabs.49.EP597

Results

In this period, 53 transplants were performed: 48 simultaneous pancreas-kidney

transplants and 5 pancreas after kidney. Age at time of transplantation was 38G7

years; 34 were male (64.2%). Patients had T1DM for an average of 26G8 years

(age at diagnosis:

12G5 years). All patients had severe CKD,

78.4% on

hemodialysis and 15.7% on peritoneal dialysis. Major postoperative compli-

cations occurred in 23 cases (43.4%): 8 infectious, 8 haemorrhagic, 7 thrombotic.

Pancreas graft survival was 86.7% at 1 year (39/45) and 83.3% after 2 years

(30/36). Kidney graft survival was 92.7% at 1 year (38/41) and 90.6% after

EP598

2 years (29/32). Graft failure ensued in 6 pancreatic grafts and 3 transplanted

The hypolipidemic and hepatoprotective efficacies of a fixed-dose

kidneys. There were 12 acute organ rejections (22.6%). Three patients died

combination of essential phospholipids with methionine (EPLCM)

(5.9%), 2 from infection, one from haemorrhagic shock. Patients had, on average,

during atorvastatin (A) therapy in hyperlipidemic patients with

2 hospital readmissions, mainly due to infection. Among those with preserved

cardiovascular diseases (CVD) and type 2 diabetes mellitus (DM)

pancreatic grafts, 93.2% are insulin-free. Over the last 2 years, compared to the

(OLYMP trial)

first

years, there were more transplants performed

(23

13), fewer

M G Bubnova, D M Aronov, Marina Bubnoa & David Aronov

postoperative complications (30.4% vs 61.5%) and higher 1-year pancreas graft

State Research Center of Preventive Medicine, Ministry of Health of the

survival rate (93.8% vs 69.2%). Young age at diagnosis of T1DM was negatively

Russian Federation, Moscow, Russia.

related to pancreas and kidney graft survival (P!0.05). Duration of dialysis and

coronary disease were negatively related to renal graft survival (P!0.05).

Conclusions

Objective

Patient and graft survival rates were similar to those described in literature. Better

Objective to study the hypolipidemic efficacy, hepatoprotective activity, and

outcomes observed in recent years reflect the experience acquired. Young age of

tolerance of the fixed-dose combination of essential phospholipids with

onset of T1DM, duration of dialysis and coronary disease may represent poor

methionine (EPLCM) - Eslidine in the combination therapy with A in patients

prognostic factors concerning graft function.

(pts) with cardiovascular diseases

(CVD) and type 2 DM who suffer from

hyperlipidemia (HL) in order to optimize their treatment in daily clinical practice.

DOI: 10.1530/endoabs.49.EP599

Subjects and methods

The trial enrolled 60 pts (mean age 58.1G4.5 years) with type 2 DM. All the pts

had essential hypertension, 84.8% were obese; 80% had increased echogenicity in

the liver and its enlargement, as evidenced by ultrasound study. The patients

received standard therapy appropriate for this disease, other than agents affecting

blood cholesterol (Ch) levels. After adherence to a hypolipidemic diet for 2

weeks, the pts were randomized to two groups: i) 30 pts received A in a dose of

EP600

20 mg/day; 2) 30 pts had the drug in the same dose in combination with Eslidine

Correlates of health-related quality of life in Bulgarian patients with

(EPLCM). The therapy duration was 12 weeks. The impact of therapy on lipid,

type 2 diabetes mellitus

lipoproteins, hepatic enzymes.

Georgi Levterov¹, Boryana Levterova² & Maria Orbetzova^2,3

Results

¹UMHAT Kaspela Ltd, Plovdiv, Bulgaria;²Medical University - Plovdiv,

After 12 weeks, the group of pts receiving A showed a significant reduction in the

Plovdiv, Bulgaria;³UMHAT St Georgi, Plovdiv, Bulgaria.

levels of total Ch by 42.4%, LDL-Ch by 44.9%, and TG by 45.4%; in the AC

Eslidine group, these indicators decreased by 37.8, 47.9, and 26.4%, respectively.

By the end of a course of therapy, the number of pts with LDL-Ch goals was 26.9

Background

and

36.4% in Groups

and

2, respectively. In the pts with significant

Diabetes mellitus (DM) is one of the greatest threats to global health and

hypercholesterolemia (LDL-Ch R4.2 mmol/l), the LDL-Ch decline was 46.9

development of the 21th Century worldwide. In Bulgaria, it affects 9.6% of

and 54.6% in those on A and ACEslidine, respectively (P!0.05); in the pts with

residents between ages 18-69 and has a profound impact on healthcare, economy

elevated TG levels

(1.7 mmol/l or higher), the fall was

36.2

and 47.2%,

and individuals. Diabetes and its complications are major causes of early death in

respectively (P!0.05). A caused a 47% increase in ALT activity (P!0.05),

our country - each year 4 125 women and 4 000 men die of diabetes-related

without exceeding the upper normal range. In the pts on therapy AC Eslidine, the

complication. Diabetes not only reduces patient’s physical wellbeing but also

activity of ALT was, on the contrary, unchanged, there was a significant decrease

compromises other aspects of Health-Related Quality of Life (HRQoL). The aim

in total bilirubin concentrations, glutamyl transpeptidase activity, and bile acid

of this study was to investigate the impact of demographic factors and glycaemic

levels.

control on quality of life in patients with type 2 diabetes.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Material and methods

hypoglycemia and improve glycemic control in clinical trials. However, in real

A cross-sectional survey was conducted in a sample of 540 adult patients under

practice we have few data in real practice.

secondary care. Respondents were recruited from nine randomly selected

Objective

outpatient endocrinology practices, 25% of all practices with contract to the

To compare the two ultralente insulin analogues in real practice. To analyze if

Regional Health Insurance Fund Plovdiv-second largest district in Bulgaria. The

they are cost effective.

survey was administered with disease-specific instrument ADDQoL -19.

Material and methods

Results

Observational study including patients with type 2 diabetes, referred to Diabetes

A total of 411 diabetic patients with average age of 59.9C11.6 years old

Day Hospital (DDH) to management diabetes in which we changed the basal

participated in this study. ‘Freedom to eat’ was the Audit of Diabetes-dependent

insulin regimen to Tresiba^w o Toujeo^w. We revised them 3-6 months from change.

Quality of Life domain with the greatest negative average weighted impact

Results

(K4.0, on a scale of K9 to 3). In univariate analyses, older age, female sex, low

123 patients were included (68.3% Toujeo^w vs 41.7% Tresiba^w). Mean age:

socioeconomic status, cardiovascular disease, microvascular complications,

52.60G19.67 years; _-58.5%. Most patients (83.7%) were with glargina basal

insulin use correlated with decreased quality of life.

insulin regimen. After 3 to 6 months from change in the insulin treatment, basal

Conclusion

blood glucose reduced significantly in both groups ((to average of 233.04G

Patients with type 2 diabetes have a substantially decreased HRQoL in association

87.80 mg/dl down from 132.39G66.03 mg/dl in Toujeo^w; P!0.001) and (to

with symptomatic complications. The data suggest that prevention of

238.44G86.28 mg/dl low from 143.11G66.90 mg/dl, in Tresiba^w; P!0.001)).

complications have the greatest potential to improve health-related quality of

We also observed a significant reduction in HbA1c levels ((average reduction in

life in type 2 diabetes.

Toujeo^w of 2.03G2.28%, P!0.001) and (average decrease of 1.19G1.46%, in

Keywords: Diabetes mellitus, Health-Related Quality of Life, ADDQoL-19,

Tresiba^w; P!0.001)). However, comparatively no differences in efficacy were

Bulgaria

found between groups (0.49G0.32%; PZ0.185). At the end of follow-up,

DOI: 10.1530/endoabs.49.EP600

the number of units of Toujeo^w increased an average of C5.08G18.55 UI

decreased an average of

(PZ0.014) while insulin requirements in Tresiba^w

K4.20 28G7.36 UI (P 0.001). With regard to the cost, an average cost of

436.84G252.57 V per person (Toujeo^w group) vs 601.82G419.61 V per person

(Tresiba^w group), (mean difference: 164.98 V, PZ0.027).

Conclusion

EP601

Both basal insulin analogues are effective in reducing basal glycemia and HbA1c.

Although there is an increase in insulin requirements when switching to Toujeo^w.

Effects of sitagliptin monotherapy on insulin resistance and immune

Potential economic savings are realized by using Toujeo^w instead of Tresiba^w.

functions in type 2 diabetic patients

Serdar Almacioglu¹, Ozen Oz Gul², Soner Cander² & Canan Ersoy²

DOI: 10.1530/endoabs.49.EP602

¹Department of Internal Medicine, Diyarbakir Gazi Yasargil Education and

Research Hospital, Bursa, Turkey;²Department of Endocrinology and

Metabolism, Uludag University Medical School, Bursa, Turkey.

Background

Sitagliptin, unlike the some major antihyperglycemic drugs, is not associated with

weight gain and has neutral effects on body weight. It is unclear whether

EP603

sitagliptin treatment alters immune functions and insulin resistance in people with

type 2 diabetes. The aim of the present study was to assess the effect of sitagliptin

Glycemic control and weight evolution in DM2 patients with

on insulin resistance and immune functions in patients with type 2 diabetes

canaglifozina

mellitus.

Lidia Urbón López de Linares, Cristina Crespo Soto, Concepción Terroba,

Methods

Sara Garrote, Marta Ventosa, Tomás Marín & Luis Cuellar

Twenty type 2 diabetic subjects were randomly assigned to receive sitagliptin

Hospital Rio Hortega, Valladolid, Spain.

(100 mg/day; nZ10) or medical nutrition therapy (MNT) (nZ10) for 12 weeks.

Changes in anthropometric variables, glycemic control, insulin resistance, lipid

In the late years ISGLT2 have became an usual choice to treat diabetes. The

parameters and immune functions were evaluated at baseline and following

inhibition of the sodium-glucose co transporters

(SLGT2) inhibits also the

12 weeks of treatment. T lymphocyte subgroups like as CD3, CD4, CD8 and

glucose reabsorption in the proximale tubule and increases the glucose excreted in

TGF-b1, IL-12 were analyzed to evaluate immune functions.

the urine. Therefore hyperglycemia decreases and so does weight. This is a very

Results

convenient side effect since type 2 DM is highly associated with overweight/-

Significant decreases in body weight and body mass index were observed over the

obesity. We show the results of HbA1c and weight evolution after starting

entire study period in MNT treatment group but not in sitagliptin group. HbA1c

canaglifozina 100 (added to the previous treatment) in 60 patients. Six of them

and postprandial plasma glucose (PPG) levels were decreased in the sitagliptin

(four women) had to stop the drug (three because of genital pruritus, one

group compared with baseline values but not statistically significant while they

deterioration of renal function and one non related metastatic cancer). We also

were unchanged in the MNT group. There was a significant decrease c-peptide

show the results of canaglifozina 300 in 17 patients. Women represented the 33%

and insulin resistance (HOMA-IR) in sitagliptin group compared with baseline

and the medium age was 62G7years. We show data after 6 and 12 months on

values but not in MNT group at the end of the 12 weeks. Compared to the MNT

canaglifozina100. We have studied separately people older than 65 years old: 15

group we found a decrease in CD4 lymphocyte count by extension CD4/CD8 ratio

patients with medium age of 71G4 years, 10 of them women. This group showed

in the sitagliptin group though statistically insignificant.

no side effects and no treatment interrumptions. In 30 people we studied uric acid

Conclusion

levels, showing a difference of -0.9 mf/dl after 6 months on canaglifozina.

In this study of patients with type 2 diabetes, treatment with sitagliptin was

Seventeen patients progress to canaglifozina 300, the medium age was 63.2

associated with a significant decrease in insulin resistance. The decrease in CD4

(G5,6) years. After 6 months they got an additional weight loss of 1.8 kg (G0.5)

lymphocyte count was thought be possibly related to the upper airway tract

and decrease on HbA1c of K0.3% (G0.1). There were 18 patients on insuline

infection-like side effect described in the literature.

therapy with an average of 32(G26) daily units one year later the average was 21

DOI: 10.1530/endoabs.49.EP601

(G30) daily units of insulin. 2 patients stopped insulin therapy. Three patients

stopped sunfonilurea previously to canaglifoniza 100. Initially HbA1c increased

0.3% (G0.1) and weight decreased 3.3 (G1.7) kg, patients referred decrease or

disappearance of hypoglycemia. After one year on canaglifozina HbA1c

decreased 0.2 (G0.1)% and weight decreased 4.8 (G2.2) kg. The 96% were

satisfied with the new treatment for cana 100 and 100% for cana 300 (Table 1).

EP602

Real practice experience: Degludec vs Glargina U300

María Rosa Alhambra Expósito, Inmaculada Prior Sánchez, Paloma

Table 1

Moreno Moreno & M Ángeles Gálvez Moreno

Hospital Universitario Reina Sofía, Córdoba, Spain.

A1c6

A1c 1

Weight 6

Weight 1

A1c

months

year

Weight

months

year

Uric

Uric 1 year

Background

All

7.5G1.2

7G0.9

6.9G1.2

89G11

82.8G12

79.5G15

6G1.1

5G1.2

In last year, different analogues of very long duration basal insulin have appeared,

O65

8.1G1.7

7.7G1.4

7.8G1.4

86.8G11

83.2G12

80.8G8

6.6G1.6

5.7G0.8

cana300

73G0.8

xxxxx

7.0G0.2

81.7G16

xxxxxx

79.9G17

xxxxx

xxxxxx

which favors the flexibility in its use. Both ensure a decrease in the rate of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

EP605

Canaglifozina 100 added to the previous treatment for DM2 improved glycaemic

Efficacy and safety of evoglipitin monotherapy in patients with

control and produced weight loss. Canaglifozina 300 improved even more this

type 2 diabetes

results. A decrease in uric acid levels was showed. The results were the same in

Doo-Man Kim¹, Sungwoo Park², Mookyu Lee² & Kunho Yoon³

the elderly group without increase of side effects. Patients on insulin decrease the

¹Hallym University College of Medicine, Seoul, Republic of Korea;

dose with an improvement in the glycemic control. Stopping sulfonylurea

²Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;

produced a transient increase in glycaemia with less hypoglycemia. The mail side

³Catholic University, Seoul, Republic of Korea.

effect was non complicated urinary infection.

DOI: 10.1530/endoabs.49.EP603

Background and aims

To evaluate the efficacy and safety of the newly developed dipeptidyl peptidase-4

(DPP-4) inhibitor evogliptin in drug-naïve patients with inadequately controlled

type 2 diabetes.

Materials and methods

In randomized, double-blind, placebo-controlled, parallel-group, multicenter,

phase III study, 160 patients with type 2 diabetes were randomized to evogliptin

5 mg or placebo for 24 weeks. The primary efficacy outcome measure was mean

changes from baseline to endpoint in hemoglobin A1c (HbA1c).

Results

The mean baseline HbA1c levels of the evoglipitin group and the placebo group

EP604

were 7.2G0.56% and 7.2G0.63%, respectively (PO0.05). Although the baseline

Intralesional epidermal growth factor treatment on diabetic foot ulcers

HbA1c was very lower when compared with other phase III clinical trials using

Aydin Cifci¹, Birhan Oktas², Senay Arikan Durmaz³, Askin Gungunes³,

DPP-4 inhibitors, evogliptin provided significant placebo-corrected reductions in

Irfan Karahan⁴ & Taner Sarak⁵

HbA1c from baseline of K0.23% (P!0.0001) at 24 weeks. Also, the response

¹Department of Internal Medicine, School of Medicine, Kirikkale

rate achieving HbA1c !6.5% was significantly higher in the evoglipitin group

University, Kirikkale, Turkey;²Department of Orthopedics and Trauma-

than placebo group

(PZ0.008). Overall, incidences of adverse event and

tology, School of Medicine, Kirikkale University, Kirikkale, Turkey;

hypoglycemia were similar between the two groups.

³Department of Endocrinology and Metabolism, School of Medicine,

Conclusion

Kirikkale University, Kirikkale, Turkey;⁴Department of Internal Medicine,

In this

24-weeks study, once-daily evoglipitin monotherapy significantly

Yenimahalle Traning and Research Hospital, Ankara, Turkey;⁵Department

improved glycemic control and was well tolerated in patients with type 2 diabetes.

of Cardiology, School of Medicine, Kirikkale University, Kirikkale, Turkey.

DOI: 10.1530/endoabs.49.EP605

Objective

Treatment of diabetic foot ulcer is complex and difficult. Blood glucose

regulation, debridment and surgical revascularization are used in management of

diabetic foot ulcer. Intralesional Epidermal Growth Factor

(EGF) is a new

treatment approach for diabetic foot ulcer. We report our experience with eight

EP606

patients with diabetic foot ulcer who were treated by intralesional EGF.

Rabson mendenhall syndrome-a dilemma to treat in a resource

Patients and methods

poor country

A total of eight patients whose diabetic foot ulcers did not fully recover with other

Shehla Tabassum & Qamar Masood

treatments were included our study (Table 1).

Aga Khan University, Karachi, Pakistan.

Results

Complete healing was observed all diabetic foot ulcers after the intralesional EGF

treatment.

Background

Conclusion

Rabson Mendenhall Syndrome (RMS) is a rare genetic syndrome that is caused by

Our diabetic foot ulcers improved with intralesional EGF. Although our results

the mutation in the insulin receptor gene. Such mutation consequently results in

are quite impressive, this treatment is very expensive and caused of some allergic

severe insulin resistance. Patients suffering from RMS develop constant

reactions. Relation with malignancies is not known for long-term. In our opinion,

hyperglycemia from a progressive decline of endogenous insulin secretion.

intralesional EGF treatment should be used on wounds that did not heal with the

Drug therapy for RMS includes metformin, pioglitazones, large doses of insulin

other treatments.

alongwith recombinant human methionyl leptin or IGF-1. Here we describe a case

Table 1

of RMS who management poses a big dilemma due to unavailabity of these

treatment options in a low income country like Pakistan.

Numbers

Case presentation

Duration

Wagner

of EGF

A young Pakistani girl of 16 years of age presented in our Endocrine clinic with

No.

Age year Sex

of dm

Lesion place Grade

Prior treatment doses

uncontrolled blood glucose levels. She was diagnosed as case of type i diabetes

Male

Right 5.

Amputation

mellitus (DM) at the age of 4 years due to the complaints of polyuria, polydipsia

Phalanx

from left

and weight loss. She was being treated with insulin since then. Initially she

4.metatars

level

attained a good diabetic control but later on, her diabetes worsened. She was

Male

Left foot 5th

DebridmentC

never admitted to a hospital as a case of Diabetic Ketoacidosis (DKA). At the time

Metatars

Negative-

of her visit to our clinic, she was taking 70 units of Humulin-70/30 twice a day.

pressure

wound

Her fasting insulin level was 589 mU/ml, HbA1C was 16.8% with self-monitoring

therapy

of blood glucose levels being always recorded as ‘High’ at home. Examination

Male

Right foot

AmputationC

showed her body mass index of 17, short stature (less than 5th centile), severe

First

debridment

Phalanx

acanthosis nigricans, coarse facial features, broad nose, thick lips, dental

Male

Left foot First

AmputationC

dysplasia, prognathism, hirsutism, small hands with thick fingersnails and

Phalanx

debridment

abdominal distension. As genetic testing for RMS is not available in Pakistan, so

Male

Left heel, 2th

AmputationC

and 3th

debridment

she was diagnosed as a case of RMS with severe insulin resistance on clinical

Phalanx

grounds only. Her insulin dosage was increased gradually to 520 units/day &

Female

Left First

Debridment

MetforminCPioglitazone were added (as insulin sensitizers) to the regimen, but

Phalanx

and heel

still her blood glucose levels were uncontrolled. At last, she was admitted to

Female

Right 3th

Debridment

hospital for diabetic control. There she received MetforminCPioglitazoneC20

and 4th

units/day of insulin

(regularCNPH) along with continuous insulin infusion

Metatars

Male

Left- Foot

Debridment

@30 units/h bur still her blood glucose levels ranged between 400 and 600 mg/dl.

sole

As the 500 U/ml insulin is not available in a resource poor country like Pakistan

along with the unavailability of latest treatment options like recombinant leptin or

IGF-1, so it becomes a big dilemma for Endocrinologists about how to treat such

patient with RMS. Currently the patient is having poorly controlled DM and has

DOI: 10.1530/endoabs.49.EP604

started developing multiple bullous, ulcerated lesions all over the body due to

poor diabetic control.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

patients. In our study, it’s aimed to evaluate the effects of exenatide and

Several challenges are encountered by healthcare professionals while treating

laparoscopic sleeve gastrectomy (LSG) in obese diabetic patients on the clinical

patients of RMS in resource poor countries of the world. Concentrated insulin (U-

and laboratory parameters.

500) is not available everywhere to ease the pain of several daily insulin injections

Subjects and methods

and to improve compliance. We hope that future will hold promising horizon for

Twenty-five patients who had undergone bariatric surgery and 25 patients who

such patients and the global equal access to its available treatment options will

started exenatide treatment and followed up in our outpatients clinic were

result in their better quality of life.

included in the study.

DOI: 10.1530/endoabs.49.EP606

Results

At the end of the six month follow-up, weight loss was approximately 35.4 kg in

the surgery group and 11.5 kg in the exenatide group. Although postprandial

glisemi (PPG) and HbA1c were significantly decreased in both groups, the

decrease was significantly higher in LSG group compared to the exenatide group.

Although there was no significant change in fasting blood glucose (FBG) in the

exenatide group, there was a significant decrease in FBG in LSG group.

Discussion

EP607

LSG is a method that should be performed upon indication and much more radical

Does tolerance develop toward GLP-1 receptor agonists’

compared to exenatide administration but appears to be a more efficient

glucose-lowering effect?

application that corrects diabetes and obesity related metabolic parameters

Tuuli Sedman^1,2, Maarja Krass¹, Kertu Runkorg¹, Eero Vasar¹ &

compared to exenatide treatment in diabetic obese patients. Both treatment

Vallo Volke^1,2

options must be evaluated for each patient regarding the advantages and

¹Department of Physiology, Institute of Biomedicine and Translational

disadvantages and appropriate treatment option for each patient should be decided

Medicine, University of Tartu, Tartu, Estonia;²Tartu University Hospital,

according to patient’s characteristics.

Tartu, Estonia.

DOI: 10.1530/endoabs.49.EP608

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become a popular

tool for the treatment of type 2 diabetes. Unlike many other antidiabetic drug

classes, distinct GLP-1 RAs have different therapeutic profiles, mostly due to their

different pharmacokinetic properties. Animal experiments and human data

indicate that tolerance develops toward at least some of their effects, e.g., gastric

EP609

motility. Whether tolerance develops toward the glucose-lowering effect of GLP-

Increase in time in target when using a basal-bolus algorithm for insulin

1 receptor agonists has never been formally tested. We have conducted a series of

dosing with insulin glargine U300 during hospital stay

experiments in mice and a pilot clinical trial in healthy volunteers to address the

Julia K Mader¹, Klaus Donsa², Felix Aberer¹, Katharina Lichtenegger¹,

hypothesis of tolerance development.

Christian Lanz¹, Edin Smajic¹, Bernhard Holl², Peter Beck³,

Methods

Thomas R Pieber^1,2 & Johannes Plank

Male C57Bl/6J mice were used. Liraglutide (600 mg/kg once a day s.c.) or

¹Medical University of Graz, Graz, Austria;²Joanneum Research GmbH,

exenatide (10 mg/kg twice a day s.c.) were given for 11 days (subchronic group)

Graz, Austria;³Decide Clinical Software GmbH, Graz, Austria.

or 18 days (chronic group). Treatment effects on nonfasting glucose level and

during the glucose tolerance test (GTT) were evaluated. Ten healthy volunteers

were treated with 0.6 mg liraglutide s.c. once daily for 21 days. The drug’s effect

Background and aims

was quantified by serial graded glucose infusion tests, with glucose and c-peptide

Insulin therapy and the use of clinical decision support systems to achieve

measured every 20 min and insulin secretion rate calculated.

glycaemic control in hospitalized patients with hyperglycaemia are recommended

Results (Mice)

by clinical guidelines. The aim of this evaluation was to assess time in target by

The effect of liraglutide on nonfasting glucose was clearly weaker after chronic

continuous glucose monitoring

(CGM) achieved by a basal-bolus insulin

administration, compared to acute administration (P!0.01 Duncan’s post hoc

algorithm using insulin glargine U300 during hospital stay in patients with type

test) while exenatide remained equally effective. During the GTT both liraglutide

2 diabetes (T2D).

and exenatide, decreased AUC for glucose significantly more after acute

Material and methods

administration compared to the chronic groups (P!0.05). Moreover, in the

30 patients with T2D (12 female, age 67G11 years, HbA1c 79G2 6 mmol/mol,

experiment with liraglutide the change in insulin-to-glucose ratio was

BMI 32G6 kg/m², diabetes duration 14G11 years) were treated with GlucoTab,

significantly blunted after subchronic

(P!0.05) and chronic treatment

a mobile system providing automated workflow support and suggestions for

(P!0.01) compared to acute effect. Humans: (will be revealed during the

insulin dosing to health care professionals, during hospital stay. Insulins glargine

presentation).

U300 and glulisine were used for basal-bolus therapy. Additionally to blood

Conclusions

glucose measurements, blinded CGM

(iPro2, Medtronic) was performed

Prolonged treatment with exenatide and liraglutide induced tolerance in mice.

throughout the study.

DOI: 10.1530/endoabs.49.EP607

Results

Mean total daily insulin dose was 63.8G39.8 U. A total of 49,846 CGM values

were collected. Mean daily sensor glucose was 8.4G1.2 mmol/l. Percentage of

CGM values in the ranges was as follows: 5.6-7.8 mmol/l

(42.0%),

3.9-

10 mmol/l (80.2%), O10 mmol/l (19.0%), O16.7 mmol/l (1.5%). Percentage in

the hypoglycaemic range were low: !3.9 mmol/l (0.77%), !3.3 mmol/l (0.35%)

and !2.8 mmol/l (0.15%), respectively. When comparing the first vs last full

24-h period, time in target 3.9-10 mmol/l (61.8% vs 85.2%) increased, whereas

EP608

time in hyperglycaemia O10 mmol/l (37.1% vs 14.2%) and hypoglycaemia !

Comparative evaluation the effects of bariatric surgery and exenatide

3.9 mmol/l (1.2% vs 0.6%) decreased.

treatment on the clinical and laboratory parameters in obese type 2

Conclusions

diabetic patients

Basal-bolus insulin therapy using insulin glargine U300

safely establishes

Onur Elbasan¹, Pinar Sisman², Hande Peynirci³, Ozen Oz Gul⁴,

glycaemic control as assessed by CGM. Over time percentage of values in target

Soner Cander⁴, Erdinc Erturk⁴ & Canan Ersoy⁴

increases without increasing the risk of hypoglycaemia.

¹Department of Internal Medicine, Uludag University Medical School,

DOI: 10.1530/endoabs.49.EP609

Bursa, Turkey;²Endokrinology and Metabolism Clinic, Harakani State

Hospital, Kars, Turkey;³Endocrinology and Metabolism Clinic, Munif

Islamoglu State Hospital, Kastamonu, Turkey;⁴Department of

Endocrinology and Metabolism, Uludag University Medical School,

Bursa, Turkey.

EP610

Background

Intensity of dapagliflozin induced glycosuria correlates with previous

Obesity and diabetes are major causes of morbidity and mortality that are

glycemic control but not with body weight or duration of type 2 diabetes

increasing all over the world. As obesity is a major risk factor for type 2 diabetic

Manuel Cayón-Blanco & Carolina García-Figueras Mateos

patients, weight loss has an important place in the treatment of type 2 diabetic

Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction

Inhibitors of sodium-dependent glucose co-transporter

(SGLT2i) reduce

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a newly developed

circulating glucose concentrations via a renal mechanism. Its metabolic effects

class of oral anti-diabetic drugs with a unique mechanism of action and its use is

have not been fully described and there is a discrepancy on some clinical results

becoming more widespread. Given that dapagliflozin was the first drug of this

found in studies on SGLT2i. Our aims were to detect if there are some predictor

class used in Spain, available since December 2013, 3 years after its inception, we

factors to identify what patients will have higher response to dapagliflozin, a

aimed to investigate whether there have been differences in prescription patterns

SGLT2i, and second, to explore whether intensity of glycosuria is correlated to

of SGLT2i (using dapagliflozin as reference) in a Sanitary district from Spain

the intensity of metabolic and anthropometric changes.

over time.

Methods/design

23 participants with type 2 diabetes (T2D) (age: 53.1G7.6 years; 56.5% males,

Using electronic medical records, data of patients with type 2 diabetes who were

T2D duration 12.1G6 years) received dapagliflozin (10 mg/day) for 18 weeks in

prescribed dapagliflozin

10 mg/day, were collected at two periods of time:

conditions of normal medical practice. Parameters related to glucose metabolism,

i) between January to June 2013 (consecutive first prescriptions of dapagliflozin

renal function and anthropometric variables were measured at baseline and at

in our area) and ii) between June to December

2016

(last prescriptions).

week 18. Glycosuria was quantitatively measured at baseline and at the end of the

Epidemiologic, clinical and metabolic data as well as antidiabetic drugs received

follow-up.

were compared between the two periods.

Results

At week 18, glycosuria increased from 6.4G2.2 to 68.9G50.4 g/24 (P!0.001).

A total of 36 prescriptions of dapagliflozin made in the first period were compared

Significant reductions in body mass index (BMI), HbA1c, fasting plasma glucose

32 prescriptions in the second period. Patients in the second period had

(FPG) were observed (P!0.01). Quantitative glucose urine levels at week 18

significantly (P!0.05) higher duration of diabetes (13.6G7.4 vs 10G9 years),

positively correlated with the following variables at baseline: FPG (rZ0.631;

lower A1C (%; 8.6%G1.3% vs 9.1%G1.1%) and a lower rate of microvascular

PZ0.001), HbA1c (rZ0.399; PZ0.03), glycosuria (rZ0.397; PZ0.034) and

(37.5% vs 78%) and macrovascular complications (18.7% vs 33.3%). Also, there

inversely correlated with albumin/creatinine ratio (rZK0.409; PZ0.037) but not

has been an increased used as second line treatment (21.9% vs 5.5%; P!0.001)

with age, T2D duration, eGFR or BMI. Intensity of glycosuria correlated with

as well as combined to basal insulin (62.5% vs 12.5%; P!0.001).

diuresis increase (rZK0.602; PZ0.002) but didn’t with and HbA1c or BMI

Conclusions

falls.

Patterns of prescriptions of SGLT2i have changed over the last 3 years in our area.

Conclusions

Its use as a second line treatment and combined with basal insulin has increased.

Glycosuric effect of dapagliflozin is correlated with glycemic control at baseline

Also, patients who are prescribed this class of antidiabetic drug have a better

independently of time of T2D evolution as result of a higher expression of SGLT2

diabetes profile and a lower rate of complications although a higher duration of

receptors in poorly controlled diabetic patients. The magnitude of glycosuria did

diabetes.

not provide higher weight loss or higher falls in HbA1c.

DOI: 10.1530/endoabs.49.EP612

DOI: 10.1530/endoabs.49.EP610

EP611

EP613

How can dapagliflozin affect blood pressure response in a real-life

cohort of people with type 2 diabetes and hypertension?

The insulin delivery system and its impact on quality of life and on

Manuel Cayón-Blanco & Carolina García-Figueras Mateos

psychopathological symptomatology

Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.

Miguel Pereira¹, Celestino Neves^1,2, César Esteves¹, Sofia Oliveira¹,

Cristina Arteiro¹, Rui Coelho^1,2 & Davide Carvalho^1,2

¹S. Joa˜o Hospital Center, Porto, Portugal;2Faculty of medicine, University

Introduction

of Porto, Porto, Portugal.

In clinical trials, dapagliflozin has been shown to lower blood glucose, reduce

weight and blood pressure in people with type 2 diabetes (T2D). However, there

are limited published data on quantitative changes on blood pressure of this drug

Introduction

in routine clinical practice. Our aim was to examine the clinical efficacy of

In chronic diseases a good psychological and behavioral adaptation is essential.

dapagliflozin in patients with T2D and hypertension in a real-life cohort.

Concerning diabetes the Insulin Delivery System (IDS) adopted tend to be an

Methods/design

important factor of adaptation, global satisfaction and, above all, quality of life

Prospective study including patients with poorly controlled T2D and hypertension

(QoL).

who were added dapagiflozin in conditions of routine medical practice. Metabolic

Objectives

profile, renal parameters and hemodynamic parameters were measured prior to

To analyze the QoL and IDS satisfaction and its relationship with psychopatho-

dapagliflozin intensification and at week 24.

logical symptomatology in patients on continuous subcutaneous insulin infusion

Results

(CSII) therapy.

16 patients were evaluated. At week 24, urine volume increased from 1761G

Patients and methods

693.6 ml/day to 2570.83G758.6 ml/day; P!0.001 as well as natriuresis (from

We gather a convenience sample of 42 type 1 (DM1) patients, with a mean age of

211.6G73.7 mEq/day at baseline to

252.8G94.5 mEq/day; pZ0.009). No

28.4G11.5 years, 61.9% female and with a mean IDS time of usage of 5.6G2

significant differences were observed in eGFR and albumin/creatinine ratio.

years. We applied the following questionnaires: the Audit of Diabetes Dependent

Systolic blood pressure significantly decreased from baseline (148.9G20.8 vs

Quality of Life (ADDQoL), o Insulin Delivery System Rating Questionnaire

141.5G17.9; PZ0.02) as well as diastolic blood pressure (84.3G11.9 vs 78.8G

(IDSRQ) e o Brief Symptom Inventory (BSI).

8.9: PZ0.001). In five patients, variability of blood pressure was measured

Results

showing a significant reduction (15.2G1.9 vs 10.4G2.1; PZ0.02).

Relatively to QoL, in this sample, the mean values were K1.68G1.37 (results go

Conclusions

from K9 to 9). We did not find any relevant psychopathological symptomatology

Our results show a higher decrease in blood pressure that observed in clinical

in general in the BSI questionnaire (GSI Z0.10G0.09). Regarding blood glucose

trials. Dapagliflozin might potentially improve not only the average blood

monitoring (BGM), 55.3% of patients perform 4-6 blood checks daily and 39.5%

pressure, but also reduces its variability. We included a little number of patients.

more than six times daily. 30% of patients carry out BMG a little more than they

Further investigations are needed to verify our observation and determine its

would like and 22.5% a lot more than they would like. We noticed a significant

potential role on cardiovascular outcomes.

statistical correlation between QoL and the level of satisfaction with BGM needed

(rZK0.50; PZ0.001) and also with psychopathological symptomatology

DOI: 10.1530/endoabs.49.EP611

(rZK0.53; PZ0.001).

Conclusions

Results in this study shows that the chosen IDS has a vital impact in

psychopathological symptomatology and in the levels of QoL that patients

reveal. This data allow us to conclude that the minor constraints that this IDS has

EP612

due to its utilization does not contribute negatively to CSII perception, moreover

Trends in prescription of Sodium-glucose co-transporter-2 inhibitors

when it is compared with multiple daily dosage.

(SGLT2i) over the last three years in a specialized setting

DOI: 10.1530/endoabs.49.EP613

Carolina García-Figueras Mateos & Manuel Cayón-Blanco

Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP614

significantly improved glucose (area under the curve: 26603 vs. 31947, P!0.001)

and insulin (area under the curve: 6981 vs 8968, P!0.001) tolerance, insulin

New long-acting insulins in type 1 diabetes: implications for real clinical

resistance, insulin sensitivity, lipid profile, and decreased fasting glucose (8%)

practice

and insulin (11%), but had no effect on GSIS and islet insulin content. In diabetic

Miguel Damas-Fuentes, Cristina Díaz-Perdigones, Araceli Mun˜ oz-Garach,

rats, nitrate significantly increased tissue levels of GLUT4 by 17% and 22% in

María Molina-Vega, Carmen Hernández-García, Isabel Cornejo-Pareja,

soleus muscle and epididymal adipose tissue, respectively. Nitrate also decreased

Isabel Mancha-Doblas & Francisco J Tinahones-Madue

˜o

elevated serum IL-1b in diabetic rats (4.7G0.5 vs. 3.2G0.6 pg/ml, PZ0.02).

Endocrinology and Nutrition Department, Virgen de la Victoria

Conclusion

Universitary Hospital, Málaga, Andalucía, Spain.

Nitrate administration had favourable effects on glucose tolerance, insulin

resistance, insulin sensitivity, inflammation, and dyslipidemia in type 2 diabetic

The emergence of a new generation of long-acting insulin analogues (insulin

rats.

degludec -ID- and insulin glargine 300 U/ml -IG300-) has increased treatment

Keywords: Glucose tolerance; Insulin resistance; Insulin sensitivity; Inflam-

options in type 1 diabetes (T1D), demonstrating in clinical trials better metabolic

mation; Sodium nitrate; Type 2 diabetes.

control with lower hypoglycemia rates.

DOI: 10.1530/endoabs.49.EP615

Objectives

To assess characteristics of T1D patients who were given ID and IG300 in clinical

practice and to evaluate their effect on metabolic control, weight, insulin dose and

hypoglycemia, comparing results obtained.

Methods

Observational, retrospective study. We studied T1D patients whose habitual

treatment had been modified. We analyzed anthropometric data (weight, BMI),

EP616

biochemical parameters (fasting glycemia, HbA1c, lipid profile), insulin dose and

Impact of a universal educational animation movie in an hour workshop

number of hypoglycemic events per month (!5; 5-10; O10, initially and after

on the knowledge of patients with gestational diabetes

6 months.

Chaïnèse Cheikh, Emilie Lacquement, Régis Cohen & Ghada Hatem

Results

Hôpital Delafontaine, Saint Denis, France.

38 patients:

50% women, age 38G12.7 years, BMI 25.8G3.9 kg/m², T1D

evolution time 14.9G8.6 years and HbA1c 7.4G0.8%. 57.9% initiated ID and

42.1% IG300. They presented: 7.9% hypertension, 13.2% retinopathy, 2.6%

history of ischemic heart disease, 2.6% nephropathy and 0% neuropathy. Initially,

This study assessed the dietary and medical knowledge before and after a

there were no differences between the two groups, except for higher blood glucose

group workshop viewing a 5-min animation film in patients with gestational

in ID group (189.2G12.1 vs 144.3G22.4 mg/dl, P 0.003). There was a significant

diabetes (GD) (https://www.youtube.com/watch?vZMaf-Uos9oLQ). This

decrease in insulin dose with ID (29.05G9.25 vs 24.82G20.8 IU, P 0.010). There

animation movie (without speech) explains the course of the patients

was a weight loss of 1.9G4.4 kg in patients with IG300, but not statistically

suffering from GD by emphasizing the stakes, the diet and the medical

significant. We observed a significant decrease in the number of hypoglycemia

measures.

events in general (75% with O10 decreased to !5; PZ0.009). When stratified by

Patients and methods

comparison groups, the significance is maintained with ID but not with IG300.

This is a prospective self-assessment study of 10 questions in 100 consecutive

Conclusions

pregnant women.

1) ID group significantly decreased basal insulin dose. 2) We observed weight

Results

loss, not statistically significant, in IG300

patients.

3) There was significant

Seventy-four out of 100 subjects were included with their clinical data. Diagnosis

reduction of hypoglycemia rates with both basal insulin analogues. 4) Further

was based on the mean blood glucose after a 75 g load charge test: T0 0.92 g/l

studies are needed to distinguish which type of patient benefits more from each

(nZ47) T1 1.75 g/l (nZ46), T2 1.53 g/l (nZ46). Patients were characterized by a

insulin analogue.

mean age of 32 years, 6% with type 1 or 2 diabetes, G3P1, 91% of foreign origin,

DOI: 10.1530/endoabs.49.EP614

predominantly from the Maghreb (59%), mainly unemployed with an average

pre-pregnancy BMI of 28 kg/m², a mean weight gain of 8 kg during pregnancy,

a 42% history of diabetes in the family, a 12% history of personal DG, a 11%

history of macrosomia and 24% insulin use. For 71/74, we collected information

on delivery accounting for

7% of macrosomia. The analysis of the

100

questionnaires revealed an average correct score of 6.3/10 before and 8.6/10

after the workshop. Before the workshop (99/100), patients were unaware of the

presence of sugar in bread, the number of dairy products to be consumed daily, the

EP615

importance of physical activity, and the possibility of using insulin if blood

Effect of oral nitrate administration on glucose metabolism and

glucose was too high. After the workshop (98/100), the score improvement was

inflammation in obese type 2 diabetic rats

mainly relevant for these four topics.

Asghar Ghasemi¹ & Sevda Gheibi^1,2

Conclusion

¹Endocrine Physiology Research Center, Research Institute for Endocrine

Our animation film is a simple pedagogical tool that allows us to improve the state

Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran;

of knowledge in an efficient manner.

²Neurophysiology Research Center and Department of Physiology, Faculty

DOI: 10.1530/endoabs.49.EP616

of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction

Type 2 diabetes is associated with impaired nitric oxide (NO) bioavailability;

nitrate administration might act as a potential therapeutic agent in diabetes

through nitrate/nitrite/NO pathway. The aim of this study was to determine the

EP617

effects of sodium nitrate on glucose tolerance, insulin sensitivity, inflammation,

Insulin requirements in pregnant women with DM 1 with different

glucose-stimulated insulin secretion (GSIS), and islet insulin content in obese

duration of the disease

type 2 diabetic male rats.

Juliya Sharipova¹, Leila Gaysina², Gulnaz Gazizova¹, Farida Valeeva¹ &

Methods

Kamilya Khasanova¹

Male Wistar rats were divided into four groups: Control, controlCnitrate,

¹Kazan State Medical University, Kazan/Republic of Tatarstan, Russia;

diabetes, and diabetesCnitrate. Diabetes was induced using high-fat diet and low-

²Kazan Federal University, Kazan/Republic of Tatarstan, Russia.

dose of streptozotocin. Sodium nitrate

(100 mg/l in drinking water) was

administered for 2 months. Serum levels of fasting glucose, insulin, and lipid

profile were measured and the insulin resistance/sensitivity indices were

Background and aims

calculated every 2-weeks. At the end of the study, tissue levels of glucose

To study the need for insulin during pregnancy, depending on the duration of the

transporter

(GLUT4) protein and serum interleukin-1

beta

(IL-1b) were

disease.

measured as well as glucose and insulin tolerance test were done. GSIS from

Methods

isolated pancreatic islets and islet insulin content were also determined.

We studied 108 pregnant women with DM 1 receiving insulin with insulin pumps.

Results

Patients were divided into three groups: in the 1st group diabetes duration was less

Compared to the control group, diabetic rats had glucose intolerance,

than 5 years, in the 2nd - 5 to 15 years, 3rd - more than 15 years. We evaluated the

dyslipidemia, and higher serum glucose and insulin. In diabetic rats, nitrate

daily need for insulin on 12, 22-25, 30-32 weeks of gestation.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

Methods

In the 1st group the daily insulin requirement (IU/kg) in the 1st trimester was 0.51,

Retrospective study of type 2 diabetic patients with newly diagnosed of pancreatic

in the 2nd 0.54, in the 3rd 0.79. Significant increase of insulin requirements was

or biliary tract cancer attended consecutively in a tertiary hospital between the

identified from the second to the third trimester (PZ0.34 between 1 and 2

years 2012 and 2015.

trimester, PZ0.005 between the 2 and 3 trimester, P!0.01 between 1 and 3

Results

trimester). By the third trimester the increase of the daily dose of insulin was on

A total of 37 patients were included. The prevalence of use for DPP-4 inhibitors in

56% (36; 87). In the 2nd group the insulin requirement was 0.6; 0.73; to

our cohort was 37.8% (sitagliptin, linagliptin and vildagliptin). No one patient

0.87 IU/kg, respectively, dose increased from trimester to trimester (P!0.01). By

was under treatment with GLP-1 receptor agonists. Subjects’ characteristics are

the third trimester, daily dose of insulin increased on 42% (28; 63). Insulin

shown in Table 1. Men developed cancer earlier than women (68.4 vs 75.5 years,

requirements in the 3rd group increased from the first (0.59 IU/kg) to second

PZ0.038). Smoking prevalence and time of diabetes evolution was higher for

(0.65 IU/kg) trimester, but in third trimester dose stabilized on

0.74 IU /kg

males. Subjects who were taking DPP4-i exhibited stages more advanced at

(P!0.01 between 1 and 2 trimester, PZ0.17 between the 2 and 3 trimester,

diagnosis (Table 2). However, this result did not reach statistically significant

P!0.01 between 1 and 3 trimester). However, the daily dose of insulin in this

differences (70 vs 50%, PZ0.250). Metformin use was not associated with

group increased only on 22% (11.5; 32.5).

different tumor staging (PZ0.169).

Conclusions

In pregnant women with DM 1 with disease duration more than 15 years we may

not see a significant rise in insulin requirements on the third trimester. This group

needs monitoring.

DOI: 10.1530/endoabs.49.EP617

EP618

Liraglutide restores the hyperglycemia-induced endothelial oxidative

stress in vitro

Sofia Gougoura, Alexandra Bargiota & Georgios N Koukoulis

Department of Endocrinology and Metabolic Diseases, University Hospital

of Thessaly, Larissa, Greece.

Introduction

Diabetes is characterised by increased oxidative stress and an insufficient

antioxidant response, which are crucial for the initiation and progression of

atherosclerosis. GLP-1 agonists, used for the treatment of diabetes, are considered

as cardioprotective agents but under that concept, there are limited data on their

ability to influence the endothelial antioxidant response.

Methods

In order to answer this question we studied the influence of liraglutide, a known

long-lasting GLP-1 agonist, on the antioxidant response markers (superoxide

dismutase (SOD), catalase, glutathione (GSH) system, endothelial nitric oxide

synthase (eNOS), intracellular reactive oxygen species (ROS) and extracellular

nitric oxide

(NOx)) of Eahy926

macroendothelial cells pre-treated in

hyperglycemic (25 mM) environment for 2 h.

Results

Hyperglycemia significantly increased the endothelial intracellular ROS content

(P!0.001) and decreased eNOS

(P!0.05), SOD (P!0.05) and catalase

(P!0.001) activity, GSH recycling rate (P!0.001) and Nox levels (P!0.05).

Conclusions

Liraglutide (40 nM) restored the increased intracellular ROS to levels comparable

This study supports DPP4-i safety from the point of view of tumorigenesis in humans.

to normal glucose treated cells (control). The elimination of intracellular ROS

However, the small sample size due to the low incidence of this lethal disease makes

was accomplished by the activation of SOD (P!0.05) and catalase (P!0.001)

us to be cautious in the conclusions. Further research is needed in order to ensure that

enzymatic antioxidant response and the increase (P!0.001) of intracellular GSH

incretin-based therapies are safe from the oncological point of view.

recycling rate. Moreover, liraglutide restored also eNOS activity and NOx release

DOI: 10.1530/endoabs.49.EP619

(P!0.05).

Conclusions

Our results indicate that liraglutide is involved in the redox balance of endothelial

cells. Its ability to counterbalance the increased endothelial free radicals induced

by hyperglycemia seems to work as a protective mechanism restoring cell

EP620

function and ameliorating the progression of atherosclerosis process.

Palpable purpura in an uncontrolled diabetic patient: an uncommon

DOI: 10.1530/endoabs.49.EP618

possible side effect of linagliptin

Omercan Topaloglu, Bahri Evren, Mahmut Kara, Seyfullah Yucel &

Ibrahim Sahin

Department of Endocrinology, Inonu University Medical Faculty, Malatya,

Turkey.

EP619

Introduction

Incretin-based therapies and pancreatic/biliary tract cancer

Incretin based therapeutics have commonly been used in the last years for the

Diana Boj-Carceller¹, Sara Cay-Melero¹, Isabel Azcona-Monreal¹,

management of patients with type 2 diabetes mellitus (DM). Linagliptin is a

Leticia Pérez-Fernández¹, Pilar Calmarza-Calmarza² &

member of “dipeptidyl peptidase 4” (DPP-4) inhibitors and often preferred owing

Alejandro Sanz-París¹

to some advantages over the others. We present a diabetic case developing skin

¹Endocrinology and Nutrition Unit, Hospital Miguel Servet, Zaragoza,

findings after the initiation of linagliptin.

Spain;²Laboratory of Clinical Biochemistry, Hospital Miguel Servet,

Case

Zaragoza, Spain.

66 year-old woman with a history of type 2 DM for 10 years was admitted to our

clinics with the complaints of dry mouth, polydipsia and polyuria. She had also

Objective

history of coronary heart disease confirmed by coronary angiography. She had

To study the relation between incretin-based therapies, DPP-4 inhibitors and

been taking metformin, acetylsalicylic acid, and oral nitrate for 10 years. On

GLP-1 receptor agonists, and tumor stage at the time of diagnosis of pancreatic

physical examination; vital signs and examinations of cardiovascular, pulmonary

and biliary tract cancer.

and gastrointestinal systems were normal. She had no skin rash or lesions. Blood

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

glucose was 319 mg/dl, urine ketone negative, creatinine 0.78 mg/dl; and liver

Background

tests and arterial blood gas analysis were in normal limits. Firstly, we initiated

One of the most significant complications of type 2 diabetes (T2D) is non-

intensive insulin regimen together with tight glucose monitoring, to improve

alcoholic fatty liver disease (NAFLD). The search for new effective approaches to

uncontrolled hyperglycemia. We increased the dosage of rapid acting insulins

the treatment of patients with comorbid chronic condition such as type 2 diabetes

gradually to achieve optimal glucose control. Metformin was continued and

and NAFLD is relevant.

linagliptin was added to treatment. Lesions like palpable purpura arised on lower

Methods

legs and upper arms of the patient on the second day of linagliptin therapy. No

We have observed 118 patients, including 64 patients with T2D and NAFLD, 26

other drugs, chemicals or herbal preparations were given at this time. After

patients with T2D and 28 patients with NAFLD. The control group consisted of

cessation of linagliptin, palpable purpura lesions both on lower and upper

25 healthy individuals. Recommended treatment included individualized diet

extremities regressed gradually.

therapy with energy value of daily ration 1800-2300 kcal/day, a hepatoprotective

Conclusion

salt of arginine and glutamic acid at 0.75 mg 3 times a day and alive multistrain

Due to impact of DPP-4 inhibitors on the other DPP enzymes to some degree,

probiotic at 10 mg twice a day. Clinical manifestations, echography semiotics,

musculoskeletal and dermatological adverse reactions may occur during the

protein, lipid, enzyme and carbohydrate metabolism, the degree of IR,

treatment with these agents. To our knowledge, palpable purpura lesions were

subpopulations of lymphocytes and interleukins, IgG antibodies to LPS, the

detected with linagliptin therapy in our patient for a first time in the literature.

range of average weight molecules, circulating immune complexes

(CIC),

DOI: 10.1530/endoabs.49.EP620

dysbiotic disorders of the intestine in patients with T2D and NAFLD were

studied.

Results

The application of the developed medical complex that included individualized

diet, the salt of arginine and glutamic acid and a multiprobiotic contributed to the

normalization of lipid, enzyme, carbohydrate metabolism, improvement of

EP621

cellular and humoral links of the immune system, reducing levels of CIC 58.3%,

Dulaglutide added on Empagliflozin improves blood pressure, body

reduction of endogenous intoxication (level MCM254 - 30.5%, MCM280 - by

weight, glycemic control and albuminuria in obese diabetic patients

32.4% and the level of IgG antibodies to LPS in 1,6 times), improvement of

Carmen Acosta-Calero¹, Claudia Arnas-Leon¹, Ana Delia Santana-Suarez¹,

intestinal microbiocenosis in 84.4% of patients with T2D with NAFLD and

Manuel Nivelo-Rivadeneira¹, Agnieszka Kuzior¹, Sara Quintana-Arroyo¹,

normalization of pathological clinical manifestations in 68.8% of patients.

Nery Sablon-Gonzalez² & Francisco Javier Martinez-Martin³

Conclusions

¹Endocrinology Department, Hospital Universitario de Gran Canaria Dr.

This study revealed the effects of proposed treatment complex on the major

Negrin, Las Palmas de Gran Canaria, Spain;²Nephrology Department,

lymphocyte subpopulations and cytokine status, reduction of endotoxemia,

Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran

promotion of the positive dynamics of lipid and carbohydrate metabolism

Canaria, Spain;³Outpatient Hypertension Clinic, Hospital Universitario de

indicators and intestinal microbiocenosis of patients with T2D and NAFLD.

Gran Canaria Dr. Negrin, as Palmas de Gran Canaria, Spain.

DOI: 10.1530/endoabs.49.EP622

Objective

GLP-1 receptor agonists and SGLT2 inhibitors improve glycemic control, body

weight, blood pressure and albuminuria by different pathways. However, their

combination is not endorsed by ADA-EASD guidelines, and available data are

scarce. Our objective in this open observational study was to elucidate the effect

of added Dulaglutide in obese type 2 diabetic patients previously treated with

Empagliflozin but insufficiently controlled.

Methods

EP623

Dulaglutide 1.5 mg/week was added to the treatment of 20 type 2 diabetic patients

The role of diabetic educational programs in glycemic control in

with BMI O30 kg/m² previously treated with Empagliflozin 10 mg/day for at

patients attending to our day hospital

least 3 months but having HbA_1C O7%. They were re-evaluated after 3-6 months

Mariana Tome¹, Guillermo Martínez de Pinillos², Fernando García², Eyvée

without additional medication changes, except for insulin dosage adjustments and

Arturo Cuéllar², Ignacio Fernández² & Juan Manuel Garcia de Quirós²

iDPP4 discontinuation. Besides clinical routine, 24 h. ABPM were performed

¹Punta de Europa Hospital, Algeciras, Spain;²Valme Hospital, Sevilla,

before and after. Stats were performed by two-tailed paired t-test, *meaning

Spain.

P!0.05. Values are given as meanGS.D.

Results

Age was 49G11 and diabetes duration 8G3 years. 53% were women. Baseline

Objective

BMI was 34.9G2.5 kg/m²; ABPM: Awake, BP 131G8/85G8 mmHg, HR 74G

To assess improvement in glycemic control in those diabetic patients who have

10 bpm; Sleep,

127G8/78G10 mmHg, 69G10 lpm. Fasting glycemia was

received structured education in diabetes in our Day Hospital.

167G46 mg/dl, HbA_1C 8.0G0.6%, urate 6.9G1.4 mg/dl, Cr 0.91G0.17 mg/dl,

Methods

GFR (CKD-EPI estimation) 87.1G16.8 ml/min/1.73 m², Albuminuria 291G

A retrospective observational study was carried out in which 42 diabetic patients

268 mg/gr Cr; median 232, IQR 23-460. At follow-up there were no withdrawals

who had attended to educational courses in 1 year were included, determining the

due to side effects, one patient was lost to follow-up and 16% reported mild

age of the patient, type of Diabetes, score obtained in the questionnaires at the

nausea and/or diarrhoea. Body weight change was K4.0G2.6* kg, BMI

beginning and end of the course, as well as HbA1c before, at 6 months and at

K1.37G0.83* kg/m². ABPM: Awake SBP K4G4*, DBP K1G3 mmHg, HR

12 months after the courses.

1G4 bpm; Sleep, SBP K6G5*, DBP K4G6* mmHg, HR C2G7 bpm. Fasting

Results

glycemia change K41G23* mg/dl; HbA_1C K1.1G0.6* %, urate K0.12G

Of the 42 patients, 25 were diabetic type 1 and 17 diabetic type 2. Mean age

0.24* mg/dl; Cr K0.04G0.11 mg/dl, GFR C1.9G7.3 ml/min/1.73 m², albumi-

43.64G14.36 years (Type 1 diabetes mellitus (DM1): 36.8G12.17 years; Type 2

nuria K71G105* mg/gr Cr (K29G31%).

diabetes mellitus (DM2): 53.7G11.2 years). Mean HbA1c before the course was

Conclusions

9.14G2% (DM1: 8.99G1.74%, DM2: 9.36G2.38%). Mean of HbA1c at

Dulaglutide added on Empagliflozin in obese type 2 diabetic patients was well

6 months of the course was 8.06G1.51%. (DM1: 8.09G1.45%, DM2: 8.03G

tolerated and effective for glycemic control, body weight, blood pressure

1.64%). A reduction of HbA1c of 1.08G1.87% (P !0.0001) was obtained. In the

(particularly nocturnal) and albuminuria.

DM1 group the mean reduction of HbA1c was 0.9G1.79% (PZ0.014) whereas

in the DM2 group it was 1.34G2% (PZ0.008). Of the 42 diabetic patients in the

DOI: 10.1530/endoabs.49.EP621

sample, HbA1c values were determined at 12 months in 27 of them (17 DM1 and

10 DM2). HbA1c at baseline in this group was 9.17G2.29%; At 6 months 8.13G

1.58% (PZ0.007) and at a year 8.05G1.25% (PZ0.007). In DM1 at the

beginning 8.64G1.47%, at 6 months 7.93G1.48% and at 12 months 8.06G1.1%.

In DM2 at baseline, 10.07G2.72%, at 6 months 8.48G1.75 (PZ0.019), at

EP622

12 months 8.02G1.78% (PZ0.009).

Modern treatment approaches of patients with type 2 diabetes and

Conclusions

non-alcoholic fatty liver disease

Attending courses in Diabetes Education significantly improved glycemic control

Kateryna Kondratiuk¹, Nazarii Kobyliak¹, Petro Bodnar¹,

in all our patients. The type 2 diabetic group showed the greatest improvement in

Mykola Lysianyi³, Liudmyla Belska³ & Valentyna Kondratiuk²

glycemic control, obtaining even greater reduction of HbA1c at one year of the

¹Bogomolets National Medical University, Kyiv, Ukraine;²State Institution

Education course. This is probably because it is the group that most benefits from

“Institute of Pediatrics, Obstetrics and Gynecology of NAMS of Ukraine”,

lifestyle modification.

Kyiv, Ukraine;³State Institution “Institute of neurosurgery named after

DOI: 10.1530/endoabs.49.EP623

academician AP Romodanov of NAMS of Ukraine”, Kyiv, Ukraine.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP624

Introduction

Real-time detection of hazardous changes in blood glucose at the first

Gestational Diabetes Mellitus

(GDM) is a pregnancy complication that has

trimester of pregnancy in women with type 1 diabetes: a pilot study

experienced a worldwide growth. The use of insulin has to be considered as it may

Orit Barenholz-Goultschin^1,2 & Michal Shauly-Aharonov¹

be beneficial for both the mother and the new-born.

¹Shaare Zedek Medical Center, Jerusalem, Israel;²Hebrew University,

Methods

Jerusalem, Israel.

Retrospective analysis of all cases of GDM, and the respective new-borns (NB),

followed in our obstetrics unit between 2012 and 2015. Clinical and workup

parameters were evaluated in 2 groups: GDM with no insulin therapy (GDMNIT)

Introduction

and GDM with insulin therapy (GDMIT). Data analysed using SPSSv23.0.

Type 1 diabetes (T1D) in pregnancy is known to be associated with increased

Results

risks of birth defects and miscarriages. Despite the technological improvement

We studied 644 GDM and 35% of them were treated with insulin. The BMI was

and availability of continuous glucose monitoring (CGM), women with T1D who

significantly higher in GDMIT (P!0.001). Induced labour occurred in 36% of

are adequately controlled according to CGM average and HBA1C still face these

GDMNIT and in 40% of GDMIT, with statistically significant difference

complications. Glucose variability was suggested as an explanatory factor of the

(PZ0.027). The number of C-sections was superior in GDMIT (41 vs 36%), but

difference between actual obstetric outcome and the expected outcome according

without significant difference. The need for hospitalization of the NB in the

to currently available monitoring tools.

Neonatal Intensive Care Unit (NICU) was significantly higher in GDMNIT. The

Aim

NB weigh (Fenton) was also significantly different between both group

To present an algorithm and to verify that it has a practical potential to notify early

(PZ0.019), with “large for gestacional age” being higher in GDMIT (7 vs 3%).

enough of increased risk of miscarriage or birth defect.

Postpartum positive screening for Diabetes Mellitus was 0% in GDMNIT and 2%

Methods

in GDMIT.

Change-point detection methods were applied on CGM data of eight pregnant

Conclusions

women with T1D during the entire first trimester of pregnancy.

One of the indications for induced labour is GDMIT because of the higher risk of

Results

fetal complications, which was verified in this study. As the literature states,

Seven pregnancies ended with good outcome and one pregnancy ended at a late

GDMIT is associated with a difficult blood sugar control during pregnancy. This

miscarriage (patient H). The average first trimester HbA1C of the pregnancies

means that an unsuccessful maintenance of euglycemia may be associated to

with good outcome was 6.58G1.2 (range 5.1-8.8), which is similar to the HbA1C

heavier NB and eventual peripartum complications. However, GDMNIT was

of the pregnancy that ended with a late miscarriage (6.6). The daily averages of

associated with more hospitalizations in NICU, and the main causes were

CGM data were not higher for patient H. Nevertheless, the statistical method

prematurity, hyperbilirubinemia and acute respiratory distress syndrome. The

(aimed at detection of an increase in the hourly StDev of glucose levels) did detect

results of postpartum screening are in accordance with the literature.

an exceptional elevation of glucose variability of patient H, at 8 weeks of

pregnancy, which was 7 weeks before the actual miscarriage. Namely, we could

DOI: 10.1530/endoabs.49.EP626

have predicted this poor outcome early enough to lessen glucose variability.

Conclusions

Analysis of eight first-trimester follow-ups (of more than 1600 hours z 20,000

measurements for each patient) showed the change-point detection method to fully

discriminate between proper pregnancies and pregnancies with adverse outcome.

This approach might serve as an additional tool to detect pregnancies at risk in real-

EP627

time and to plan better glucose control in order to improve pregnancy outcome.

Evaluation and descriptive analysis of our type 1 diabetes population

DOI: 10.1530/endoabs.49.EP624

and their insulin therapy

Cristina Díaz Perdigones, Araceli Mun˜ oz Garach, María Molina Vega,

Carmen Hernández García, Miguel Damas Fuentes &

Francisco J. Tinahones Madue

˜o

EP625

Endocrinology, Malaga, Spain.

Sense of coherence and glycaemic control among a sample of newly

diagnosed type II diabetics in rural Crete

Objectives

Dimitrios Anyfantakis^1,2, Anastasios Anyfantakis⁴, Michaela Foukaki³

To evaluate the different insulin regimens and types of insulin used in our

& Serafim Kastanakis²

population of type 1 diabetes (DM1) patients in the last revision in our clinic.

¹Primary Health Care Centre of Kissamos, Chania, Crete, Greece;²Saint

Method

George General Hospital of Chania, Chania, Crete, Greece;³Day-Care

A descriptive study was carried out in our population of 535 DM1 patients. They

Center for Elderly, Gortyna’s Municipality, Heraklion, Crete, Greece;

had their initial diagnosis between 1967 and 2014.

⁴Endocrinology Department, Veneizeleio Hospital, Heraklion, Crete,

Results

Greece.

In our population, 47.3% were women and 52.3% were men. The mean age of our

patients was 33.8 years (S.D. G12.31 years) and the mean age of diagnosis was

Aim

16.67

(S.D. 11G years). 17.39% of our population was taking antiplatelet therapy.

Currently there is much discussion on the protective effects of the sense of coherence

17.4% had hypertension, and 36% cdyslipidemia. There were 22.9% smokers and

(SOC) on health. Our aim was to examine possible associations between SOC and

10.3%. who had given up. The glycated hemoglobin value was 7.8 (S.D. G1.28%)

glycemic control among 60 newly diagnosed adults with type 2 diabetes.

and the body mass index 27.18 (S.D. 4G kg/m²). 91% had previously received

Methods and results

diabetic education assistance, and 32.1% completed the program. Total insulin

Thirty males and 30 females diagnosed 3 months before with type 2 diabetes

dose was 40.52 units (S.D. G29.9 IU) with 0.68 (S.D. G0.33 U/kg). Insulin

mellitus were included in the study. SOC was measured with the Greek translated

regimes used were: basal-bolus 91.3%, basal alone 1.5%, prandial plus mix 2.7%

and validated version of Antonovsky’s

item sense of coherence scale.

and mix combination 4.5%. In those using basal-bolus regimen, 42.67 (S.D. G

Biochemical tests and blood pressure measurements were also performed in all

25.8%) of total insulin dose (TID) was prandial insulin and basal insulin 54.05

participants. SPSSv 20 was used for the statistical analysis. Blood pressure has been

(S.D. G17.2%):

associated with low sense of coherence levels (P!0.001). Remarkably albuminuria

- Prandial insulins used were: lispro 41%, aspart 46.5%, glulisin 7.7% and regular

presence has been associated with poor SOC (P!0,001) while good glycemic

4.9%.

control presented a statistic significant positive association with SOC (P!0.001).

- Basal insulin used were: glargine 85.4%, detemir 13.5%, lispro protamine 0.2%,

Conclusion

NPH 0.8%.Time of injection was breakfast in 17.9%, lunch 15.8%, dinner 17.6%,

Further future investigations are required in order to address the effect of SOC on

before bedtime 34.2%; 14.5% in split doses. In 86%, the split dose regimen was

diabetic patients

given breakfast and dinner and 14% breakfast and before bedtime. We observed a

DOI: 10.1530/endoabs.49.EP625

higher dose of insulin among patients with two daily doses of basal insulin: 35.9

(S.D. G20) vs 25.54 (S.D. G12.2) IU (P !0.05).

Conclusions

Basal-bolus therapy is the most used regimen in our DM1 population. Those

patients using two basal doses per day needed higher TID. The majority of our

EP626

patients had educational support but less than a half complete the educational

Gestacional diabetes mellitus with and without insulin therapy: a case

program. It is important to aware our patients to finish these activities to better self

study

control of their disease.

Francisco Evora, Marta Pinto & Céu Almeida

DOI: 10.1530/endoabs.49.EP627

Bissaya Barreto Maternity - CHUC, Coimbra, Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP628

EP630

Effects of dapagliflozin in treatment of gastroparesis considering the

Determinants of patient’s adherence and its relation to therapeutic

state of carbohydrate metabolism in patients with type 2 diabetes

success after hospital admission for decompensated diabetes

mellitus

Daniela Magalhães^1,2, Ana Saavedra^1,2, Pedro Souteiro^1,2, Rita Bettencourt-

Iryna Kostitska

Silva^1,2, Maria Manuel Costa^1,2, José Luís Castedo^1,2, Paula Freitas^1,2,

Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine.

Cláudia Nogueira³, Joana Queirós^1,2 & Davide Carvalho^1,2

Diabetic gastroparesis (DG) is associated with high morbidity and is the most

¹Department of Endocrinology, Diabetes and Metabolism of Centro

common precipitating factor to decompensation of carbohydrate metabolism.

Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, Porto,

SGLT2 inhibitors are becoming a common and useful drug to treat type 2

Portugal;³Department of Endocrinology of Centro Hospitalar de

diabetes. Principle treatment of gastroparesis considering the state of

Trás-os-Montes e Alto Douro, Vila Real, Portugal.

carbohydrate metabolism in patients with type 2 diabetes mellitus are very

limited. The aim of this study was to compare the effects of dapagliflozin for

Introduction

management patients with DG. 16 patients with type 2 DM were randomly

Diabetes mellitus (DM) is a chronic disease that requires continuous medical care. Health

allocated into 2 groups: a first group (nZ8 (3M/5F), mean age was 41.4G6.7

care providers should adopt approaches that improve patient outcomes and adherence.

years old, DM during 12.2G5.4 years, body mass index (BMI) was 33.7G

Aims

1.4 kg/m²) with gastroparesis, and a second (control) group (nZ8 (4M/4F), mean

To evaluate the adherence to Endocrinology ambulatory follow-up after elective hospital

age - 45.3G3.9 years old, DM - 13.2G6.2 years, BMI - 32.9G2.5 kg/m²) to take

admission for decompensated DM and to determine the relationship between adherence

dapagliflozin (daily doses -10 mg) for 3 months. Gastric emptying rate (GER)

and therapeutic success after discharge.

measurement with the help¹³C-octanoic breath test (¹³C-OBT), prandial and

Methods

postprandial glucose levels and glycated haemoglobin (HbA₁C) were performed

Retrospective study of 86 patients admitted at Endocrinology department in 2014-

at entry and at end of treatment period as well. Low gastric motility has been

2015. Two types of assessment were available after discharge: consultation and

diagnosed in all patients first group with help of¹³C-OBT: T¹

98.84G

blood analysis. Adequate adherence was defined by the compliance to R80% of the

4.22 min, in the second group that result is T¹² - 69.82G9.23 min. After the end

evaluations. We considered therapeutic success as A1c reduction R1.5% after

of 3 months therapy in the first group significantly improved T¹²

-83.11G

discharge and persistence of success as no increase of A1c after success achievement.

2.31 min (P!0.05). In the result after treatment we show that glycemic control to

Results

be significantly higher

(prandial glycemic-7.81G0.6 mmol/l, postprandial

After discharge, 79 patients maintained ambulatory follow-up, 62 with adequate

8.57G0.88 mmol/l, P ! 0.05) in the patients of the first group than subjects of the

adherence. Noncompliant patients were younger (52(IQR 39-60) years) than

second group (prandial glycemic- 8.44G0.34 mmol/l, postprandial - 9.28G

compliant patients (60(IQR 51-67) years) (PZ0.041). For each year of increase in

0.13 mmol/l, PO0.05). After treatment level of HbA₁C significantly decrease in

patient’s age at admission we observed a 4% increase in adherence (ORZ1.04,

both groups (P!0.05).Dapagliflozin is an useful drug for treating type 2 diabetes

95%CI 1.00-1.08, PZ0.035). Hypertensive(HBP) patients showed

88.5%

with and without of gastroparesis. Patients with DG get normalization of gastric

compliance (P!0.05). Patients with HBP, compared to those without HBP,

emptying rate. It appears that this effect may be due to non-specific mechanisms.

showed an adherence of 9.6:1 (ORZ9.60, 95%CI 2.85-32.61, P!0.001). Previous

DOI: 10.1530/endoabs.49.EP628

treatment with metformin, DPP4i and statins was associated with a 3.9-fold (ORZ

3.90, 95%CI, 1.16-13, 46, PZ0.028), 4.7-fold (ORZ4.70, 95%CI 1.22-17.87,

PZ0.025) and

3.5-fold

(ORZ3.50, 95%CI,

1.15-10.6, PZ0.027) higher

adherence, respectively. The degree of adherence to follow-up didn’t influence

the therapeutic success at 6 (PZ0.547) nor 12 months(M) (PZ0.611). Of the

compliant patients, 55.4% achieved therapeutic success at 6M, however only 26.9%

of these maintained success at 12M. On the other hand, of compliant patients who

did not achieve therapeutic success at 6M, only 20.8% achieved it at 12M.

Conclusions

Approximately 80% of our sample showed adequate adherence. Advanced age,

HBP and previous therapy with metformin, DPP4i or statin were associated with

greater adherence. Therapeutic success was not related to follow-up adherence.

EP629

DOI: 10.1530/endoabs.49.EP630

Self-monitoring of blood glucose: how are glycemic readers used in

practice?

Meriem Haddad, Samir Aouiche & Aissa Boudiba

Department of Diabetes Research CHU Mustapha Bacha, Algiers, Algeria.

Endocrine Disruptors

Introduction

EP631

In recent years, the technique of ASG has gained much in simplicity, speed and

Study of metabolic and some hormonal aspects among pubertal type 1

acceptability, using readers more and more reliable. Despite this, some patients do

diabetic girls

not acquire the skills needed to achieve it. The aim of this study is to evaluate the

Fatma Hamad & Mohsen Khalid

technical gestures of use of blood glucose readers in current practice.

National Institute of Diabetes and Endocrinology, Cairo, Egypt.

Material and method

This is a prospective descriptive study including 369 diabetics for over a year,

followed in diabetic consultation in Algiers. A questionnaire was drawn up using

Background

the following items: frequency of capillary blood glucose checks, blood glucose

The onset of type 1 diabetes before menarche was a risk factor for the subsequent

readers

(choice, number of years of use, rhythm of change), modalities of

development of hyperandrogenic disorders. It has been also suggested that the use

capillary sampling,, The possible impact on daily life.

of exogenous insulin to treat type 1 diabetes mellitus in those patients may

Results

contribute to the development of PCOS. Abnormal lipid levels were also reported

Of the 369 diabetics we found 17% type 1 and 83% type 2, sex ratio at 1, the

in children with type 1 diabetes mellitus during pubertal years.

average age is 52.6G15.5 years, with a duration of diabetes of 10.3G8 years.

Aim of work

More than half are treated with insulin. Their average HbA1c is 8.25G1.8%.

This study was designed to investigate metabolic and some hormonal changes in

Patients have more than two readers in 33.9% of cases, the latter are changed with

relation to puberty among type 1 diabetic girls.

an average rhythm of 4G2.9 years, 22.36% of patients do not systematically wash

Subjects and methods

their hands before capillary blood glucose, and use of alcohol or other antiseptics

The study was carried out on 60 girls, 40 of them were type 1 diabetic patients (the

is observed in 32.5% of patients, 59.2% use recommended sites for stitching,

diabetic group), subdivided into two groups (according to age and Tanner breast staging),

alternative stitch sites are never used, the regular change of the lancets is observed

and 20 of them were normal healthy girls (the control group), also subdivided into two

in 2/3 of the cases and the elimination of the lancets is done with the household

groups (according to age and Tanner breast staging). All girls were subjected to full

waste In 86% of cases.

history taking, thorough clinical examination, estimation of fasting blood glucose and

Conclusion

HbA1c (as an estimation for glycemic control), lipid profile, hormonal profile (FSH, LH

Learning from the GSM must be included in a therapeutic patient education

and free testosterone) in addition to pelvic ultrasound.

program, as the Haute Autorité de Santé1 has highlighted, practical workshops

Results

will help them to master the GSM and easy use of the blood glucose meters.

There is an increased frequency of dyslipidemia in the form of hypercholesterolemia

DOI: 10.1530/endoabs.49.EP629

and increased levels of LDL among type 1 diabetic girls, and pubertal type 1 diabetic

girls show higher BMI and cholesterol levels compared to controls, and also show

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

higher levels of LDL compared to prepubertal type 1 diabetic children. Age at

Observations

menarche is delayed in pubertal type 1 diabetic girls having PCOS, while not delayed in

We report the case of a patient, aged 32 years with a personal history of total

those without PCOS but positively correlated to the longer duration of diabetes and

gastrectomy for gastric adenocarcinoma, regularly followed surgery consultation,

with the level of HbA1c. Both the frequency of PCOS and the level of free testosterone

a family history of diabetes and hypertension. The onset of the disorders dates

are higher in pubertal type 1 diabetic girls compared to their normal controls.

back to a postoperative month marked by the appearance of signs of adrenergic

DOI: 10.1530/endoabs.49.EP631

hypoglycemia without glycogenic signs in late postprandial periods i.e. 2-3 h

after a meal. Capillary glucose levels were made with regard to clinical

symptomatology Have returned to

!0.50 g/l. Patient in average general

condition with a normal BMI of 19 kg/m². Remainder of the review is without

peculiarities. On the biological level, GAJ: 0.79,. GR 3.6, Hb 10.3, VGM 91,

CCMH 31%, GB 5360, Correct renal count: MDRD at 107. Hepatic balance

without abnormalities. Malabsorption balance: Normal calcium an 2.28 mmol/l,

Phosphoremia:

1.46 mmol/l, Serum iron:

9.65 mmol/l. ECG and Telthorax

EP632

without abnormality. Glycemic variability is high in our patient, with

Bone-to-muscle endocrine axis modulating adaptation to exercise in

hypoglycemia and abnormalities in the glycemic Holter

(CGMS) or even

athletes of mountain cycling in a Portuguese Marathon

recording.The symptoms disappeared following a dietary treatment with

Isanete Alves de Alonso¹, Andreia Matos^1,2, Ângela Gil^1,2, Carlos Cardoso³,

improvement of the quality of life of the patient, without any medicinal

Luis Bettencourt Sardinha⁴ & Manuel Bicho^1,2

intervention.

¹Genetics Laboratory and Environmental Health Institute of Faculdade de

Discussions

Medicina da Universidade de Lisboa, Lisbon, Portugal;²Instituto de

Hypoglycemia of the syndrome is hyperinsulinic, by histological abnormalities of

Investigação Científica Bento da Rocha Cabral, Lisbon, Portugal;

the pancreas (neisidioblastosis), and/or by stimulation of insulin secretion by

³Laboratório de Análises Clínicas, Grupo Dr Joaquim Chaves, Lisbon,

incretin, including glucagon-like peptide-1 (GLP-1). The absorption of glucose is

Portugal;⁴Exercise and Health Laboratory, CIPER, Faculty of Human

both accelerated and exaggerated due to direct communication between the

Kinetics, Universidade de Lisboa, Lisbon, Portugal.

stomach and duodenum. It is an exaggeration after the surgery of a phenomenon

of adaptation which exists in the non-operated ones to whom the glucose is

Introduction

infused directly in the duodenum. Patient semiology is not always accompanied

Besides the benefits of low-to-high intensity physical activity

(PA) on

by biological abnormalities. However, if hypoglycaemia is severe and

metabolism, it is currently emerging that excessive PA can be deleterious with

neuroglucopenic symptoms, hyperinsulinemia is constant. For the other cases,

serious implications not only in muscle but also, bone remodeling. Despite recent

the possibility that stress and physical exercise increase the semiology. The

findings remains still unclear and controversial, we hypothesize that exercise of

treatment consists of dietary measures: split the diet into 5 or 6 meals, slow down

impact, like mountain cycling, beyond influencing the metabolic and skeletal

gastric emptying, reduce glycemic load and glycemic index of food, avoid stress

profile, represents an important model of profoundly changes in bone metabolism.

at mealtime. Acarbose is also effective; other treatments (insulin, glucagon,

calcium channel blockers, hyperglycaemic sulfamides, somatostatin analogs,

Methods

GLP-1 analogues) have not been validated on a sufficient number of subjects to be

55 participants

(mean age 44.8G7.1 years old) of mountain cycling race

recommended.

(TransPortugal) were evaluated at the beginning/basal (M0) and 9-days post-race

Conclusion

(M9). Anthropometric/body composition parameters, haematological and liver

It is necessary to educate the patients operated on for gastric surgery, after the

function were evaluated by conventional methods. Serum Irisin and plasma

resumption of the oral feeding, so that he learns how to manage his functional

osteocalcin and IL-6 measurements were evaluated with ELISA (R&D systems

disorders, that he understands the interest of a supplementation, of fat soluble

and Phoenix Pharmaceuticals-Irisin). Statistical analyses included departure from

vitamins and Calcium and accepts the idea of regular clinical, biological and

normality and adequate parametric or non-parametric test to compare the means

ideally osteodensitometric monitoring, unlimited in time.

and the medians. The results were significant for P!0.05.

Results

DOI: 10.1530/endoabs.49.EP633

In the metabolic point of view, we found that this strenuous exercise induced a

significant decrease of fasting insulin, triglycerides, total-cholesterol, non-HDL

cholesterol, LDL and an increase of glucose, creatinine, uric acid, HDL, HOMA-

B (P!0.05). These results reflected the important modifications in muscle, being

the myokine/adipokine, irisin, significantly decreased post-race (PZ0.002). In

EP634

terms of bone remodelling, although not statistically significant, osteocalcin was

decreased post-race (PZ0.154), yet the plasma IL-6, a cytokine involved in

A case report of insulinoma in a patient with chronic headache

Enalda Demaj & Marjeta Kermaj

osteoclastic proliferation, was significantly increased post-race (P!0.0001).

¹Regional Hospital of Berat, Berat, Albania;²University Hospital Center

Conclusions

‘Mother Theresa’, Tirana, Albania.

Our preliminary results, revealed a possible regulation of osteocalcin in glucose

and insulin metabolism, being the slowdown in bone formation observed, a

prompt metabolic response of bone to the increased energy demands of the

Introduction

muscle.

Pancreatic endocrine tumors are rare lesions, with an incidence of 4 cases per 1

DOI: 10.1530/endoabs.49.EP632

million pts-yr. Of these lesions,insulinomas are the most common. The

nonspecific symptoms and small sizes of these tumors led to difficulties of

diagnosis and localization.

Case report

A 60 year female pts, had history of episodic and repetitive symptoms of strong

headaches for the last 5 years; which were relieved with eating or taking glucose

Endocrine tumours and neoplasia

water orally. She noticed increased appetite over the past few years. No

medications at the time of evaluation. She was obese. Normal visual field exam.

EP633

On admission serum glucose level 55 mg/dl, insulin, c-peptide in normal range.

Dumping syndrome post total gastrectomy

Prolonged supervised fasting test was applied and produced symptomatic

Samir Ait Abderrahmane, Soumia Abdelkrim, Fadoua Boucelma,

hypoglycemia (33 mg/dl), with slightly elevated insulinemia

26 mU/l(4-23),

Lila Brakni & Brahim Oudjit

normal levels of C-peptide, cortisolemia and chromogranina A; interrupted on the

HCA, Kouba, Algeria.

first day after 5hours.Abdominal RMN with contrast demonstrated a well-defined

hypervascular lesion involving head-body of pancreas measuring about 1.6 cm.

Introduction

Postoperatively the patient was discharged in good health with normal glucose

Dumping syndrome, also known as rapid gastric emptying, is a relatively rare

level.

disorder. It is conventionally due to the brutal flooding of the small bowel by a

Conclusion

hyperosmolar food bolus and to the release of various digestive hormones whose

Insulinoma remains a diagnostic challenge to practitioners. This case illustrated

real responsibility in the syndrome remains poorly known. It is usually a

the importance of carefully questioning and examining patient for subtle

complication of the gastrectomy (10 to 40% of the cases). Hypoglycemia after

symptoms and signs of hypoglycemia. A chronic headache may hide an

surgery for digestive cancer is sometimes severe, but rare, and revealed by the

insulinoma.

monitoring of blood glucose, and then more frequent. The variability of the

Keywords: insulinoma, headache

definitions in the studies supports a single definition, Whipple, with a blood

DOI: 10.1530/endoabs.49.EP634

glucose level below 0.55 g/l.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Female Reproduction

signaling, suggesting a change in the type of oxidative metabolism in the muscle

tissue and increase in adipogenesis.

EP635

DOI: 10.1530/endoabs.49.EP636

Real-time continuous glucose monitoring during pregnancy in women

with type 1 diabetes: glycemic control and key obstertric outcomes

Harold de Valk¹, Judith van Niel², Bianca Silvius¹ &

Nel Geelhoed-Duijvestijn²

¹University Medical Center, Utrecht, The Netherlands;²Medisch Centrum

Haaglanden, den Haag, The Netherlands.

EP637

Introduction

The evaluation of sexual function of women with type 1 diabetes mellitus

Real time continuous glucose monitoring (RTCGM) has been shown to improve

Edita Prakapiene², Kornelija Bagdonaite¹, Lina Radzeviciene^2,3 &

glycemic control. Limited data are available on the effects of RTCGM during

Birute Zilaitiene^2,3

pregnancy. The current study assesses glycemic control and obstetric outcomes in

¹Faculty of Medicine, Lithuanian University of Health Sciences (LUHS),

women with type 1 diabetes, comparing RTCGM with usual self measurement of

Kaunas, Lithuania;²Department of Endocrinology, Lithuanian University of

blood glucose (SMBG).

Health Sciences (LUHS), Kaunas, Lithuania;³Institute of Endocrinology,

Patients and methods

Lithuanian University of Health Sciences (LUHS), Kaunas, Lithuania.

Patients were recruited from two hospitals. All patients were eligible. Glycemic

control was assessed by preconception HbA1c and HbA1c during pregnancy.

Obstetric outcomes reported are premature delivery (PD, !37 weeks), and

Aim

macrosomia (Large for Gestational Age (LGA; birth weight R90th percentile;

The aim of this study was to evaluate the influence of age, disease duration,

Very Large for Gestational Age (VLGA; birth weight R97.7th percentile).

glycaemic control and diabetic nephropathy for the sexual function of women

Results

with type 1 diabetes mellitus (T1D).

67 women were included; 53 (79%) used RTCGM PD occurred in 22% of the

Methods

pregnancies, 19.6% with RTCGM, 31% on SMBG (PZ0.5). LGA occurred in

Study subjects - 18-52 year old women with type 1 diabetes. Participants filled

58% of pregnancies, VLGA in 31%. LGA with RTCGM 61%, with SMBG 46%

the Female Sexual Function Index (FSFI) and questionnaires about T1D, disease

(PZ0.4). VLGA with RTCGM 37.5%, SMG 50%, PZ0.9). Mean HbA1c was

duration, glycaemic control and complications. Laboratory tests including

significantly lower before pregnancy

(52.1G6.1

67.8G18.4 mmol/mol,

glycated hemoglobin (HbA₁C), creatinine, testosterone, Sex hormone-binding

P!0.001) and during the first trimester

weeks:

47.9G5.4

58.9G

globulin

(SHBG), estradiol levels and albumin in

24h urine sample were

18.1 mmol/mol, PZ0.002) and

weeks

(43.9G7.0 mmol/mol vs

53.6G

performed. Postmenopausal women were excluded from the study. Female sexual

12.8 mmol/mol, P!0.05), but not later in pregnancy.

dysfunction (FSD) was diagnosed based on FSFI total score lower than 26.55.

Conclusion

Results

RTCGM was associated with better early HbA1c. Premature delivery occurred

113 women (mean age 34.82G8.34) with T1D were included to the study.

less frequently with RTCGM, macrosomia more frequent. Future analysis with

Diabetic nephropathy (DN) was diagnosed to 43.4% (mean age 35.24G9.50),

this expanding group will assess whether these differences persist; at this moment,

56.6% had no DN (mean age 34.50G7.50). FSD was diagnosed to 42.6% (NZ40)

better early control is not readily associated with less macrosomia.

of participants. Neither age nor disease duration had influence to FSD. Worse

DOI: 10.1530/endoabs.49.EP635

glycaemic control had a statistically significant impact to the prevalence of FSD

(PZ0.028). Negative correlations between participant age and FSFI subscales of

desire and arousal were observed (P!0.001). Lubrication (PZ0.015) and orgasm

(PZ0.027) subscales were negatively affected by age only in the group of DN.

Statistically significant negative impact was found between glycaemic control

and lubrication in group without DN (PZ0.009). There was no statistically

significant difference between FSFI scores or sex hormones and disease duration

EP636

or DN. Free androgen index had impact neither to the FSFI subscale scores nor to

total score. Negative SHGB and high glycaemic level correlation was observed

Differential pattern of insulin signaling in adipose tissue and skeletal

only in DN group (PZ0.031).

muscle in adult female sheep exposed prenatally to testosterone

Conclusion

Daniel Sandoval¹, Mónica P Recabarren¹, Albert Carrasco¹,

Female sexual function is often diagnosed in women with type 1 diabetes

Teresa Sir-Petermann² & Sergio E Recabarren¹

mellitus. Sexual function correlates with glycaemic control and age. Worse

¹Laboratory of Animal Physiology and Endocrinology, Faculty of

glycaemic control has negative impact to SHBG levels.

Veterinary Medicine, University of Concepcion, Chillan, Region BioBio,

Chile;²Laboratory of Endocrinology and Metabolism, Western School of

DOI: 10.1530/endoabs.49.EP637

Medicine, Universidad de Chile, Santiago, Chile.

Insulin resistance is defined as the incapacity of insulin to increase glucose uptake

by peripheral tissues

(skeletal muscle and adipose tissue principally). This

phenomenon is present in different animal models for PCOS by prenatal exposure

to androgens. In the PCOS condition, the metabolic pathway of insulin activity is

Growth hormone IGF axis - basic

defective in skeletal muscle and adipocyte whereas the activation of

steroidogenesis is maintained. The decreased insulin stimulated glucose uptake

EP638

is due to impaired signaling and multiple downstream intracellular defects

GH is related to hepatic mitochondrial activity in humans

including impaired glucose transport and glucose metabolism. Previous results

Peter Wolf, Sabina Smajis, Martin Gajdosiik, Lorenz Pfleger,

from our laboratory have demonstrated that female sheep born to mothers

Yvonne Winhofer, Christian-Heinz Anderwald, Siegfried Trattnig,

receiving testosterone during part of their pregnancy exhibit features from early

Anton Luger, Martin Krssak & Michael Krebs

postnatal life until adulthood resembling those of PCOS women. In the present

Medical University of Vienna, Vienna, Austria.

work, the programming effect of prenatal testosterone on the insulin signaling was

explored in adult females born to testosterone treated mothers (testosterone-

females), and born to untreated mothers (C-females). Our aim was to define if

Background

prenatal exposure to testosterone affects insulin signaling in adipose tissue and

Altered hepatic mitochondrial activity plays a key role in the development of

skeletal muscle. Adults females (38 weeks of age) were sacrificed and samples of

non-alcoholic fatty liver disease (NAFLD). GH has been shown to stimulate

skeletal muscle

(Gluteus superficialis) and adipose tissue

(visceral) were

mitochondrial function in skeletal muscle. Therefore we hypothesize that the time

collected. The qPCR assays were performed to analyze gene expression of IR,

course of serum GH concentrations during an oral glucose tolerance test might be

IRS-1, IRS-2, PI3K, Akt, PKC, GLUT4 and b-actin. Expression pattern of insulin

related to hepatic mitochondrial energy metabolism in vivo in humans.

signaling were similar between groups with the exception that in skeletal muscle,

Methods

IRS-2

showed higher expression in testosterone-females

(P%0.05) than

volunteers

(male/female:

7/8;

55G8 years; BMI 25G4 kg/m²) were

C-females while on the contrary, the GLUT4 RNAm was lower in testosterone-

investigated on two study days; i) oral glucose tolerance tests were performed

females compared to C-females (P%0.05). In the visceral adipose tissue, AKT

to assess dynamics of glucose, insulin, C-peptide and GH concentrations and ii)

transcript expression was higher in testosterone-females

(P%0.05) than

hepatic lipid content was measured by 1H/31P magnetic resonance spectroscopy

C-females. Results show that prenatal exposure to testosterone affects the insulin

(MRS). Saturation transfer technique was applied to assess ATP synthesis rate (k).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

Intervention

Basal GH concentrations and GH dynamics strongly correlated with hepatic

In terms of methodology, we studied: a family history of diabetes, hypertension

mitochondrial activity

(GH_baseline&k_liver:rZ0.783; P!0.001; GH_AUC& k_liver:

and dyslipidemia; Girth, body mass index (BMI), hypertension, diabetes mellitus

rZ0.676; PZ0.008). There was no association between HCL and GH, as well as

or impaired glucose tolerance and dyslipidemia in these patients.

between HCL and k_liver. Six subjects fulfilled criteria for NAFLD (HCLR5.5%).

Main outcome measure

They presented significantly higher glucose levels and insulin resistance. The

Glucose intolerance and diabetes with insulin resistance are commonly

strong relationship between GH and k_liver did not differ between patients with and

encountered complications acromegaly. Some studies have shown a direct

without NAFLD.

correlation between the rate of GH and the degree of glucose intolerance. The

Discussion

hyperinsulinemia and insulin resistance may play an important role in the

Our data indicate that basal as well as postprandial (oGTT) GH concentrations are

cardiovascular risk of these patients. The role of insulin resistance, but also of

directly related to hepatic energy metabolism in insulin sensitive and insulin

pancreatic b dysfunction has been invoked in the pathogenesis of carbohydrate

resistant humans.

metabolism disturbances secondary to chronic excess GH.

DOI: 10.1530/endoabs.49.EP638

Result

The average age was 43 years (20-63) with a sex ratio (M/F) Z0.33. The duration

of the disease at diagnosis was on average 7 years (3-14). Family history were

13.3% diabetes mellitus and heart disease. Pathological BMI was objectified in

52% of cases; 46.6% of these patients had pre-diabetes, 40% diabetic (a total of

84.6% of carbohydrate anomalies) and 46.7% had dyslipidemia. Moreover 26.6%

of our patients where hypertensive.

EP639

Conclusion

Modulation of the 22 kD/20 kD growth hormone (GH) ratio by exercise,

Approximately 84.6% in our series of cases had carbohydrate abnormalities.

fasting and glucose load in premenopausal women

Diagnostic and therapeutic delay can worsen or even cause the patient’s death.

Michael Haenelt, Katharina Schilbach, Christina Gar, Andreas Lechner,

After surgical recovery, the evolution of diabetes and/or glucose intolerance is

Rita Schwaiger & Martin Bidlingmaier

usually favorable.

Medizinische Klinik und Poliklinik IV, Klinikum der Universitat Munchen,

DOI: 10.1530/endoabs.49.EP640

Munchen, Germany.

We previously have shown in a cohort of 236 non-fasted women that before and

after a short high intensity exercise protocol

(HIP) till exhaustion serum

concentrations of 20 and 22 kD growth hormone (hGH) are highly correlated

(P!0.0001). Although the GH response to exercise exhibited huge inter-

individual differences, the 20 kD/22 kD-GH-ratio remained unchanged (9.6% vs

Neuroendocrinology

11.1%, PZ0.313). A subgroup of the women was also studied under fasted

EP641

conditions in a moderate intensity protocol, applying an exercise (70% VO2 peak)

over a longer time (mean duration 45 min). In contrast to the HIP under non-

Comparison of GHRH C arginine vs glucagon test for the evaluation of

fasted conditions, baseline and post exercise

20 kD/22 kD GH ratio were

growth hormone secretion status in a cohort of adults with Prader-Willi

significantly higher in the fasted protocol

(mean 15.33% vs. mean 10.85%,

syndrome (PWS)

PZ0.0021). To further investigate the impact of fasting and glucose intake on the

Laia Casamitjana, Giménez-Palop Olga, Corripio Raquel, Pareja Rocío,

20 kD/22 kD-GH-ratio, we analyzed GH isoform secretion before and after an

Hurtado Marta, Gabau Elisabet, Cobo Jesús, Berlanga Eugenio,

oral glucose tolerance test (OGTT, 75 g glucose) in a subset of the cohort (nZ60;

Cano Albert, Albert Lara, Rigla Mercedes & Caixàs Assumpta

mean age 36 years (yr), range 20-44yr; BMI: mean 23, 2 kg/m²). GH isoforms

Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc

were measured using the IDS-iSYS GH CLIA specific for 22 kD GH and an

Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona,

in-house IFMA for 20kD GH (LoQ 0.025 ng/ml), respectively. 20 kD GH was O

Spain.

LoQ of the assay in all subjects at baseline and in 86% 60 minutes after glucose

ingestion. At baseline, fasting 20 kD/22 kD ratio in the subset was 12.9%. Ratio

Background

was not changed 60 min after glucose intake (12.3%; PO0.05). Due to the

Prader-Willi syndrome (PWS) is a rare genetic disorder evolving morbid obesity

expected suppression of GH following glucose intake, after

120 min the

and growth hormone deficiency (GHD). Testing GH-IGF1 axis is required before

20 kD/22 kD-ratio could only be measured in 18.3% of the subjects, but no

treatment with rhGH in adults with PWS (1). The most common used tests in

significant change in the abundance of 20 kD GH was observed (mean ratio

these patients are GHRHCarginine (GHRHCa) and insulin tolerance test. There

12.1%; PO0.05). In conclusion, the 20kD/22kD-GH ratio is lower in the non-

are no prospective data for glucagon test (GT) in comparison to GHRHCa in

fasted compared to the fasted state, both at baseline and following exercise.

adults with PWS. Mechanism by which GT causes GH release remains unclear,

However, short-term oral glucose intake per se does not significantly influence the

glucagon-induced GH release via noradrenaline secretion has been postulated.

20 kD/22 kD-GH ratio.

Objectives

DOI: 10.1530/endoabs.49.EP639

To compare two diagnostic tests to evaluate GH secretion status in a cohort of

adults with PWS.

Methods

Twenty-one SPW (8M and 13F, aged 29(17-51), BMI 36.2C/K10.2 kg/m²)

participated in the study. After an 8-10 h fast, all patients underwent the two

different provocative tests in separate days: GHRH (1 mg/kg, max 100 mg) C

arginine (5 g/kg, max. 30 g) and GT (1 mg). We considered GHD according to

BMI-specific cut-offs in GHRHCa (2) and when GH peak was !3 ng/ml in GT.

EP640

Results

Insulin resistance and acromegaly: about 15 cases

With the GHRHCa test, 14 of 21(66⁰ 7%) met diagnostic criteria for GHD and 19

El Ansari Nawal & Sara Askaoui

of 21 (90%) with GT. Only two patients did not meet criteria for GHD with both

Service of Endocrinology Diabetes and metabolic diseases, Cadi Ayad

tests. Most patients achieved GH peak at minute 45: 3.31 ng/ml (1.6-9.6), median

University, CHU Mohamed VI., Marrakech, Morocco.

(interquartile range) with GHRHCa test, whereas GH response was blunted with

GT. After the glucagon injection, an increment in plasma glucose levels was

Contexte

observed at 30 min with a peak at 60 min. One patient suffered an asymptomatic

Acromegaly is a rare disease, usually caused by hypersecretion of growth

hypoglycemia during the test.

hormone (GH) by a pituitary adenoma and very rarely by ectopic secretion of

Conclusions

GHRH. It remains a serious disease reduces life expectancy because of its

Glucagon seems to fail to stimulate GH in adults with PWS. Further studies are

cardiovascular and metabolic impact.

necessary to elucidate if the underlying autonomic dysfunction described in PWS

Objective

could be involved.

The objective of this study is to report the glycemic profile in patients followed for

References

acromegaly in the endocrinologic center of CHU Med VI of Marrakech.

1. J Clin Endocrinol Metab, 2013,98:E1072-E1087.

Patient - Intervention

2. Ther Clin Risk Manag 2016, 12;873-81.

We performed a retrospective study over a period of 2 years. Fifteen cases were

DOI: 10.1530/endoabs.49.EP641

identified.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Nuclear Receptors and Signal Transduction

drinking, exercise habit, medication and sleep condition were assessed by

multiple regression analysis. Having a short lunch time, preferring salty taste,

EP642

snacking after dinner and dinner within

2 h before sleep were positively

Dietary intake of linoleic, linolenic, oleic, and arachidonic acid PPAR-

associated with BMI, WC and WHO-5 score after adjusting for all confounders.

gamma gene expression in visceral and subcutaneous adipose tissue

Although eating vegetable and fruits were not independent of BMI, both are

among healthy subjects

positively associated with WHO-5 score. The present data demonstrate that

Emad Yuzbashian^1,2, Maryam Zarkesh³, Golaleh Asghari¹,

adjusting meal intake behavior could be helpful in preventing psychological

Azita Zadeh-Vakili³, Behnaz Mahmoodi¹, Afsoon Daneshafrooz³,

distress as well as obesity.

Mehdi Hedayati³ & Parvin Mirmiran¹

DOI: 10.1530/endoabs.49.EP643

¹Nutrition and Endocrine Research Center, Research Institute for Endocrine

Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran;

²Student Research Committee, Biochemistry of Nutrition Research Center,

School of Medicine, Mashhad University of Medical Sciences, Mashhad,

Iran;³Cellular and Molecular Endocrine Research Center, Research

Institute for Endocrine Sciences, Shahid Beheshti University of Medical

Sciences, Tehran, Iran.

Objective

To investigate whether peroxisome proliferator-activated receptor gamma

EP644

(PPAR-gamma) gene expression in visceral and subcutaneous adipose tissue

A comparison of the metabolic parameters of obese and non-obese nafld

was related to intake of several fatty acid intakes.

patients with insulin resistance

Methods

Pinar Karakaya¹, Bahar Pehlivan², Meral Mert¹, Hamide Karagoz¹ &

For the current study 97 subjects (41 non-obese, 18 obese, and 38 morbid obese)

Yildiz Okuturlar²

were selected. All of the subjects were free of diabetes and cancers and without

¹Department of Endocrinology, Bakirkoy Sadi Konuk Training and

using anti-lipid medication. Visceral and subcutaneous adipose tissues were

Research Hospital, Bakirkoy, Turkey;²Department of Internal Medicine,

obtained during an abdominal open surgery with minimal impact on dietary

Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Bakirkoy,

intake. The PPAR-gamma gene expression was assessed by Real-Time PCR.

Turkey.

Usual dietary intake was measured using a validated semi-quantitative food

frequency questionnaire. For calculation linoleic (18:2), linolenic (18:3), oleic

Introduction-aim

(18:1), and arachidonic acid (20:4) intakes, the USDA Food Composition Table

Non-alcoholic fatty liver disease (NAFLD) is a clinical condition of uncertain

was used.

etiology, in whose pathogenesis several mechanisms are involved and which is

Results

defined by fat vacuoles in more than 5% of hepatic histiocytes in the absence of

The PPAR-gamma expression in visceral adipose tissue among non-obese

serious alcohol consumption. It is frequently comorbid with obesity and insulin

subjects was correlated with oleic acid (rZK0.417, PZ0.007) and linoleic acid

resistance. However, NAFLD is also seen in non-obese individuals. The purpose

(rZK0.401, PZ0.009). Were seen significant correlations between subcu-

of this study was to compare insulin resistance and metabolic parameters in obese

taneous adipose tissue PPAR-gamma expression and linoleic acid (rZK0.310,

and non-obese NAFLD patients.

PZ0.049) among non-obese subjects. PPAR-gamma expression among obese

Materials-method

subjects in visceral adipose tissue was correlated with oleic acid (rZK0.686,

50 obese (BMI OZ30) and 50 non-obese (BMI !30) presenting to the Bakırkoy

PZ0.002) and linolenic acid (rZK0.699, PZ0.031) and also in subcutaneous

Dr. Sadi Konuk Education and Research Hospital Endocrinology, Diabetes and

adipose tissue was correlated with oleic acid

(rZK0.453, PZ0.048).

Obesity Clinic with hepatic steatosis determined at ultrasonography (USG) and

Furthermore, among morbid-obese subjects PPAR-gamma expression in visceral

with no causes such as alcohol use, viral diseases or drug use to account for fat

adipose tissue was correlated with linoleic acid (rZK0.336, PZ0.039) and in

deposition and consenting to participate were included in the study. Patients’

subcutaneous adipose tissue was correlated with linoleic acid

(rZK0.326,

demographic characteristics, biochemical tests and insulin levels were

PZ0.046) and oleic acid (rZK0.352, PZ0.030). Were seen no significant

investigated. Insulin resistance was determined using homeostasis model

association of dietary intakes of arachidonic acid with PPAR-gamma gene

assessment (HOMA-IR), a mathematical technique, with the formula fasting

expression.

insulin (U/ml) ! fasting glucose (md/dl)/405. Insulin resistance was defined as

Conclusions

HOMA-IR O2.5.

PPAR-gamma gene expression was negatively correlated with linoleic and oleic

Results

acids among non-obese and obese subjects.

One hundred patients with NAFLD, 63.3% female, were enrolled in this study.

Conflict of Interest

Fifty were obese and 50 were non-obese. Mean age was 44.1G11.1 years.

None of the authors has any personal or financial conflict of interest.

Hepatomegaly accompanied steatosis in 55% of patients. Mean BMI was 37.3G

Funding

5.63 in the obese group and 28.2G1.35 in the non-obese group. Mean blood sugar

Not applicable.

values were 99.3G9.78 in the obese group and 103.40G8.3 in the non-obese

DOI: 10.1530/endoabs.49.EP642

group, and the difference was not statistically significant (P:0.08). Insulin levels

were 10.1G3.3 in the obese subjects and 13.85G12.3 in the non-obese subjects,

while HOMA-IR values were 3.48G3.38 in the obese subjects and 2.57G.91 in

the non-obese subjects, and the difference was not statistically significant

(PO0.05). Insulin resistance was determined in 60% of obese patients and 50% of

non-obese patients (in 55% of the entire group). The difference was not significant

(P:0.3). When the general characteristics and metabolic parameters of the groups

Obesity

with and without insulin resistance were compared

(Table

1), significant

differences were observed in terms of BMI, waist circumference, insulin level,

EP643

HOMA-IR, GGT and indirect bilirubin levels, but none between the other

Association between meal intake behavior and body

parameters.

composition/psychological well-being in Japanese adults

Toshihiro Takao, Yoshiyuki Yamanaka, Sohachi Fujimoto &

Tomoari Kamada

Table 1

Kawasaki Medical School, Kurashiki, Japan.

Parameter

With IR

Without IR

P value

The study aims to evaluate the association between body composition/psycho-

logical well-being with meal intake behavior such as eating fast, snacking after

Age

46.48G11.77

41.3G9.78

0.072

dinner, dinner within

2 h before sleep. This cross-sectional study includes

Sex

F: 52.6%

F: 47.4%

0.098

nZ3066 participants aged 19-89 who had participated in an annual health

BMI (kg/m²)

34.48G6.84

30.71G4.5

0.017

checkup in 2015. BMI, Waist circumference

(WC) and the World Health

Waist

103.67G10.72

97.07G10.79

0.022

Organization (WHO)-5 Well-Being Index were assessed to determine. The meal

circumference (cm)

intake behavior were assessed with a modified questionnaire based on focused on

FBS (mg/dl)

103.88G8.63

98.26G9.17

0.01

metabolic syndrome in Japan. In addition, the relation with BMI/WC/psycholo-

Insulin (IU/dl)

15.62G10.99

7.55G1.88

0.000

gical well-being and meal intake behavior by controlling age, smoking, alcohol

HOMA-IR

4.03G3.01

1.79G0.42

0.000

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

authentic metabolic syndrome including obesity is very rare, though possible,

We compared metabolic parameters of obese and non-obese patients with

with a mixed clinical picture. The goal of our study is to evaluate the association

NAFLD and insulin resistance. Insulin resistance was present in 55% of the total

of type 1 diabetes with the metabolic syndrome.

group. We observed significant differences between insulin levels, HOMA-IR,

Material and methods

GGT and indirect bilirubin levels in subjects with insulin resistance. In

This is a retrospective cross-sectional study based on the observation of patients

conclusion, we think that fatty liver disease is by itself a risk factor for insulin

admitted for diabetes with insulin deficiency. The positivity of anti-pancreas

resistance independent of obesity, and that GGT and indirect bilirubin levels in

antibodies testified to the auto-immune characteristic; anti glutamic acid

particular can show insulin resistance in patients with hepatic steatosis.

decarboxylase GAD and/or anti tyrosine phosphatase IA2. The goal of the

Key words: Non-alcoholic fatty liver disease, insulin resistance, GGT

study is to determine the patients’ clinical and biological aspects as well as their

metabolic profile.

DOI: 10.1530/endoabs.49.EP644

Results

Our series was conducted with 359 patients: 209 men and 150 women, aged

between 10 and 69 years with an average of 28.75 years. Metabolic heredity was

found in 26 patients (7.2%), Diabetes heredity in 216 patients (60.1%); 147

(40.9%) of whom with type 2 history and 69 (19.2%) with type 1 history. Vascular

heredity was found in 27 patients (7.5%). 117 patients (32.6%) were smokers and

alcohol consumption was found in 85 of them (23.7%). The clinical picture was

ketotic in the majority of cases: 336 (93.6%), with inaugural ketosis in 313 cases

EP645

(87.2%). Insulin deficiency varied between one week an 36 months, with an

Associations between dietary food patterns and metabolic syndrome

average of 3.75 months and a standard deviation of 6.8 months, exceeding 6

risk in Albanian adolescents

months achieving a slow form and a previous oral treatment in 24% of cases.

Alba Themeli & Edmond Pistja

Regarding weight, the average BMI was 22 (extremes: 15 and 39), over 30 in

Medical Training Center Santa Maria, Lezhe, Albania.

22 patients. Overweight was more significant in patients over 20 years old, with

6% in the younger population, 14% between the ages of 20 and 40, and 34% in the

Background

patients over 40 years of age. Regarding waist size in women, a size over 80 cm

Adolescence is a period of rapid body growth and cognitive development,

was more significant in patients over 40 (38%) against 4% in women younger than

requiring balanced and sufficient nutrient intake. Since dietary habits are usually

20. Men’s waist size over 94 cm was more significant in patients over 40 (19%),

acquired in this period and could affect dietary practice in later life. It is crucial for

against 4% in the ones younger than 20. An obesity previous to the discovery of

adolescents to acquire healthy dietary behaviors for long-term health. However,

Diabetes was found in 80 patients (22%). Hypertension was found in 14 patients

the prevalence of diet-related metabolic syndrome risks such as obesity, glucose

(4%). Upon admission, average blood sugar levels were 16.40 mmol/l with an

average glycosylated hemoglobin HbA1C of 12.32%. Average LDL levels were

intolerance, elevated blood pressure, and dyslipidemia is increasing worldwide

of 0.912 g/l with a minimum of 0.2 g/l and a maximum of 3.18 g/l.

due to unbalanced nutrient intake among adolescents.

Conclusion

Objectives

Even though obesity is often associated with type 2 Diabetes, some type 1

The main objective of this study is to assess the association between habitual

Diabetics present with a metabolic syndrome that could mislead the diagnosis and

dietary patterns and the MetS risks after adjustments for biological and lifestyle

delay the appropriate management. Obesity in type 1 Diabetes is more correlated

variables in 112 adolescents aged 14-19 in Albania.

with advanced age and metabolic heredity.

Methods

A validated food frequency questionnaire was used to assess dietary patterns, in

DOI: 10.1530/endoabs.49.EP646

which three dietary patterns were identified and labeled as ‘ western -based’,

‘healthy based’ and ‘typical food’ patterns, whereas MetS risks was determined

using multiple indicators such as waist circumference (WC), systolic and diastolic

blood pressure (BP), and fasting glucose, triglycerides and HDL cholesterol

levels. The outcome variables were statistically normalized and expressed as

z-scores. A MetS risk score was computed as the means of these z scores.

Results

Multivariate analyses show that higher intake of western-based diet was

significantly associated with the MetS risk scores

(PZ0.003) and WC

(P!0.0001) and BP compared to those at lower intakes of western-based diet,

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after adjusting for age, gender,ethnicity, pubertal growth status, total physical

Intima media thickness of carotid arteries and cognitive function in

activity and sedentary screen-based levels. Similar pattern was found in typical-

Georgian nondiabetic obese and overweight hypertensive subjects

based diet, whereby adolescents who had higher intake of typical-based diet was

Ketevan Chagunava¹ & German Lomtatidze²

significantly associated with higher levels of BP (PZ0.001) and MetS risk score

¹New Hospitals, Tbilisi, Georgia;²Chaphidze Heart Centre, Tbilisi,

(PZ0.002) compared to those at lower intake group. In contrast, high intake of

Georgia.

‘healthy’ diet pattern was significantly associated with lower WC (P!0.0001),

BP (PZ0.022) and MetS risk scores (P!0.001) than those at lower health diet

Purpose

pattern.

Obesity is a serious health problem that has reached very high proportions in our

Conclusion

country; prevalence of obesity and overweight together is

56%. Obesity is

These findings suggest that high intake of ‘healthy’ diet that is high in dairy foods,

strongly associated with risk factors for cardio and cerebrovascular disease, AH,

legumes, fruits and vegetables and low-intake of western-based diet and typical

type 2 diabetes and cognitive disorders. The aim of our study was to analyze the

based diet were significantly associated with lower risks of abdominal obesity and

impact of AH and weight change on carotid artery intima-media thickness (IMT)

MetS among adolescents. Hence, effective dietary intervention strategies should

and cognitive function in Georgian nondiabetic obese and overweight

emphasize the promotion of healthy dietary practices among adolescents during

hypertensive individuals.

these critical years of growth in order to prevent the risk of excessive weight gain

Materials and methods

and metabolic-related disorders.

We studied 131 patients with mild to moderate AH (89 males/42 females, mean

DOI: 10.1530/endoabs.49.EP645

age 53.4G3,1 years, BMI 29.8G3.4 kg/m², duration of AH 5.5G2.3 years).

Examination included: color triplex carotid artery scanning; 24-h BP monitoring,

mini-mental state examination test.

overweight patients

(25!BMI!

29.9 kg/m²) were assigned to group 1 and 71 obese patients (BMIO30 kg/m²)

to group 2.

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Results

The groups were comparable by the age, duration of AH, daily mean BP values.

Type 1 diabetes and metabolic syndrome

Mean values of IMT (gr1:1,04G0.04 mm;gr2: 1.09G0.05 mm) were certainly

Ach Taieb, Hasni Yosra, Maaroufi Amel, Kacem Maha, Chaieb Molka &

increased in obese patients compared with overweight ones

(P!0.001).

Ach Koussay

Prevalence of carotid atherosclerosis was higher in gr2 (78% vs 65%). Occurrence

CHU Farhat Hached Sousse, Sousse, Tunisia.

of cognitive disorders was significantly higher in gr 2 (38vs26%)(P!0,05). BMI

positively correlated with IMT (rZ0.25, P!0.02).

Introduction

Conclusion

Contrary to type 2 diabetes, type 1 often occurs in young people, without obesity

Thus, in Georgian obese nondiabetic hypertensive subjects we detected more

or cardiovascular or metabolic diseases. The association of type 1 diabetes with an

pronounced and frequent carotid artery affection and cognitive dysfunction

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

comparing with overweight ones. Data of our study demonstrate importance of

Subjects and methods

more profound examination of cardiovascular system and neurological status in

The study was carried out on 140 subjects; 70 controls and 70 obese subjects (38

obese hypertensive patients to ensure further more aggressive blood pressure and

with metabolic syndrome and

32 without metabolic syndrome). All were

weight reduction.

subjected to full history taking, thorough clinical examination, fasting and post

DOI: 10.1530/endoabs.49.EP647

prandial blood glucose, HbA1c, lipid profile, fractalkine level and hs-CRP.

Results

Serum fractalkine level was significantly raised in obese subjects compared to

lean controls (being higher in those with metabolic syndrome). There was a

significant positive correlation between serum fractalkine level and BMI, WC,

WHR, fasting and post prandial blood glucose, HBA1c, total cholesterol,

triglycerides and LDL and it was inversely correlated with HDL while there was

no significant correlation between serum fractalkine level and hs-CRP.

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Conclusions

CGI-58 gene expression profile in individuals with different body mass

Fractalkine, like otherknown adipocyte-derived chemokines was increased in

index

obese individuals and associated mainlywith metabolic syndrome. This is a step

Daisy Crispim^1,2, Jakeline Rheinheimer^1,2, Milene Moehlecke¹,

in the way to understand and explain the exact pathogenesis of metabolic

Bianca de Souza^1,2 & Cristiane Leitao^1,2

syndrome as well as obesity linked complications.

¹Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre,

DOI: 10.1530/endoabs.49.EP649

Rio Grande do Sul, Brazil;²Post-graduation Program in Medical Sciences:

Endocrinology, Faculdade de Medicina, Universidade Federal do Rio

Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Background and aim

Although chronic low-grade inflammation is observed in obese subjects, the

underlying mechanisms modulating this process are still unclear. The

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Comparative Gene Identification-58 (CGI-58) is a lipid droplet-associated protein

The case of 36 years old obese male patient with high degree of

that has an important role in mediating intracellular fat hydrolysis by acting as a

proteinuria and a loosing weight as the major strategy of treatment

coactivator of the adipose Triglyceride Lipase (ATGL). Recent evidence suggests

Natia Katamadze, Natalia Chochishvili & Anna Shamanadze

that CGI-58 also has a role in chronic inflammation and insulin resistance (IR).

V.Iverieli Endocrinology, Metabology, Dietology center ‘ENMEDIC’,

Accordingly, macrophage specific Cgi-58 knockout aggravated high fat diet-

Tbilisi, Georgia.

induced inflammation and IR in mice through activation of the NLRP3

inflammasome. However, to date, only few studies have evaluated CGI-58

expression in obese patients, with inconclusive results. Therefore, the aim of this

Introduction

study was to evaluate CGI-58 expression in subcutaneous adipose tissue (SAT)

Obesity-related glomerulopathy(ORG) is a secondary form of focal segmental

from subjects with different BMI. Methods: SAT was obtained from

glomerulosclerosis

(FSGS) occurring in obese patients with a body mass

individuals who undergone bariatric surgery or elective abdominal surgery.

index(BMI) higher than 30 kg/m².ORG is typically manifested by nephrotic-

Twenty-six patients were classified as having morbid-obesity (BMI R40 kg/m²),

range proteinuria without full nephrotic syndrome, and progressive renal

27 as having moderate-obesity (BMI: 30.0 - 39.9 kg/m²), and 14 as non-obese

insufficiency.

subjects (BMI !25 kg/m²). CGI-58 expression was quantified using RT-qPCR

Case presentation

technique. Basal metabolic rate (BMR) was measured by indirect calorimetry and

Thirty-six years old male patient (BMI 59.2 kg/m²) visited endocrinologist with

body composition variables by dual-energy X-ray absorptiometry. All subjects

complains of weight gain, hypertension, swollen lower extremities, dyspnea.

underwent complete physical and laboratory evaluations. Results: CGI-58

Laboratory studies revealed: dyslipidemia, primary hypothyroidism and nodular

expression was decreased in morbid-obese and moderate-obese patients

goiter. Liver function- normal. Fasting glucose, postprandial glucose and A1C

compared with the non-obese group (median 0.59 (minimum 0.18 - maximum

was normal-diabetes mellitus was excluded. In urine with dipstick proteinuria was

1.39) vs 0.83 (0.28 - 2.15) vs. 1.70 (0.73 - 3.63) n-fold change; P !0.001). CGI-

found O3.0 g/l. The patient was sent to nephrologist. The level of Creatinine-

58 expression was also negatively correlated with BMI (rZK0.432, P !0.001),

normal, Urea- normal, 24 hour protein urine test: 18872 mg/24 h (N!150) and

fat mass (rZK0.380, PZ0.003), free fat mass (rZK0.488, P !0.001), and

kidney biopsy was recommended. The patient was given low calorie diet

BMR (rZK0.373, PZ0.002). Regarding lipid profile, CGI-58

expression

(1600 kkal), L-Thyroxine 50 mkg., Simvastatin 20 mg. Because of Heart failure

negatively correlated with triglycerides (rZK0.585, P !0.001) and cholesterol

(NYHA), arterial hypertension III (ESC) AR blockers and diuretics were

levels (rZK0.305, PZ0.015) while positively correlated with HDL levels (rZ

advised. Despite of strict diet and high doses of diuretics he gained 6 kg in 7 days.

0.250, PZ0.046). Negative correlations were also found between CGI-58

Laboratory tests-slightly decreased albumin. Because of no effect of diuretics

expression and HbA1c (rZK0.421, P !0.001), insulin levels (rZK0.332,

Albumin transfusion was performed. For 4 days he lost 9 kg. Only moderate

PZ0.009) and IR (rZK0.317, PZ0.013). Conclusions: CGI-58 gene expression

edema of lower extremities rested, with AR blockers T/A was within normal

is decreased in obese patients compared to non-obese subjects and is inversely

range. After month proteinuria decreased till-2641 mg/24 h. He lost nearly 20 kg.

correlated with a worse metabolic profile.

He disappeared for 10 months, started to gain weight and whole clinical picture

DOI: 10.1530/endoabs.49.EP648

restored. Proteinuria was 4250 mg/24 h. Kidney biopsy was performed-secondary

form of FSGS was diagnosed. Treatment strategy remain the same. We concluded

that the main reason for proteinuria in this case was obesity.

Conclusion

ORG is in correlation with BMI. With the weight gain the level of proteinuria

increases.In the early stage of kidney disease process can be reversible. Loosing

weight is one of the most effective strategy of treatment.

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DOI: 10.1530/endoabs.49.EP650

Fractalkinea as an inflammatory marker in obese subjects

Fatma Hamad, Mohsen Khalid, Asmaa Ibrahim & Ayat Ghanem

National Institute of Diabetes and Endocrinology, Cairo, Egypt.

Background

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Fractalkine (CX3CL1) is known to convey its signals through a single G-protein

Mobile and wireless technology to combat obesity. Using on-line

coupled receptor

(CX3CR1). It is characterized as a structurally unique

program of good nutrition and wright diet: prevention and part of the

chemokine with both membrane-bound and soluble forms. Fractalkine expression

treatment of diabetes mellitus

has been detected in activated or stressed endothelial, smooth muscle, skeletal

Vadim Krylov

muscle, macrophages, neurons, hepatocytes and adipocytes. Inflammation up

First Moscow State Medical University, Moscow, Russia.

regulates Fractalkine particularly in adipose tissue of obese individuals.

Aim of Work

This study was designed to assess fractalkine level in obese subjects and its

Introduction

relation with some clinical and laboratory findings. It compares basal plasma

It is too much easier and cheaper to combat obesity, than in the future to treat

fractalkine and hs-CRP in obese patients (with and without metabolic syndrome)

diabetes mellitus and its complications.

and lean healthy controls.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

decreased in GB (PZ0.008). Mean WC increased in GA (PZ0.027). Percentage

We used an online system for patient education based on the video lessons, full of

of subjects with high diastolic BP (DBP) in GB decreased significantly from 36%

humor, pictures, and cartoons to convey the necessary information on good

to 9% (PZ0.031), and percentage of subjects with metabolic syndrome decreased

nutrition, necessary to do exercises and the need for exposure to the sun to our

significantly from 27% to 5% (PZ0.039) by the end of the study.

patients.

Conclusion

Results

Oligonol supplement succeeded in reversing MS in obese Saudi females by

Watching the short movies, the patients formed the habits of good nutrition during

controlling abdominal obesity, and DBP, and decreasing hypertriglyceridemia,

the first month already, which includes a diet with restriction of fat, digestible

thus decreasing cardiometabolic risk without dietary restriction or lifestyle

carbohydrates and daily consumption of low-fat dairy products, slow

modification.

carbohydrates, protein and fiber. Were also presented recommendations for

DOI: 10.1530/endoabs.49.EP652

compliance with the physical activity, as well as vitamin D consumption. A

patient was in touch with a doctor-endocrinologist, if he has any additional

questions. We examined data from a survey of 500 patients registered in the

online system and

100 patients control group who were given the same

recommendations on the appointment. Surprisingly, persistent decrease in body

weight by an average of 6.5 kg over 6 months was demonstrated in all patients of

the main group, the consumption of milk and dairy products increased by 2.6

times, compared with patients in the control group. The exposure to the sun was

observed 15 to 30 minutes daily, compared with the control group 5-10 minutes.

Regular physical activity were the main group of 260 minutes per week, in control

group 80 minutes per week.

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Discussions

Metabolic and bone effects of high fat diet on adult zebrafish

Mobile and wireless technology helps physicians to combat obesity and be a part

Marta Carnovali¹, Livio Luzi^2,3, Giuseppe Banfi^4,5 & Massimo Mariotti^3,5

of the treatment of Diabetes Mellitus and we need to improve the quality of

¹Gruppo Ospedaliero San Donato Foundation, Milan, Italy;²IRCCS

information material, including using online technologies to improve the quality

Policlinico San Donato, San Donato Milanese, Milan, Italy;³University of

and duration of life of our patients.

Milan, Milan, Italy;⁴Vita-Salute San Raffaele University, Milan, Italy;

DOI: 10.1530/endoabs.49.EP651

⁵IRCCS Galeazzi Orthopedic Institute, Milan, Italy.

Obesity and type II diabetes have been linked to several health issues, including

an increased risk of bone fractures. It is well known that an increase of visceral fat

affects bone health causing fragility, mechanical strength reduction and increased

propensity of fractures because of impaired bone matrix microstructure and

aberrant bone cells function. Adult Danio rerio (zebrafish) represents a powerful

model to study fat and bone metabolism. Then, the aim of this study was to

evaluate bone and metabolic effects of high fat diet in adult zebrafish. Fish blood

glucose levels have been monitored in time course experiments and glycaemia

EP652

curve was found altered in fat fish compared to non-fat ones (Figure 1). The adult

bone remodeling has been evaluated in fish using the scales as read-out system.

Oligonol supplementation decreases abdominal obesity and the

The scales of high-fat diet fish shown bone resorption lacunae associated with an

prevalence of metabolic syndrome in a sample of overweight and obese

intense osteoclast activity. In addition, high-fat fish scales shown a significant

Saudi females without dietary restriction or lifestyle modification

decrease of alkaline phosphatase (ALP) activity and increase of tartrate-resistant

Suhad Bahijri^1,2, Ghada Ajabnoor^1,2, Zuheir Awan^1,2, Anwar Borai^2,3 &

acid phosphatase (TRAP) activity. These data suggests that an imbalance in fat

Altaf Abdulkhaliq^2,4

metabolism leads to an alteration of glucose metabolism and an osteoporotic-like

¹Department Clinical Biochemistry, Faculty of Medicine, King Abdulaziz

phenotype in adult zebrafish. The zebrafish model of obesity can contribute to

University (KAU), Jeddah, Saudi Arabia;²Saudi Diabetes Research Group -

elucidate in vivo the molecular mechanisms of metabolic changes derived from a

KAU, Jeddah, Saudi Arabia;³Pathology Department, King Abdullah

high fat diet, which influence the bone tissues regulation and insulin signaling in

International Medical Research Center, King Saud bin Abdulaziz University

for Health Sciences, King Abdulaziz Medical City, Jeddah, Saudi Arabia;

human obese patients.

⁴Department Clinical Biochemistry, Faculty of Medicine, Umm Al-qura

University, Makkah, Saudi Arabia.

Background

Obesity, and metabolic syndrome (MS) are highly prevalent in Saudi Arabia,

increasing the risk for type 2 diabetes (T2DM), and cardiovascular disease (CVD).

Oligonol produced from lychee fruit polyphenols (LFP) has been reported to

reduce visceral obesity, and ameliorate MS in Japanese subject.

Aim

To investigate the effect of oligonol supplementation on MS risk factors in

overweight and obese Saudi females.

Subjects and methods

Sixty obese and overweight healthy Saudi females were recruited. Blood pressure

(BP), height, weight, waist circumference (WC) were measured, and glucose,

triglycerides, and HDL cholesterol were assayed in fasting serum samples.

Dietary intake, and lifestyle habits were recorded by questionnaire. Subjects were

divided into two groups with equal mean body mass index (BMI), in a double-

blind /Case-Control study design. Group A (GA) was given placebo, and group B

(GB) was given oligonol, and were followed for three months, with all

measurements being repeated at the end.

Figure 1

Results

Some subjects were excluded for various reasons, leaving 25 in GA, and 22 in

GB. Therefore, the two groups differed significantly in recalculated mean BMI at

zero time (29.30G3.97 for GA, and 31.63G4.16 for GB, PZ0.046). No side

effects or significant differences in diet or lifestyle were found at the end of the

DOI: 10.1530/endoabs.49.EP653

study. Mean triglycerides was significantly increased in GA (PZ0.011), and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

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PF and increased in L. Among the studied cytokines, fractalkine and TNF-a were

decreased in the L group, with no changes in PF rats.

Growth hormone signaling and action in obese versus lean human

Conclusion

subjects: evidence of increased hepatic GH sensitivity in obesity

Central leptin infusion could preserve UCP-1 expression in brown adipose tissue

Morten Høgild Pedersen¹, Ann Mosegaard Bak¹, Steen Bønløkke Pedersen¹,

through activation of insulin-related signaling.

Niels Jessen², Niels Møller¹ & Jens O.L. Jørgensen¹

¹Department of Endocrinology and Internal Medicine, Aarhus University

DOI: 10.1530/endoabs.49.EP655

Hospital, Aarhus, Denmark;²Department of Clinical Pharmacology, Aarhus

University Hospital, Aarhus, Denmark.

Context

Obesity is accompanied by blunted GH secretion but relatively normal serum

IGF-I levels, which suggests increased GH sensitivity. This, however, remains to

EP656

be tested at the level of GH signaling in human subjects.

Objective

Can night eating syndrome increase basal metabolic rate?

Senay Topsakal, Guzin Fidan Yaylalı & Semin Melahat Fenkçi

To compare the effects of an acute intravenous GH bolus in obese vs normal

Endocrinology Department, Pamukkale University Medical Faculty Denizli,

weight subjects on GH signaling pathways in adipose and muscle tissue, substrate

Turkey.

metabolism and insulin sensitivity.

Subjects and methods

Nine obese (BMI 35.7G0.9) and nine lean (BMI 21.5G0.4) young men were

Introduction

studied twice in a randomized crossover design: (1) After an overnight fast (12 h)

Night eating syndrome (NES) is an eating disorder associated with obesity,

(‘Control’) and

(2) After an overnight fast with an intravenous GH bolus

characterized by a delayed pattern of food intake in which recurrent episodes of

(0.005 mg/kg) (‘GH bolus’). Each study day consisted of a 4-h basal period (tZ0

nocturnal eating and/or excessive food consump-tion occur after the evening

- tZ240 min) followed by a 2-h hyperinsulinemic, euglycemic clamp (HEC). GH

meal.

(1) Studies showed significant weight gain among patients with

was injected at tZ0 and biopsies from muscle and fat were drawn. Muscle and fat

NES.However, the underlying reason is still controversial.The aim of this study

biopsies were taken at tZ60 min.

is to investigate the body composition and energy metabolism in patients with

Results

NES.

Spontaneous serum GH levels were lower in obese subjects, whereas the PK of

Methods

the GH bolus was comparable. The GH bolus was associated with a BMI-

Obese patients were divided into two groups according to the diagnostic criteria.

independent increase in STAT5b phosphorylation and CISH mRNA transcription

Diagnostic crite-ria for NES include: (1) recurrent episodes of night eating, as

in muscle and adipose tissue. The GH bolus, however, produced a larger relative

manifested by eating after awakening from sleep or by excessive food

increase in serum IGF-I levels in obese subjects

(P ! 0.01). GH acutely

consumption following the evening meal, (2) awareness of those eating episodes,

stimulated lipolysis (DFFA in serum, serum palmitate levels and fluxes) to the

and (3) significant distress or impairment caused by the disorder. Patients meeting

same extent in both groups. GH significantly reduced glucose uptake during the

these three criteria were considered NES(C) (2). 281 women and 46 men, (101

HEC in both groups (PZ0.23), but GH only antagonized insulin-induced

NES(C), 226 NES(K)) were included to study. Body mass index (BMI) and

suppression of endogenous glucose production (EGP) in the obese (PZ0.01).

waist to hip ratio (WHR) were measured. Biochemical tests were performed.

Conclusions

Total fat mass (FM), fat-free mass (FFM), Body Water (BW), basal metabolic rate

(1) Acute GH exposure induces pSTAT5b and CISH mRNA and transcription in

(BMR)were measured by Bioelectrical Impedance Analysis (BIA).

fat and muscle, and lipolysis to the same extent in obese and lean subjects, (2) A

Results

GH-induced relative increase in serum IGF-I levels and suppression of EGP was

BMI and WHR were similar in both groups. There were no significant differences

only recorded in the obese, (3) Our data thus suggest increased hepatic sensitivity

in total cholesterol, triglyceride, LDL, HDL, ALT, GGT, fasting glucose, insulin

to GH in obesity, which in turn may contribute to the blunted endogenous GH

levels, postprandial glucose and insulin levels. There were significant increase in

secretion.

BMR in patients with NES, and not significant differences in FM, FFM, BW.

DOI: 10.1530/endoabs.49.EP654

Conclusion

BMR is the least amount of energy necessary for life. It accounts for 60-70% of

the total energy expenditure in sedentary man and hence forms the basis for

human energy requirements. In this study, BMR was found high in patients with

NES. Fat distrubution was similar in both groups. There is no study that examines

the effects of this syndrome on energy metabolism. There was a need for further

EP655

work in this regard.

Insulin signaling is involved in the regulation of UCP-1 expression in

DOI: 10.1530/endoabs.49.EP656

brown adipose tissue after chronic central leptin infusion

Vicente Barrios¹, Laura M. Frago¹, Sandra Canelles¹,

Emma Burgos-Ramos², Julie A. Chowen¹ & Jesús Argente¹

¹Department of Endocrinology, Hospital Infantil Universitario Nin˜o Jesús,

Instituto de Investigación La Princesa and CIBERobn, Instituto de Salud

Carlos III, Madrid, Spain;²Facultad de Ciencias Ambientales y Bioquímica,

Universidad Castilla-la Mancha, Toledo, Spain.

EP657

Association between cardiometabolic risk indicators and FGF 19 in

Background

healthy Saudi individuals of different BMI grades

Brown adipose tissue (BAT) plays a pivotal role in the regulation of energy

Ghada Ajabnoor^1,2, Yomna Hajjar^2,3, Suhad Bahijri^1,2 & Anwar Borai^2,4

homeostasis and thermogenesis. This tissue responds to insulin, favoring the

¹Department of Clinical Biochemistry, Faculty of Medicine, King

expression of uncoupling protein-1 (UCP-1), that in turn is inhibited by insulin-

Abdulaziz University, Jeddah, Saudi Arabia;²Saudi Diabetes Study

desensitizing cytokines. Leptin may abolish some of the effects of fasting on these

Research Group, King Fahd Medical Research Center, King Abdulaziz

parameters through its cross-talk with insulin-related signaling targets.

University, Jeddah, Saudi Arabia;³Postgraduate Student, Department of

Objectives

Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University,

We hypothesized that leptin infusion prevents UCP-1 depletion induced by food

Jeddah, Saudi Arabia;⁴King Abdullah International Medical Research

restriction through activation of insulin signaling in brown adipose tissue.

Center (KAIMRC), College of Medicine, King Saud Bin Abdulaziz

Methods

University for Health Sciences (KSAU-HS), Jeddah, Saudi Arabia.

We studied 18 male Wistar rats divided into three groups: rats receiving saline icv

(controls, C), those treated icv for 14 days with a daily dose of 12 mg of leptin (L)

and a pair-fed group (PF) that received the same food amount consumed by L. We

Background

analyzed relative mRNA levels of UCP-1 and glucose transporter 4 (GLUT4) by

Fibroblast growth factor 19 (FGF19) is an enterokine derived from the ileum, and

real time-PCR and changes in the cytokine levels and activation of insulin-related

synthesized in response to release of bile acids following food ingestion. It was

signaling targets by multiplexed bead immunoassay.

proposed to be an important regulator of the postprandial adaptive metabolic

Results

response. by stimulating glycogen and protein synthesis in the liver, and down

Relative UCP-1 mRNA levels were reduced in PF and unchanged in the L group.

regulating glucose production after a meal. There is limited research investigating

The mRNA levels of GLUT4 were increased in L rats, as well phosphorylation of

the association between FG-19 and metabolic dysregulation in overweight and

insulin receptor substrate 1. Akt phosphorylation on threonine 308 was reduced in

obese Saudi subjects.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Aim

Introduction

To study association of circulating FGF 19 in healthy individuals of different BMI

Obesity and diabetes mellitus type 2 (T2DM) are considered as one of the major

grades, with some cardiometabolic risk indicators.

risk factor for coronary heart disease (CHD) development, but the mechanisms

Subjects and methods

beyond this relationship still need to be clarified. miRNAs are supposed to be

Healthy adults aged

19-36 years were recruited. Height, and weight were

involved in regulatory mechanisms in this relationship.

measured to calculate body mass index (BMI). Sixty males and 60 females were

Aim

included in the study, divided equally between BMI categories (underweight,

To determine miRNAs expression in patients with obesity and T2DM.

normal, overweight and obese). Waist, hip, and neck circumference (WC, HC,

Methods

NC) were measured. Glucose, total cholesterol, triglycerides, high-density

MiRNAs were detected in peripheral blood of 43 patients, aged 48-65 years with

lipoprotein cholesterol (HDL-C), insulin, FGF19 and highly sensitive CRP (hs-

obesity and T2DM. Patients were divided in two groups: 1^st group - 21 patients

CRP) were estimated in fasting serum samples, and low-density lipoprotein

with CHD, 2^nd group - 22 patients with excluded CHD after Tredmil-Test. All

cholesterol (LDL-C), Atherogenic index of plasma (AIP), and homeostatic model

patients from the 1^st group underwent coronary angiography (CAG).

assessment-insulin resistance (HOMA-IR) were calculated.

Results

Nine CHD-related mRNAs were selected as candidates for the investigation:

No significant correlation (PZ0.457), or difference in means of FGF19 was noted

miRNA-1, miRNA-21, miRNA-26a, miRNA-27a, miRNA-33a, miRNA-33b,

between different BMI categories (PZ0.905). A negative significant correlation

miRNA-133a, miRNA-133b and miRNA-208. Expressions of these miRNAs

was found between FGF19 and WC, NC, and LDL-C: HDL-C ratio (rZK0.203,

were compared in studied groups. Expression of miRNA-21 (3.44 vs. 0.37;

PZ0.027, rZK0.297, PZ0.002, rZK0.187, PZ0.041 respectively).

PZ0.007) and miRNA-27a (0.86 vs.0.31; PZ0.013) in patients with CHD were

Conclusions

higher than that in 2^nd group, while expression of miRNA-26a (1.06 vs. 2.14;

Serum FGF19 levels do not appear to be related to general obesity expressed as

PZ0.022) was lower in patients with CHD. Spearman correlation analyses

BMI. However, it was found to be associated negatively with indicators of

showed that miRNA26a was positively associated with cholesterol level (rZ

abdominal, and upper torso obesity, reported to be associated with increased

0.316, PZ0.042). MiRNA-21 and miRNA-27a were negatively correlated with

cardiometabolic risk, indicating the relationship of FGF19 with this risk. The

HbA_1c in both groups

(rZK0.363, PZ0.042 and rZK0.420, PZ0.036,

strong correlation between FGF19 and serum LDL-C:HDL-C;a well established

respectively). MiRNA-208 was positively correlated with hypertrophy of the

indicator of cardiometabolic risk; validate the link further.

interventricular septum (rZ0.61, PZ0.027) and number of significantly affected

DOI: 10.1530/endoabs.49.EP657

coronary vessels according to CAG (rZ0.65, PZ0.034), negatively - with left

ventricular diastolic dimension (rZK0.52, PZ0.029).

Conclusion

1) Expression of miRNA-21 was increased by 9 times, miRNA-27a in 2.5 times in

patients with CHD, while miRNA26a compared with patients with type 2 diabetes

and obesity was lower in 2 times.

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2) We revealed correlations of miRNA-208,

27a,

with pathological

The role of pioglitazone and vitamin E for the treatment of NASH with

angiogenesis, and heart remodeling processes in patients with obesity and T2DM.

or without metabolic syndrome

3) Increased expression of miRNA-208

can determine the severity of

Nino Khabeishvili, Gocha Barbakadze, Ketevan Mikadze & Koba Burnadze

cardiovascular disease in patients with obesity and T2DM.

Clinic “Enmedic”, Tbilisi, Georgia.

DOI: 10.1530/endoabs.49.EP659

Introduction

Obesity is a global public health problem and is associated with metabolic

syndrome and dyslipidemia as well as very often with non-alcoholic

steatohepatitis (NASH).

Aim & methods

The aim of the present study was to evaluate the preventive and curable role of

EP660

vitamin E and pioglitazone (thiazolidinedione-type) in NASH patients with or

The surgical approach to obesity in numbers

without metabolic syndrome. 51 patients with NASH were divided into two

Nuno Cordeiro Raposo, Andreia Sousa Ferreira, Sónia Pratas &

groups: 26 patients with insulin-resistance (IR) plus obesity and 24 patients

Cristina Valadas

without IR. 12 patients from 1-st group (another 14 patients from this group

Hospital Beatriz Ângelo, Loures, Portugal.

served as a control subgroup) and 12 patients from 2-nd group were treated at

least during 3 months with vitamin E (500-1000 mg daily) plus pioglitazone 15-

30 mg/d (another 13 patients - control subgroup) as well as put on the low-fat

The prevalence of obesity has greatly increased worldwide in the last decades,

diet. Gender distribution of the patients was equal in each subgroup (26 male,

particularly in Europe and Portugal. It is associated with many health problems,

25-female). Mean age was 46.6G6.4 years. Mean BMI (body mass index) -

including cardiovascular diseases, cancer and diabetes.

34.6G4.1 kg/m². HOMA-IR of patients from 1-st group was 2.7G0.8.

Methods

Results

Revision of the clinical records of all 61 patients who underwent bariatric surgery

The concentration of the serum aspartate aminotransferase

(AST), alanine

between 2013 and 2015. Analysis of their metabolic profile prior to surgery and

aminotransferase (ALT) levels (P!0.01) as well as cholesterol and triglycerides

its evolution after the operation.

(P!0.05) were found to be higher in the both subgroups without pointed

Results

treatment. HDL level, however, was comparable in both groups (PO0.05).

61 patients were reviewed, namely 90.2% females and 9.8% males. The mean age

Results also indicated that this therapy reduced BMI (P!0.05) and HOMA-index

was 43.6 years. All patients had class II or III obesity according to their BMI, with

(P!0.05) in both subgroups.

an average score of

46.4 kg/m². The associated cardiovascular risk factors

Conclusions

include: hypertension (47.5%), total cholesterol O200 mg/dl (35.8%) and type 2

Insulin resistance appears to be the underlying pathophysiological defect leading

diabetes mellitus (10.6%). 60% had an apnea-hypopnea index great than 5/h.

to NASH. The data from this study demonstrate the possible mechanism by which

Most patients underwent gastric sleeve surgery (93.4%) and only 6.6% received a

pioglitazone and vitamin E mediate their beneficial clinical and metabolic effects

bypass surgery. Six patients were treated with an endoscopic intragastric balloon

in patients with NASH. To prevent this condition is to maintain a healthy diet and

prior to surgery. Weight was evaluated at 3 months’ intervals in the first 1.5 years,

rigorous exercise regimen.

and then every 6 months. 13.6 months was the mean follow-up time after the

DOI: 10.1530/endoabs.49.EP658

procedure. The average weight loss prior to surgery was 9.6% of the initial body

weight. After the operation, weight loss was more pronounced between the first

and third months (7.4% of the initial body weight). The trend of weight loss

remained until 9 months, stabilizing afterwards. The mean BMI reduction was

27.1% at the end of the follow-up time. Both HbA1c and triglycerides were

reduced by 11% and 15%, respectively, after surgery. HDL increased by 16%.

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Conclusions

MicroRNAs, associated with coronary heart disease in patients with

The majority of patients eligible for bariatric surgery were young females with

obesity and diabetes mellitus type 2

class II or III obesity. Many had other cardiovascular risk factors, particularly

Teona Shvangiradze¹, Irina Bondarenko¹, Ekaterina Troshina¹ &

hypertension and dyslipidemia. Gastric sleeve was the preferred technical

Marina Shestakova^1,2

procedure and only a few patients received an endoscopic intragastric balloon to

¹Endocrinology Research Centre, Moscow, Russia;²I.M. Sechenov’s First

aid weight loss prior to surgery. Weight loss was more pronounced in the first

Moscow State Medical University, Moscow, Russia.

3 months after surgery, but that tendency was mitigated after only 9 months.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Nevertheless, body mass index was reduced by a quarter at the end of follow-up.

Introduction

These results show the importance of the multidisciplinary approach to obesity

Peroxisome proliferator activated receptor-g

(PPAR-g) is a distinguished

and the potential benefits with bariatric surgery. However, we emphasize the short

transcription factor abundantly expressed in the adipose tissues and plays a key

follow-up time and the need to maintain evaluation of these patients in the future.

role in the regulation of adipocyte differentiation and development of obesity. In

DOI: 10.1530/endoabs.49.EP660

the current study, we aimed to investigate the association of PPAR-g mRNA

expression in omental and subcutaneous adipose tissues with anthropometric

indices and blood pressure (BP) among healthy adults.

Methods

97 subjects (41 non-obese, 18 obese, and 38 morbid obese) were eligible for the

study. Omental and subcutaneous adipose tissues were obtained during open

abdominal surgery. The PPAR-g mRNA level was evaluated in omental and

subcutaneous adipose tissues using Real-Time PCR assay. Height, weight, BMI,

waist, hip, and neck circumferences, and BP were determined according to

standard protocols.

EP661

Results

Decreased HDL cholesterol efflux capacity in morbidly obese

The mean of BMI was 24.8, 34.9, and 46.8 kg/m² in morbid obese, obese and non-

individuals as a surrogate marker for increased cardiovascular risk

obese subjects, respectively. PPAR-g gene expression was not significantly

Idit Dotan^1,2, Anouar Hafiane², Isabelle Ruel², Rajesh Aggarwal¹,

different between omental and subcutaneous adipose tissues in each group.

Amin Andalib¹, Jacques Genest^1,2 & Mark Sherman^1,2

However, PPAR-g mRNA expression was down-regulated in omental adipose

¹McGill University Health Center, Montreal, Québec, Canada;²Research

tissues of non-obese subjects compared to obese subjects and up-regulated

Institute of the McGill University Health Center, Montreal, Québec,

compared to morbid obese ones (P!0.05). Among morbid obese subjects,

Canada.

diastolic and systolic blood pressures were positively correlated with omental

PPAR-g expression (rZ0.409, PZ0.020 and rZ0.371, PZ0.037, respectively);

waist and neck circumferences were positively correlated with both adipose

Background

tissues (P!0.05). Among obese subjects, PPAR-g expression in both tissues had

Obesity has become a worldwide epidemic and carries excess cardiovascular

significant positive correlation with waist circumference (P!0.05).

morbidity and mortality. HDL efflux capacity (HEC) was shown to be inversely

Conclusion

correlated with cardiovascular risk (CVR), both in the acute and the chronic

Our study suggested that several obesity-related indices have a positive

phases. Our aim was to understand if decreased HEC can serve as a surrogate

correlation with PPAR-g expression in omental and subcutaneous adipose tissues.

marker for the increased CVR in this population.

DOI: 10.1530/endoabs.49.EP662

Methods

Forty patients: 10 obese diabetic (OD), 10 obese non-diabetic (OND), 10 with

stable Coronary Artery Disease (sCAD) and 10 healthy controls were blindly

selected from another cohort and their HECs were studied using radioactive cell-

based assays.

Results

The mean age of the cohort was 50G12 years, with 72.5% men. Mean BMI for

EP663

the obese groups was 46.8G7.03 kg/m², for the sCAD group 27.7G3.3 kg/m²

Results of computer-assisted intravital microscopy in overweight

and for the controls 24.2G2.26 kg/m². Mean HEC (adjusted to ApoA1 mass) was

and obesity

14.18G0.95% for the OD group, 14.73G3.18% for the OND group, 19.11G

Volha Shyshko¹, Tatjana Mokhort¹, Elena Konstantinova² &

1.6% for the sCAD group and 16.01G1.6% for the controls. A linear regression

Natalia Tsapaeva¹

model adjusted for age, sex, BMI and TG has found that both OD and OND have

¹Belarussian State Medical University, Minsk, Belarus;²Institute of Heat

significantly lower HEC in comparison to controls (P!0.05 for both), whereas

and Mass Transver, National Academy of Science, Minsk, Belarus.

the sCAD did not.

Discussion

In the current study, we found that morbidly obese individuals have significantly

Rationale

lower HEC in comparison to controls. Given that HEC has an inverse correlation

Obesity, prediabetes and diabetes are strongly associated with microcirculation

with CVR, these finding may explain, at least in part, the increased CVR in

(MC) abnormalities. It is known that pathological changes in microvessels

morbidly obese patients. It is unclear if bariatric surgery improves HEC, but it is

predispose to CHD, CKD and retinopathy. Also it is widely recognized that

reasonable to speculate it does, given the other metabolic effects the surgery

biochemical and immunological changes accompanied with obesity and

exerts.

overweight lead to MC damage.

Conclusion

Objective

HDL function is compromised in morbidly obese individuals and contributes to

Of the study was to assess changes in MC in patients with overweight and obesity.

progressive atherosclerosis and increased CVR in this population. If HEC does

Materials and methods

improve post-metabolic surgery, decreased HEC might serve as another

Computer-assisted intravital microscopy (CAIM) was used to assess intra- (six

indication for bariatric surgery.

scores), extra-

(three scores) and vascular

(11

scores) changes of bulbar

DOI: 10.1530/endoabs.49.EP661

conjunctiva and vascular indexes were calculated. We included 91 patients

with overweight

(group

1),

103 patients with obesity

(group

2) both with

concomitant prediabetes and diabetes and 58 almost healthy person (group 3).

Results

Overweight and obesity are characterized by progressive changes in MC. A

significant difference was observed in perivascular edema in patients with

overweight (0.5 (0.0;1.0) as well as in patients with obesity (1.5 (0.5;1.0) (P_1-3Z

0.025, P_2-3Z0.012) compared to group

3. There were no any significant

intravascular changes between groups. Vascular changes included inequality in

vessels size (1.0 (1.0;1.0) in groups 1 and 2 vs 1.0 (0.0;1.0) in group 3) P_1-3

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0.012, P_2-3Z0.010), meandrous tortuosity of venules (1.0 (0.0;1.0) in groups 1

The association of anthropometric measurements and PPAR-g gene

and 2 vs 0.0 (0.0;1.0) in group 3) P_1-3Z0.002, P_2-3Z0.001) and meandrous

expression among healthy adult subjects

tortuosity of capillaries (0.0 (0.0;1.0) in groups 1 and 2 vs 0.0 (0.0;0.0) in group 3)

Maryam Zarkesh¹, Emad Yuzbashian², Azita Zadeh-Vakili¹,

P_1-3Z0.001, P_2-3Z0.004). Calculating of partial vascular indexes and total

Kimia Tabaei³, Afsoon Daneshafrooz¹, Golaleh Asghari²,

vascular index optimizes results of CAIM. Vascular index was significant higher

Parvin Mirmiran², Mehdi Hedayati¹ & Alireza Khalaj⁴

in patients with overweight (10.0 (8.0;11.0) compared to patients with obesity

¹Cellular and Molecular Endocrine Research Center, Research Institute for

(10.0

(9.0;11.0) (P_1-3Z0.001, P_2-3Z0.001).

Endocrine Sciences, Shahid Beheshti University of Medical Sciences,

Conclusion

Tehran, Iran;²Nutrition and Endocrine Research Center, Research Institute

Overweight and obesity are associated with MC abnormalities and mostly

for Endocrine Sciences, Shahid Beheshti University of Medical Sciences,

expressed in extra and vascular changes. Use of partial and total vascular indexes

Tehran, Iran;³School of Advanced Sciences in Medicine, Tehran Medical

optimizes evaluation of MC changes.

Sciences Branch, Islamic Azad University, Tehran, Iran;⁴Tehran Obesity

DOI: 10.1530/endoabs.49.EP663

Treatment Center, Department of Surgery, Shahed University, Tehran, Iran.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP664

Table 1 BMI, handgrip and biochemical measurements before and after

Assessment of adipose tissue distribution in youg women with polycystic

surgery in obese patients

ovary syndrome

A Savchanka & Tatjana Mokhort

Before

3rd mo. After

6th mo.fter

Belarussian State Medical University, Minsk, Belarus.

surgery

BMI (kg/m²)

48.3G8.9

40.4G7.9

38.1G11

0.0001

PCOS is characterized by abdominal obesity along with conventional diagnostic

Handgrip (kg)

28.1G9.2

21.6G7.5

21.3G6.4

0.001

features.

25OHD (ng/dl)

14.4G20

25.6G15.7

31.9G49

0.0001

Objective

Vitamin B12

284G154

339G219

326G208

0.004

To assess body composition in women with PCOS and normal body weight.

(ng/dl)

Materials and methods

Albumine (mg/dl)

4.42G0.2

4.30G0.3

4.07G0.9

0.0001

35 women (24G1.1 years old) with confirmed diagnosis of PCOS according to

Rotterdam criteria, 27 almost healthy women (25G1.2 years old), both groups

wotn normal weight. Whole Body Dual-energy X-ray Absorptiometry (DEXA

Total Body) scans were carried out using ‘Prodigy Lunar’ machine (USA).

shown in Table 1. Serum ferritin and, creatinine levels were in reference range

Results

and not change during the follow-up. In a multivariate regression model showed

Registered differences included increase of total fat accumulation, fat

that

25OH D and creatinine levels were independent risk factor for muscle

accumulation in android compartments as well as android-gynoid fat ratio

strength

(r²:16.2, P!0.0001). Serum albumin and handgrip measurements

index. Basic antropometric measurements and DEXA of patients with POCS and

showed a positive correlation (r:0.23, P!0.001).

control group. 29 (82.86%) patients in study group demonstrated significantly

Conclusion

higher waist circumference (77.1G11.2 cm) and higher percentage of adipose

Although appropriate vitamin and protein supplementation bariatric surgery

tissue in android area (37.9G3.0%) correspondingly compared to control group

patients are at risk of decreased muscle strength related complications.

(R - 0.846176 at P !0.05).

Conclusion

DOI: 10.1530/endoabs.49.EP665

Abdominal fat accumulation is attributable to patients with PCOS. Lack of

significant differences between BMI and total fat accumulation is apparently

explained by age, dietary habits, patient’s disease awareness as well as reasonable

life style modification and physical exercises modification.

Table 1

Study group,

Control group,

Measurements

nZ35

nZ27

Total fat content, g

34.257G5.763

17.737G2.393

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Total fat content by

37.3G6.7. P!0.05

29.2G4.9

Comparison between mathematical indexes and histopathological

DEXA, %

findings in the diagnosis of nonalcoholic fatty liver disease in mexican

Trunk fat accumulation, g

11.315G3.400

6.326G1.592

population

Trunk fat accumulation, %

31.2G4.7

29.3G2.7

Karen-Ivette Gutierrez-Aguirre¹, Maria-Luisa Lazo-de-la-Vega-Monroy¹,

Fat accumulation in android

37.9G3.0, P!0.05

30.9G3.1

Yeniley Ruiz-Noa¹, Lorena-del-Rocio Ibarra-Reynoso¹,

compartments, %

Juana-Rosalba Garcia-Ramirez², Benjamin Jordan-Perez²,

Fat accumulation in gynoid

40.5G4.3

39.3G2.8

Serafin Garnelo-Caban˜ as2 & Monica-del-Carmen Preciado-Puga1

compartments, %

University of Guanajuato, Leon, Guanajuato, Mexico;²Hospital General

Android-gynoid fat ratio index

0.91G0.1, P!0.05

0.76G0.1

Leon, Leon, Guanajuato, Mexico.

(A/G)

Introduction

Non-alcoholic fatty liver disease (NAFLD) is an emerging disease in Mexico,

DOI: 10.1530/endoabs.49.EP664

comprising a spectrum of histopathological findings ranging from simple steatosis

to steatohepatitis and cirrhosis. The gold standard continues to be the liver biopsy,

but several mathematical indices have been proposed, such as non-invasive

techniques, however there are very few studies in our population.

Objetive

This study aims to compare mathematical indexes and histopathological findings

for the detection of NAFLD in Mexican population.

Methods

A cross-sectional study was performed at the ‘Hospital General León’ between

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November 2016 and January 2017. Patients aged

18 years or above that

Decreased muscle strength is associated with vitamin D and albumin

underwent laparoscopic cholecystectomy were recruited. No history of alcohol

levels after bariatric surgery

consumption habit or hepatic diseases characterized the patients. The fatty liver

Dilek Gogas Yavuz & Meliha Melin Uygur

index

(FLI) and the lipid accumulation product

(LAP) were calculated.

Marmara University School of Medicine Section of Endocrinology and

Demographics, blood samples, and a liver biopsy were obtained. Results between

Metabolism, Istanbul, Turkey.

FLI, LAP and livery biopsy were compared.

Results

Bariatric surgery patients are at risk of decreasing in muscle mass, vitamin and

A total of 59 patients were included (80.1% women and 19.1% men). The mean

protein deficiency. The aim of this study is to asses muscle strength, serum protein

age was 39.6G14.8 years, BMI 29.7G10.11 kg/m². The FLI identified 31

and vitamin levels after bariatric surgery.

patients with NAFLD of which 11 were corroborated with biopsy, whereas the

Methods

LAP identified 26 patients of which 17 were corroborated with biopsy. From the

264 patients underwent bariatric surgery who completed 6 th month policlinic

patients with negative FLI index (nZ26), a total of 11 (42%) were diagnosed with

visits were included in the study. Patients were followed appropriately

steatosis by histopathology. For LAP, 31 patients (54.3%) were negative, four of

supplemented protein and vitamins as suggested; all study parameters were

which (7.01%) presented positive for NAFLD by histopathological diagnosis.

assessed before and after 3rd. mo. and 6th mo. of bariatric surgery. Handgrip

Conclusion

dynamometry was used to measure static muscle strength. Serum Albumin, 25OH

According to our results, at least in our population these two mathematical indices

vitamin D (25OHD), Vitamin B12, ferritin and creatinine levels were measured

are not useful for the diagnosis of NAFLD, so liver biopsy remains to be the gold

by immune- chemiluminecanse method.

standard for the detection of NAFLD. Future studies should be performed in order

Results

to continue looking for other non-invasive markers for NAFLD.

Postoperatively, all patients showed a significant decrease in the BMI in 3 mo and

DOI: 10.1530/endoabs.49.EP666

6 mo compared to preoperative levels (P:0.0001). Biochemical measurements are

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP667

EP669

Obesity and infertility among Tunisian women of reproductive age:

Menopause is a major determinant of endocannabinoid

about 40 cases

2-arachidonoylglycerol plasma level and of its relevance as biomarker

Faten Hadjkacem¹, Mariem Rebai², Dalila Saidane², Dorra Ghorbel¹ &

of dyslipidemia and insulin resistance in lean women

Mohamed Abid¹

Flaminia Fanelli, Marco Mezzullo, Margherita Baccini, Elena Casadio,

¹Department of Endocrinology and Diabetology of Hedi Chaker Hospital,

Daniela Ibarra Gasparini, Valentina Vicennati, Renato Pasquali &

Sfax, Tunisia;²Faculté de Pharmacie, Monastir, Tunisia.

Uberto Pagotto

Endocrinology Unit and Center for Applied Biomedical Research

Department of Clinical and Surgical Science, University of Bologna,

Obesity is on the increase worldwide and mainly in women of reproductive age.

S.Orsola-Malpighi Hospital, Bologna, Italy.

In turn, it is associated with various reproductive complications. To assess the

detrimental effect of obesity on reproductive health and the means of its

management, this retrospective cohort study of 40 obese and infertile women has

Context

been conducted in the department of endocrinology and diabetology of Hedi

The endocannabinoid system

(ECS) hypertonicity contributes to obesity

Chaker hospital in Sfax-Tunisia from 2009 to 2014. These patients have a mean

development and maintenance. Excess circulating levels of ECS mediator

age of 34 years and a mean BMI of 37.29 kg/m². They were to suffer from

2-arachidonoylglycerol

(2AG) were reported in obese humans, however,

infertility for a mean period of 5,7 years. The polycystic ovary syndrome was the

unstandardized experimental settings (i.e. analytical conditions, sample size,

most common cause of infertility diagnosed in 52.5%. Classic morbidities of

concurrent diseases/medications, statistics, gender, body mass index (BMI) and

obesity were dominated by metabolic

(52.5%) and cardiovascular

(37.5%)

age), clouded its role in dysmetabolism and its usefulness as biomarker. The study

complications. Ovulation disorders were identified in 77.5% of cases and serious

aimed at describing

2AG associations with visceral obesity, dyslipidaemia,

complications during pregnancy were observed. These complications affect the

insulin resistance and hypertension in females according to BMI and menopausal

obese mother as well as the child: abortions (52.5%), delivery by caesarean

status.

section (35%), gestational diabetes (20%), foetal malformation (12.5%), neonatal

Methods

death (7.5). Though the management of the combination of obesity and infertility

Adult, unmedicated, disease-free premenopausal (preMP, nZ103) and meno-

was quite difficult, a weight loss of 5-8% has resolved 61.2% of menstrual

pausal (MP, nZ81) females were stratified in normal weight (NW, BMI:18.5-

irregularities and improves the chances of pregnancy in 20% of cases. Insulin

24.9kg/m²), overweight

(OW; BMI: 25.0-29.9kg/m²) and obese

(BMI

resistance and hyperleptinemia are the main mechanisms linking obesity to

R30.0kg/m²) classes. Plasma 2AG, anthropometric and metabolic parameters

infertility. Thus the establishment of a healthy lifestyle since a young age is the

were assessed.

best therapeutic solution for obesity-induced infertility. Obese women have a

Results

higher prevalence of infertility, maternal morbidity, mortality and foetal

Menopause (P!0.001) and BMI (PZ0.001) independently increased 2AG

anomalies. For these reasons it’s necessary to raise the public awareness on the

levels. NW (PZ0.001) and OW (P!0.001), but not OB, MP women, displayed

detrimental effects of obesity on reproductive health.

higher

2AG than preMP counterparts. 2AG increased with BMI in preMP

DOI: 10.1530/endoabs.49.EP667

(P!0.001), but not in MP cohort. 2AG displayed BMI-independent relationships

with triglycerides in both preMP (PZ0.006) and MP (PZ0.005) and with glucose

in MP (PZ0.036). When analyzed within preMP BMI classes, only in OB class

2AG significantly associated with total cholesterol

(TC, PZ0.040) and

triglycerides (PZ0.020). In MP cohort, 2AG associated with TC (PZ0.006),

glucose (P!0.001), HOMA-IR (PZ0.035) and triglycerides (PZ0.001) within

NW, with triglycerides in OW (PZ0.034) and with none of the parameters in OB

class. Moreover, increasing BMI significantly reduced 2AG associations with TC

(PZ0.037) and glucose (PZ0.002) in MP cohort, while 2AG associations with

TC, glucose and HOMA-IR significantly distinguished NW MP from NW preMP

women (PZ0.036, PZ0.005 and PZ0.027, respectively). No 2AG associations

EP668

were found with waist circumference and blood pressures.

Conclusions

Mindfulness-oriented weight management course in a tier 3/tier 4

Plasma

2AG is a valuable biomarker of clustering insulin resistance and

obesity service

dyslipidemia in lean menopausal women, and may play a causative role in

Petra Hanson, Louise Halder & Thomas Barber

menopause-related metabolic worsening.

University Hospital of Coventry and Warwickshire, Coventry, UK.

DOI: 10.1530/endoabs.49.EP669

Overeating contributes to obesity epidemic and has many causes. Evidence shows

that problematic eating behaviours can be modified with mindfulness. In the UK

the use of mindfulness in management of obesity has been studied only once

before. We aimed to pilot a new weight management course that would improve

patients’ skills and confidence in ability to lose weight, and reduce patient waiting

time. The course covered mindful eating, compassion and self-esteem, managing

EP670

relapses and weight loss orientated marketing. Four interactive sessions were

Genetical predictors of neuroendocrine disturbances in children with

delivered by dietitians and psychologists over 8 weeks, resulting in frequent

severe obesity

contact with participants. Patients were invited to participate in this course

Anzhalika Solntsava¹, Olga Zagrebaeva¹, Elena Aksyonova²,

following their first appointment, and received normal follow-up regardless of

Tatsiana Shatarnova² & Tatsiana Yemelyantsava³

their participation. Ten patients were included in the final analysis. Anonymized

¹Belarusian State Medical University, Minsk, Belarus;²Institute of Genetics

feedback and eating style questionnaires were collected before and after the

and Cytology of NAS of Belarus, Minsk, Belarus;³Republican Research and

course. The average weight and age were 120 kg and 45 respectively, and eight

Practice Center for Mental Health, Minsk, Belarus.

were women. 90% of patients lost weight (0.4-5 kg). Average weight loss was

1.54 kg. Patients were seen more frequently in the initial phase of their treatment

pathway, leading to improved experience.30% of participants heard of mindful

Objectives

eating prior to our course, with 90% finding it a useful concept for weight

Neurogenetical predictors of psychological disturbances in children with severe

management on completion. Patients became more confident, compassionate and

obesity.

felt more in control. Eating styles were assessed by a validated questionnaire.

Methods

Paired t-test was applied to analyse results. Statistically significant improvement

We examined 254 pubertal obese children: group1 (simple obesity) 187 children,

was found in emotional eating (PZ0.010), food fretting (PZ0.022), unappetizing

14.3G2.0 yrs, 30.4G2.8 kg/m²; group2 (severe obesity) 67 children, 14.7G2.1,

atmosphere (PZ0.042) and overall eating style (PZ0.017). This holistic course

39.1G3.8. Control 80 children, 14.4G2.0 yrs, 19.7G1.7 kg/m². Dopamine levels

equipped patients with new skills to change eating behaviours, coping strategies

were determined. Genotyping was performed on polymorphic genes COMT,

and changed their mindset and will be incorporated into the standard service for

MAOA, A1 Tag 1A allele of DRD2/ANKK1 polymorphism (rs1800497).

all bariatric patients. However, the results of this project have global implications

Results

as management of obesity should incorporate holistic approach and utilize

A statistically significant difference between dopamine levels were in patients

mindfulness in future.

with simple (8.8(4.8; 20.7)) and severe obesity (48.8(29.8, 163.9)) ng/ml and AA

DOI: 10.1530/endoabs.49.EP668

genotype (PZ0.05). We found the significant increasing of dopamine levels (82.5

[61.3; 116.3]) in boys with severe obesity and 3-3 MAOA genotype comparison

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

to 4-4 genotype (35.7 [23.2; 54.9]) (UZ4.0; PZ0.03). We determined more

EP672

frequent occurrence of GA (Val/Met) genotype COMT gene in children with

Unfavourable blood pressure and lipid levels in obese individuals from

severe obesity (54.3%) compared to simple disease (32.7%) (c²Z6.9; PZ0.03).

the general population

AA genotype frequency was 21.7% in patients with severe obesity, which were

Bruce Wolffenbuttel, Sandra Slagter, Robert van Waateringe,

higher than control (16.6%) (c²Z14.6; PZ0.006). We revealed significantly

Jana van Vliet-Ostaptchouk, André van Beek & Melanie van der Klauw

higher BMI in children with severe obesity and the presence of GA genotype

Univ Med Ctr Groningen, Groningen, The Netherlands.

(41.3G4.5 kg/m²) compared to GG (37.4G3.1) (PZ0.006) and AA (38.6G2.8)

(PZ0.04) genotypes. The more frequent presence of A1 allele, associated with

low dopamine D2 receptors density (A1A1 and A1A2) was detected in children

Background

with morbid obesity (17.9%) in comparison with alimentary obesity (4.8%),

Early diagnosis and treatment of high blood pressure (BP) and high cholesterol is

(c²Z9.7, PZ0.008). The positive reliable correlation was found between A1A2

important to reduce cardiovascular mortality risk.

genotype and BMI (r_sZ0.8, PZ0.001).

Methods

Conclusions

We assessed actual BP and LDL-cholesterol

(LDL-C) levels in

88,029

A large frequency of AA genotype were found in children with severe and simple

participants (36,122 men), aged 18-80 yrs, without diabetes, from the Dutch

obesity. Higher BMI levels were in children with severe obesity and genotype

Lifelines Cohort study. Participants were categorized according to degree of

GA. The more frequent presence of A1 TaqIA allele, associated with low

obesity

(normal weight, overweight, obese) and age decade group. BP

dopamine D2 receptors density was found in children with morbid obesity.

measurement was rigorously standardized. Mean systolic and diastolic BP were

DOI: 10.1530/endoabs.49.EP670

calculated depending on BP-treatment status for the three BMI classes, and for

each age group. We repeated these evaluations for LDL-C levels.

Results

In total, 13.3% of men and 15.6% of women were obese. BP increased gradually

in each age group, with mean levels of 124/68 mmHg in the youngest and

142/77 mmHg in the oldest male participants, and was significantly higher in

obese vs. non-obese and overweight individuals in all age groups (P!0.01). The

largest difference (10-11 mmHg) between obese and non-obese was observed in

males below 50 yrs. Despite the use of BP-lowering medication (5.1-6.2% in non-

obese,

21% in obese), still

20-50% had elevated systolic BPR140 mmHg.

Overall mean LDL-C was 3.5G0.9 mmol/l in obese vs. 3.2G0.9 mmol/l in non-

obese men (P!0.001), and 3.3G0.9 vs 2.9G0.8 mmol/l in women (P!0.001).

EP671

More untreated obese than non-obese participants had an LDL-C R3.5 mmol/l

Endocannabinoid 2-arachidonoylglycerol plasma level is a BMI-

(men: 56% vs 37%, women: 41% vs 24%, both P!0.001). Only 37% of obese

independent biomarker of cardiometabolic risk in adult males with

men and 28% of obese women treated with statins reached an LDL-C target

higher relevance in lean and aged conditions

!2.5 mmol/l. A small percentage of obese individuals treated with BP-lowering

Flaminia Fanelli, Marco Mezzullo, Margherita Baccini, Elena Casadio,

drugs also were using statins (33% in men, 16% in women).

Daniela Ibarra Gasparini, Valentina Vicennati, Renato Pasquali &

Conclusions

Uberto Pagotto

Obese individuals have higher BP and LDL-C compared to non-obese, and

Endocrinology Unit and Center for Applied Biomedical Research

especially obese men younger than 50 yrs have elevated BP levels. There is

Department of Clinical and Surgical Science, University of Bologna,

considerable undertreatment of elevated BP and elevated LDL-C in the general

S.Orsola-Malpighi Hospital, Bologna, Italy.

population.

DOI: 10.1530/endoabs.49.EP672

Context

Ageing and obesity are similarly characterized by metabolic impairment in terms

of visceral fat, dyslipidaemia, insulin resistance and hypertension. Obesity is

featured by endocannabinoid system (ECS) hyperactivation. Increased levels of

endocannabinoid 2-arachidonoylglycerol (2AG) found in obesity were variously

associated to dysmetabolic features, however, it is not clear whether such

EP673

associations exist in normal weight conditions. Moreover, ageing contribute in

Relation of insulin resistance to neurocognitive function and

modulating 2AG tone and involvement in worsening metabolic profiles was not

electroencephalography in obese chıldren

addressed. The study aimed at defining 2AG relevance as BMI-independent

Onur Akın, İbrahim Eker, Mutluay Arslan, Suleyman Tolga Yavuz,

biomarker of metabolic impairment in males and whether its relevance is

Sevil Akman, Mehmet Emre Ta¸c¸ılar & Bulent Unay

modified by ageing.

Gulhane Education and Research Hospital, Ankara, Turkey.

Methods

Unmedicated, disease-free male volunteers (nZ144) aged 18-84yo were stratified

in normal weight (NW, BMI:18.5-24.9 kg/m², nZ61), overweight (OW; BMI:

Background

25.0-29.9 kg/m², nZ61) and obese (BMI R30.0 kg/m², nZ22) classes. Plasma

This study aimed to investigate neurocognitive functions and electroencephalo-

2AG, anthropometric and metabolic parameters were assessed.

graphy (EEG) parameters in normoglycemic obese children.

Results

Method

Age did not influence 2AG levels in the overall cohort nor within BMI classes.

A total of 73 obese children (38 male and 35 female) and 42 healthy children (21

2AG levels increased with BMI (PZ0.019), however, significance was lost after

male and 21 female) were recruited. Biochemical disturbances and insulin

adjustment for each metabolic parameter.

2AG displayed age- and BMI-

resistance (IR) were investigated. The Wechsler Intelligence Scale for Children-

independent positive relationships with SBP (PZ0.020), insulin (PZ0.011),

Revised (WISC-R) and EEG were performed for all children. Obese participants

HOMA-IR (PZ0.006), total cholesterol (PZ0.001) and triglycerides (P!0.001)

were classified according to the presence of IR. Data were compared between

and negative with HDL-cholesterol (PZ0.046). 2AG correlation with triglycer-

these subgroups.

ides was confirmed in each BMI class (NW and OW: P!0.001; OB: PZ0.029).

Results

Positive 2AG correlation was found with SBP (PZ0.023) and DBP (PZ0.048)

Verbal scores on the WISC-R of the IRC Group were significantly lower than the

within OB, and with total cholesterol within OW (P!0.001) class. Finally, within

control group and the IR- Group. There were no differences between groups with

the NW class, 2AG negatively associated with HDL-cholesterol (PZ0.004) and

respect to other parameters of the WISC-R and EEG. Verbal and total scores of

positively with glucose

(PZ0.015), insulin

(PZ0.003) and HOMA-IR

the WISC-R were negatively correlated with HOMA-IR values. In the EEG study,

(PZ0.001); notably, the last two correlations were positively influenced by age

slowing during hyperventilation was seen significantly more frequently in obese

(both PZ0.004). No associations were detected between

2AG and waist

children than non-obese children.

circumference.

Conclusion

Conclusions

Neurocognitive functions, particularly verbal abilities, were impaired in obese

Plasma 2AG is a valuable biomarker of clustering hypertension, insulin resistance

children with IR. On the other hand, EEG results did not differ in terms of obesity

and dyslipidemia in male gender. Results in lean males may suggest a causative

and IR. IR may be associated with neurocognitive abnormalities in obese

role for 2AG in age-related insulin resistance.

children.

DOI: 10.1530/endoabs.49.EP671

DOI: 10.1530/endoabs.49.EP673

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP674

(P:0,85), before and after surgery, respectively. We didn’t find any correlation

between BMI and BMD but there was a negative correlation between 25-OH D

and PTH (r: K0,298 P:0,0003)

Abstract withdrawn.

DOI: 10.1530/endoabs.49.EP676

EP677

Effects of mediterranean diet in obese patients with metabolic syndrome

and depression

Vesna Dimitrijevic-Sreckovic^1,5, Hristina Janeski², Branko Sreckovic³,

EP675

Ivan Soldatovic^4,5, Nevena Nesovic¹ & Milica Vujovic¹

Lipid profiles and vitamin D receptor polymorphisms in overweight/

¹Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical

obese dialysis patients

Center of Serbia, Belgrade, Serbia;²University Children’s Hospital,

Gokhan Bagci¹, Can Huzmeli², Binnur Bagci³, Ferhan Candan²,

Belgrade, Serbia;³Clinical Center Bezanijska Kosa, Belgrade, Serbia;

Lale Akkaya² & Mansur Kayatas²

⁴Institute for Medical Statistics and Informatics, Belgrade, Serbia;⁵Faculty

¹Cumhuriyet University, Medical Biochemistry, Sivas, Turkey;

of Medicine, Belgrade University, Belgrade, Serbia.

²Cumhuriyet University, Nephrology, Sivas, Turkey;³Cumhuriyet

University, Nutrition and Dietetics, Sivas, Turkey.

Introduction

Central obesity is the source of inflammatory factors, causing endothelial

Background

dysfunction. In central nervous system, inflammatory factors mediate neuro-

Vitamin D receptor (VDR) is present on adipocytes, and many studies were

transmitter metabolism promoting excitotoxicity and increase oxidative stress,

carried out to investigate the association between single nucleotide polymorph-

and a major clinical symptom is depression. Mediterranean diet (MD) resulted as

isms (SNPs) in VDR gene with obesity. However, little is known about the role of

a good prevention method for depression.

VDR gene polymorphism with obesity in dialysis patients. Therefore, we aimed

Aim

to investigate lipid profile and VDR gene TaqI, ApaI and FokI SNPs in

To examine the relationship of depression with abdominal obesity and metabolic

overweight/obese dialysis patients.

syndrome (MS) criteria, blood pressure, lipids, glycaemia and inflammation

Methods

factors. Analysing effects of MD on weight correction, abdominal obesity and

Seventy one normal weight and 68 overweight/obese patients were included in

consequent less score points in Hamilton scale for depression.

study. PCR-RFLP method was used for genotyping.

Methods

Results

Study included 36 adolescents and youth (16-30 years) and 22 adults over 30

For all three SNPs, no significant association was found between normal and

years, overweight and obese patients with MS, diagnosed with depression using

overweight/obese patients (PO0.05). The level of LDL, total cholesterol and

Hamilton scale. MS was diagnosed using ATP III classification criteria. The

triglycerides was found significantly high, and HDL level was found significantly

following parameters were observed: BMI, waist circumference (WC), blood

low in overweight/obese patients compared to normal weight patients (P!0.05).

pressure, lipids, CRP and basal glycaemia and insulin. Seven day scheduled MD

In overweight/obese patients, patients carrying ApaI CC genotype have higher

was used by patients.

triglyceride levels compared to AA and AC genotype (CC vs AA PZ0.001;

Results

CC vs AC P!0.001) and CC Z627G653; AC Z193G85; AA Z233G156).

Correlation is found between Hamilton’s scale score and body weight, BMI, WC

No significant association was found between other SNPs and lipid profiles.

(P!0.01) and CRP (P!0.05) in adolescents and youth. Implementation of MD

Conclusions

resulted in reduction of body weight and WC (P!0.05), Hamilton’s scale score

Our results suggest that ApaI polymorphism are associated with high triglyceride

(P!0.001), insulinemia, HOMA-IR and CRP (PO0.5). Hamilton’s scale and

levels in overweight/obese dialysis patients.

Hamilton’s scale score correlated with insulin

(P!0.05) and glycaemia

DOI: 10.1530/endoabs.49.EP675

(P!0.05), basal insulin correlated with CRP (P!0.05). After MD values of

Hamilton’s score, WC, insulin and CRP were lower (PO0.5).

Conclusions

Mediterranean diet resulted with reduced values of Hamilton’s scale score, waist

circumference, insulinemia and CRP in patients with MS and depression. Positive

correlation of Hamilton’s scale score with glycaemia and insulinemia suggest

importance of insulin resistance and glucoregulation disorder on occurrence and

stage of depression in obese patients with metabolic syndrome. CRP is useful

marker for low grade inflammation in obese patients with MS, hence depression.

EP676

Keywords: metabolic syndrome; obesity; depression; Mediterranean diet;

Bone mineral density and bone turnover markers after bariatric

hyperinsulinism

surgery

DOI: 10.1530/endoabs.49.EP677

Meliha Melin Uygur & Dilek Gogas Yavuz

Marmara University School of Medicine, Endocrinology and Metabolism

Disease Department, Istanbul, Turkey.

Although bariatric surgery has beneficial effects on obesity related complications,

rapid weight loss might have negative effects on skeletal health. The objective of

our study was to evaluate changes in bone mineral density (BMD) and bone

EP678

biochemical markers in patients, before and 1 year after bariatric surgery.

Visceral obesity in youth followed by decreased testosterone leading to

Methods

erectile dysfunction and risk of early atherosclerosis

One hundred and two morbidly obese subjects (mean 43G15 years, BMI

Vesna Dimitrijevic-Sreckovic^1,5, Hristina Janeski², Branko Sreckovic³,

48,5 g/cm²) performed either Roux en Y gastric bypass

(n:9) or sleeve

Ivan Soldatovic^4,5, Milica Pajovic¹ & Marko Stojanovic¹

gastrectomy (n:93) were included in the study. Serum vitamin D, calcium,

¹Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical

parathyroid hormone (PTH), C-terminal telopeptide (CTX), osteocalcin levels

Center of Serbia, Belgrade, Serbia;²University Children’s Hospital,

were measured with immunochemiluminescence method. BMD measured with

Belgrade, Serbia;³Clinical Center Bezanijska Kosa, Belgrade, Serbia;

Dual X ray absorbsiometry (DEXA) before and after first year of the surgery.

⁴Institute for Medical Statistics and Informatics, Belgrade, Serbia;⁵Faculty

Results

of Medicine, Belgrade University, Belgrade, Serbia.

BMI decreased significantly after surgery compared to baseline (30,5G8.5kg/m

versus 48.5G9.08 P:!0.0001). Serum CTX levels were significantly higher at 1

year (P:!0,0001). Changes in calcium, PTH, 25 OH vitamin D, CTX and

Background

osteocalcin at baseline and first year of the surgery. Lumbar BMD was 1,284

Abdominal obesity, which in fact is a metabolic syndrome (MS), is related to

versus 1.260 g/cm² (P:0,32), femoral neck BMD was 1.034 versus 1.030 g/cm²

decreased testosterone, insulin resistance (IR), increased inflammatory factors,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

non-alcoholic fat liver disease

(NAFLD) and risk of early atherosclerosis.

controlling body weight. It is possible to prevent most of the morbidities and

Elevated inflammatory markers

(CRP) may interfere with insulin signal

mortality related to obesity by preventing weight gain. Every effort should be

transduction at the neuronal level inducing hypogonadotropic hypogonadism.

made to increase the level of education about healthy nutrition habbits and

Objective

importance of regular physical activity.

To examine testosterone relationship with abdominal obesity, lipid status, blood

DOI: 10.1530/endoabs.49.EP679

pressure, IR and NAFLD in obese young males with pre-MS and MS.

Methods

The study included 52 obese male individuals with pre-MS or MS (age16-30)

classified in two groups: I-with low testosterone

!12.0 nmol/l; II-with

testosterone R12,0 nmol/l. The following parameters were observed: waist

circumference (WC), blood pressure, lipids, microalbuminuria. SGOT, SGPT and

g-GT were liver function parameters. ATP III classification was applied for

EP680

diagnosing MS. Patients with less than three above criteria were considered pre-

MS. IR was determined by HOMA IR. OGTT was used to evaluate

Effect of Vitamin D supplementation on body composition in overweight

glycoregulation disorder. Testosterone was determined by radioimmunoassay.

men: A randomized controlled trial

Christos Karefylakis^1,2, Annaclara Ariander², Stefan Särnblad², Peter Rask³

Results

& Eva Rask^1,2

BMI:I-35.7G35, II-33.0G4.9 kg/m²; WC:I-117.3G15.5, II-109.9G14.2 cm;

¹Department of Internal Medicine, Division of Endocrinology and Diabetes,

HDL:I-0.96G0.18, II-1.04G0.2 mmol/l; triglycerides: I-2.74G1.6, II-1.8G

Orebro University Hospital, Orebro, Sweden;²Faculty of Medicine and

1.0 mmol/l; insulin

0’:I-113G128. II-40.1G61.2 IU/l; insulin

30’:I-199.8G

Health, School of Health and Medical Sciences, Orebro University, Orebro,

124.II-124.1G90 IU/l; insulin 120’:I-119.8G114. II-53.9G70.8 IU/l; HOMA

Sweden;³Department of Clinical Physiology, Orebro University Hospital,

IR:I-26.8G31, II-9.1G14 mmol/mU/ml; SGOT:I-50.5G39.3, II-26.8G

Orebro, Sweden.

7.8;SGPT:I-81.8G48.2, II-40.2G18.0 U/l; g-GT:I-49.8G19.3 U/l, II-39.7G

21.9 U/l.CRP:I-5.2G2.5, II- 5.25G5.8 mg/l.

Correlations

Introduction

Testosterone negative with body weight, BMI and WC (P!0.05). Decreased

The prevalence of vitamin D deficiency is higher in obese individuals but it is

testosterone

(!12.0 nmol/l) was found in 13.5% obese young males (8.5G

unclear whether vitamin D deficiency impacts body composition or if body

2.6 nmol/l), with normal FSH, LH and estradiol. A statistically important

composition impacts the vitamin D status. The research regarding vitamin D

difference between groups was found for 0, 30 and 120 minute insulin values

supplementation and weight loss in obese individuals is ambiguous. One

(P!0.05) and for liver function parameters SGOT and SGPT (P!0.001).

hypothesis for the presumed fat reductive effect of vitamin D is that vitamin D

Conclusion

inhibits adipocyte differentiation.

Low testosterone is characterized by obesity, MS parameters, hyperinsulinism, IR

Aim

and NAFLD. Negative correlation of testosterone with WC and statistical

To investigate if treatment with vitamin D can reduce fat mass in obese men with

importance of insulinemia and liver function parameters differences confirm the

vitamin D deficiency.

important effect of visceral obesity and IR on the occurrence of erectile

Methods

dysfunction, NAFLD and risk of early atherosclerosis in obese adolescents and

This study was designed as a randomized prospective, placebo controlled, double

youth.

blind intervention. Thirty eight overweight men (BMI O 25 kg/m²) with vitamin

DOI: 10.1530/endoabs.49.EP678

D deficiency (25(OH)D ! 55 nmol/l) were randomized to receive 2000 IU

Cholecalciferol drops or the equivalent amount of placebo drops for 6 months. At

baseline and after 6 months body composition and BMI was measured and blood

samples were obtained; body composition was measured using bioelectrical

impedance analysis (BIA).

Results

The mean change in body fat percentage for the vitamin D group and the placebo

EP679

group was a 0.6%-units (baseline compared to follow up; PZ0.222) and a 0.1%-

The prevalence of obesity and related factors: An urban survey study

units (PZ0.857) increase, respectively. The mean change in BMI in the vitamin

Ayla Gokmen Salici¹, Pinar Sisman², Ozen Oz Gul³, Tugce Karayel⁴,

D g roup was a 0.2 kg/m² decrease (PZ0.272) and for the placebo group a mean

Soner Cander³ & Canan Ersoy³

decrease in BMI of 0.5 kg/m² (PZ0.049). There was no statistically significant

¹Department of Internal Medicine, Usak State Hospital, Usak, Turkey;

difference between the placebo group and the intervention group regarding

²Department of Endocrinology, Kars State Hospital, Kars, Turkey;

change in fat percentage or BMI (PZ0.544, PZ0.256, respectively). Moreover

³Department of Endocrinology and Metabolism, Uludag University Medical

no statistically significant difference was observed between the groups regarding

School, Bursa, Turkey;⁴Department of Internal Medicine, Uludag

change in any of the metabolic laboratory values.

University Medical School, Bursa, Turkey.

Conclusion

We conclude that treatment with 2000 IU vitamin D daily for 6 months does not

impact BMI or fat percentage in overweight men with vitamin D deficiency.

Objectives

Obesity is a chronic and progressive disease that limits physical activity, causes

DOI: 10.1530/endoabs.49.EP680

psychological problems, and finally leads to social isolation of the person.

Detecting the factors affecting obesity and its prevalence in the populaton are

important steps in dealing with the problem. In this study, we aimed to evaluate

the obesity prevalence and the factors affecting this prevalence in randomly

selected volunteers from residents of the city of Bursa.

Methods

EP681

A questionnaire consisting of 40 questions evaluating the sociodemographic

Intensified telematic treatment for obesity using the web platform

aspects, healthy nutrition and exercise habbits and comorbidities of the subjects

PREDIRCAM2, descriptive basal characteristics and preliminary

was performed face to face to

528 volunteers

(414

females,

114 males)

results

participating in our study. Height, weight, waist, hip, neck and wrist

Valeria Alcantara-Aragon¹, Susana Rodrigo-Cano^2,5, Maria José Martínez¹,

circumferences and random blood glucose levels were measured. BMI and

Carmen Martínez¹, José Tapia^3,6, José Iniesta^3,6, Ascension Lupia

˜ez¹,

waist to hip ratio were calculated for each participant.

Susana Tenés^2,5, M Elena Hernando^3,6, J Francisco Merino-Torres^2,5,

Results

Alberto de Leiva^1,4 & Cintia Gonzalez^1,4

The mean age of the whole study population, female and male participants were

¹Endocrinology and Nutrition Department, Hospital de la Santa Creu I Sant

39.6G12.8, 40.2G12.7 and 37.1G12.9 years, respectively. According to BMI

Pau, Barcelona, Spain;²Endocrinology and Nutrition Department, Hospital

values 23.5% of the whole study population, 25.8% of females and 14.9% of

Universitari i Politècnic La Fe, Valencia, Spain;³Telemedicine and

males were obese. For the female subjects, the obesity prevalence was found to be

Bioengineering Group, Universidad Politécnica de Madrid, Madrid, Spain;

increasing with age, being married, being housewife and having lunch at home

⁴Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales

and decreasing with higher education level and income. When we investigated the

y Nanomedicina (CIBER-BBN), and Eduab-HSP Group, Universitat

male subjects, the only factor related to and found to be increasing the obesity

Autònoma de Barcelona, Barcelona, Spain;⁵Unidad Mixta de Investigación

prevalence was having lunch at home.

Endocrinología, Nutrición y Dietética. Instituto Investigación Sanitaria La

Conclusions

Fe-Universitat de Valencia, Valencia, Spain;⁶Centro de Investigación

Obesity is a worldwide problem. Its prevelance is increasing in our city and

Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina

country. Education level of the subjects seems to be the most important factor in

(CIBER-BBN), Madrid, Spain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

model which included AST/ALT and BARD was 0.75. BARD and APRI were

PREDIRCAM2 is a web platform for obesity treatment and follow-up. It contains

significant factors (PZ0.03, PZ0.04) on stepwise regression for F3/4 cirrhosis

modules for: dietary prescription and registry with nutritional analysis based on

and they were included in the final model, which had AUROC 0.73. Only Fib4

individualized and mediterranean dietary goals, physical activity prescription and

scoring was independently associated with cirrhosis

(F4) on multivariate

tracking with individualized targets, and anthropometric tracking. An ongoing

regression analysis (PZ0.04) and AUROC for the final model incorporating

multicenter randomized clinical trial evaluates the intervention’s effectiveness in

this factor was 0.70. In contrast to observations in non-bariatric patients, the NFS

obesity treatment and cardio-metabolic-risk prevention.

was of limited value and not an independent factor in predicting NASH, advanced

Methods

fibrosis or cirrhosis.

Inclusion criteria: 18-65 years-old, BMI 30-39.9 kg/m², no medication for type-2

Conclusion

Diabetes Mellitus (DM), dyslipidemia (DLP) or hypertension (HT). Randomiz-

Currently used non-invasive serum-based scoring systems have only a modest

ation to intensified technological intervention (TI) supported by PREDIRCAM2

predictive value for staging the severity of NAFLD in patients undergoing

platform, or traditional non-technological face-to-face intensified treatment

bariatric surgery. Intra-operative liver biopsy to detect and subsequently manage

intervention

(NTI). Both groups receive one year follow-up through

advanced liver disease therefore remains of value. There is a need to develop and

appointments with health-care professionals, 4 of which are exclusively telematic

validate non-invasive biomarkers of disease that offer better predictive value in

in the TI group.

the bariatric population.

Basal characteristics

DOI: 10.1530/endoabs.49.EP682

183 participants have been included, BMI 34.74G2.74, age 44.27G10.62, 84%

female (31% postmenopausal, 6.5% history of gestational DM),

54% high

education level, 54% married. Comorbidities: 2.2% type-2 DM, 5.5% HT, 11.5%

DLP, 6.5% Depression,

2.7% diagnosed eating disorders.

56% received

medication, most frequently antidepressants (24.5%) followed by vitamin D

supplements (11.8%). 68% reported anxiety towards food, overeating in the form

of: pecking 84.7%, binge-eating 35.5%, binge-and-vomiting 3.2%.

Preliminary results

EP683

119 participants have completed 3-month follow-up: 60 TI, 59 NTI. Both groups

Discussion with cases: Could we achieve the goal with non-surgical

have lost weight significantly (P!0.0001). 26.7% TI, and 25.4% NTI have

treatments in morbid obese patients?

achieved at least a 5% weight-loss (PZ0.88). 81 participants have completed

Aydin Cifci¹, Senay Arikan Durmaz², Askin Gungunes², Irfan Karahan³,

6-month follow-up: 41 TI, 40 NTI. Both groups have lost weight significantly

Selim Yalcin⁴ & Kubra Ozdemir¹

(P! 0.0001). 46.3% TI, and 32.5% NTI have achieved at least a 5% weight-loss

¹Department of Internal Medicine, School of Medicine, Kirikkale

(PZ0.20). Both groups have achieved a reduction in HbA1c levels (P!0.0001),

TI K0.81G1.9% and NTI K1.36G2.2% (PZ0.24).

University, Kirikkale, Turkey;²Department of Endocrinology and

Conclusion

Metabolism, School of Medicine, Kirikkale University, Kirikkale, Turkey;

Our study population is mostly composed of highly educated females who report a

³Department of Internal Medicine, Yenimahalle Traning and Research

high frequency of anxiety towards food and eating. PREDIRCAM2 shows to be a

Hospital, Ankara, Turkey;⁴Department of Oncology, School of Medicine,

promising tool for obesity treatment and cardio-metabolic-risk prevention.

Kirikkale University, Kirikkale, Turkey.

DOI: 10.1530/endoabs.49.EP681

Objective

Diet, lifestyle changes, medical agents and surgical approaches are treatment

options in obese patients. We reported two morbid obese patients who lost 25 and

21% of their previous weight respectively with only lifestyle changes and orlistat

therapy.

Case 1

Forty nine year-old woman had type 2 diabetes mellitus for 20 years. She took

premix insulin twice a day. Her height was 157 cm, her weight was 120 kg, body

EP682

mass index was 48.6 kg/m². One month later, she lost 3 kg with diet and exercise

Suboptimal prediction of advanced fibrotic liver disease by standard

and then orlistat was started. After seventh month of orlistat therapy, her weight

non-invasive scoring systems in obese patients undergoing bariatric

reduced to 85 kg and body mass index was 34.4 kg/m².

surgery

Case 2

Niall Dempster^1,3, Michael Watson⁴, Rachel Franklin¹, Maciej Juszczak²,

Fifty-four year-old man has type 2 diabetes mellitus and took metformin for 10

Lisa Rickers³, Caroline Fletcher³, Bruno Sgromo³, Richard Gillies³,

years. His height was 168 cm, his weight was 118 kg, BMI was 41.8 kg/m². One

Jeremy Cobbold⁴, Leanne Hodson¹, Jeremy Tomlinson¹ & John Ryan⁴

month later, he lost 2.5 kg with diet and exercise and then orlistat was started.

¹Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill

After seventh month of orlistat therapy, his weight reduced to 93 kg and body

Hospital, Oxford, UK;²Department of Vascular Surgery, John Radcliffe

mass index was 32.9 kg/m². Both patients lost their weight

35 and 25 kg

Hospital, Oxford, UK;³Department of Bariatric Surgery, Churchill

respectively with lifestyle changes and orlistat therapy. First year of treatment,

Hospital, Oxford, UK;⁴Department of Hepatology, Churchill Hospital,

patients maintain their weight without any gain.

Oxford, UK.

Conclusion

The number of patients undergoing obesity surgery has increased at the present

Introduction

time. Patients prefer surgery instead of lifestyle changes. Our results of patients

Non-Alcoholic Fatty Liver Disease (NAFLD), is present in over 90% of obese

with morbid obese emphasize importance of lifestyle changes and orlistat therapy.

patients undergoing bariatric surgery. It is a spectrum of pathology ranging from

DOI: 10.1530/endoabs.49.EP683

steatosis through to inflammation (Non-Alcoholic Steatohepatitis, NASH) and

fibrosis. Bariatric surgery is currently the most effective treatment for NAFLD,

but post-operative hepatic decompensation can occur and therefore pre-operative

stratification of liver disease severity is beneficial. Several non-invasive scoring

systems have been developed to stage NAFLD, but validation in the bariatric

surgical population has been limited.

Methods

135 consecutive patients who underwent bariatric surgery in a tertiary referral unit

EP684

from November 2014 to December 2016 were identified and the following

Body compositions in obesity may corralete the minimal change of

NAFLD risk scores calculated: AST/ALT, APRI, BARD, Fib4 and NAFLD

tyhroid functions within normal range

Fibrosis Score (NFS). All patients had an intraoperative liver biopsy performed

Veysel Urun¹, Kemal Ureten², Ozlem Gul Utku⁴, Askin Gungunes³ &

for accurate histological staging of disease. Logistic regression analysis was used

Senay Arikan Durmaz³

to determine their efficacy in detecting NASH (NAFLD Activity Score R5),

¹Department of Internal Medicine, School of Medicine, Kirikkale

advanced fibrosis (Brunt F3/4) and cirrhosis (F4) identified on liver biopsy using

university, Kirikkale, Turkey;²Department of Rheumatology, School of

R software.

Medicine, Kirikkale University, Kirikkale, Turkey;³Department of

Results

Endocrinology and Metabolism, School of Medicine, Kirikkale University,

BARD and AST/ALT were independent predictors of NASH on multivariate

Kirikkale, Turkey;⁴Department of Gastroenterology, School of Medicine,

logistic regression analysis. However, only AST/ALT ratio was significant in the

Kirikkale University, Kirikkale, Turkey.

final model (AST/ALT PZ0.04, BARD PZ0.08). AUROC for the regression

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction and aim

Conclusions

Overt thyroid dysfunction is well recognized to affect weight, but the influence of

1. FGF-21 and TGF-b reduction were associated with CHD in patients with

minor perturbations of thyroid function remains unclear. There is ongoing debate

obesity.

regarding the influence of minor changes in thyroid hormones status within the

2. Increased TGF-b may play a protective role in atherosclerosis in patients with

normal range and BMI. The aim of this study was to investigate the association

diabetes and obesity.

between thyroid function within normal ranges and obesity via BMI and body

DOI: 10.1530/endoabs.49.EP685

compositions analyzed by bioelectrical impedance.

Materials and methods

One hundred twenty persons with normal thyroid functions were included in our

study. According to the BMI, the patients were divided into 5 groups. Group1;

normal weight (nZ40), group 2; overweight (nZ20), group3; classI obesity

(nZ20), group4; class II obesity (nZ20), group 5 morbid obesity (nZ20).

Measurements of serum TSH, free T3, free T4 and lipid profile were recorded.

EP686

Body compositions and BMI were evaluated by bioelectrical impedance

The dynamics of anthropometric data in fertile age women by various

(TANITA).

types of the treatment

Results

Maryam Abduvakhabova & Saidganikhoja Ismailov

In group 1, TSH was negatively correlated with BMI (rZK0.430, PZ0.006). On

Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan.

the contrary, TSH was positively correlated with percentage of body fat (BF%)

(rZ0.391, PZ0.014). Free T3 was positively correlated with BF% (rZ0.333,

PZ0.038). In group 2, free T3 was positively correlated with BF% and fat mass

The aim

(rZ0.657, PZ0.010, rZ0.751, P!0.001 respectively). In group 3, free T3 was

To study efficiency of pathogenetic therapy and dynamics of anthropometric

positively correlated with BF%, fat mass, HOMA-IR and LDL (rZ0.521,

indexes for women with obesity of fertile age at different endocrinopathies to and

PZ0.018; rZ0.543, PZ0.013; rZ0.512, PZ0.021; rZ0.469, PZ0.037,

through 6 months after treatment.

respectively). Similarly, TSH was positively correlated with BMI (rZ0.553,

Material and research methods

PZ0.011). In group 5, free T4 was negatively correlated with LDL (rZK0.485,

On the etiologic factor of patient with obesity were up-diffused on three groups:

PZ0.030).

1 g. are patients with obesity at the polycystic syndrome of ovaries (PCOS) - 30

Conclusion

patients, 2 g. are patients with hypothalamic obesity - 21 cases and 3 g - patient

We demonstrated that differences in thyroid function within the normal range

with endocrine obesity (at a primary hypothyroidism) - 20 patients. Age of

may correlate with differences in BMI and body compositions in subjects within

patients in a 1th group hesitated 39 from 20 to and 28.3G0.64 averaged year. To

different BMI categories. Further large scale data from the population is required

all patients have been conducted spectrum of investigations, which include

to confirm our findings.

clinical, biochemistry, hormonal analysis of the blood. Besides of this,

DOI: 10.1530/endoabs.49.EP684

electrocardiography, ultrasound investigation of uteri and ovarium during 11-

14 days of periods, and MRY of pituitary. For the

1 g. we administered

combination of Syofor 1000 mgs C spironolacton 100 mgs C yodmarinum

100 mgs CL-thyroxine 50 mgs in the morning C antiandrogens C antidepress-

ants. For the 2 group: combination of Syofor 1000 mgs C spironolacton 100 mgs

C Yodmarin 100 mgs CL-thyroxine 50 mgs iC methaboliks C Reduxine

(Sibutramin)

15 mgs C antidepressants. For the 3 groups: combination of

Yodmarin 100 mgs CL-thyroxine 50 mgs.

The results

EP685

In 1 and 2 groups of patients marked reliable decline of BMI 1 and 2 degrees after

Association of Transforming growth factor b and Fibroblast growth

6 months of treatment, while for patients 3 groups of reliable changes of BMI

factor 21 with cardiovascular diseases in obese patients

through 6 months of treatment were not attained at none of degree of BMI Thus,

Teona Shvangiradze¹, Ekaterina Troshina¹, Irina Bondarenko¹,

for patients 1 and 2 groups with BMI 3 degrees through 6 months a tendency was

Marina Shestakova^1,2 & Larisa Nikankina¹

attained to the decline of BMI. In addition, renewal of fecundity and pregnancy

¹Endocrinology Research Centre, Moscow, Russia;²I.M. Sechenov’s First

was attained for the patients of a 1 group - in 19.5% cases (at 10 patients).

Moscow State Medical University, Moscow, Russia.

Conclusions

Optimization of treatment of obesity for the women of reproductive age is based

on drafting of the individual programs, the choice of that is determined by the

Introduction

values of anthropometric indexes, state of hormonal and metabolic status, features

Obesity and type 2 diabetes mellitus (T2DM) are associated with cardiovascular

of food behavior and personality-emotional sphere, state of menstrual and

diseases (CVD). Fibrotic changes in obesity include several molecular processes,

reproductive function.

including activation of Transforming growth factor b (TGF-b). Recent data

indicate the involvement of Fibroblast growth factor 21 (FGF-21) as an important

DOI: 10.1530/endoabs.49.EP686

metabolic regulator, and even biomarker of metabolic changes in obesity and

T2DM.

Aim

To determine TGF-b and FGF-21 level in patients with obesity and T2DM.

Methods

TGF-b and FGF-21 were identified in peripheral blood of 66 patients, aged 48-65

years with obesity. They were divided into 3 groups. 1st - 21 patients with

coronary heart disease (CHD) (confirmed by coronary angiography (CAG)) and

EP687

T2DM, the 2nd - 22 patients with T2DM, in the 3rd - 23 patients without T2DM

Effects of IL-1b on the hypothalamic-pituitary-gonadal axis in men with

and CHD. CHD was excluded in the 2nd and 3rd groups by Tredmil test. Control

obesity and metabolic syndrome - A randomized, double-blind,

(4th) group included 14 healthy person matched by age and sex.

placebo-controlled trial

Results

Fahim Ebrahimi^1,2, Philipp Schuetz^2,3, Beat Mueller^2,3, Sandrine

TGF-b was significantly different in the studied groups (PZ0.046). We found

A Urwyler^1,2, Marc Y Donath^1,2 & Mirjam Christ-Crain^1,2

that TGF-b was significantly lower in patients with CHD (group 1) compared with

¹Department of Internal Medicine, Division of Endocrinology, Diabetes and

the group of

“metabolically healthy” obesity

(PZ0.02). TGF-b negatively

Clinical Nutrition, University of Basel Hospital, Basel, Switzerland;

correlated with. atherogenic fractions of cholesterol

- LDL (rZK0.426,

²Department of Clinical Research, University Hospital Basel, Basel,

PZ0.043) and with the degree of internal carotid artery 0stenosis (rZK0.426,

Switzerland;³University Department of Medicine, Kantonsspital Aarau,

PZ0.039) in patients with T2DM. In contrast, patients with verified CHD

Aarau, Switzerland.

demonstrated a negative correlation with the duration of obesity (rZK0.395,

P!0.033), and the processes of heart muscle remodeling (thickness of the left

ventricular posterior wall (rZK0.386, PZ0.029) and interventricular septum

Background

(rZK0.335, PZ0.031). FGF-21 and TGF-b in the 1st group showed a negative

Low testosterone levels in men appear to be an independent cardiovascular risk

correlation with the number of significantly affected vessels according to CAG

factor closely associated with the metabolic syndrome. Reciprocally, the

(rZK0.73, PZ0.041 and rZK0.52, PZ0.036, respectively). All patients with

metabolic syndrome leads to a decrease in testosterone levels, suggesting a

obesity had significantly increased level of FGF-21 compared with the control

bidirectional relationship. It has been hypothesized that increased inflammation is

group (PZ0.03) and FGF-21 positively correlated with BMI (rZ0.47, PZ0.021)

causative for the development of obesity-associated hypogonadism. However,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

clinical evidence supporting this hypothesis is lacking. The aim of the present

EP689

study was to determine whether anti-inflammatory treatment may restore

Clinical and metabolic markers of X-syndrome

endogenous testosterone production in obesity-associated hypogonadism.

Irina Savasteeva¹, Yana Navmenova¹, Yulia Yarets¹, Alena Makhlina²,

Methods

Marina Kaplieva², Tamara Yeudachkova¹ & Elena Vaschenko¹

This is a randomized, placebo-controlled, double-blind, trial including

¹Republican Scientific and Practical Center for Radiation Medicine and

hypogonadal men with the metabolic syndrome. Patients were randomly assigned

Human Ecology, Gomel, Belarus;²Gomel State Medical University, Gomel,

to either receive

100 mg of a recombinant human interleukin-1-receptor

Belarus.

antagonist subcutaneously twice daily for 4 weeks or to receive placebo. The

primary endpoint was the change in total testosterone levels between baseline and

4 weeks. Predefined secondary end points included a change by week 4 in insulin

resistance, body composition, muscle strength, hypogonadal symptoms and

We identified factors that significantly influenced the development of the

hemodynamic parameters.

X-syndrome. A significant influence on the development of X-syndrome

Results

have increase the level of total cholesterol (bZ0.65; PZ0.036; Exp (b) Z

From April 2016 to January 2017, 66 patients have been enrolled at two tertiary

1.92

(1.04O3.54)). Increases the risk of X-syndrome increase the level of

care centers in Switzerland. Median age was 51 years (IQR 41-65) and patients

apo-B-protein (bZ4.79; PZ0.014; Exp (b) Z12.69 (2.68O54.41)). The

had a median BMI of 37 kg/m² (34-39 kg/m²). Patients had hypogonadotropic

increase in linear dimension of preperitonialy fat increased the risk of

hypogonadism with median baseline testosterone levels of 8.8 nmol/l (231 ng/dl)

developing X-syndrome (bZ1.14, PZ0.036; Exp (b)Z3.14 (1.08O9.16)).

(7.6-10.1), median LH levels of 3.7 IU/l (3-5.2 IU/l), and median C-reactive

By reducing the level of free thyroxine was a consistent trend of formation of

protein levels of 2.9 mg/l (1.4-4.0 mg/l) mirroring a low-grade inflammatory

X-syndrome (bZK0.25; PZ0.09; Exp (b) Z1.08 (0.57O1.10)). When

state. Final results will be available in March 2017 and will be presented first at

using the ROC analysis were obtained by the cut-off point, allowing to

the ECE 2017.

calculate the relative risk. The critical cut-off point for preperitonealny fat

Significance

figure was more linear size 2.1 sm (P!0.02); total cholesterol - more than

This study will show whether there exists causality between obesity-associated

6.36 mmol/l (P!0.02), apo-B-protein - more than 1.15 g/l (P!0.001), free

inflammation and hypogonadism.

thyroxine - less than 13.40 pmol/l (P!0.001). If the linear dimension

DOI: 10.1530/endoabs.49.EP687

preperitonealny fat more 2.1sm RR X-syndrome was 3.00 [0.87O10.39].

When total cholesterol level of more than 6.36 mmol/l RR X-syndrome was

16.50

[2.05O33.05]. When damage apo-B protein over

1.15 g/l RR

X-syndrome was 22.00 [2.49O94.44]. By reducing the thyroxine levels

below 13.40 mmol/l RR X-syndrome was 13.00 [1.53O110.51].

DOI: 10.1530/endoabs.49.EP689

EP688

Demographic and baseline characteristics of an obese population

admitted for bariatric surgery in a secondary care centre

Daniela Gallo¹, Silvia Ippolito¹, Giovanni Veronesi¹, Eugenia Dozio¹,

Francesco Frattini², Eugenia Trotti¹, Adriana Lai¹, Lorenza Sassi¹,

Jessica Sabatino¹, Elvira Masiello¹, Paola Premoli¹, Eleonora Bianconi¹,

Claudio Cusini¹, Sara Rosetti¹, Maria Laura Tanda¹, Gianlorenzo Dionigi²,

EP690

Luigi Bartalena¹ & Eliana Piantanida¹

Impact of weight changes on the incidence of diabetes mellitus: a

¹Department of Medicine and Surgery, University of Insubria, Varese, Italy;

Korean nationwide cohort study

²Research Center for Endocrine Surgery, University of Insubria, Varese,

Eun Sook Kim, Jee Sun Jeong, Kyungdo Han, Mee Kyoung Kim,

Italy.

Seunghwan Lee, Yong-Moon Park, Ki-Hyun Baek, Sung Dae Moon,

Je-Ho Han, Ki-Ho Song & Hyuk-Sang Kwon

Catholic University of Korea, Seoul, Republic of Korea.

Obesity has become one of the greatest public health concerns and is known

to be a major risk factor for cardiac, respiratory and metabolic diseases.

Objective

Bariatric surgery is the most effective treatment for morbid obesity.

Obesity is a well-known risk factor for type 2 diabetes, but few data exist on the

According with guidelines, surgery is indicated for treatment of patients

association between weight changes and future diabetes risk in non-obese

with BMI greater than 40 kg/m² or above 35 kg/m², with at least one

subjects. This study aimed to investigate the effect of weight changes on the

obesity-related comorbid condition, such as as type 2 diabetes, hypertension,

incidence of type 2 diabetes in Korea, using prospective nationwide data.

dyslipidemia, sleep apnea, osteoarthritis. Nowadays, sleeve gastrectomy is

Research design and methods

one of the most common techniques, able to cure metabolic disorders,

A total of 51 405 non-diabetic subjects were included who had undergone health

allowing a shorter convalescence and fewer complications. We herein

examinations in 2002 and completed follow-up in 2006.

describe the baseline characteristics of 38 adults (35 women, mean age 41G

Results

13 years), suitable for surgery. Patients were referred by Surgeons or other

Individuals who developed type 2 diabetes were more likely to be older and male,

Specialists such as Cardiologists, Pulmonologists, Nephrologists or

to have high BMI, blood pressure, fasting plasma glucose, and total cholesterol, to

Orthopedicians. Three patients were admitted for the conversion of

be a current smoker, to consume larger amounts of alcohol, to be hypertensive and

laparoscopic adjustable gastric banding, to achieve additional weight loss.

hyperlipidemic, and to have a family history of diabetes, compared to those

In keeping with guidelines, BMI was 43.3G6 Kg/m² (71% R40 kg/m²,

without type 2 diabetes. Compared with the consistently non-obese group, there

23.5% 35-39.9 kg/m², 5.3% !35 kg/m²), with a visceral pattern of obesity

was a higher hazard ratio for incident diabetes (95% confidence interval) in

(waist circumference

123G11 cm). Half of the patients suffered from

subjects becoming obese (1.50 (1.27-1.78)), losing weight (1.89 (1.61-2.22)),

metabolic syndrome, defined according to IDF/AHA/NHLB harmonized

and remaining obese (2.60 (2.56-3.05)), over 4 years, after adjustment for

definition. Actually,

29% had diabetes,

37% hypertension and

53%

confounding factors. When stratified by BMI categories, risks for incident

dyslipidemia. Among the others, arthropathy was the most frequent

diabetes were significantly decreased with lower BMI and the trends were more

comorbidity (21%), followed by respiratory diseases (chronic obstructive

evident in the non-obese group. However, there was no significant association of

or restrictive pulmonary disease, 19%), chronic venous insufficiency (11%)

high BMI with incident diabetes.

or heart diseases (5.3%). We observed gastric diseases in almost half of the

Conclusions

population (44%), and, as expected, 24% had hiatal hernia. Beyond these,

Weight loss was significantly associated with decreased diabetes risk both in non-

71% of patients emerged to have thyroid disease, with a high prevalence of

obese and obese Koreans, but particularly in the non-obese. Further long-term

non-toxic goiter and Hashimoto’s thyroiditis. During the screening,

studies are needed to establish weight reduction as a preventive strategy for type 2

papillary thyroid cancer was disclosed in two patients (5.3%). According

diabetes.

to the literature, these data underscore the high prevalence of obesity-related

DOI: 10.1530/endoabs.49.EP690

morbilities and the need for an effective and urgent treatment.

DOI: 10.1530/endoabs.49.EP688

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP691

mice deficient in HSD17B13 (HSD17B13KO). The data revealed normal serum

sex steroid concentrations and proper reproductive performance in both male and

Metabolic profile reversal after bariatric surgery

female HSD17B13KO mice, indicating a minor role for HSD17B13 in sex steroid

Daniela Gallo¹, Silvia Ippolito¹, Giovanni Veronesi¹, Eugenia Dozio¹,

metabolism and reproduction. In line with the strong expression in the liver,

Francesco Frattini², Eugenia Trotti¹, Adriana Lai¹, Lorenza Sassi¹,

histological analysis showed the presence of liver steatosis in HSD17B13KO

Jessica Sabatino¹, Elvira Masiello¹, Paola Premoli¹, Eleonora Bianconi¹,

mice that was associated with inflammation. The phenotype was more

Sara Rosetti¹, Claudio Cusini¹, Maria Laura Tanda¹, Gianlorenzo Dionigi²,

pronounced in males than females. The severity of the phenotype progressed

Luigi Bartalena¹ & Eliana Piantanida¹

with aging, and accumulation of triglycerides was observed in the livers of the

¹Department of Medicine and Surgery, University of Insubria, Varese, Italy;

male mice from 3 months onwards. Furthermore, metabolic profiling showed a

²Research Center for Endocrine Surgery, University of Insubria, Varese,

tendency for increased hepatic phospholipid content in the

month-old

Italy.

HSD17B13KO males with two acylcarnitines (C16:0 and C18:1) showing the

most profound increase (w2-fold). Additionally, presence of microgranulomas

(Kupffer cell aggregations) with increased portal inflammation and ductular

Bariatric surgery is the most-effective treatment for morbid obesity, superior

proliferation was observed in liver specimens from HSD17B13KO mice. This

to medical treatment. Metabolic syndrome (MS) is a condition characterized

was associated with increased expression of immune response genes in the

by multiple major risk factors for coronary heart disease, diabetes, fatty

HSD17B13KO male liver. In conclusion, the lack of HSD17B13 impairs hepatic

liver, and several cancers; the main, diagnostic, components of MS are low

lipid metabolism in mice, resulting in liver steatosis and inflammation. The data,

HDL-cholesterol

(!40 mg/dl in man,

!50 mg/dl in woman), raised

thus, indicate that HSD17B13 is involved in fatty acid metabolism in the liver,

triglycerides

(O150 mg/dl), blood pressure O130/85 mmHg, fasting

while the enzyme does not play a major role in the regulation of reproductive

plasma glucose O100 mg/dl and waist circumference O94 cm in man

functions.

and O80 cm in woman. Indeed, in addition to weight loss, changes in

DOI: 10.1530/endoabs.49.EP692

metabolic profile after bariatric surgery could improve long-term outcomes.

Complete demographic, clinical and laboratory data from 38 people (35

women, mean age 41G13 years) undergoing bariatric surgery and followed

by a dedicated clinical team were analyzed. Descriptive statistics detailed

clinical characteristics of the cohort of patients. Paired T-test compared

baseline clinical parameters, lipid and glycemic profile index at three (T3)

and six (T6) months after surgery. General Linear Model for Repeated

Measure compared the five conditions defining MS over time. Weight, BMI,

waist circumference and systolic blood pressure decreased significantly at

T3 and T6, compared to baseline [all P!0.05]. Triglycerides and LDL

cholesterol decreased at T3 and T6, HDL notably raised at T6 [all P!0.05].

EP693

Fasting plasma glucose and HbA1c decreased at T3 and T6; HOMA index

Visceral vs subcutaneous white adipose depots response to insulin

improved over time

[all P!0.05]. Prevalence of MS according to

treatments in rats

IDF/AHA/NHLB harmonized definition in our population was 50% at

Milica Markelic¹, Aleksandra Jankovic², Igor Golic¹, Marija Aleksic¹,

baseline, 10 times higher for age than average prevalence in literature; at 6

Ana Stancic², Vesna Otasevic², Sava Masovic², Marija Marin¹, Bato Korac²

months such prevalence decreased to 16%. In conclusion, in our population

& Aleksandra Korac¹

of patients undergoing bariatric surgery and a dedicated follow-up program,

¹University of Belgrade, Faculty of Biology, Belgrade, Serbia;²University

we observed a trend towards a noticeable improvement of the metabolic

of Belgrade, Institute for Biological Research “Sinisa Stankovic”, Belgrade,

profile in the mid-term.

Serbia.

DOI: 10.1530/endoabs.49.EP691

White adipose tissue (WAT) has an important role in the regulation of metabolic

homeostasis. It is well known that two distinct WAT depots in mammals,

subcutaneous WAT (sWAT) and visceral WAT (vWAT) display different

metabolic roles and it could be presumed that exert different response to various

hormones. Numerous studies revealed leading role of insulin in both fat

accumulation (lipogenesis) and adipocyte differentiation (adipogenesis) although

it is not clear is there a difference in response among these two depots. The aim of

this study was to reveal effects of insulin treatments on sWAT and vWAT

EP692

morphology. Male Wistar rats were treated acutely (1 day) or chronically (3 days)

with low (0.4 IU/kg bm) or high (4 IU/kg bm) dose of insulin. Saline-treated

Hydroxysteroid (17beta) dehydrogenase 13 knockout mice present with

animals served as controls. The portions of retroperitoneal, epididymal and

inflammation associated liver steatosis

subcutaneous WAT (rWAT, eWAT, sWAT, respectively) were removed and

Hanna Heikela¹, Marion Adam¹, Dorothea Portius², Jenni Mäki-Jouppila¹,

prepared for microscopic and Western blot analyses. Tissue components

Arfa Mehmood^1,3, Prem Adhikari¹, Irene Esposito⁴, Laura Elo^3,5,

(adipocytes, blood vessels and stroma) volume density and cell profile density

Fu-Ping Zhang¹, Suvi T Ruohonen¹, Leena Strauss¹, Michelangelo Foti² &

per unit area were determined. To establish adipogenic origin of multi-

Matti Poutanen¹

locular/paucilocular cells PCNA immunoexpression was examined, while protein

¹Department of Physiology, Institute of Biomedicine and Turku Center for

expression and cell presence of phosphorylated form (phospho-IR) of insulin

Disease Modeling University of Turku, Turku, Finland;²Department of Cell

receptor (IR) was used to analyze insulin signaling. Our results demonstrate

Physiology and Metabolism, Faculty of Medicine, Centre Médical

slightly higher number of adipocytes and adipogenic cells and increased

Universiatire, Geneva, Switzerland;³Turku Centre for Biotechnology,

capillarization in vWAT depots. A stronger response of vWAT to insulin

University of Turku and

˚boAkademiUniversity,Turku,Finland; 4Institute

treatment in comparison to sWAT is due to higher phospho-IR expression in

of Pathology, Technische Universitat Munchen, Munich, Germany;

endothelial and multilocular/paucilocular cells of analyzed vWAT depots.

⁵Department of Mathematics and Statistics, University of Turku, Turku,

Namely, in hyperinsulinaemia canonical insulin-signaling pathway favors

Finland.

adipogenesis and capillary remodeling in vWAT to a greater extent than in

sWAT depot. Our results suggest that insulin-induced differences in remodeling

of sWAT and vWAT depots may contribute to visceral obesity and development

Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) form a group of enzymes

and progression of insulin resistance and diabetes type 2 among other visceral

that are characterized by their sequence similarity at the active site, and their

obesity-associated metabolic diseases.

ability to catalyze the conversion between the weak 17keto- and the highly active

DOI: 10.1530/endoabs.49.EP693

17beta-hydroxysteroids. To study the physiological role of HSD17B13, a lipid

droplet associated protein, we characterized the phenotype of knockout (KO)

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP694

detected in patients with obesity and hypogonadism as compared with the 1st

group. There were a significant activation of CD16C lymphocytes (19.0[16.0;

Association between obesity and glomerular hyperfiltration: impact on

23.0] vs 12.0[9.0; 15.0]%) and reduction of the CD25C cells number (1.4[1.0;

metabolic risk factors

1.7] vs 1.9[1.8; 2.11]%), which reflects the early T-lymphocyte activation, in

Mirjana Sumarac-Dumanovic^1,2, Ana Gligic-Kuzmanovic²,

patients of the 2nd group (P!0.0001).

Danica Stamenkovic-Pejkovic^1,2, Snezana Polovina², Danka Jeremic²,

Conclusion

Goran Cvijovic^1,2, Svetlana Zoric² & Dragan Micic^1,2

The excessive accumulation of adipose tissue leads to dysfunction of the helper-

¹School of Medicine, University of Belgrade, Belgrade, Serbia;²Clinic for

cell immunity. Hypogonadism with obesity aggravates the imbalance of cell

Endocrinology, Diabetes and Diseases of Metabolism, Center for Obesity,

immunity, which could contribute to the formation of additional metabolic and

Clinical Center of Serbia, Belgrade, Serbia.

immunological disturbances.

DOI: 10.1530/endoabs.49.EP695

Abstract

Glomerular hyperfiltration has been suggested as a possible mechanism linking

obesity and chronic kidney disease, independently of classical risk factors such as

diabetes. In terms of determining the creatinine clearance has numerous

drawbacks, in clinical use are predictors of glomerular filtration rate (GFR)

which show varying degrees of accuracy in obese patients. The aim of our study

was to determine whether it is in our group of obese patients without type 2

EP696

diabetes, glomerular hyperfiltration associated with metabolic disorders. This

GLP-1 therapy and the immune system - can we predict responders

cross-sectional study included 30 obese patients at the beginning of treatment in

from non-responders?

Center for Obesity. Excluded were patients with type 2 diabetes, moderate/severe

Donal O’Shea^1,2, Laura Tobin^2,3, Declan Cody³, Arimin Mat^1,2,

hypertension and cardiovascular comorbidity. We analyzed metabolic parameters

David Kinlen^1,3 & Andrew Hogan^1,3

(fasting glucose and insulin, HOMA-IR, HbA1c, liver enzymes and renal function

¹University College Dublin, Dublin, Ireland;²St Vincent’s University

(GFR, proteinuria and albuminuria). According to the degree of GFR determined

Hospital, Dublin, Ireland;³National Children’s Research Centre, Dublin,

by: 1. the creatinine clearance (CCR); 2. The use of predictors GFR - MDRD and

Ireland.

Cockcroft-Gault (CGO) equation, patients were divided into two groups: with

hyperfiltration and with normal levels of glomerular filtration rate. According

to the level of GFR,

44.4% (CCR),

25.9% (MDRD), 66.7% (CCE) had

Abstract

hyperfiltration, while 55.6% (CCR), 74.1% (MDRD) 33.3% (cGO) patients had

Obesity has reached epidemic proportions globally. At least 2.8 million people die

normal filtration. Patients with hyperfiltration had significantly higher fasting

each year as a result of being overweight or obese, the biggest burden being

glycemia (CCR: 4.9G0.8 vs 4.7G0.5, PZ0.038; MDRD: 5.1G0.3G0.9 vs 4.9,

obesity-related diseases. Glucagon like peptide 1 (GLP-1) targeted therapies show

PZ0.039; cGO: 5.2G0.9 vs 4.7G0.5, PZ0.049) and HbA1c (CCR: 6.1G0.4 vs

the greatest potential for intervention and are approved as weight loss agents.

5.6G0.6, PZ0.015; MDRD: 5.8G0.9 vs 5.3G0.3, PZ0.022; cGO: 6.1G0.4 vs

However not all patients respond to GLP-1

therapy. Understanding the

5.3G0.3, PZ0.038) compared to patients with normal filtration. The value of

mechanisms of bodyweight regulation and their role in GLP-1 responders vs.

gamma-GT was significantly higher in the group of patients with hyperfiltration

non-responders is essential to better serve our patients. We have previously shown

compared another group [CCR: 30 (18-80) vs 24 (15-58), PZ0.080; MDRD:

that invariant natural killer T (iNKT) cells, which resides in adipose tissue, and

29.5

(19-80) vs 24.5 (15-58), PZ0.006; CGO: 41 (15-80) vs 18 (15-27),

acts as adipose tissue regulators are required for the full weight loss effect of GLP-

PZ0.003]. In our group of patients has been shown that obese patients with

1, a licensed weight loss therapy. In the absence of iNKT cells, GLP-1 therapy is

glomerular hyperfiltration had significantly higher values of the parameters of

30% less effective at inducing weight loss, due to a loss of FGF-21

and

glycemic control and gamma-GT compared to those with normal levels of

thermogenic reprogramming. In the current project we have extended our findings

filtration, regardless of age and BMI, which could suggest important

from murine models into humans investigating the adipose tissue metabolic

interrelationship among the initial development of chronic kidney disease with

pathways induced by GLP-1 therapy in patients who display significant weight

rediabetes and nonalcoholic fatty liver disease in obesity.

loss and a subset who fail to lose weight. We have also investigated if two

DOI: 10.1530/endoabs.49.EP694

immune cell derived proteins associated with obesity and insulin resistance

(soluble CD163 and Galectin-3) could be used to predict responses to intervention

(GLP-1 therapy or RYGB). We show that sCD163 but not Gal-3 is elevated in

obesity from childhood through to adulthood, and within 1 week of RYGB and

8 weeks of GLP-1 therapy sCD163 levels are significantly reduced. Overall this

project sheds light on novel mechanisms of bodyweight regulation and highlights

the possible use of sCD163 in mapping the progression of obesity and predicting

responders from non-responders to intervention.

EP695

DOI: 10.1530/endoabs.49.EP696

Characteristics of cellular immunity in men with obesity and

hypogonadism

Elizaveta Dzantieva, Irina Khripun, Zalina Gusova, Sergey Vorobiev,

Yanina Allakhverdieva, Natalia Kuzmenko & Ekaterina Petrovskaya

Rostov State Medical University, Rostov-on-Don, Russia.

Abstract

EP697

There are few studies of the cellular immunity in men with obesity and

An assessment of the relationship between abdominal obesity and the

hypogonadism. The aim was to study the parameters of cellular components of the

severity of upper extremity lymphedema

immune system in patients with obesity and hypogonadism.

YunKyung Jeon, MyungJun Shin, YongBeom Shin, InJoo Kim &

Materials and methods

BoHyen Kim

The study included 120 men aged 40-65 years with obesity (mean BMI - 35G

Pusan National University Hospital, Busan, Republic of Korea.

5.6 kg/m²). Patients were divided into two groups depending on the level of total

testosterone (T). The first group included 56 patients with T levelO12.1 ng/ml

(mean T

16.3G3.8 ng/ml), the second group

patients with T

Abstract

level%12.1 ng/ml (mean T - 8.3G1.9 ng/ml). The control group consisted of

Obesity is one of the well-known initiating and aggravating factor of

25 healthy men with BMI up to 25 kg/m². Levels of CD3C,CD4C,CD8C,

lymphedema. BMI is typically used to define obesity, but in Asian populations,

CD16C,CD25C lymphocytes were analysed. Statistical data were analysed

health risks are elevated at lower BMI levels and abdominal fat may be a better

using Mann-Whitney U-test.

obesity metric. Thus, we assessed the potential association between abdominal

Results

obesity and lymphedema severity in postoperative breast cancer patients. Thirty-

Level of CD4CT helper cells was significantly lower in the 1st group as

three women with breast cancer-related lymphedema participated in this study.

compared to the control group (41[38; 45]% vs 46[44; 47]%, P!0.005). Level of

Arm circumference was measured at four locations per arm to identify the

cytotoxic lymphocytes CD16C was higher in the 1st group as compared to the

maximal circumference difference (MCD) between the affected and unaffected

control (12.0[9.0; 15.0] vs 9.0[9.0; 10.0]%, (P!0.005). Significant changes in

sides. All patients underwent lymphoscintigraphy and we calculated the

other parameters were not found. Changes in T-cell immune system, namely in

quantitative asymmetry index (QAI) of both arms. A computed tomography

reduction of CD4C lymphocytes (32[28; 39] vs 41[38; 45]%, (P!0.001) and

(CT) was also performed to assess abdominal obesity after lymphedema.

increasing of CD8C lymphocytes (28[26;30] vs 24[20; 29]%, (P!0,05), were

Abdominal obesity was classified as a visceral fat cross-sectional area larger than

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

70 cm^2. Fourteen women (42%) were obese (BMIR25 kg/m²) and 18 women

involvement with cardiovascular disease (CVD), however, has not yet been

(54%) had increased abdominal fat. BMI obesity and abdominal obesity were

elucidated. The aim of the current study was to shed light on the potential

significantly correlated, but five patients were classified with abdominal obesity

association with irisin and cardiovascular risk.

despite a BMI below 25 kg/m². There were no significant differences in age, time

Methods

after surgery, cancer stage, history of axillary lymph node dissection,

Eighty patients with obesity (BMI R 30 kg/m²) and mean age 50,4G10,6 years

chemotherapy, or radiotherapy between patients with and without obesity. The

were included in the study which was realized in a third level university endocrine

mean arm circumference difference was 2.8G2.4 cm. Decreased axillary QAI

department. Biochemical measurements consisted of fasting plasma glucose,

was significantly correlated with obesity, and increased arm edema

serum immunoreactive insulin, serum uric acid, lipid profiles, liver enzymes.

(MCDR2 cm) was significantly correlated with abdominal obesity. Abdominal

Measurements of weight, height, waist circumference and arterial blood pressure

obesity was significantly correlated with increased MCD and should be

were performed. Cardiovascular risk was estimated by means of Framingham

considered along with obesity as an aggravating factor for lymphedema severity.

Risk Score calculation and a measurement of mean carotid intima media

DOI: 10.1530/endoabs.49.EP697

thickness (CIMT) as measured by an automated software via B-mode ultrasound.

Ankle-brachial index (ABI) measurement was also performed. Circulating serum

irisin was measured by a commercially available ELISA kit.

Results

Among parameters of interest, circulating irisin correlated positively with BMI

(rZ0, 246, P!0,05) and negatively with age (rZK0,457, P!0,001), total

EP698

cholesterol (rZK0,246, P!0,05), LDL-cholesterol (rZK0,234, P!0,05), ABI

(rZK0,272, P!0,05). CIMT (rZK0,353, P!0,01) and with Framingham Risk

Associations between the dysregulation of splicing machinery

Score (rZK0,400, P!0,01). Associations with CIMT, Framingham Risk Score

components and the development of hepatic steatosis in obese women

and ABI persisted after adjustment for age and sex. In a ROC-curve analysis

Mercedes del Río-Moreno¹, Sergio Pedraza-Arévalo¹, Sandra González-

circulating serum irisin was of use

(AUCZ0,665, 95%CI:

0,525-0,804,

Rubio², Gustavo Ferrín², Manuel Rodríguez-Perálvarez², Rhonda

PZ0,037) for distinguishing subjects with CIMT R 75^th percentile, which was

D Kineman³, Alejandro Ibán˜ez-Costa1, Manuel de la Mata2, Justo

found in 32,5% of the study participants

P Castan˜o1, Raúl M Luque1 & Manuel D Gahete1

Conclusions

¹Maimonides Institute of Biomedical Research of Cordoba (IMIBIC); Reina

Circulating irisin levels were negatively associated with established CVD

Sofia University Hospital (HURS); Department of Cell Biology, Physiology

estimates. Irisinaemia could be useful for distinguishing subjects with increased

and Immunology, University of Cordoba (UCO); CIBER Physi, Cordoba,

CIMT. Larger, prospective studies are required to establish the particular

Spain;²Department of Hepatology and Liver Transplantation, HURS/I-

mechanisms for these observations.

MIBIC; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd),

Cordoba, Spain;³Research and Development Division, Jesse Brown

DOI: 10.1530/endoabs.49.EP699

Veterans Affairs Medical Center and Department of Medicine, Section of

Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago,

Chicago, Illinois, USA.

Hepatic steatosis is a common obesity-associated pathology characterized by the

accumulation of fat within the liver, which can progress to liver fibrosis, cirrhosis

EP700

and ultimately lead to hepatocellular carcinoma. Remarkably, obesity and cancer

course with a profound dysregulation of the genetic expression patterns and,

Circulating adipomyokines, inflammatory marker, insulin resistance,

particularly, with the aberrant expression of splicing variants that could contribute

and physical fitness among severely obese Korean children and

to the aggressiveness and comorbidities of these pathologies. Since the

adolescents

appearance of alternative splicing variants could be related to a dysregulation

Kyung Hee Park¹, Young-Gyun Seo¹, Hye Ja Lee², Han Byul Chang², Sang

of the cellular machinery responsible for this process ((spliceosome core elements

Ick Park², Yoon Myung Kim³ & Hyun Jung Lim⁴

and splicing factors (SFs)), the objective of the present study was to determine the

¹Hallym University Sacred Heart Hospital, Anyang-si, Republic of Korea;

association between the expression pattern of the components of this machinery

²National Institute of Health, Cheongwon, Republic of Korea;³Yonsei

and hepatic steatosis of obese patients. To this end, we collected clinical and

University, Seoul, Republic of Korea;⁴Kyung Hee University, Seoul,

demographic data and liver biopsy samples from obese women (IMCO30) with

Republic of Korea.

(nZ32) and without (nZ9) hepatic steatosis. RNA from liver samples was

extracted and retrotranscribed to determine the expression levels of selected

Background

components of the major (nZ13) and minor spliceosome (nZ4), and associated

Associations between obesity and adipomyokines, inflammatory marker, and

SFs (nZ28) using a qPCR-based array. Results revealed that the liver of steatotic

level of physical fitness have not been well evaluated in severe obesity in children

patients exhibit a profound dysregulation of certain spliceosome components and

and adolescents.

SFs compared to non-steatotic patients (e.g. RNU6, SF3b1, etc.). Although these

Method

alterations were not associated with the hepatic steatosis level, the expression

Data on leptin, irisin, FGF21, hsCRP, glucose, insulin, physical fitness measured

pattern of the components of this cellular machinery could define discrete groups

by arm curl test for upper extremity)and wall sit test for lower extremity were

of steatotic patients that presented similar alterations in certain spliceosome

obtained in 266 participants who were recruited for ICAAN study, community-

components and SFs. Interestingly, these groups of patients were also

based multidisciplinary weight control program in severely obese Korean

characterized by particular hepatic and clinical-metabolic alterations (e.g. ALT,

children and adolescents. Participants were classified into 3 groups according to

hyperglicemia, hyperinsulinemia, etc.). Therefore, although further confirmatory

their BMI status based on sex and age-specific BMI percentiles: severely obese

studies are needed, these results could suggest that the development of hepatic

(SO,R120% of the 95th percentile), overweight or obse (OB, 85th-!120% of the

steatosis and its associated comorbidities could be linked to the dysregulation of

95th percentile), and non-obese (NW,!85th). Levels of circulating adipomyo-

certain components of the splicing machinery, which may provide novel

kines, inflammatory marker, insulin resistance (HOMA-IR), and physical fitness

diagnostic/therapeutic tools for this pathology.

were compared across the groups adjusted for sex and age. Cross-sectional

DOI: 10.1530/endoabs.49.EP698

associations between obesity status and biomarker levels and physical fitness

were assessed.

Results

Participants in SO group tended to have higher levels of leptin(NW, 12.19G1.05:

OB, 25.64G1.05: SO, 40.77G1.09), hsCRP (NW, 0.37G1.09: OB,1.18G1.09:

EP699

SO,1.82G1.16), and HOMA-IR (NW, 1.78G1.06: OB, 3.55G1.06: SO, 6.28G

1.10) compared to participants in NW or OB(all P for trend !0.001). Levels of

Irisin and cardiovascular risk

physical fitness tended to be significantly decreased across the BMI groups (P for

Yavor Assyov^1,2, Antoaneta Gateva^1,2 & Zdravko Kamenov^1,2

trend, arm curl test 0.03: wall sit test !0.001). Circulating levels of irisin showed

¹Medical University, Sofia, Bulgaria;²University Hospital Alexandrovska,

overall significance (P for trend 0.04), but did not show significant difference

Sofia, Bulgaria.

between groups. FGF-21 did not show significant difference across the BMI

groups.

Aims

Conclusions

Irisin is a recently discovered myokine that has been implicated in the

Severe obesity in children and adolescents compared with NW or OB is

pathogenesis of type

2 diabetes

(T2D) and metabolic syndrome (MS). Its

associated with higher levels of leptin, inflammatory marker and insulin

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

resistance and lower levels of physical fitness, which implies problems with

positively related with E/A ratio (rZ0.26 P!0.001) and inversely with left

further weight gain and cardio-metabolic health risks.

ventricular mass index (LVMi) (rZK0.20 P!0.01) and carotid intima-media

DOI: 10.1530/endoabs.49.EP700

thickness (cIMT) (rZK0.24 P!0.005). Urinary free cortisol was positively

related with EFT (rZ0.22 P!0.001). Circulating IGF1 levels were positively

related to E/A ratio (rZ0.27 P!0.001) and negatively correlated with EFT

(r-0.14 P!0.001), LVMi (rZK0.16 P!0.001), end diastolic left ventricular

diameter (rZK0.16 P!0.001), cIMT (rZK0.25 P!0.001), and left atrial

diameter

(rZK0.14 P!0.001). All the echocardiographic and hormonal

parameters evaluated showed significant correlation with the degree of weight

excess and the duration of obesity (P!0.001). In conclusion, cardiac function and

EP701

morphology associate with weight excess, duration of obesity and anabolic

Genetic variants of the adiponectin gene and its association with

hormones deficiencies.

adiponectin level in metabolic syndrome women

DOI: 10.1530/endoabs.49.EP702

Abhishek Gupta^1,2, Sunita Tiwari¹, Suraksha Agrawal³,

Arun Kumar Singh¹, Bhola Nath Paul⁴ & Katherine Cianflone⁵

¹Department of Physiology, King George’s Medical University, Lucknow,

Uttar Pradesh, India;²Department of Molecular and Clinical Medicine,

University of Gothenburg, Gothenburg, Sweden;³Department of Medical

Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences,

Lucknow, Uttar Pradesh, India;⁴Immunobiology Division, Indian Institute

of Toxicology Research, Lucknow, Uttar Pradesh, India;⁵Department of

EP703

Medicine, Institut Universitaire de Cardiologie et de Pneumologie de

Are there any associations between vitamin D levels and insulin

Québec, Quebec, Canada.

resistance in obese patients?

Omercan Topaloglu¹, Bahri Evren¹, Saim Yologlu² & Ibrahim Sahin¹

Inonu University Medical Faculty, Department of Endocrinology, Malatya,

Background

Turkey;²Inonu University Medical Faculty, Department of Biostatistics,

Adiponectin is an adipocyte-derived adipokine, down-regulated in obesity linked

Malatya, Turkey.

disorders. Here, we investigated the genotypic variability of adiponectin (at

position; CT45G and CG276T) and its association with circulating adiponectin

and metabolic syndrome in North Indian adult women.

Introduction

Methods

Most of the human studies suggested an association between obesity and low

We compared metabolic syndrome (MetS; 269) women to without metabolic

25(OH)D3 0levels. It has been proposed that co-existence of vitamin D deficiency

syndrome (wMetS; 272) women of North India. Genotype frequencies of the

may have a role in the development of IR in obesity. We aimed to reveal whether

adiponectin gene were performed using PCR-RFLP method and circulating

any association was present between IR and 25(OH)D3.

adiponectin estimated by sandwich ELISA method.

Materials-methods

Results

223 obese patients referred to our clinics were evaluated for the study. 24 patients

Low level of adiponectin (P!0.001) and high HOMA-IR were found (P!0.001)

with known diabetes mellitus were excluded. Finally, 199 patients were included

in MetS women. Gene frequency of combined mutant genotype (TGCGG) at

and anthropometric (height, body weight, body mass index) and biochemical

position C45T/G of adiponectin was found to be significantly less (PZ0.017)

(fasting blood glucose, HbA1c) and hormonal (fasting insulin, C-peptide, 25(OH)

while mutant G allele was significantly high (PZ0.008) in MetS women as

D3) measurements were assessed. We evaluated IR by ‘homeostasis model

respective to wild type. However, frequency of mutant T allele in MetS women

assessment of IR’ (HOMA-IR). The patients having HOMA-IR value of equal to

was found to be significantly (PZ0.027) less as compared to wMetS at position

or greater than 2.5 were accepted as insulin resistant. The patients were grouped

C276G/T of adiponectin gene. The mutant genotype GG of C45T/G and TT of

according to body mass index (BMI), HOMA-IR, and 25(OH)D3.

C276G/T of adiponectin were significantly associated with lower adiponectin

Results

level and higher HOMA-IR (all P!0.001) in adult metabolic syndrome.

25(OH)D3 levels were significantly lower in the groups of BMI O50 kg/m2 and

Conclusions

BMI 40-50 kg/m² in comparison to the group of BMI!40 kg/m² (mean 25(OH)

Results suggest that adiponectin gene variants might be associated with lower

D3 levels

12.0,

12.12,

17.02 ng/dl; respectively)

(PZ0.042, PZ0.025;

adiponectin level and metabolic syndrome.

respectively). BMI levels were significantly lower in the group of 25(OH)D3O

DOI: 10.1530/endoabs.49.EP701

30 ng/ml in comparison to the group of 25(OH)D3!10 ng/ml (mean BMI 42.27

; respectively) (PZ0.05). Likewise, there was significant negative

vs 45.59 kg/m²

correlation between BMI and 25(OH)D3 (PZ0.045, rZK0.142).There was no

difference between 25(OH)D3 levels in patients with IR (HOMAR2.5) and not

IR (HOMA!2.5) patients (PZ0.071). Similarly, there was no significant

correlation between HOMA-IR values and 25(OH)D3 levels (PZ0.98).

Conclusion

Our study showed that 25(OH)D3 levels decreased in obesity; and 25(OH)D3

EP702

levels were not different in patients having IR or not. These findings suggest

Obesity, cardiomyopathy and anabolic hormones

that decreased vitamin D levels in obesity may be result of increasing BMI rather

Elena Gangitano, Daniela Costantini, Rossella Tozzi, Francesca De Giorgi,

than IR.

Eleonora Poggiogalle, Stefania Mariani, Elisa Petrangeli, Lorenzo

DOI: 10.1530/endoabs.49.EP703

Maria Donini, G. Barbaro, Lucio Gnessi & Carla Lubrano

Sapienza University, Department of Experimental Medicine, Rome, Italy.

Obesity is associated with hemodynamic alterations that may lead to heart failure

(HF), through the development of cardiac structural abnormalities and

impairment of ventricular function. Obesity-related neurohormonal and meta-

bolic disturbances may predispose to HF, even in the absence of comorbidities.

EP704

Excess adipose tissue and in particular visceral adiposity contributes to the altered

Elevated serum adiponectin in Alzheimer’s disease as neuroprotective

production of a number of anabolic hormones also involved in the regulation of

strategy

the cardiac function. The aim of the present study was to evaluate cardiac

Liliana Letra^1,2, Tiago Rodrigues¹, Paulo Matafome¹, Diana Duro²,

morphology and function by echocardiography and the relationships between

Raquel Lemos², Miguel Patrício⁴, Miguel Castelo-Branco³, Inês Baldeiras⁵,

echocardiographic parameters, BMI and hormonal status in a population of obese

Raquel Seiça¹ & Isabel Santana^2,6

patients. 1821 patients (mean age 46.94G13.62 yrs, 1331 females and 490 males)

¹Physiology Laboratory, IBILI, Faculty of Medicine, University of

were studied. 157 were normal weight (BMI 22.14G1.83), 247 overweight (BMI

Coimbra, Coimbra, Portugal;²Neurology Department, Centro Hospitalar e

27.76G1.45), and 1417 obese (BMI 39.39G6.88). Anthropometric data, blood

Universitário de Coimbra, Coimbra, Portugal;³IBILI, Faculty of Medicine,

pressure, lipid and glycemic parameters and a complete hormonal status were

University of Coimbra, Coimbra, Portugal;⁴Laboratory of Biostatistics and

recorded. Two-dimensional echocardiography and carotid intima/media thickness

Medical Informatics, IBILI, Faculty of Medicine, University of Coimbra,

measurement were performed. Total testosterone in males and SHBG in both

Coimbra, Portugal;⁵Laboratory of Neurochemistry, Centro Hospitalar e

sexes were significantly and inversely correlated with epicardial fat thickness

Universitário de Coimbra, Coimbra, Portugal;⁶Faculty of Medicine,

(EFT) (rZK0.33 and rZK0.44, P!0.001). Circulating levels of DHEAS were

University of Coimbra, Coimbra, Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

therapeutic use gets more difficult, because it was restricted to dietetic

Several studies have highlighted the contribution of adipose tissue dysfunction to

modifications and not having medicines that have indication by FDA during

the development and progression of Alzheimer’s Disease (AD), which may

pregnancy.

depend on alterations in adipokine secretion. Leptin and adiponectin are the most

DOI: 10.1530/endoabs.49.EP705

abundant adipokines in circulation, with recognized systemic effects, but also able

to cross the blood-brain barrier and influence cognitive-related structures, such as

the hippocampus.

Objective

To determine if serum and CSF adiponectin and leptin/adiponectin ratio are

correlated with AD biomarkers and can constitute predictors of progression.

Methods

EP706

A total of 53 AD and 71 aMCI subjects (mild cognitive impairment amnestic

Folate: a new player in metabolic syndrome?

type) were included and underwent a thorough clinical and neuropsychological

Silvia Paredes^1,2, Marta Alves¹, Maria Lopes Pereira¹, José Maia da Costa¹,

evaluation (MMSE, MoCA, ADAS-Cog). Serum and CSF adiponectin and leptin,

Aline Fernandes¹, Fernando Manso¹, Olinda Marques¹ & Laura Ribeiro^2,3

serum insulin and AD biomarkers (CSF Ab_42, t-tau, p-tau and hippocampal

¹Hospital de Braga, Braga, Portugal;²Faculty of Medicine, University of

formation volumetry) were also performed. Sixty-seven MCI patients had clinical

Porto, Porto, Portugal;³I3S-Instituto de Investiga

˜o e Inova

¸a˜o em Saúde,

and neuropsychological follow-up in order to identify progression to AD.

Universidade do Porto, Porto, Portugal.

Results

Serum adiponectin was 33% higher in AD when compared to MCI. In CSF, leptin

and t-tau showed a negative correlation in AD patients (rZK0.597, PZ0.026)

Introduction

while adiponectin was positively correlated with Ab₄₂ (rZ0.590, PZ0.002), but

Bariatric surgery (BS) candidates display several nutritional deficiencies that can

only in women. A robust association between CSF adiponectin and hippocampal

aggravate after surgery. Metabolic syndrome (MS) is a cluster of cardiovascular

volume was observed in a subgroup of patients with CSF-based AD diagnosis.

risk factors with several disturbed metabolic pathways. Therefore, individuals

However, no correlation was found with total cognitive scores. Twenty-seven

with MS submitted to BS are probably more prone to nutritional deficiencies.

MCI progressed to AD upon a mean follow-up of 38.2G18.83 months, whereas

Objective

40 maintained the diagnosis. Baseline serum and CSF adipokine levels were

To evaluate the prevalence of nutritional deficiencies and eventual differences

similar in both groups. Only serum adiponectin positively correlated with time of

between BS candidates with and without MS.

progression (rZ0.484, PZ0.049), though incapable of predicting progression to

Materials and methods

dementia.

Retrospectively, databases of 385 patients who underwent BS between 01/2011

Conclusions

and 07/2015 were analyzed. Nine subjects were excluded due to missing data on

Higher CSF adiponectin levels are associated with less Ab₄₂ deposition and

MS parameters. Subjects with R3 criteria according to the NCEP ATP III report

higher hippocampal volume. Accordingly, higher adiponectinemia observed in

were classified as having MS.

AD could be looked as a strategy to maintain its central levels and, consequently,

Results

its beneficial effects.

A total of 181 individuals with MS (150 females, body mass index (BMI) 44.56G

DOI: 10.1530/endoabs.49.EP704

6.4, mean age 45.14G10.9) and 195 without MS (174 females, BMI 42.98G5.9,

mean age 39.44G9.3) were included. No significant differences were found in

iron metabolism (iron/ferritin/hemoglobin), vitamin B12, vitamin D, albumin and

homocysteine between males and females with and without MS. However, both

males and females with MS had significantly higher levels of folate than

individuals without MS. Males with MS exhibited significantly lower levels of

magnesium comparing to males without MS. In females, folate was positively

associated with glucose

(rZ0.206; P!0,001), glycated hemoglobin

(A1c)

EP705

(rZ0.294; P!0,001), total cholesterol (rZ0.153; PZ0.006) and low-density-

Late dumping syndrome in pregnant women after ROUX-EN-Y gastric

lipoproteina cholesterol (rZ0.117; PZ0.037). In males, folate was positively

bypass (RYGB) surgery

associated with glucose (rZ0.402; PZ0.003), A1c (rZ0.362; PZ0.012) and

Lucía Vera Pacheco¹, María Teresa Gallego García², Cristina Del Peso

triglycerides

(rZ0.372; PZ0.007), whereas magnesium was negatively

Gilsanz², Lorena Rentero Redondo², Carles Iniesta Navalón², Noelia

associated with glucose

(rZK0.437; PZ0.01) and A1c

(rZK0.298;

Victoria García-Talavera Espín², M^a Bienvenida García-Talavera Espín²,

PZ0.042).

Manuel Romero Mun˜oz1 & Amparo Meoro Avilés2

Conclusion

¹University Hospital Rafael Mendez, Lorca,Murcia, Spain;²University

There were no significant differences in nutritional deficiencies between

Hospital Reina Sofía, Murcia, Spain.

individuals with and without MS. However, in our study individuals with MS

presented significantly higher folate levels than individuals without MS.

Interestingly enough, folate levels positively associated with lipid and glucose

Introduction

metabolism. The metabolic and clinical significance of our results warrants

Dumping syndromes are common after bariatric surgery and can present

further investigation.

diagnostic and therapeutic challenges in pregnancy.

DOI: 10.1530/endoabs.49.EP706

Case report

A 23-year-old female who underwent a RYGB surgery because of morbid obesity

in 2013. She had no medical history of diabetes nor any other comorbidity related

to obesity. Two years later, her weight had reduced from 128 to 76 kg and also her

body mass index

(BMI) from

43.8

26 kg/m². She was treated with

multivitamins, iron vitamin B12

and calcium. She remained clinically

EP707

asymptomatic. In 2016, she got pregnant and on the 24th gestational week she

Evolution of body composition 3 years after sleeve gastrectomy

checked herself post prandial capillary blood glucose (CBG) that confirmed

Silvia Paredes^1,2, Marta Alves¹, Maria Lopes Pereira¹, José Maia da Costa¹,

hypoglycemia, with glucose levels from 55 mg/dl to 30 mg/dl, accompanied

Aline Fernandes¹, Fernando Manso¹, Olinda Marques¹ & Laura Ribeiro^2,3

by clinical intense asthenia. Fasting plasma glucose was 71 mg/dl and insulin

¹Hospital de Braga, Braga, Portugal;²Faculty of Medicine of the University

5 mIU / ml (2.6-24.9). Dietary modification with frequent intakes every 3 hours,

of Porto, Porto, Portugal;³I3S-Instituto de Investiga

˜o e Inova

˜o em

with low glycaemic index food and avoidance of physical activity immediately

Saúde, Universidade do Porto, Porto, Portugal.

after oral intake were recommended. At the beginning, the episodes were reduced,

but on the 35^th gestational week hypoglycemia episodes had increased in severity

and frequency, raising concerns of the risk of maternal neuroglycopenia and

Background

fetal hypoglycemia, that’s why it was decided to treated with Diabetes-specific

Sleeve gastrectomy (SG) has effective results on weight loss, which should result

Oral Nutritional Supplement (low in carbohydrates with no added sucrose, high

from fat mass loss and efforts should be made to preserve lean mass. Few studies

in protein and contains soluble fiber) twice a day between the main meals.

have evaluated body composition (BC) changes after SG for periods O2 years.

Finally, on the 39th gestational week an induced birth was planned of a healthy

Objective

31oo-g infant, with a nearly complete remission of the dumping syndrome after

To investigate the impact of SG on weight and BC, comparing by gender.

giving birth.

Materials and methods

Conclusions

Retrospectively, databases of patients who underwent SG between 2011 and 2013

Dumping syndromes in pregnant women that have gone through a RYGB surgery

were analyzed. Data was obtained before and 1, 2 and 3 years after SG. BC was

need to be distinguished from common symptoms of a normal pregnancy. Its

measured by bioelectrical impedance.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

Introduction

Fifty-five females, mean age 42.11G10 years, mean body mass index (BMI)

Phthalates are ubiquitous endocrine disruptors (EDs). EDs induce obesity. MEP

44.59G4.9 Kg/m² and 11 males, mean age 39.55G10.9 years, mean BMI

and MEHP affect thyroid function.

44.66G5.4 Kg/m² were included. One year after SG, males had lost 36% of

Aim

weight, 67% of fat mass and 18% of lean mass. In females, 1 year after SG, weight

Estimation of burden of MEP and MEHP in our population, evaluation of leptin in

decreased 32%, fat mass 52% and lean mass 12%. Two and 3 years after surgery,

obese MEP and MEHP positive and negative subjects and evaluation of

males had lost 33% and 30% of weight, 59% and 53% of fat mass and 20% and

connection between leptin, MEP, MEHP and thyroid indicators in that subgroup.

19% of lean mass, respectively. In females, 2 and 3 years after surgery weight

Materials and methods: a cross-sectional study, with 201 subjects divided into

decreased 33% and 30%, fat mass 52% and 48% and lean mass by 14% and 13%,

MEP/MEHP positive and negative, subdivided in obese and lean. Anthropometric

respectively. Males presented the lowest weight and fat mass 1 year after surgery;

parameters done: body height, weight, waist and body mass index. Laboratory

females had the lowest weight and fat mass 2 years after SG.

tests: morning urine sample for MEP/MEHP and venous sample for free

Conclusion

thyroxine (FT₄), free tri-iodothyronine (FT₃), thyroid stimulating hormone (TSH)

Despite both genders show a weight loss of 30% 3 years after SG, males initially

and leptin. Statisycal analysis was done in SPSS. Results: Mean age of

lose more weight that is regained after the first year. Males also present a greater

36.74

participants was

(G8.55) years, 86 (42.8%) males and 115 (57.2%)

loss of lean mass. Our results highlight the need to develop strategies to avoid

females. There were 64 (31.2%) MEPC, and 44 (22%) MEHPC participants,

weight regain, which seems to start 1 and 2 years after SG, respectively for males

and 5 (5.05%) positive for both. There were 93 (46.3%) participants in obese

and females. Efforts should be also made in order to avoid lean mass loss.

subgroup, MEHP- 64 (68%), MEHPC29 (32%; MEPK 58(62%), MEPC38%).

DOI: 10.1530/endoabs.49.EP707

Independent t-test and Mann Whitney U test did not show statistical significance

in leptin level neither in MEPC and MEPK (t K0.316, P!0.753; Z K0.242,

P!0.809), nor in MEHPC and MEHPK obese participants

(t K1.049,

P!0.297; Z K1.377, P!0.169). Pearson correlation for leptin and FT₄ in

obese MEPC subgroup was statistically significant (r K0.347, P!0.041). No

significant correlations were found for leptin with FT3 (r K0.123, P!0.48) and

EP708

TSH (r 0.078; P!0.655). In MEHPC obese patients we did not find any

Comparative study between laparoscopic gastric bypass and

significance (FT₄: r 0.189, P!0.25; FT₃: r K0.023, P!0.897; TSH r 0.062,

laparoscopic sleeve gastrectomy

P!0.928).

Aurora Aragón-Alonso, Mercedes Ferrer Gómez, José Ramón

Conclusion

Cuenca Sánchez, David Ruiz de Angulo Martín, María Dolores

Half of our population is exposed to MEHP and MEP. In obese subjects higher

Frutos Bernal, María Ángeles Campillo Espallardo, Pedro Segura Luque &

leptin correlates with lower FT₄.

Antonio Hernández Martínez

DOI: 10.1530/endoabs.49.EP709

Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.

Introduction

Bariatric surgery is currently considered the most effective treatment for morbid

obesity. Laparoscopic gastric bypass (LGB) and laparoscopic sleeve gastrectomy

(LSG) are the most widely used bariatric procedures today.

EP710

Objectives

Using diaserein on the patients with glucose intolerance

In this study we compared LGB and LSG in order to establish whether there is any

Kenan Cadirci^1,2 & Kadri Yildiz^1,2

superiority of one or the other in effectiveness and complications.

¹Erzurum Regional and Educational Hospital, Erzurum, Turkey;

Methods

²Erzurum Palandoken State Hospital, Erzurum, Turkey.

We included all the patients who underwent bariatric surgery in Hospital

Universitario Virgen de la Arrixaca during one year (nZ101) of which 62

received LGB and 39 LSG. Both groups were comparable in age, body max

Diaserein is used in the spesific and long-term treatment of degenerative joint

index, rates of hypertension (HT), type 2 DM (T2DM), hypercholesterolemia

diseases (as osteoarthritis). In vitro studies have showed that Diaserein and its

(Hchol), hypertriglyceridemia

(HTG) and obstructive sleep apnea syndrome

active metabolyte Rheinin inhibate production and activity of interleukin-113

(OSA). A higher percentage of women was present in the LGB group. We

(IL-113), some proinflamatuar and pro-catabolic cytokines. Interleukin-113 play

retrospectively compared postoperative complications and excess weight loss

important role to trigger production of more pro-inflamatuar factors as cytokines,

(EWL) and comorbidity resolution (HT, T2DM, Hchol, HTG and OSA) at one

cyclo-oxygeneas, prostogalandines, nitric oxide, matrix metalloproteinases in

year after surgery.

chondrocyte degradation, snobial enflamation, remodelling of subchondral bone.

Results

Diaserein stimulates Transformic Growth Factor 13 (TGF-13) even if IL-113

LGB was superior to LSG in HT remission (75% vs 43.8%, PZ0.046) and Hchol

exists. Diaserein stimulates synthesis of chondral matrix components as

remission (96.3% vs 33.3%, P!0.001). We found no significant differences

proteoglicans, glicoseaminoglicans, hyaluronic asids. After all Diaserein

between LGB and LSG regarding EWL (77.7%G23.3 vs 76.9%G17.8), T2DM

decreases the lost of chondral components continuously. We present 41 case

remission (78.6% vs 75%), HTG resolution (86.7% vs 75%) and OSA remission

series of patients that is used Diaserein on the treatment of osteoarthritis in

(55.6% vs 16.7%). Also, both techniques were comparable regarding rate of

various joints

(gonarthroisis, coxarthritis, dejenerative lomber diseases).

postoperative complications (17.7% vs 10.3%).

patients have followed up clinically in 2014-2016. 17 patients in this serie have

Conclusions

show intolerance to medicine by diarrhea, vomitting and some clinical

At one year postsurgery, LGB was superior to LSG in HT and Hchol remission.

compliants. At the research of these intolareted patients 16 patients have glucose

However, both techniques are comparable in terms of safety, weight loss and

intolerance as Diabetes Mellitus Type 1 and 2. At the researching of literature,

resolution of other comorbidities (T2DM, HTG and OSA).

Diaserein were not advised severe renal insufficiency, gastrointestinal disorder

(Chrone, Ulserative Colit.), hepatic insufficiency and also glucose intolerance.

DOI: 10.1530/endoabs.49.EP708

Diaserein must be used carefully on the patients that have renal and hepatic

insufficiency and failure. And also it must not be preferred on the patients which

have glucose intolerance because of seein severe side effects.

DOI: 10.1530/endoabs.49.EP710

EP709

Prevalence of mono-ethyl-hexyl phthalate and mono-ethyl phthalate in

Serbian population and their influence on leptin and thyroid function in

obesity

EP711

Ivana Bajkin^1,2, Natasa Milic^2,3, Jovanka Novakovic-Paro^1,2, Tijana Icin^1,2,

Bone mineral density in obese patients

Jovana Prodanovic¹, Nikola Curic^2,4, Bojan Vukovic^1,2 &

El Ansari Nawal, Fatima Zahra Zaher & Ghizlane Elmghari

Milica Medic-Stojanoska^1,2

Department of Endocrinology, Diabetes, Metabolic diseases and Nutrition,

¹Clinic of Endocrinology, Diabetes And Metabolic Disorders, Clinical

Mohammed VI University Hospital, Marrakesh, Morocco.

Center of Vojvodina, Novi Sad, Vojvodina, Serbia;²Faculty of Medicine,

University of Novi Sad, Novi Sad, Vojvodina, Serbia;³Department of

Pharmacy, University of Novi Sad, Novi Sad, Vojvodina, Serbia;⁴Center for

Background

Laboratory Medicine, Clinical Center of Vojvodina, Novi Sad, Vojvodina,

Obesity and osteoporosis are two public health problems with an increasing

Serbia.

prevalence and high impact on morbidity and mortality which, during the last two

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

decades, have become major health threats worldwide. However, obesity has long

lean body mass. The aim of the present study was to explore muscle strength (as a

been considered as a protective factor against osteoporosis. The purpose of our

functional consequence of sarcopenic obesity) and muscle quality

(namely,

study was to evaluate the bone mineral density in obese patients followed at

myosteatosis) in women with and without the Metabolic Syndrome (MetS).

Mohammed VI university hospital.

Methods

Study participants were enrolled at the Sapienza University, Rome, Italy. Body

Our study has included 35 patients followed for obesity. Bone mineram density

composition was assessed through DXA. The Handgrip strength test (HGST) was

was ordered in all patients.

performed to assess muscle strength using a dynamometer (Dynex, Akern).

Results

HGST was normalized to arm lean mass; intramuscular adipose tissue (IMAT)

The mean age was 40 years, ranging between 21 and 69 years, 94.2% of our

and intramyocellular lipid content (IMCL) were measured by magnetic resonance

patients were female, mean body mass index was 43.9 kg/m² with an average

spectroscopy, and used as indicators of myosteatosis. The MetS was diagnosed

waist circumference of 120 cm, over two thirds of the patients were morbidly

according to the NCEP-ATPIII criteria. HOMA-IR was calculated; C-reactive

obese, 31.4% had diabetes and 14.2% had hypertension, 18.1% of our female

protein

(CRP) levels were measured. The International Physical Activity

patients were postmenopausal. One female patient had osteopenia with a T score

Questionnaire (IPAQ) was administered to assess the physical activity level

of K1.2 at the spine. The rest of our patients had normal bone mineral density

(PAL).

with a mean T score at the spine and the femur of 0.65 and 1.39 respectively.

Results

Conclusion

54 women (age: 48G14 years, BMI: 37.9G5.4 kg/m²) were included. MetS was

Obesity is associated with normal bone mineral density even in postmenopausal

diagnosed in 54% of subjects. HGST/arm lean mass was lower in women with the

obese women, suggesting a protective effect of obesity against osteoporosis that

MetS compared to their counterparts without the MetS (6.3G1.8 vs 7.8G1.6,

was highlighted in several literature studies. That said, this beneficial effect

PZ0.03). HGST/arm lean mass was negatively associated to HOMA-IR (beta:

should always be weighed against its adverse effects especially the metabolic and

K0.37, S.E.:0.16, PZ0.02), after adjustment for age, body fat, CRP levels, and

cardiovascular ones.

PAL. IMAT (2655G1710 vs 1614G642 mm²) and IMCL (25.0G21.4 vs 23.1G

DOI: 10.1530/endoabs.49.EP711

20.6%) were not different in obese women with the MetS compared to women

without the MetS (PO0.05). No association emerged between HGST/arm lean

mass and IMAT or IMCL.

Conclusion

Insulin resistance, and not muscle fatty infiltration per se, may play a role in the

decline of muscle strength in subjects with obesity, leading to the phenotype of

dynapenic obesity.

EP712

DOI: 10.1530/endoabs.49.EP713

Role of cognitive-behavioral therapy in the treatment of obesity

Snjezana Popovic-Pejicic

Faculty of Medicine, University of Banja Luka, Republic of Srpska, Banja

Luka/Republic of Srpska, Bosnia and Herzegovina.

Dietary therapy, programmed physical activity and cognitive-behavioral therapy

are basic measures in the treatment of obesity. Cognitive-behavioral therapy

applies methods which change eating habits of obese persons, aiming to remove

EP714

barriers relating dietary therapy and programmed physical activity. The goal is to

Concern about body image, impulsiveness and personality traits in the

try efficiency of applying cognitive-behavioral therapy in the program for the

morbidly obese before bariatric surgery and in patients who have

reduction of body mass of obese persons, versus the application of dietary therapy

undergone surgery

and programmed physical activity alone. The study included 60 obese persons,

Isabel Mateo-Gavira¹, Daniel Medina-Rivero¹, José Pedro Novalbos-Ruiz²,

who were divided into two groups with 30 patients in each group, 20 to 58 years of

Amelia Rodríguez-Martín², María José Santi-Cano³, D Ogalla de Castro³ &

age with the body mass index R30 kg/m² and hyperlipidemia (LDL cholesterol

Manuel Aguilar-Diosdado¹

R 4.2 mmol/l). Patients from both groups were on hypocalorie diet, individually

¹Endocrinology. Puerta del Mar Hospital, Cádiz, Spain;²Preventive

designed and had programmed physical activity every day. Patients in group II

Medicine and Public Health, University of Cadiz, Cádiz, Spain;

underwent group cognitive-behavioral therapy under the supervision of

³Nursing and physiotherapy, University of Cadiz, Cádiz, Spain.

psychiatrist once a week with the duration of 120 min. Both groups also went

to see an endocrinologist 6 times, on which occasions their body weigh, blood

pressure, parameters of lipid status serum and level of glucose in serum were

Objectives

mesured. Results showed that in group II the medium value of body mass

To analyse the levels of anxiety, depression, impulsiveness, bulimic behaviour,

reduction after twelve weeks of treatment was 9.5 kg (8.9%) and in group I 4.4 kg

concern about body image and the quality of life of patients included in the care

(4.1%). In group II, LDL cholesterol decreased for 34.5% and in group I for 5.0%;

process following bariatric surgery, in our field.

HDL cholesterol increased for 2.7% while in group I it decreased 2.5%; total

Methods

triglycerides decrased for 15.3% and in group I for 5.4%; values of glicaemia

Observational study of the patients included in the care process for bariatric

decreased for 14.8% while in group I they remained unchanged. Cognitive-

surgery at University Hospital Puerta del Mar. Two cohorts were identified

Behavioral therapy affected the improvement of motivation and readiness of

according to their situation before or after surgery. Studies were made of variable

patients to stick to the dietary regime and programmed physical activity. In

antropometrics, clinics, personality traits and quality of life. The instruments used

designing the program for the reduction of obesty it is necessary to include

were: Anxiety inventories

(BAI) and Depression

(Beck); Body Sharp

cognitive-behavioral therapy, which brings significantly better therapy outcomes.

Questionnaire

(BQ21); BULIT-R test of bulimic behaviour, impulsiveness

(BIS) and SF12 questionnaire on quality of life.

DOI: 10.1530/endoabs.49.EP712

Results and conclusions

A total of 198 patients were studied, women constituted 69.2% of the subjects; the

average age was 45 without differences in the cohorts before/after 12 months; the

BMI in patients before surgery was 48 (S.D. 7) and in patients post surgery, 34 (S.D.

6). The patients on waiting lists presented higher levels of concern with regard to

their body image (BQ21: 65), bulimic behaviour (BULIT: 62) and depression

(BECK: 15). The SF12 reflected good mental health but scored lower on points

EP713

for physical health. The levels of impulsiveness were not high (BIS: 53), so no

Dynapenic obesity and myosteatosis in women with and without the

patient reached the cut off point (104). The cohort of post-surgery patients

metabolic syndrome

presented high levels of concern about body image (BQ21: 65) and anxiety (BAI:

Eleonora Poggiogalle, Lorenzo Donini, Lucio Gnessi, Stefania Mariani,

34). Impulsiveness was moderate (BIS: 58). It was noted that the proportion of

Michele Di Martino, Barbara Ciccantelli, Cecilia Mancini, Marcello Arca,

patients with extreme concern about their body image (BQ21 O 105) was higher

Andrea Lenzi & Carla Lubrano

in patients who had already undergone surgery (12.5 vs 6.5%). Attending to the

Sapienza University, Rome, Italy.

depressive state of patients (BECK) prior to surgery required professional care for

35.9% for the morbidly obese, against 16.7% of post-surgery patients; severe

depression was detected in 11.7% and 4.8% of patients respectively.

Introduction

Insulin resistance is a well-known hallmark of the metabolic syndrome (MetS),

DOI: 10.1530/endoabs.49.EP714

and it detrimentally affects also protein metabolism, favoring to the decline of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP715

sensitivity, glucose tolerance and reduced MWAT inflammatory cytokines

content, which are known to induce insulin resistance.

Lifestyle of morbidly obese patients awaiting bariatric surgery and in

Conclusions

the cohort of patients who have undergone surgery

The present data provide evidence that thyroid function is reduced in obese rats

Isabel Mateo-Gavira, Daniel Medina-Rivero¹, Amelia Rodríguez-Martín²,

and reinforce the role of T3 treatment on improvement of insulin sensitivity by its

José Pedro Novalbos-Ruiz², María José Santi-Cano³, A Díaz-Yelamos³

negative modulation of inflammatory cytokine expression in metabolic disorders

& Manuel Aguilar-Diosdado¹

as obesity or diabetes mellitus.

¹Endocrinology, Puerta del Mar Hospital, Cádiz, Spain;²Preventive

Medicine, University of Cadiz, Cádiz, Spain;³Nursing and Physiotherapy,

DOI: 10.1530/endoabs.49.EP716

University of Cadiz, Cádiz, Spain.

Objectives

To determine the habits and lifestyle of the morbidly obese before and after

bariatric surgery.

Material and methods

Transversal study of two groups of morbidly obese patients attending the

Endocrinology Unit of Puerta del Mar, Cádiz: one group before and the other after

bariatric surgery. Clinical and analytical data of the patients was collected: socio-

EP717

demographic and lifestyle characteristics, Bulit-R Questionnaire (Bulimia), BIS

Predictive factors of outcome in bariatric surgery

(impulsiveness), BQ1 (body image), BAI (anxiety), BECK (depression) and

Aurora Aragón-Alonso, Mercedes Ferrer Gómez, José Ramón

quality of life through questionnaire SF12.

Cuenca Sánchez, David Ruiz de Angulo Martín, María Dolores

Results

Frutos Bernal, María Ángeles Campillo Espallardo, Pedro Segura Luque

111 morbidly obese were studied before surgery (31.5% men, 68.5% women) and

& Antonio Hernández Martínez

87 morbidly obese post-surgery (29.9% men and 70.1% women). Before surgery

Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.

mean weight was 133.4 (S.D. 24.4) and BMI 48.6 (S.D. 7.0), and post-surgery 94.9

(S.D. 19.8) and BMI 34.5 (S.D. 6.5). In both groups there was a predominance of

primary and lower secondary education (25.8% of total); the greater proportion of

Introduction

subjects with a higher level of education was in the post-surgery group (3.6% vs

Bariatric surgery is currently considered the most effective treatment for morbid

13%). Only 25% were actively in work before surgery, rising to 36.5% in the post-

obesity, although rates of weight loss and comorbidities resolution differ among

surgery group. Significant differences were observed between the two groups in

bariatric techniques and depending on preoperative factors.

relation to habits and lifestyle sucha as tobacco consumption (21.1 vs 7.1%),

Objectives

alcohol consumption (21.1 vs 17.4%), physical exercise (55 vs 82.6%), hours of

In this study we analyse possible factors that influence the outcome of bariatric

physical exercise (4.75 hours/week vs 5.9) and increase in meals per day from 3 to

surgery (weight loss and improvement in metabolic comorbidities) in order to

5. Family support is greater for the post-surgery group (90 vs 83.8%), excluding

identify those patients most likely to benefit from surgery.

differences in professional support services (14%).

Methods

Conclusions

We included all the patients who underwent bariatric surgery in Hospital

Significant differences were observed in patients’ habits and lifestyle before and

Universitario Virgen de la Arrixaca during one year (nZ101) of which 62

after bariatric surgery; factors which could contribute to the care, prognosis and

received LGB and 39 LSG. We retrospectively analysed which preoperative

evolution of the patients. Social and family support is greater for post-surgery

factors were related to percentage of excess body mass index

(BMI) loss

patients.

(%EBMIL), type 2 diabetes remission (T2DM), and higher rates of hypertension

(HT) and hypercholesterolemia (Hchol) persistence one year after surgery.

DOI: 10.1530/endoabs.49.EP715

Results

%EBMIL one year after surgery was significantly higher (PZ0.016) in patients

with preoperative BMI %50 kg/m² vs BMIO50 kg/m² (79.4G21.3 vs 65.6G

15.4). Age, sex and presurgery T2DM were not associated with %EBMIL one

year after surgery. Absence of insulin treatment at baseline

(89% vs 50%,

PZ0.03), less than five years after diagnosis of T2DM (100 vs 53.8% PZ0.017)

were associated with higher T2DM remission one year post surgery. Age, sex,

EP716

presurgery BMI, HbA1c and smoking status were not associated with higher

Thyroid hormone treatment reduces inflammatory cytokines in

remission rates. HT persistence one year after surgery was significantly associated

mesenteric adipose tissue improving insulin sensitivity of obese rats

to age O50 (30.3% vs 8.2% PZ0.005) and baseline T2DM (30.8% vs 10.3%,

Ana Carolina Panveloski-Costa, Caroline Serrano-Nascimento,

PZ0.015). HChol persistence one year after surgery was significantly associated

Leonice Poyares, Gabriela Souza Viana, Paula Bargi-Souza &

to ageO50 (28.1% vs 8.5%, PZ0.013) and baseline T2DM (28% vs 10.6%,

Maria Tereza Nunes

PZ0.04). Sex, baseline BMI nor smoking status were not associated with HT nor

University of Sao Paulo, Sao Paulo, SP, Brazil.

HChol persistence.

Conclusions

There is a heterogeneous pattern of presurgical factors that predict the outcomes

Thyroid hormone plays an important role on carbohydrate and lipid metabolism.

of bariatric surgery.

In hypothyroidism is observed reduction of glucose transporter-4 expression and

insulin sensitivity and in hyperthyroid states the key enzymes of gluconeogenesis

DOI: 10.1530/endoabs.49.EP717

and glycogenolysis are induced, and both conditions lead to glucose intolerance.

It has been reported an increased prevalence of thyroid dysfunction in obese and

diabetic patients. Recently we have demonstrated a hypothyroid state in alloxan-

induced diabetic rats, in which the treatment with triiodothyronine (T3) improved

glycemia control and insulin sensitivity. These alterations were accompanied by

reduction of inflammatory cytokines in white adipose tissue and skeletal muscle.

The present study aimed at evaluating the thyroid function of cafeteria diet-

EP718

induced obese rats and the effects of thyroid hormone treatment on their glycemia

Prevalence of obesity in Algeria

control, insulin sensitivity and subclinical inflammation.

Nadira Fafa^1,2, Djamila Meskine^1,2, Saida Fedala^1,2 & Lamia Kedad^1,2

Methods

¹Laboratory of Endocrinology and Metabolism LEM1, Algiers, Algeria;

Obesity was induced in male Wistar rats by cafeteria diet. A subset of the obese

²Ibn Ziri Bologhine Hospital, Algiers, Algeria.

rats was treated with T3 (1.5 mg per 100 g body weight) for a 28-day period (DT₃).

Thyroid function was evaluated by molecular

(TG, NIS, TSHR and TPO

expression in thyroid gland) and biochemical parameters (serum TSH, T4 and T3

Introduction

concentrations). Cytokines concentration was measured in mesenteric white

The epidemiological transition has resulted in a major increase in the prévalence

adipose tissue (MWAT) (MILIplex assay kit).

of obesity in our country. Obesity is closely associated with chronic diseases such

Results

as type 2 diabetes, hypertension and dyslipidemia. The aim of our study is

Obese rats exhibited decreased insulin sensitivity, thyroid function and serum

assessing the prevalence of general obesity, central obesity (OA), associated risk

TSH concentration, and increased MWAT inflammatory cytokines, NIS and

factors

(D2, HTA and dyslipidemia) and tries to provide information on

TSHR expression in thyroid gland. Thyroid hormone treatment improved insulin

determinants of obesity in Algerian adult.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

EP720

This was a cross sectional study conducted among 2210 subjects (1583 women

Anthropometric and metabolic effects of a milk-based intensive lifestyle

and 627 men) aged 18 to 64 years old, living in Algiers (Algeria). Subjects were

intervention in severely obese adults

randomized, anthropometric parameters, socio demographique situation; infor-

Iulia Andrada Ioana, Faraz Rafey Mohammed, Conor Murphy,

mations about food habits and physical activity were collected using a

Katriona Kilkelly, Colm Brassil, Katie Cunningham, Robert Mcgrath,

questionnary. Fasting blood glucose, cholestrol, triglycerids and blood presure

Helena Griffin, Paula O’Shea & Francis M Finucane

were mesured.

Galway University Hospital, Galway, Ireland.

Results

The prevalence of obesity (BMI O 30 kg/m²) was 24, 9% (12, 7% for males and

66, 4% for females). The prevalence of central obesity (WC O 80 cm for women

Therapeutic options for patients with severe obesity are limited. Low energy meal

and 94 cm for men) was 66, 4%, 41% for males and 76, 4% for females. Multi

replacement regimes can induce significant short-term weight loss and

variable logistic regression showed that elderly, female gender, low educationnal

improvements in metabolic variables. We sought to estimate the effect size on

level, a history of familial or personnal obesity and menopause were at risk of

adiposity and cardiovascular risk factors of a relatively inexpensive 24-week

obesity classified by BMI or WC. Wheras a young age, a higher level of

regime based on meal replacement with semi-skimmed milk in severely obese

education, male gender, current smoking, celibacy and hight physical activity

adults. A retrospective cohort analysis showed that of 206 patients in our hospital-

were at low risk of obesity. Obeses subject’s definied by BMI or Waist

based bariatric medicine service who started,

112

(54%) completed the

circumference had an increased risk of type

2 diabetes, hypertension and

programme and underwent an initial milk-based weight loss phase, followed by

dyslipidemia.

weight stabilization and weight maintenance phases, each lasting

8 weeks.

Conclusion

Patients were seen every two weeks by the bariatric physician, nurse and dietitian.

The caracterization of these factors will contribute to defining more effective and

We compared outcomes in completers (who had similar baseline characteristics to

specific strategies to screen and control obesity.

non-completers) at time 0, 8, 16 and 24 weeks, with repeated measures ANOVA.

DOI: 10.1530/endoabs.49.EP718

50.9% of completers were female, 40.2% had diabetes, mean age was 50.9G10.3

years. BMI decreased from

52.7G9.3 to 46.9G8.7, 44.8G8.6 and 43.8G

9.2 kg/m² at 0,

16 and 24 weeks, respectively (P!0.001 with repeated

measures ANOVA), equivalent to 24.8 kg weight loss and a reduction in excess

body weight from 110.6G37.2 to 75.2G36.9%, P!0.001 over 24 weeks.

In patients with diabetes, HbA1c decreased from 63G18.3 to 48G14.5 mmol/mol,

PZ0.01. There were very significant reductions in all diabetes medications,

except for metformin. These preliminary findings suggest that a 24-week milk-

based meal replacement programme can have large effect sizes on important

outcomes in severely obese. However, attrition was high. A more formal

assessment of the efficacy of the intervention as well as its safety, feasibility and

EP719

cost-effectiveness seems warranted.

Testosterone deficiency in obese males: is insulin resistance the one to

DOI: 10.1530/endoabs.49.EP720

blame?

Pedro Souteiro^1,2, Daniela Magalha˜es1,2, Jorge Pedro1,2,

Sofia Castro Oliveira^1,2, João Sérgio Neves^1,2, Sandra Belo^1,2,

Maria Manuel Costa^1,2, Rita Bettencourt-Silva^1,2, Ana Varela^1,2,

Joana Queirós^1,3, Paula Freitas^1,2, Davide Carvalho^1,2 & Group AMTCO³

¹Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-

EP721

talar São João, Porto, Portugal;²Faculty of Medicine of University of Porto,

Association of cortisol, DHEA-S and cortisol/DHEAS ratio with insulin

Porto, Portugal;³Multidisciplinary Group for Surgical Management of

resistance in overweight and obese women

Obesity, Centro Hospitalar São João, Porto, Portugal.

Adam Maciejewski¹, Monika Litwinowicz², Emilia Marcinkowska²,

Marian Grzymislawski² & Katarzyna Lacka¹

Department of Endocrinology, Metabolism and Internal Medicine, Poznan

Introduction

University of Medical Sciences, Poznan, Poland;²Department of Internal

Obesity is a growing worldwide public health issue and it is associated with

Medicine, Metabolic Diseases and Dietetics, Poznan University of Medical

multiple comorbidities, namely the so called Male Obesity-associated Secondary

Sciences, Poznan, Poland.

Hypogonadism (MOSH). However, the mechanisms that explain this association

are not fully understood.

Methods

HPA axis that plays important controlling and modulating functions in organism

Cross-sectional study of 163 obese men that were evaluated for several clinical

is also linked with insulin resistance and weight control. The number of evidences

and analytic parameters. Testosterone deficiency was defined as: total

linking cortisol secretion with obesity and other metabolic complication increase,

testosterone !2.8 ng/ml and/or free testosterone calculated by the Vermeulen

but still there is a lack of definitive results. Therefore the aim of our study was to

formula !50 pg/ml.

compare adrenal function parameters between high and normal insulin resistant

Results

overweight and obese women. This retrospective analysis was performed on the

The studied population had a mean age and BMI of 40.8G10.5 years-old and

group of 70 adult polish Caucasian overweight and obese women with the mean

45.8G6.7 kg/m², respectively. Testosterone deficiency prevalence was 47.2%.

age of 40 years. Mean BMI for the whole group was 38 kg/m². Exclusion criteria

The majority (96.1%) of these men had hypogonadotropic dysfunction and 2.9%

were: pregnancy or breastfeeding, history of any pituitary or adrenal gland

presented high gonadotrophins. When only calculated free testosterone was

disorders, current or previous usage of any glucocorticoid-containing medi-

considered, the deficiency prevalence was 18.1%. Higher BMIs correlated with

cations, other drugs known to affect cortisol level and patients with diagnosis of

lower levels of SHBG (sex hormone binding globulin): rZK0.19; P!0.05. BMI

severe liver or kidney dysfunctions and acute or chronic inflammatory disorder at

(rZK0.26; P!0.001), age (rZK0.21; P!0.05) and HOMA-IR (rZ0.39;

the time of measurements. Patients were divided into two groups according to

P!0.001) had a negative correlation with calculated free testosterone levels,

HOMA-IR value (cut-off point of 3.8). Statistical analysis was performed using

while SHBG levels exhibited a positive correlation (rZ0.18; P!0.05). There

Statistica software. Differences between lower HOMA-IR and higher HOMA-IR

was no significant correlation between oestradiol levels and free/total testosterone

groups were determined by student t test and Mann-Whitney U test when

or BMI. When the aforementioned significant variables were included in a linear

appropriate. To analyze correlations between measured values Spearman

regression model, HOMA-IR (bZK0.33; P!0.001) and SHBG levels (bZ0.20;

correlation coefficiency was calculated. P value

!0.05 was considered

P!0.01) could predict the free testosterone levels, while age (PZ0.07) and BMI

statistically significant. Patients with higher HOMA-IR have higher morning

(PZ0.23) lost their significance after the adjustment. In accordance, males with

cortisol concentration (504.36 vs 425.82 nmol/l) and lower DHEA-S concen-

normal glucose tolerance had higher free testosterone levels than those with pre-

tration (170.18 vs 227.49 mg/dl), although these differences were not statistically

diabetes or diabetes even after adjusting for age and BMI (bZ0.22; P!0.01).

significant. There was statistically significant difference between higher and

Conclusions

lower HOMA-IR groups in evening cortisol concentration

(248.28

and

Testosterone deficiency is frequent in obese males, with most of them presenting

186.02 nmol/l, respectively, PZ0.007) and cortisol/DHEA-S ratio

(5.73

hypogonadotropic dysfunction. SHBG levels and mainly insulin resistance, and

2.73, PZ0.003). For the whole group studied there was statistically significant

not obesity per se, seem to be the true mediators of this interplay. We found no

positive correlation between cortisol/DHEAS ratio and HOMA-IR (rZ0.39,

correlation between oestradiol and testosterone levels suggesting that androgen

PZ0.001). There is a significant association between evening cortisol secretion

aromatization in adipose tissue is not a key determinant as previously thought.

and HOMA-IR and between cortisol/DHEA-S ratio and HOMA-IR.

DOI: 10.1530/endoabs.49.EP719

DOI: 10.1530/endoabs.49.EP721

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP722

Paediatric Endocrinology

Obesity and fruit and vegetables consumptions in children

EP724

Bruno Sousa^1,2

Intracranial lesions in children and adolescents with morbid obesity;

¹Universidade Lusófona de Humanidades e Tecnologias, Lisboa, Portugal;

results of long-term follow-up

²Research Center for Biosciences and Health Technologies, Lisboa,

Ayca Torel Ergur¹, Sevinc Odabasi Gunes¹, Sinan Tan² &

Portugal.

Umit Ayse Tandircioglu²

¹Department of Pediatric Endocrinology, Kirikkale University Faculty of

Introduction

Medicine, Kirikkale, Turkey;²Department of Radiology, Kirikkale

Obesity is associated with the low consumption of fruit and vegetables.

University Faculty of Medicine, Kirikkale, Turkey.

Objective

Evaluate the obesity and the fruit and vegetables consumptions in children after

Introduction

an intervention of school food education program.

Childhood obesity has become an important health problem nowadays.

Methodology

Intracranial lesions

(IC) can affect the hypothalamic

- hypophyseal axis

It was implemented a food education program in three classes (nZ55) of 1st

depending on the localization of the lesion and lead to hypophyseal hormone

cycle, on school year (2016/2017) and the evaluation of this action was done

deficiencies, especially growth hormone. Although IC lesions are important in the

comparing fruit and vegetables consumptions and nutritional status of this

etiology of obesity, There’s limited data in the literature about this subject. Aim of

children between beginning and the end of the program (after 12 weeks). Fruit and

this study is to evaluate the incidence of IC lesions and their role in clinical

vegetables consumptions were assessed through the application of a food

symptoms and etiology in cases with morbid obesity (MO) in childhood.

frequency questionnaire and the nutritional status was determined by BMI.

Materials and methods

Weight and height were assessed in all children and BMI was calculated. To

One hundred twenty cases admitted with the complaint of MO in 13 years (2002-

determine the obesity was used CDC criteria. The educational intervention

2015) were included in this study. Anthropometric evaluation and detailed

consisted in promoting fruit and vegetables consumptions at school environment,

physical examinations were performed. Biochemical and hormonal parameters

involving formative and recreational activities, as well as a greater supply of fruit

(glucose, lipid metabolism, adrenal steroids and diurnal cortisol) were evaluated.

and vegetables in school.

Contrast-enhanced dynamic magnetic resonance imaging (CDMRI) technique

Results

was used to assess the hypothalamo-hypophyseal field. Height of hypophysis was

This sample had between 6 and 8 years old and 54.5% were girls. Fruit

evaluated according to age and sex.

consumption increased and considering the

3-5

pieces of fruit per day

Results

recommended by the Portuguese Food Wheel, the consumption in these students

In our study, 16.6% of the MO patients had an IC lesion. Most of the cases had

evolved from 16.3% to 41.8%. Vegetables consumption also increased. At

adenoma of the hypophysis (55% of the cases with IC lesion.) Six of the patients

beginning 54.5% ate two or more servings per day of vegetables, and at end

with IC lesion had high prolactin levels. Prolactin levels were increased in the

74.5%. In nutritional status, it was observed that obesity decreased from 20% to

6 patients but front hypophyseal hormone levels were in between normal range

16.4%.

in the rest of the patients. None of the patients had decreased growth velocity.

Conclusions

Conclusion

This type of educational intervention in schools increased fruit and vegetables

In this long-term study, the important result is that; IC lesion frequency was

consumptions and reduce the prevalence of obesity in children.

significantly higher in children and adolescents with MO than those of the normal

DOI: 10.1530/endoabs.49.EP722

population. Moreover, these lesions show no other endocrinological or

neurological symptom besides obesity. Furthermore; due to this study; we

suggest that cranial imaging with CDMRI in these cases, even if the physical-

neurological examination is normal, will contribute greatly to the early diagnosis

and treatment of lesions without causing other symptoms.

DOI: 10.1530/endoabs.49.EP724

EP723

Neuromedin B receptor: role in adipogenesis and a possible target for

obesity treatment

Gabriela Paula¹, Marianna Wilieman¹, Luana Souza¹, Karina Ribeiro²,

Leandra Baptista² & Carmen Cabanelas¹

¹Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil;

EP725

²National Institute of Metrology, Quality and Technology, Duque de Caxias,

Congenital hyperinsulinism in two siblings due to the same ABCC8

Rio de Janeiro, Brazil.

mutation: the clinical importance of an early diagnosis and treatment

Francisco Sousa Santos^1,3, Helder Simo˜ es2, Lidia Castro-Feijóo3,

Neuromedin B (NB) is a peptide highly expressed in adipose tissue (AT) but its

Paloma Cabanas Rodríguez³, Ana Fernández-Marmiesse⁶, Rebeca

function remains unclear. We showed that NB receptor (NB) knockout mice

Saborido Fian˜o6, Teresa Rego4, Angel Carracedo5 & Jesús Barreiro Conde3

(NBR-KO) are resistant to diet-induced obesity compared to wild type (WT) and

¹Serviço de Endocrinologia, Centro Hospitalar Lisboa Ocidental, Lisboa,

now we aimed to analyze NBR influence in adipocytes. Mesenchimal cells from

Portugal;²Serviço de Endocrinologia, Instituto Português de Oncologia de

perigonadal AT of WT and NBR-KO mice were isolated and maintained in

Lisboa, Lisboa, Portugal;³Unidad de Endocrinología Pediátrica y

growth medium (GM) as control group or in differentiation medium (DM) as

Crecimiento, Pediatría, Hospital Clínico Universitario y Universidad de

induced group. After 2 weeks cells were fixed and lipid accumulation was

Santiago de Compostela, IDIS, Santiago de Compostela, Spain;⁴Serviço de

evaluated by Oil Red O staining. NBR-KO cells accumulated 56% less lipids than

Endocrinologia, Centro Hospitalar Lisboa Central, Lisboa, Portugal;

WT cells in DM. To analyze NBR antagonist intervention during adipogenesis

⁵Fundación Publica Galega de Medicina Xenómica, Hospital Clínico

3T3-L1 cells were cultured in GM (GMC), or in DM in the absence (DMC) or

Universitario de Santiago de Compostela, Universidad de Santiago de

presence of 3 mM of NBR antagonist (DMA), during 21 days. In parallel NBR

Compostela, Santiago de Compostela, Spain;⁶Pediatría, Hospital Clínico

antagonist was added to DMC group for 6 days after 21 days in culture to verify

Universitario de Santiago de Compostela, Santiago de Compostela, Spain.

its influence after differentiation. Cells were fixed and stained with Dapi and

Bodipy for cell and lipid measurements. After 21 days DMC group exhibited 2.7

Introduction

times more cells number than GMC but DMA group presented similar cell

Congenital hyperinsulinism (CHI) is a heterogenous disease caused by insulin

number as GMC. DMC group reached 83% of well area as lipid while DMA did

secretion regulatory defects, being ABCC8/KCNJ11 the most commonly affected

only 7% although it was corrected by cells area. When NBR antagonist was added

genes. It can present as focal or diffuse pancreatic disease, which is mainly

for 6 days to DMC it decreased cells number by 40% and lipid accumulation

determined by the genotype. Diazoxide is the first-line medication in diffuse

diminished 10%. In conclusion NBR-KO AT cells have impaired induced-

cases, however many do not respond satisfactory. Second-line options include

adipogenesis and NBR antagonist promoted less adipogenesis, reduced

somatostatin analogues and surgery, which is curative in case of focal CHI.

adipocytes number and decreased lipid accumulation. Data demonstrate, for the

Case report

first time, a role for NBR in adipocyte differentiation, suggesting it is a possible

We report the case of two siblings that presented with hypoketotic

target for obesity treatment. Presently, we are analyzing hormones and factors

hyperinsulinemic persistent hypoglycemias during neonatal period. The diagnosis

involved in adipogenesis, lipogenesis and cell death to clarify mechanisms.

of diffuse CHI due to an ABCC8 compound mutation (c3576delG and c742COT)

DOI: 10.1530/endoabs.49.EP723

was concluded. They did not benefit from diazoxide therapy (or pancreatectomy

performed in patient no

1 when he was 3 months old) yet responded to

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

somatostatin analogues. Patient no 1 developed various cognitive deficits and

Introduction

epilepsy, however patient no 2 experienced an entirely normal neurodevelopment.

11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) has been associated with

Conclusion

several human metabolic disorders and is converted from inactive 11-keto form to

We report the case of two siblings with diazoxide-resistant CHI caused by the

glucocorticoid (GC or cortisol). GC overproduction or hypercortisolism is a major

same compound ABCC8 mutation (which was never before described, to the best

diagnostic factor of Cushing syndrome and Anorexia. GCs regulate carbohydrate,

of our knowledge). Their phenotype and therapeutic management had some

fat, and protein metabolism.

differences and this could offer a potential explanation for the distinct

Materials and methods

neurological outcomes, despite the same genetic basis for the disease. Molecular

Previously we established porcine fibroblasts overexpressing 11b-HSD1. Based

diagnosis and better knowledge of the disease behaviour seemed to contribute to a

on these, transgenic piglets overexpressing 11b-HSD1 were born through somatic

better medical care in patient no 2, which ultimately resulted in a better outcome.

cell nuclear transfer (SCNT) and re-cloning methods. Transgenic piglets were

This highlights the importance of early recognition and diagnosis of this disease.

identified by PCR methods using specific primers for the targeting cassettes from

DOI: 10.1530/endoabs.49.EP725

the genomic DNA of piglets. HepG2 cell line overproducing 11b-HSD1 (11b-

HSD1-HepG2) was established for in vitro model. In vivo porcine and in vitro

hepatic models were analyzed by real-time PCR, immunohistochemistry and

Western blotting methods.

Results

Six live piglets were born. Integration of target gene into the genomic DNA was

confirmed from all of them. Excessive expression of

11b-HSD1 induced

up-regulation of gluconeogenesis

(G6PT, G6Pase, PEPCK and etc.) and

lipogenesis related genes (FASN, ACC, and SCD) in in vivo and in vitro models.

EP726

To compensate for energy loss by anabolism, it stimulates AMPK and SIRT

Association between oxidative stress and bone turnover markers in the

signaling, which controls energy balance and mitochondrial biogenesis.

obese children

Conclusions

Pawel Matusik¹, Magdalena Olszanecka Glinianowicz², Jerzy Chudek²

These results suggest that the overproduction of 11b-HSD1 induce activation of

& Ewa Malecka-Tendera¹

complementary energy gaining processes through mitochondrial respiration. Our

¹Department of Pediatrics and Pediatric Endocrinology, Medical University

in vivo and in vitro models will be useful for further study and potential

of Silesia, Katowice, Poland;²Department of Pathophysiology, Medical

application in metabolic diseases.

University of Silesia, Katowice, Poland.

DOI: 10.1530/endoabs.49.EP727

Background

Recent data have been showed that free radicals are involved in either bone

resorption and atherosclerosis development in adults. In paediatric population the

important risk factor for the early atherosclerosis development is obesity, which

can be also associated with the disturb bone turnover.

Objective and hypotheses

The aim of the study was to evaluate the interrelationship between oxidative stress

EP728

and bone turnover markers in obese children vs lean controls and correlated them

Hepatic and adipose tissue insulin resistance as a consequence of

with the anthropometrical status and metabolic activity of adipose tissue.

intermittent hypoxia are exacerbated by glucocorticoid receptor

Method

antagonism in man

Bone turnover markers (osteocalcin (OC), N-terminal telopeptide of type I

Jonathan Hazlehurst, Catriona Charlton, Diana Mantripp, Leanne Hodson

collagen (NTx)), oxidative stress markers (TAC - total antioxidative capacity,

& Jeremy Tomlinson

glutathione peroxidase, oxLDL) and leptin were determined in 50 obese children

Oxford Centre for Diabetes, Endocrinology & Metabolism and NIHR

and 79 healthy controls. Anthropometrical status by BMI calculation and body

Biomedical Research Centre, University of Oxford, Oxford, UK.

composition parameters as: fat mass (FAT), fat-free mass (FMM), predicted

muscle mass

(PMM) and total body water

(TBW) were evaluated using

bioelectrical impedance analyzer (BIA) in all children.

Introduction

Results

Obstructive sleep apnea (OSA) affects up to 20% of a Western population and is

OC was significantly lower in obese children and correlated significantly

associated with non-alcoholic fatty liver disease and type 2 diabetes (T2D). OSA

(negatively P!0.01) with BMI in the lean group. There was also significant

is characterized by intermittent episodes of hypoxia (IH) that occur during sleep.

positive correlation between OC and TAC in obese children. NTx correlated

It is not yet known if IH is directly linked to insulin resistance within key

significantly with oxy-LDL (positively) in either, obese and lean group (P!0.05

metabolic target tissues (adipose; liver and skeletal muscle) and what the potential

and P!0.01 respectively). In the lean group only, there were significant relations

underlying mechanism may be. It has been suggested that individuals with OSA

between NTx vs leptin and body composition parameters (rZ0.245 vs leptin,

have high circulating glucocorticoid levels which may be linked to the

rZ0.245

vs FAT%, rZK0.252 vs PMM%, and rZK0.245 vs FFM%

development of IR and T2D.

respectively).

Methods

Conclusion

17 healthy male volunteers were recruited and underwent detailed metabolic

Bone turnover seems to be disturbed in the obese children and pathophysiological

phenotyping in a fasted state including a hyperinsulinaemic-euglycaemic clamp,

factor with can be involved in that mechanism may be an increase oxidative stress

incorporating the use of stable isotopes of glucose and palmitate to measure fatty

level. Osteocalcin and NTx levels seem to be related to the anthropometrical

acid partitioning. Initial assessments were made in normoxic conditions;

status and adipose tissue activity (leptin level).

volunteers were then randomised either to no treatment (nZ9) or treatment

DOI: 10.1530/endoabs.49.EP726

with the glucocorticoid antagonist Mifepristone (600 mg once a day) (nZ8).

After 1 week of treatment, assessments were repeated under conditions of IH (12

desaturations/h to arterial saturations of 85-91%).

Results

Global insulin sensitivity as measured by M/I values was unchanged by IH or by

IHCMifepristone (control: 8.65G4.1; IH: 9.13G5.4; control (pre_drug): 8.9G

3.7; MifeprisoneCIH: 10.13G3.3). However, IH impaired the ability of insulin

to suppress TAG, an effect that was worsened by Mifepristone ((insulin mediated

suppression of TAG: control: K449G124; IH: K218G131 (PZ0.0034); control

(pre_drug): K339G201; MifeprisoneCIH: K76G128; (PZ0.008). In addition,

Steroid Metabolism C Action

adipose tissue IR, as measured by a reduction in the ability of insulin to suppress

EP727

circulating NEFA, was worsened by Mifepristone under conditions of IH (insulin

In vivo porcine and in vitro HepG2 models with 11b-HSD1

mediated change in plasma NEFA control: K501G164; IH: K411G187 (PZns);

overproduction

control (pre_drug): K549G130; MifeprisoneCIH: K367G109; (PZ0.03)).

Hee Young Kang, Jae Hwan Lee, Jin Yong An, Dinh Nam Tran &

Conclusion

Eui-Bae Jeung

Acute IH causes insulin resistance in liver and adipose tissue. These effects are

Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

worsened rather than improved by antagonism of the glucocorticoid receptor,

highlighting the importance of understanding tissue specific glucocorticoid

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

actions and suggesting activation of the HPA axis is not the link between OSA

EP730

and metabolic risk

Gender specific metabolic phenotype in the 5b-reductase knockout

DOI: 10.1530/endoabs.49.EP728

mouse

Laura Gathercole^1,2, Petra Klusonova³, Nikolaos Nikolaou¹,

Jonathan Hazlehurst¹, Ahmad Moolla¹, Niall Dempster¹, Trevor Penning⁵,

Roger Cox⁴, Alex Odermatt³ & Jeremy Tomlinson¹

University of Oxford, Oxford, UK;²Oxford Brookes University, Oxford,

UK;³University of Basel, Basel, Switzerland;⁴Medical Research Council

EP729

Harwell, Oxfordshire, UK;⁵University of Pennsylvania, Philadelphia, USA.

Dexras1 regulates MSC-derived adipogenesis and osteogenesis

Jo Woon Seok¹, Daeun Kim¹, Hye min Lee¹, Bo kyung Yoon¹,

Hyo Jung Kim¹ & Jae-woo Kim^1,2

Steroid hormones and bile acids are potent regulators of metabolism. The enzyme

¹Department of Biochemistry and Molecular Biology, Integrated Genomic

5b-reductase

(AKR1D1) has a crucial role in bile acid synthesis and also

Research Center for Metabolic Regulation, Institute of Genetic Science,

generates 5b-reduced dihydrosteroid metabolites, regulating intra-cellular steroid

Yonsei University College of Medicine, Seoul, Republic of Korea;

availability though the clearance of cortisol, testosterone, androstenedione, and

²Severance Biomedical Science Institute, Yonsei University College of

progesterone. As AKR1D1 sits at the interface of bile acid synthesis and steroid

Medicine, Seoul, Republic of Korea.

metabolism, we have hypothesised that it plays a key role in metabolic

homeostasis and have generated and characterised an entirely novel, global

AKR1D1 knockout (KO) mouse. As expected AKR1D1 KO mice had altered

Mesenchymal stem cells

(MSCs) are multipotent stromal cells that can

hepatic steroid (in vitro cortisone clearance: 100% (WT), 70% (KO); in vitro

differentiate into various types of cells including chondrocytes, osteoblasts and

5a-cortisone/cortisol metabolite generation increased 3.9-fold (KO)) and bile

adipocytes. Since these types of cells are simultaneously derived from the same

acid metabolism (hepatic bile acid concentration males: 1164G626 pmol/mg

precursor cell, adipogenesis and osteoblastogenesis are thought to be counter-

(WT), 122G42 pmol/mg (KO) P!0.05; females: 310G67 pmol/mg (WT),

related. It is well-known that chronic treatment of steroid can induce Cushing’s

113G23 pmol/mg (KO) P!0.01). At

weeks male, but not female,

syndrome which has phenotypes like visceral adiposity and osteoporosis. Cell fate

AKR1D1KO animals were lighter than wildtype (WT) littermates

(males:

of differentiation into either adipocytes or osteoblasts is one of the critical factors

35.6G0.9 g (WT), 33.2G0.6 g (KO) P!0.05; females: 25.3G0.6 g (WT),

of these symptoms, but the molecular mechanism of cell fate decision of MSCs

24.9G0.4 g (KO) PZns) with lower total (9.7G0.7 g (WT), 7.4G0.5 g (KO)

under the streroid treatment is unclear. Recently, we showed that Dexras1

P!0.05) and % (29G1.4% (WT), 24G1.5% (KO) P!0.05) fat mass, as

mediates glucocorticoids and IGF-I signaling followed by MAPK activation and

determined by DEXA. At termination, male AKR1D1 KO mice had smaller

results in increased adipogenesis while its abolishment decreases adipogenesis.

subcutaneous adipose depots (1.0G0.1 g (WT), 0.7G0.1 g (KO) P!0.05) and,

Now we established that lack of Dexas1 exhibited increased osteogenesis in

despite no difference in body weight or composition, female KO animals had

mesenchymal stem cells including both bone marrow derived stem cells (BMSCs)

smaller gonadal fat depots (0.5G0.1 g (WT), 0.3 gG0.03 g (KO) P!0.05). Both

and mouse embryonic fibroblasts (MEFs). Corroborative to our previous data,

male and female AKR1D1KO mice had enhanced insulin sensitivity (ipITT AUC

decreased adipogenesis in MSCs was also observed in the absence of Dexras1.

males:

793 mMol min (WT), 647 mMol min (KO); ipITT AUC females:

Despite less dramatic change in differentiation, it is also shown that lessened

663 mMol min (WT), 568 mMol min (KO)), without changes in glucose

mature osteoblasts in Dexras1-overexpressing preosteoblast cell line, MC3T3-E1,

tolerance. AKR1D1 KO mice display a sexually dimorphic metabolic phenotype.

down regulating Smad signaling in the early period of differentiation.

Whereas both male and female AKR1D1 KO mice have increased insulin

Furthermore, we found that Dexras1 is involved in increased central obesity

sensitivity, only male AKR1D1 KO mice have a lean phenotype. Although the

associated with chronic treatment of steroids but rescued steroid-induced

underpinning mechanisms remain to be fully defined, AKR1D1 may represent a

osteoporosis in mouse model treated with dexamethasone for 8 weeks followed

future novel therapeutic target for the treatment of metabolic disease.

by increased gene expression related to osteoblast in the murine bone. Above all

DOI: 10.1530/endoabs.49.EP730

these results, we suggest that Dexras1

is a key molecule which stimulates

adiposity and down regulates osteogenesis via counter regulating action.

DOI: 10.1530/endoabs.49.EP729

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Cardiovascular Endocrinology and Lipid Metabolism

consider confounding factors such as time taken from the dictation of letters to

typing and postal delays, and observer effect from trainees. The endocrine

EP731

meeting is not happening every week, and trainees are not attending it

Measuring of quality of life and health characteristics among 40-79 old

consistently due to other clinical commitments. We are actively looking to

population in Hungary

rectify these issues.

Anita Zubrecki¹, Ivan Devosa², Maria Jako¹, Attila Vass³, Klara Deak³,

DOI: 10.1530/endoabs.49.EP732

Sandor Kolosszar¹, Melinda Vanya^4,5, Imre Foldesi⁶ & Gyorgy Bartfai¹

¹Department of Obstetrics and Gynaecology, University of Szeged, Szeged,

Hungary;²Athene Pallasz University, Kecskemét, Hungary;³Department of

Ophtalmology, University of Szeged, Szeged, Hungary;⁴Mediteam Zrt,

Szeged, Hungary;⁵Department of Obstetrics and Gynaecology, Kalman

Pandy Hospital Gyula, Gyula, Hungary;⁶Department of Laboratory

Developmental Endocrinology

Medicine, University of Szeged, Szeged, Hungary.

EP733

Endocrinology training programs in member countries of the

Introduction

International Society of Endocrinology (ISE): a pilot survey evaluation

Life expectancy is increasing in most developed countries, in part due to

comparing regions and cultures

improved socio-economic conditions and in part to advances in healthcare. It is

Maite P Bastyr & Juan C Galofré

widely acknowledged that the promotion of healthy ageing by delaying,

Department of Endocrinology, University of Navarra, Pamplona, Spain.

minimizing or preventing disabilities or diseases is one of the most important

public health objectives in this century.

Methods

Background

243 Women and 181 men aged 40-79 years were recruited in Szeged (Hungary)

Endocrinology is a relatively young subspecialty of internal medicine. No

consensus on international standards for training has been established, and hence

Subjects were recruited from population registers and those who agreed to take

the variability between training programs and endocrinologist qualifications may

part completed a detailed questionnaire including aspects of personal and medical

be great.

history, lifestyle factors. Objective measures of body size, cognition, vision,

Methods

skeletal health and neuromuscular function were obtained. Internal consistency of

A standardized questionnaire was constructed to explore individual national

the questionnaire was also investigated (Cronbach alfa: 0.715).

standards for endocrinology training, evaluating the responding programs for

Results

physician entry criteria for each program, medical content, duration of the

Mean age of participants was 59.17 S.D.:10.71 years. There were significant

programs, procedural competency, and qualification and re-qualification

correlation between the quality of life and systolic blood pressure of the right &

requirements. Representatives from member societies of the ISE were solicited

left hand

(PZ0.007

and PZ0.013) and smoking use

(PZ0.002) The

to provide specific characteristics of their respective national training programs

cardiovascular risk was significantly higher in the 40-50 age groups compared

via a questionnaire on SurveyMonkey.

to the older age groups (PZ0.002).

Results

Conclusion

Sixteen of 54 (30%) ISE member countries responded regarding training program

We provide new data among the health characteristics of older population in

characteristics. Spanish-speaking (SS) countries were more likely to have an

South Hungary. Such information is an important prerequisite to develop effective

entrance exam compared with non-SS countries (80 vs 27%, c²Z3.88, PZ0.049).

strategies to reduce age-related disabilities and optimise health and well-being

On average 62-85% of programs included all general endocrinology knowledge

into old-age.

content with the exception of endocrine surgery (15%) and genetics (31%).

DOI: 10.1530/endoabs.49.EP731

Genetics was included more frequently in SS vs non-SS countries (60 vs 13%,

c2Z3.26, PZ0.071) and less frequently in European Union (EU) vs non-EU

countries

(17

43%, c²Z3.61, PZ0.057). Pediatric endocrinology was

included more frequently in SS vs non-SS countries (100 vs 43%, c²Z4.29,

PZ0.038). Endocrinology research was included less frequently in EU vs non-

EU countries (50 vs 86%, c²Z3.26, PZ0.071). Thyroid procedures were taught

Clinical Case Reports - Thyroid/Others

only 33-38% of the time across programs while diabetes-related procedures and

EP732

DEXA were required by 62-69% of the programs, and both were included more

Does standardising the dynamic endocrine testing process improve

frequently in the SS vs non-SS countries

(c²Z8.70, PZ0.003, c²Z5.08,

patient communication and safety?

PZ0.024, respectively). While

100% of countries required certification to

Rahat Tauni^1,2 & Ritwik Banerjee²

practice endocrinology, only 38% had a certifying examination, with significantly

¹Cambridge University Hospitals, Cambridge, UK;²Luton and Dunstable

lower administration in EU vs non-EU (17 vs 57%, c²Z5.08, PZ0.024).

University Hospital, Luton, UK.

Conclusion

The questionnaire identifies differences in endocrinology training, which can be

addressed by ISE member countries in the hope of an overall improvement in the

Background and objectives

quality of training and international harmonization of the discipline of

Ineffective communication is one of the leading causes of medical errors and

endocrinology.

patient dissatisfaction. We implemented an initiative for dynamic endocrine tests

DOI: 10.1530/endoabs.49.EP733

to enhance communication with primary care colleagues and patients.

Methods

We introduced a comprehensive system of organising dynamic tests, structured

documentation, weekly endocrine meeting to discuss the results and standardised

escalation process for suspected abnormal results. We retrospectively analysed 50

tests prior to and 50 after the initiative was introduced (nZ100). Most were

EP734

routine short synacthen tests (SST) with a small proportion of other tests including

The basic characteristics of delivery of endocrinologic care in Slovakia

urgent/semi-urgent SST, dexamethasone suppression tests, TRH and GnRH

from outpatients care perspective

stimulation tests, prolonged oral glucose tolerance test and prolonged supervised

Jan Bielik¹ & Peter Glatz²

fast.

¹Trencin University of Alexander Dubcek, Trencin, Slovakia;²Consultancy,

Results

Bratislava, Slovakia.

The mean time from the date of test and the letter to general practitioner/patient

of routine tests reduced from 22.07 days to 13.92 days for normal SSTs and

The prevalence of endocrinologic diseases in Slovak Republic in 2015 was about

5.16 days to 4.83 days for abnormal SSTs, although the latter was not statistically

390 000 patients e.g. the prevalence was about 7.1%. The objective of this study

significant. The other test numbers were too small to establish significance. There

was to find out the basic relevant characteristics of delivery of endocrinologic care

was no significant difference in time taken for organising the tests and no patient

based on data from General Insurance Company with covering cca 63% of all

inhabitants.

harm was reported in both groups. Anecdotal reports from trainees suggested that

Methods

there were more training opportunities with the introduction of the new process.

Discussion

The combined analysis from the GIC data was used.

Our data suggests that streamlining the dynamic endocrine function test system

Results

reduces the delay in communicating normal routine dynamic endocrine test

246 195 patients, 212 977 women and 33 597 men, were examined in this study.

results and can increase the training opportunities for trainees. We aim to perform

The patients visited 150 endocrinologic outpatients departments (EOD). The

another analysis with a larger sample and analyse patient satisfaction data and

number amounted from 1100 to 2800 patients per one department. The prevalence

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

of endocrinologic diseases differed from 6.1% to 9.3% compared 8 administrative

Goal

regions. The ratio of EOD varied between

2.9% and

6.7% per

100 000

Decrease a number of lower limb amputations in PDM in Uzbekistan by

inhabitants. The migration of patients among regions varied from 3% to 10%.

improvement of specialised help given to patients with DFS.

The thyreoid diseases represented 88.4% of all patients, metabolic diseases

Materials and methods

- 8.3%, bone diseases - 6.5%, all other diseases - 5.4% (1 patients had one and

Prior to 2010 there were only 2 ‘Diabetic foot’ rooms in Tashkent, Uzbekistan. In

more diseases). The prevalence of benign tumors in patients was cca 1.85% and

2010-2012, CPA ‘UMID’ jointly with Uzbekistan Ministry of Health and

malignant tumors about 1.7%. Some endocrinologic diseases were treated by

Research Centre for Endocrinology implemented a project ‘Prevention of lower

more than 50 other specialists like internal specialists etc. In this thyreoid diseases

limb amputations in people with diabetes mellitus in Uzbekistan’ granted by the

represented about 21.9%, bone diseases - 686%, metabolic diseases - 18.6% and

World Diabetes Fund (WDF).

all others diseases - 65.4%. From 2013 to 2015 y. was observed an increase of

Results

patients with thyreoid diseases in 7.0%, bone diseases - 4.5%, other diseases

Within the framework of the project for the first time in Uzbekistan, 288 ‘Diabetic

5.3%. Together 21 activities from daily practice were observed and evaluated.

foot’ rooms were set up under 14 endocrinological dispensaries and in 274 rural

The most often were: first and followed examination, blood taking, evaluation

district clinics which were also equipped with a medical armchair for feet

of laboratory exams, ultrasonography, advice to the patients, densitometry,

examination, a tuning fork, monofilament, percussion hammer, kit of dressing

biopsy, etc.

materials. To work in these rooms, 615 podiatrists were trained who render a

Conclusions

qualified medical help to PDM and teach them rules of foot care. Annually over

The prevalence of endocrinologic diseaseas in Slovakia is high. There are some

28 800 PDM undertake feet examination and training in these rooms. A twofold

non explanable differences among administrative reasons in access to

decrease in a number of amputations and increased awareness of PDM in foot care

endocrinologic outpatients care and high level of overlapping among

proves improvement of specialised help to people with DFS. Within the

endocrinology and other medical specialties.

framework of the project, 288 multidisciplinary teams (surgeon C endocrinol-

DOI: 10.1530/endoabs.49.EP734

ogist C podiatrist) were trained throughout the country and now they render a

specialised help to patients with DFS.

Conclusions

Implementation of the project ‘Prevention of lower limb amputations in people

with diabetes mellitus in Uzbekistan’ improved a specialised help to people with

DFS due to launching a network of ‘Diabetic foot’ rooms and an effective work of

podiatrists and multidisciplinary teams trained on sites and that lowered a number

of amputations in PDM by two times; increased awareness of people with diabetes

on prevention of DFS.

Diabetes (to include Epidemiology, Pathophysiology)

DOI: 10.1530/endoabs.49.EP736

EP735

Gestational diabetes risk in three Israeli population subgroups

Anat Jaffe¹, Shmuel Giveon², Carmit Rubin³, Ilia Nvokov³, Arnona Ziv³ &

Ofra Kalter-Leibovici^2,3

¹Hillel Yaffe Medical Center, Hadera, Israel;²Sackler School of Medicine,

Tel Aviv, Israel;³Gertner Institute for Epidemiology and Health Policy

Research, Ramat Gan, Israel.

EP737

Assessment of the prevalence of type 1 diabetes microvascular

complications in young adults in the repablic of Belarus with regard to

Objective

the duration of the disease

Israeli Ethiopian Jews (EJ) and Arabs have at reproduction age higher incidence

Yuliya Dydyshka¹, Alla Shepelkevich¹, Vladislav Yurkovets¹,

of diabetes than other Israeli Jews. We aimed to compare gestational diabetes

Elena Brutskaya-Stempkovskaya^1,2 & Marina Mantachik¹

(GDM) risk among these population subgroups.

¹Belarusian State Medical University, Minsk, Belarus;²31th city polyclinic

Methods

in Minsk, Minsk, Belarus.

The study cohort included age-matched EJ, non-Ethiopian Jews (NEJ) and Arab

women age 20-45 years. GDM diagnosis was based on the two step screening

method of 50 and 100 g oral glucose load tests. Univariate comparisons and the

Background and aims

association between population subgroups and the risk for GDM were tested in

According to current recommendations of the American Diabetes Association

multiple logistic regression analysis, adjusted for age, parity and pre-gestational

expedient screening of microvascular complications in all patients with type 1

levels of the metabolic syndrome components.

diabetes (T1D) with a duration of 5 years of the disease. Therefore, the aim of

Results

study was to assess the prevalence of microvascular complications in T1D

The study included 13 943 women (2938 EJ, 5156 NEJ and 5849 Arabs). During

patients aged 30K45 years with regard to the duration of the disease 5K10 years

the years 2008-2011, birth rate was 0.358, 0.475 and 0.526 (P!0.001), diabetes

and over 10 years.

screening was performed in 84, 81, 85 and GDM prevalence was 4.3, 2.2 and 2.9%

Materials and methods

among Ethiopian, non-Ethiopian and Arab women respectively. The multivariate

We examined 360 patients with type 1 diabetes, 196 (54.4%) men and 164

odds ratios (OR) for GDM were age 2.9-per 10 years (95% CI 2.1-4.1), BMI 1.12

(45.6%) women. The average age of the patients was 37.9G4.5 (37.4K38.4)

(95% CI 1.1-1.2), triglycerides 1.05-per 10 mg/ml (95% CI 1.0-1.1), systolic

years, the age of onset of diabetes - 28.1G6.2 (27.5K28.8) years, duration of the

blood pressure 1.05-per 10 mmHg (95% CI 1.02-1.1), parity 0.8 (95% CI 0.7-

disease - 9.0 (7.0K12.0) years, BMI - 24.8G3.95 (23.6-25.2) kg/m², Hb_A1c -

0.9) and Ethiopian ethnicity 2.55 (95% CI 1.6-4.1). Arab-ethnicity 1.4 (95% CI

8.37G1.83 (8.18K8.56). In the study, carried out a detailed clinical examination

0.95-2.15) and HDL-c 0.99 (95% CI 0.91-1.08) were not associated with risk for

of patients with medical records analysis.

GDM.

Results

Conclusions

Diabetic peripheral neuropathy (DPN) was diagnosed in 133 (36.9%) patients;

Ethiopian ethnicity is an independent risk for GDM. The higher GDM prevalence

diabetic retinopathy (DR) K 78 (21.7%) patients, diabetic nephropathy (DN) K

in Arab women is mainly explained by higher obesity rates.

in 146 (40.6%) patients, albuminuria was detected in 137 (38.1%) persons. In

DOI: 10.1530/endoabs.49.EP735

general, microvascular complications of diabetes were set at 270 (75%) patients.

With increasing duration of the disease for more than

10 years showed a

significant increase in microvascular complications: DPN 30.6 vs 47.1% (c²Z

9.91; PZ0.002); DN K 34.2 vs 50.7% (c²Z9.60; PZ0.002); albuminuria K

31.9 vs 47.8% (c²Z9.06; PZ0.003); DR - 40.1 vs 71.7% (c²Z34.2; P!0.005);

any microvascular complications K 67.6 vs 86.9% (c²Z17.06; P!0,001).

Diabetes Complications

However, no significant differences in Hb_A1c:

8.32G1.83 vs 8.45G1.82%

(PZ0.539).

EP736

Conclusions

Improvement of specialised help to patient with diabetic foot syndrome

Patients with type 1 diabetes with disease duration 5K15 years microvascular

in Uzbekistan

complications recorded in 75% of cases. The increase in the prevalence of

Nilufar Ibragimova, Telman Kamalov, Hamidulla Shakirov,

microvascular complications associated with the duration of the disease, but not

Oxana Platonova & Lyudmila Kokareva

with the level of Hb_A1c.

Charity Public Association of the Persons with Disabilities and People with

DOI: 10.1530/endoabs.49.EP737

DM ‘UMID’, Tashkent, Uzbekistan.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Endocrine Disruptors

EP741

EP738

24 hrs chronomics of BP/HR in terms of double amplitude, acrophase,

hyperbaric index and its relation with circadian rhythm of 6-sulfatoxy

Endocrine disrupting chemicals exacerbate type 1 diabetes mellitus

melatonin in night shift nursing professionals: A Case-control study

model

B Anjum^1,2, Narsingh Verma¹, Sandeep Tiwari³, Ranjana Singh² &

Changhwan Ahn, Jin Yong An, Dinh Nam Tran, Seon Young Park &

Abbas Mahdi²

Eui-Bae Jeung

¹Department of Physiology, King George’s Medical University, Lucknow,

Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

UP, India;²Department of Biochemistry, King George’s Medical

University, Lucknow, UP, India;³Department of Surgery (Gen), King

It has been proposed that cellular Ca^2C signals activate hormone secretion. In

George’s Medical University, Lucknow, UP, India.

pancreatic b cells, which produce insulin, Ca^2C signals have been known to

contribute to insulin secretion. In previous study, demonstrated that endocrine

The present study was aimed to investigate the 24 hours chronomics of BP/HR in

disrupting chemicals (EDCs) such as bisphenol A (BPA) and Octylphenol (OP)

terms of Double amplitude, Acrophase and Hyperbaric index and its relation with

could cause increase in insulin level and insulin transcription factors. But in

circadian rhythm of 6-sulfatoxy melatonin in night shift nurses and actual day

regulations of plasma glucose level were not decreased as much as insulin increase.

workers. 56 night shift nurses, aged 20-40 years, performing day and night shift

For identifying this phenomenon, we evaluate the HOMA-IR which is used for

duties were recruited from the Trauma Center, KGMU, India, and 56 age sex

calculating insulin resistance, trace that EDCs has ability to increase insulin

matched actual day workers were also enrolled as controls. BP and HR were recorded

resistance. We hypothesized that EDCs disrupts calcium homeostasis and the

by ABPM at every 30 min intervals in day time and each hour in night time

altered intracellular calcium levels may induce insulin resistance. The expression

synchronically with circadian rhythm of 6-sulfatoxy melatonin during shift duties.

of genes involved in transporting calcium ions to the endoplasmic reticulum (ER)

Highly significant difference was found in double amplitude (2DA) of SBP between

was decrease while the expression of those affecting the removal of calcium from

night (23.10G14.68) and day shift (34.27G16.44) (P!0.0005). In night shift,

the ER was increased. Depletion of calcium from the ER leads to ER-stress and can

hyperbaric index (HBI) of mean SBP was found to be increased at 00-03 am

induce insulin resistance. Taken together, these results imply that the disruption of

(midnight) while during day shift, peak was found at 06-09 am. HBI of mean HR was

calcium homeostasis by EDCs induces ER-stress and leads to the insulin resistance.

found to be increased at 18-21 pm during night shift while in controls, peak was

Additionally, findings from this study suggest that imbalances in calcium

found at 09-12 & again 15-18 pm of SBP, DBP & HR. Alterations in Acrophase of

homeostasis due to EDCs such as BPA and OP could promote insulin resistance

BP/HR were very common among night shift workers and Ecphasia was found in

and its harmfulness especially to the Type I diabetes mellitus patients.

few night shift workers. Alteration in morning and night melatonin level was also

DOI: 10.1530/endoabs.49.EP738

found during night shift as compare to their day shift and in actual control group.

Reverse pattern of Acrophase and HBI of BP & HR along with 6-sulfatoxy melatonin

during night shift represents desynchronization. It indicates that the circadian rhythm

was disrupted during night shift and recovery occurs during day shit.

DOI: 10.1530/endoabs.49.EP741

EP739

Stimulating effect of 17b-estradiol and TCDD and on the protein

expression of cytochrome P450 1A1 gene in cellular and xenografted

models of breast cancer

Ryeo-Eun Go, Kyung-A Hwang & Kyung-Chul Choi

EP742

Laboratory of Biochemistry and Immunology, Veterinary Medical Center

The effects of halogenated-hydrocarbon uron herbicides, as endocrine

and College of Veterinary Medicine, Chungbuk National University,

disruptor compounds on the oxytocin (OT) hormone regulation in vitro

Cheongju, Chungbuk, Republic of Korea.

Krisztian Sepp¹, Zsuzsanna Valkusz¹, Zsolt Molnar², Anna Laszlo⁴,

³, Marianna Radacs² & Marta Galfi²

Tunde Alapi

Cytochrome P450 (CYP) 1A1 plays a major role in the metabolic activation of

¹First Department of Medicine, University of Szeged, Szeged, Hungary;

procarcinogens to carcinogens via aryl hydrocarbon receptor (AhR) pathway.

²Department of Environmental Biology and Education of Gyula Juhasz

Especially, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known as an agonist of

Faculty of Education, University of Szeged, Szeged, Hungary;³Department

AhR. In estrogen responsive cancers, 17b-estradiol (E2) may influence on AhR

of Inorganic and Analytical Chemistry of Faculty of Science and

dependent expression of CYP1 family via the interaction between estrogen receptor

Informatics, University of Szeged, Szeged, Hungary;⁴Department of

(ER) and AhR. In the present study, the effect of E2/ER on the expression of AhR and

Biometrics and Agricultural Informatics Szent Istvan University, Godoll

˝,

CYP1A1 genes was investigated for MCF-7 clonal variant (MCF-7 CV) breast

Hungary.

cancer cells expressing ER. In reverse transcription (RT)-PCR and western blot

analysis, mRNA level of AhR was not altered, but its protein level was increased by

The biological organisms are complex systems regulated by the homeostatic

TCDD or E2. The transcriptional and translational levels of CYP1A1 appeared to be

back-end network. In these days the growing environmental loads (from industry,

increased by TCDD or E2. The increased expression of AhR and CYP1A1 induced

household, etc.) contain chemical exposure eg. halogenated hydrocarbons

by E2 was restored to the control level by the co-treatment of ICI 182,780, indicating

(monuron: MU (C₉H₁₁ClN₂O), diuron: DU (C₉H₁₀Cl₂N₂O)), which can be

that E2 induced the protein expression of AhR and CYP1A1 like TCDD via an ER

endocrine disruptor compounds (EDCs). Synthesis, release of hormones and cell

dependent pathway. In an in vivo xenograft mouse model transplanted with MCF-7

processes of endocrine cells, and the biochemical properties of hormones can be

CV cells, the protein levels of AhR and CYP1A1 of tumor masses were also

changed by these agents. The disturbance of endocrine regulation by the EDCs

increased by E2 or TCDD. Taken together, these results indicate that E2 may

can induce different diseases for example in the reproductive-, neurological,

promote AhR dependent expression of CYP1A1 via ER dependent pathway in MCF-

and/or psychical, and/or immunological system. In this study the aim was to

7 CV cells expressing ER in the absence of TCDD, an agonist of AhR. The relevance

investigate the effects of uron herbicides (fenuron: PU (C₉H₁₂N₂O); MU, DU) on

of E2 and ER in CYP1A1 activation of estrogen responsive cancers may be targeted

the monoamine activated ocytocin (OT) release from neurohypophysis (NH)

for developing more effective cancer treatments. (This research was supported by a

cells. The primary monolayer NH cell cultures were prepared from the evidenced

grant (14182MFDS977) from Ministry of Food and Drug Safety in 2016.)

Wistar rats (_) for the experiments. The separated NH tissues were dissociated

Keywords: Dioxin, 17 b-estradiol, breast cancer, xenograft models, CYP1A1

by enzymatic (trypsine, collagenase, DNA-se I; II) and mechanic methods. The

DOI: 10.1530/endoabs.49.EP739

14 days old cultures were standardized for cell-viability and OT content. The NH

cells were tested for functionally OT hormone volume by aspecific stimulus

(30 mM [K^C]). The untreated cultures were the controls, and the treating system

was the consequential: A: 1 hour 0.1 mg/ml EDCs; B: 10^-6M monoamines

(epinephrine, norepinephrine, dopamine, histamine, serotonine) alone; C:

EP740

combined the monoamines agents with EDCs. The OT content was measured

from supernatant media by RIA method. The results showed that the uron

herbicides alone did not have significant effects on the OT release in the primary

monolayer NH cell cultures. The EDCs caused alteration of the monoamine

Abstract withdrawn.

activated hormone release. The uron herbicides can play as strong environmental

stress factors in the homeostatic system regulation. This work was supported by:

TÁMOP-4.2.2.D-15/1/KONV-2015-0010, TÁMOP-4.2.4.A/2-11-1-2012-0001.

DOI: 10.1530/endoabs.49.EP742

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP743

Conclusion

In conclusion, our study demonstrates consistently that several behavioral traits

The protective role of Zingiber officinale extract against methyl

and fat-soluble vitamins may have detrimental effects on BMD, while reinforcing

thiophanate induced toxicity in male rats

the benefit of physical activity for skeletal health.

Rachid Mosbah^1,2, Malika Bahri¹, Said Azzoug³, Zouhir Djerrou⁴ &

Alberto Mantovani⁵

DOI: 10.1530/endoabs.49.EP744

¹Department of Biology, University of Boumerdes, Boumerdes, Algeria;

²Laboratory of Eco-biology, ENS Kouba, Algiers, Algeria;³Hospital of

Lamine Debaghine B.E.O, Algiers, Algeria;⁴University of Skikda, Skikda,

Algeria;⁵Istituto Superiore di Sanità, Rome, Italy.

In this study, we attempted to assess the toxicity of Methyl Thiophanate (MT) on

the biochemical and reproductive parameters in male Wistar rats as well as the

possible protective role of Zingiber officinale (Ginger, Ging) extract against

MT-induced toxicity. Hence, forty adult Wistar rats were allocated into four

EP745

groups of 10 rats for each; the first group served as control, groups 2, 3 and 4 were

Quantitative image based analysis of endocrine disruptor effects on

treated orally (5/week) for 8 weeks by MT (150 mg/kg bw), Ging (100 mg/kg bw)

mitochondria morphology-function in prostate cancer cells

and MT plus Ging respectively. At the end of experiment, blood samples were

Aurélie Charazac¹, Célia Deconde Le Butor¹, Mamadou Gueye¹,

collected under anesthesia for measuring the biochemical parameters and

Jérôme Gilleron¹, Kévin Giulietti³, Patrick Fenichel², Xavier Descombes³,

testosterone level, while, the reproductive organs were excised and used for

Frédéric Bost¹, Stéphan Clavel¹ & Nicolas Chevalier²

semen quality analysis and histopathological examinations. Results indicated that

¹Institut National de la Santé et de la Recherche Médicale (INSERM) UMR

MT exposure increases the level of blood glucose, cholesterol, triglycerides, urea,

U1065/UNS, Centre Méditerranéen de Médecine Moléculaire (C3M), Nice,

uric acid, AST, ALT and total protein, whereas, no clear impact on testosterone

PACA, France;²Centre Hospitalier Universitaire de Nice, Hôpital de

level was noted compared to the control. Semen analysis showed a decrease in

l’Archet 2, Service d’Endocrinologie, Diabétologie et Médecine de la

spermatids number, sperm count, motility and viability. Moreover, a marked

Reproduction, Nice, PACA, France;³INRIA CRI-SAM, Nice, PACA,

histopathological damage in testis and epididymis was detected which reflect a

France.

poor semen quality. Ginger extract co-treatment with MT alleviates and/or repairs

all adverse toxic effects caused by MT on the reproductive, biochemical and

hispathological parameters. This amazing preventive role may be related to its

Persistent organic pollutants

(POPs) are environmental contaminants that

potential antioxidant properties. In conclusion, ginger extract supplementation

interfere with normal hormonal homeostasis and act as endocrine disrupting

plays crucial protective role against MT-induced toxicity in male rats.

compounds (EDC). These molecules can mimic hormone effects on metabolism.

The links between metabolism and cancer are now well established. Metabolism

DOI: 10.1530/endoabs.49.EP743

generates reactive oxygen species (ROS), which contribute to mutations and

induces oncogenic transformation. In turn, cancer cells display high metabolic

flexibility allowing them to grow in various cellular environments and favoring

their proliferative and invasive capacities. Mitochondria are key players in this

complex interplay since they produce ROS, generate energy, and participate in

nucleotide synthesis and in glutamine metabolism of cancer cells. Regarding the

importance of hormones on prostate cancer risk and outcomes, we are developing

a multiple parameters in vitro assay conducted in a high-throughput screening

format relevant for prostate cancer metabolism and aggressiveness. This

screening method includes, inter alia a microscopy based analysis of

mitochondria structure and function. We analyzed the effects of five EDCs

EP744

(Aldrin, BDE28, TCDD, PCB153, PFOA) identified in the plasma of patients on

Systematic screening for environmental and behavioral determinants

two prostate cancer cell lines,

22RV1 (androgen-responsive) and DU145

identifies factors detrimental to skeletal health

(androgen-unresponsive). Each compound was tested in a dose dependent

Ling Oei^1,2, Joy Wu³, Edwin Oei⁴, Fernando Rivadeneira^2,5,

manner to determine its effects on ROS production, mitochondrial membrane

Andre Uitterlinden^2,5, John Ioannidis⁶, Michael Snyder¹ & Chirag Patel⁷

potential, mitochondrial biogenesis and mitophagy. In addition, we performed an

image based computational analysis of the mitochondrial network morphology

¹Department of Genetics, Stanford University School of Medicine, Stanford,

and dynamics. This strategy allows us to extract some quantitative parameters on

CA, USA;²Department of Internal Medicine, Erasmus MC, Rotterdam,

the mitochondrial network as fragmentation index, compactness, average volume,

The Netherlands;³Division of Endocrinology, Stanford University School

of Medicine, Stanford, CA, USA;⁴Department of Radiology and Nuclear

etc. When combined, morphological and functional parameters allow us to

Medicine, Erasmus MC, Rotterdam, The Netherlands;⁵Department of

discriminate subtle perturbations of the mitochondrial structure-function induced

Epidemiology, Erasmus MC, Rotterdam, The Netherlands;⁶Stanford

by EDCs in prostate cancer cells. We are confident that this multiparameter

University School of Medicine, Stanford Prevention Research Center, USA;

analysis strategy could represent a new perspective in identification and

⁷Department of Biomedical Informatics, Harvard Medical School, Boston,

characterization of EDCs based on their effects on cell metabolism (phenoscore)

MA, USA.

in order to estimate their potential risk on human health.

DOI: 10.1530/endoabs.49.EP745

Background

An increasing amount of biomedical data is becoming available, and methods are

needed to tackle these “big data”.

Methods

We performed a systematic evaluation of 138 environmental and behavioral

factors in relation to bone mineral density (BMD) in the National Health and

Nutrition Examination Survey (NHANES). Dual energy X-ray absorptiometry

(DXA) scans were available for total body, head, pelvis and lumbar spine for

27,259 participants from NHANES surveys 1999-2000 (A), 2001-2002 (B),

Endocrine Tumours and Neoplasia

2003-2004 (C) and 2005-2006 (D). A discovery Environment-Wide Association

Study (EWAS) was performed on cohorts B and D, and replication was sought in

EP746

cohorts A and C.

NENs, NETs, NECs: Accessing expert care

Results

Nicola Jervis & Catherine Bouvier

Higher serum levels of a-tocopherol (per S.D. bZK0.25% for lumbar spine) and

NET Patient Foundation, Leamington Spa, UK.

of g-tocopherol (bZK0.54% for total body), forms of vitamin E, were associated

with decreased BMD. In contrast, retinol serum levels were related to higher

BMD (per S.D. bZC0.21% for total body). Serum lead levels had a negative

Endocrine tumours are a heterogenous group of tumours, that are frequently

relationship to BMD of the lumbar spine (per S.D. bZK0.43%) and head (per S.D.

described as “complex”, “diverse”and, with few exceptions, “rare”. According to

bZK0.87%). Higher levels of physical activity were associated with higher

the Giwice Position Statement (as issued by the European Task Group for

BMD (total body: per MET C1.2%). Being a current or past smoker was

Endocrine Tumours): Endocrine Tumours are defined.as malignant tumours

associated with decreased BMD of the total body, pelvis and head.

arising from endocrine organs including thyroid, adrenal, parathyroid, as well as

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

neuroendocrine tumours in general. The research supported recommendation, to

Pituitary - Clinical

improve care, experience and outcomes, is for patient-centric endocrine cancer

EP748

care in specialist centres, by multidisciplinary teams (Box: MDT members), with

access to enrolment into clinical and translational research. Specialism being

Learning from adult growth hormone deficient patients’ advisory panel

determined by patient volume (geographical prevalence and incidence) and

Judith Hey-Hadavi¹, Cecilia Camacho-Hubner¹ & Nicky Kelepouris²

centre/MDT experience in disease subtype. The Taskforce points to the ENETs

¹Pfizer Inc, Endocrine Care, New York, NY, USA;²Pfizer Inc, US

Centre of Excellence Programme as an exemplar of specialist accreditation.

Endocrine Care, Collegeville, PA, USA.

Neuroendocrine neoplasms (NENs) can be found in endocrine glands and more

diffusely throughout the body, including respiratory, digestive and urinary tracts,

Introduction

breast, skin and nerve structures. They display a variety of functional and

Adult Growth Hormone Deficient (AGHD) patients have often a difficult path

infiltrative behaviours, and growth patterns. Nomenclature varies but in general is

from diagnosis to treatment. A patient advisory panel was conducted to better

based on site of origin, grading

(utilising morphology and proliferation),

understand the AGHD patient journey and how this could be supported. This

functionality then staging - though determining malignancy for some types is

format was chosen to allow for direct patient to patient interactions and

based predominantly on the presence

/ absence of metastases. The global

discussions and for physicians to learn.

incidence of NENs is rising. However despite expert recommendations and

Findings

European guidelines, NET Patient experience reports suggest ongoing care

A total of nine patient advisors (three childhood-onset; six adult-onset, age 33-67

deficits related, amongst other issues, difficulty in accessing clinically appropriate

years; 4M: 5W) were invited through different US endocrinology offices for a one

diagnostics, treatment and psychosocial care, including information and support.

day meeting. All had multiple pituitary hormone deficiencies (MPHD) and

1. http://www.endocrinecancer.eu/en/pages/statement

received daily GH. Six HCPs attended the meeting to learn from the interactions.

2. http://jgo.ascopubs.org/content/early/2016/06/03/JGO.2015.002980.full

An independent moderator facilitated the meeting and discussion. All patients

3. http://www.netpatientfoundation.org/2016/10/npf-patient-experience-survey/

reported that their journey was challenging regardless of age at diagnosis or

DOI: 10.1530/endoabs.49.EP746

MPHD. They felt that there is a lack of AGHD knowledge, and unawareness

among physicians and patients. Symptoms went unrecognized for years prior to-

diagnoses/treatment: and included: weight gain, arthralgia, social withdrawal/a-

pathy and extreme fatigue (labelled ‘laziness’). The majority was misdiagnosed:

mainly with depression and treated with antidepressants for variable period of

time. The patients felt their ‘life caving in’. Some were too fatigued to go to the

doctor. After diagnosis, it sometimes took months to get on GH replacement

therapy due to insurance issues and finding a physician who would treat.

Support was very limited without the opportunity to learn about AGHD or

connect with other patients. The advisors proposed several ideas to improve their

experience, i.e. education of HCPs, and patients, patient ambassador programs,

patient panels etc.

Female Reproduction

Conclusions

EP747

Hearing live from patients is an innovative way of learning outside the traditional

clinical setting. We identified a major need for more education, awareness, and

The accuracy of lifestyle management information on websites for the

resources for AGHD patients as well as physicians to improve their care.

management of PCOS

Thaw Dar Htet¹, Samatha Cassar², Millicent Burggraf¹, Jacqueline Boyle¹,

DOI: 10.1530/endoabs.49.EP748

Melanie Gibson-Helm¹, Nigel Stepto^1,2 & Lisa Moran^1,2

¹Monash Centre for Health Research Implementation, School of Public

Health and Preventive Medicine, Monash University, Melborune, Australia;

²Clinical Exercise Science Program, Institute of Sport Exercise and Active

Living, Victoria University, Melbourne, Australia.

Thyroid (non-cancer)

Background

Lifestyle approaches (diet, physical activity and/or behavioural) play an integral

EP749

part in Polycystic Ovary Syndrome (PCOS) management. The internet is widely

Iodine supplementation in children and pregnant women from rural

used as a resource for health information. However, the accuracy of lifestyle

areas of Belarus in 2015-2016

information on PCOS websites is unknown. This study aimed to assess the

Tatsiana Mokhort¹, Sergey Petrenko², Boris Leushev², Olga Bartoshevich³,

accuracy of lifestyle recommendations on PCOS websites.

Nataliya Kolomiets⁴, Elena Mokhort¹ & Ekaterina Fedorenko⁵

Methods

¹Belarusian State Medical University, Minsk, Belarus;²International

The internet search was conducted through three search engines across different

Sakharov Environmental Institute, Minsk, Belarus;³Liakhovichy Central

web browsers and countries. Keywords “PCOS”, “Polycystic Ovary Syndrome”

Regional Hospital, Brest Region, Belarus;⁴Belarusian Medical Academy of

and “Polycystic Ovarian Syndrome” were used to identify websites using a

Post-Graduate Education, Minsk, Belarus;⁵Republican Research and

previously defined internet search protocol. Websites providing lifestyle

Practical Center ‘Hygiene’, Minsk, Belarus.

information in less than

10 sentences were excluded. The accuracy of the

information was assessed through a checklist of 29 questions developed based on

National and International guidelines for diet, physical activity or weight

The efficiency of the Belarusian model for iodine deficiency elimination based on

management for the general population and PCOS with higher scores indicating

obligatory use of iodized salt in the industrial food production and bread baking

greater accuracy. Websites were scored by two independent reviewers.

has been often challenged in other countries. In support the facts are presented

Results

evidencing of insufficient iodine intake in groups of increased risk of iodine

Fifteen websites were eligible from 72 websites in total (20%). The total accuracy

deficiency in children and pregnant women from the rural areas of Belarus. The

score was 56G13 (potential range K29 to 87) comprising 23G6 for diet

goal of the recent study is to compare the dynamics of iodine supplementation for

(potential range K11 to 33), 15G5 for physical activity (potential range K9 to

the period of 2015-2016 in groups of increased risk in Brest region. The iodine

27) and 14G3 for weight management (potential range K8 to 24). A moderate

status of the body was determined by the iodine urine concentration. The study

proportion of websites provided general information on appropriate diet (40-

included

30 pregnant women examined in

2015 and 40 pregnant women

80%) or weight management strategies (47-60%) but only 10-40% of the

examined in 2016 aged 23-32 years, and 51 children examined in in 2015 and 44

websites provided information on aspects such as core food, discretionary foods,

children examined in 2016 aged 8-14 years. Statistical processing was performed

exercise quantity/intensity, specific energy deficits or behavioural strategies.

by nonparametric statistics.In

2015

in the rural area ioduria median was

Conclusion

165.7 mg/l in children and 107.5 mg/l in pregnant women. Iodized salt was used by

A limited number of Internet sites for PCOS contain information on lifestyle

86.2% of schoolchildren and only 66.7% of pregnant women. In 2016 ioduria

management. Of these, the majority provided information on general diet,

median in children of the same region increased to 233.0 mg/l, and in pregnant

physical activity and weight recommendations but less information on a healthy

women to 152.4 mg/l. Iodized salt in 2016 was used by 89.4% of schoolchildren

lifestyle implementation. These findings suggest that PCOS-related websites need

and 78.8% of pregnant women. Thus, the Belarusian model of iodine deficiency

elimination having been used since 2001 has demonstrated its long term efficiency

to be improved to provide more detailed and practical information for consumers

even in the risk groups of iodine deficiency development.

to apply to their PCOS management.

DOI: 10.1530/endoabs.49.EP749

DOI: 10.1530/endoabs.49.EP747

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Adrenal Cortex (to include Cushing’s)

Conclusion

In recipients who underwent Ptx before and after KT, PTx provided sustained

EP750

decrease in serum Ca and PTH levels without affecting graft function.

Comparison of 17-OH-Progesterone results by a radioimmunoassay

DOI: 10.1530/endoabs.49.EP751

and a chemiluminescent assay

Conceicao Godinho & Isaura Rodrigues

Centro Hospitalar Lisboa Central, Lisboa, Portugal.

Introduction

The major clinical importance of 17-OH-Progesterone is related to the diagnosis

EP752

and therapeutic monitoring of Congenital Adrenal Hyperplasia

(CAH).

Radioactive assays are widely used in clinical laboratories for measuring

The effect of corticosteroids on development of femoral head

17-OH-Progesterone. The appearance of a non-isotopic, chemiluminescent

osteonecrosis in patients after kidney transplantation

automatic assay, may be an interesting alternative if the performance of the

Enis Gursel¹, Omer Faruk Bilgen¹, Sadik Bilgen¹, Basak Erdemli Gursel²,

assay remains the same or higher.

Canan Ersoy³ & Alparslan Ersoy⁴

Obective

¹Department of Orthopedics, Uludag University Medical Faculty, Bursa,

Turkey;²Department of Radiology, Uludag University Medical Faculty,

To compare the 17-OH-Progesterone results by a radioimmunoassay (RIA) and a

chemiluminescent assay (CLIA) and to analyze the clinical impact taking into

Bursa, Turkey;³Endocrinology and Metabolism, Uludag University

account the % concordance.

Medical Faculty, Bursa, Turkey;⁴Department of Nephrology, Uludag

Material and methods

University Medical Faculty, Bursa, Turkey.

We studied 74 patients, aged 6 months to 83 years old, observed at CHLC

endocrinology appointments, in Lisbon. The serum samples were analyzed by

Corticosteroid-induced osteonecrosis is seen in 3-4% of patients undergoing

‘17a-Hydroxyprogesterone

(17-OHP)-RIA-CT’, DIASource

(wr:

0.04-

kidney transplantation (KT), especially at the head of the femur. The use of

12.5 ng/ml) and

‘Maglumi

17-OH Progesterone

(CLIA)’ Snibe

(wr:

0.1-

corticosteroids for any reason is responsible for approximately 41% of total hip

20 ng/ml). An excel tool was used for statistical treatment and the clinical

arthroplasty performed due to osteonecrosis. In this study, we investigated factors

concordance of patients was analyzed according to the reference values of both.

affecting osteonecrosis development after KT

For statistical comparison nine patients were excluded and to analyze the clinical

Methods

impact we divided patients into groups according to age and gender.

Among 205 recipients who underwent KT, 32 (15.6%) had symptomatic femoral

Results

head osteonecrosis (FHO group). Fifty patients who were similar in terms of age,

Pearson correlation coefficient rZ0.90 and the equation of linear regression

sex, and posttransplant follow - up period constituted the non-FHO group.

was:yZ0.46xC0.17. Group 1Z24 both gender (6m-11y); Group 2: 12 male

Results

(12 y-47y); Group 3: 38 female (13y-83y). For the group 1 and 2: % agreement

The gender, age and pre-transplant BMI of both groups were similar. In patients

was 62.5 and 66; It was impossible to classified 25% of group 1 because CLIA has

who developed FHO, the onset of symptom was median 6 months (range: 1-40).

no reference values for age. Group 3 had insufficient clinical data.

In patients who developed bilateral FHO, the mean duration of symptomatic

Conclusion

change in the other hip was 2.1 months (range: 0-6). The median value of the

There is a good correlation but in order to become an alternative to RIA it is

patients’ diagnosis time was 9 months (range: 1-40). The serum creatinine,

fundamental to have reference values between 3 months and 3 years for a further

calcium, phosphorus, ALP and PTH values at 1st, 6th and 12th after KT in both

reassessment since its main usefulness is the diagnosis and monitoring of CAH.

groups did not differ. There was no significant difference in hip and lumbar

DOI: 10.1530/endoabs.49.EP750

DEXA values between the groups in terms of osteonecrosis development. Three

patients (9.4%) in the FHO group and seven patients (14%) in the non-FHO group

had steroid treatment before KT. Cumulative steroid doses taken after KT the

FHO and non-FHO groups were 6366 mg (range: 3230-10947) and 5664 mg

(range: 3717-13887) at 12th month (PZ0.068). A total of 17 hips total hip

prosthesis were performed in 11 patients (six female, five male, mean age 45.2)

who developed FHO.

Calcium and Vitamin D Metabolism

Conclusion

We did not find any association between post-transplantation FBO development,

EP751

lumbar and femoral bone density measurements, and steroid doses.

The effect of parathyroidectomy on graft function in kidney transplant

DOI: 10.1530/endoabs.49.EP752

recipients with persistent hypercalcemia

Aysegul Oruc¹, Alparslan Ersoy¹, Ozen Oz Gul² & Canan Ersoy²

¹Department of Nephrology, Uludag University Medical Faculty, Bursa,

Turkey;²Endocrinology and Metabolism, Uludag University Medical

Faculty, Bursa, Turkey.

Although serum calcium (Ca), phosphorus and parathyroid hormone (PTH) levels

Cardiovascular Endocrinology and Lipid Metabolism

tend to normalize after successful kidney transplantation

(KT), persistent

EP753

hyperparathyroidism (PHPT) can have deleterious effects on graft function. We

aimed to evaluate the effect of parathyroidectomy (PTx) on graft function in

Resveratrol increases hepatic SHBG expression through human

recipients after KT.

constitutive androstane receptor: a new Contribution to the French

Methods

Paradox

This retrospective study conducted in 319 adult KT recipients. PHPT is defined as

Cristina Saez-Lopez¹, Laura Brianso-Llort¹, Javier Torres-Torrenteras²,

serum corrected Ca level O10.2 mg/dl (at least twice in a 6 month period) and

Rafael Simo¹, Geoffrey Hammond³ & David Selva¹

PTH O150 pg/ml at 6th month of KT.

¹Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca

Results

(VHIR), Barcelona, Spain;²Research Group on Neuromuscular and

The mean follow up time was 49.4G1.4 months. Mean serum PTH levels before

Mitochondrial Diseases, Vall Hebron Institut de Recerca (VHIR),

and at 12th month of KT and prevalence of hyperparathyroidism were 529G474

Barcelona, Spain;³Cellular & Physiological Sciences, University of British

and 212G236 pg/ml, and 83.9% and 51.9%, respectively. Fifteen recipients with

Columbia, Vancouver, British Columbia, Canada.

PHPT received cinacalcet for an average of 14.2G5.7 months. After cessation of

cinacalcet therapy, serum Ca levels increased within 6 month. Mean serum Ca

Sex hormone-binding globulin (SHBG) carries sex steroids in blood regulating

levels at 1st, 6th and 12th months of 12 recipients who underwent PTx before KT

their bioavailability. Red wine consumption increases plasma SHBG levels, and

were 9.3G1.2, 9.6G0.8 and 9.2G1.2 mg/dl, respectively. The duration between

we have discovered that resveratrol, a polyphenol enriched in red wine, acts

PTx and KT in 16 recipients who underwent PTx after KT was 17.1G8.9 months

specifically through the human constitutive androstane receptor

(CAR), a

(range 5-41 months). Two of 16 had operation at 5th and 1 at 7th month of KT

drug/xenobiotic detoxification gene regulator, to increase hepatic SHBG

because of severe hypercalcemia. Mean serum Ca levels of 16 recipients at 1st,

production. Chromatin immunoprecipitation and luciferase reporter gene assays

6th and 12th months of KT were 10.5G0.9, 10.8G0.9 and 10.6G0.9 mg/dl,

show that human CAR binds to a typical direct repeat 1 nuclear hormone

respectively. There was no significant difference in graft function between post-

receptor-binding element in the human SHBG proximal promoter. Resveratrol

transplant follow-ups in both groups.

also increased hepatic SHBG production in humanized SHBG/CAR transgenic

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

mice. Moreover, SHBG expression correlated significantly with CAR mRNA

CVD, Diabetes 18.2%, smokers 18.2%,HTA 36.4%, high lipoprotein(a) 45.5%,

levels in human liver biopsies. We conclude that the beneficial effects of red wine

early CVD 54.6%. 72.7% treated with statins (73.6% rosu and 9.1% atorvastatin)

on the metabolic syndrome and it associated co-morbidities, including

and ezetimibe. 44.4% had elevated transaminases with at least two statins and

cardiovascular disease and type

2 diabetes, may be mediated in part by

27.3% did not tolerate any statin. Patients performed regular physical exercise (at

resveratrol acting via CAR to increase plasma SHBG levels.

least 180 min per week) and diet (100% BMI!30).100% of the subjects had LDL

DOI: 10.1530/endoabs.49.EP753

levels at least 60 mg/dl above therapeutic target. The mean pre and postreatment

levels were: TC: 243.8G27.7 vs 148.5G47.4 mg/dl (P 0.01), LDL-C: 159G23.9

vs 69.9G39.3 (P 0.01), 100% in therapeutic objective, HDL-C 58.5G14.4 vs

56.6G16.1 (P 0.7), non-HDL-C 185.3G21.5 vs 91.8G32.7 (P 0.01), 100% on

therapeutic target, TG 130G46.2 vs 109G54.8 (P 0.3), Apo B 136G19.9 vs

64.3G11.04 (P 0.01), lipoprotein (a) 133.1G9.9 vs 112.5G5.1 (P 0.04). Only 2

patients had mild side effect: one patient with pseudogripal syndrome that

spontaneously disappeared in 2 days and another patient with injection site

EP754

reaction.

Therapeutic potentials of small molecular weight allosteric agonist of

Conclusion

relaxin receptor

PCSK9 inhibitors were well tolerated and significantly reduced levels of TC,

Alexander Agoulnik¹, Irina Agoulnik¹, Xin Hu², Elena Kaftanovskaya¹,

LDL-C, ApoB, non-HDL C and lipoprotein a, with 100% of patients achieving

Zaohua Huang¹, Courtney Myhr¹, Jingbo Xiao², Mariluz Soula¹, Brian Ho¹,

therapeutic goals after 3 months of treatment.

Elena Barnaeva², Noel Southall², Marc Ferrer² & Juan Marugan²

DOI: 10.1530/endoabs.49.EP755

¹Herbert Wertheim College of Medicine, Florida International University,

Miami, Florida, USA;²NIH Chemical Genomics Center, National Center

for Advancing Translational Sciences, National Institutes of Health,

Rockville, Maryland, USA.

The anti-fibrotic, vasodilatory, and angiogenic therapeutic properties of relaxin

EP756

peptide have been shown in several animal models of human diseases and in

clinical trials. Using high-throughput screening of small molecule library,

Non-lipidic effects of PCSK9 inhibitors in real life

structure-activity relationship (SAR) studies, ligand-receptor interaction model-

Inmaculada Gonzalez-Molero, Viyu Doulatram, Marta Domínguez,

ing, site-specific mutagenesis, and transgenic animal studies we discovered the

Francisco Sanchez Torralvo, Ignacio Ruiz García, Gabriel Olveira &

first series of small molecule agonists of relaxin GPCR, RXFP1. The lead

Francisco Tinahones

compound ML290 is a selective RXFP1 agonist with low cytotoxicity, preferred

Hospital Regional de Málaga, Malaga, Spain.

in vitro ADME and in vivo pharmacokinetic properties. ML290 displays efficacy

similar to the natural hormone in several functional assays in vitro. ML290

Objective

activates human, macaque, pig, and rabbit RXFP1, but not rodent receptors.

Analyse possible effects on physical examination, blood count, liver and kidney

Computational modeling of small molecule binding with human RXFP1 and

function, and steroidogenic hormones synthesis. Know the satisfaction of patients

related receptors in combination with site-directed receptor mutagenesis studies

with the first injectable treatment for hypercholesterolemia approved in our

indicated that the small molecules activated RXFP1 through an allosteric site and

country.

did not compete with relaxin binding to RXFP1. To test agonist activity in vivo we

Material and methods

produced mice with knock-in of human RXFP1 into mouse gene. The analysis of

Data were collected from patients with heterozygous familial hypercholester-

transgenic mice showed that the human receptor fully complement the deletion of

olemia treated with PCSK9 inhibitors. Clinical, physical and analytical data were

mouse gene. Intravenous injection of relaxin led to a rapid increase in heart rate in

collected at baseline, 1 month and 3 months. Satisfaction test (TQ21M-9) was

unconscious WT and humanized mice, but not in Rxfp1 deficient animals. The

performed 3 months after treatment.

ML290 injection increased heart rate in humanized but not in WT animals

Results

suggesting specific target engagement by small molecule agonist in vivo. Similar

Data were obtained from 13 patients, 45.5% male. Mean age: 49.5 years (26-74).

to relaxin IV injections of ML290 caused increased blood osmolality. Therapeutic

Mean pre and postreatment levels were: TC: 243.8G27.7 vs 148.5G47.4 mg/dl

potentials of the small molecular weight relaxin receptor agonist can be now

(P 0.01), LDL-C: 159G23.9 vs 69.9G39.3 (P 0.01), non-HDL-C 185.3G21.5 vs

tested in various preclinical cardiovascular and fibrotic models of human diseases.

91.8G32.7 (P 0.01), Apo B 136G19.9 vs 64.3G11.04 (P 0.01), lipoprotein (a)

DOI: 10.1530/endoabs.49.EP754

133.1G9.9 vs 112.5G5.1 (P 0.04). HbA1c 5.9G0.4 vs 5.70.3 (NS), creatinine

1.01G0.3 vs 0.92G0.2 (NS), GOT 34.7G34.2 vs 34.6G21.9 (NS), GPT 29.8G

18.7 vs 28.2G13.9 (NS). Weight: 70.9G11.2 vs 73.5G11 kg (NS). No effects

were detected in blood count, systolic, diastolic BP or heart rate. The mean levels

of hormones were: Testosterone 4.3G1.4 vs 4.04G1.8 ng/ml (NS), TSH 2.2G0.8

vs 2.14G0.8 mU/l (NS), T4l 16.3G1.1 vs 14.8G0.4 (NS) ACTH 24.2G17.7 vs

30.2G25.2 (NS), Cortisol 14G2.9 vs 16.6G2.1 (NS) Vitamin D3 41.5G49.1G

18.2 ng/ml (NS). Patients showed a high level of satisfaction with treatment, with

EP755

mean scores of 75.9% for effectiveness items, 80.2% convenience items and

85.2% overall satisfaction.

PCSK9 inhibitors effects on lipid profile in familial

Conclusion

hypercholesterolemia in a specific Lipid Unit: experience in first year

Despite the decrease in TC and LDL C levels, there were no significant changes in

commercialization

the levels of stereogenic hormones or vitamin D levels. Treatment with PCSK9

Inmaculada Gonzalez-Molero, Viyu Doulatram, Monserrat Gonzalo Marin,

inhibitors did not change hemogram, hydrocarbon metabolism, kidney, liver

Jose Abuin, Virginia Morillas, Gabriel Olveira & Francisco Tinahones

function, or physical examination parameters. Patients show a high satisfaction

Hospital Regional de Málaga, Malaga, Spain.

with this injectable treatment for hypercholesterolemia.

DOI: 10.1530/endoabs.49.EP756

Objective

Analyse the features of first patients treated with PCSK9 inhibitors in a specific

Familial dyslipidemia Unit and the effects on lipid profile in first months of

treatment.

Material and methods

Data from patients with heterozygous familial hypercholesterolemia treated with

EP757

PCSK9 inhibitors were reviewed. Clinical data, physical examination and

Renal function preservation with Manidipine vs Amlodipine in type 2

analytical data were collected at baseline, one month and 3 months.

diabetic hypertensive patients with persistent microalbuminuria

Results

Sara Quintana-Arroyo¹, Claudia Arnas-Leon¹, Ana Delia Santana-Suarez¹,

Data were obtained from 13 patients, 45.5% male. Mean age: 49.5 years (26-74).

Manuel Nivelo-Rivadeneira¹, Agnieszka Kuzior¹, Carmen Acosta-Calero¹,

Mean follow-upin our Unit:12 years. Diagnosis by DLC: 100% score higher

Margarita Saiz-Satjes³ & Francisco Javier Martinez-Martin²

than 6. 54.6% had been detected with family cascade screening, 45.5% cases with

¹Endocrinology Department, Hospital Universitario de Gran Canaria

mutation detected in LDL-R. Initial levels in our clinic: CT: 313.5 mg/dl, TG:

Dr Negrin, Las Palmas de Gran Canaria, Spain;²Outpatient Hypertension

102 mg/dl, LDL 228 mg/dl, HDL: 52 mg/dl, non-HDL C: 202 mg/dl, despite

Clinic, Hospital Universitario de Gran Canaria Dr Negrin, Las Palmas de

45.5% had already started treatment. 72.7% had a family history of premature

Gran Canaria, Spain;³CAP Rambla HUMT, Terrassa, Barcelona, Spain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Objectives

EP759

The AMANDHA randomized study (PROBE design) showed that the addition of

Anthropometric measurements, nutrition and exercise habits in kidney

Manidipine 20 mg vs Amlodipine 10 mg for 2 years in 91 hypertensive type 2

transplant recipients

diabetic patients with persistent microalbuminuria, uncontrolled with a renin-

Alparslan Ersoy¹, Nizameddin Koca¹, Tuba Gullu Koca¹ & Canan Ersoy²

angiotensin system inhibitor (given full-dose for at least the 6 previous months)

¹Uludag University Medical Faculty, Department of Nephrology, Bursa,

was more effective in reducing albuminuria in spite of similar blood pressure

Turkey;²Uludag University Medical Faculty, Endocrinology and

control. Patients with significant renal impairment (PlCr O1.4 mg/dl in women

Metabolism, Bursa, Turkey.

and O1.5 in men) had been excluded. However, no data were published on the

progression of renal dysfunction, with only PlCr values reported, which were not

significantly different. We undertook to establish if there were differences in

After a successful kidney transplant, the nutrition of patients is improved and they

glomerular filtration rate (GFR) progression.

gain weight. Increased appetite due to medication, age of transplant, gender, race,

Methods

pre-transplant obesity story and dialysis type increase the obesity frequency. We

Post-hoc analysis of AMANDHA. GFR was estimated by the MDRD-4 equation

aimed to evaluate the effect of gender on nutrition and exercise habits on

for each individual measurement. Point-to-point GFR were compared by unpaired

transplant recipients.

t-test and progression was compared by the Kruskal-Wallis test. (non-parametric

Methods

ANOVA). Values are given as mean (GS.E.M).

Stable patients were divided into two groups according to gender: 29 males and 33

Results

females. Their nutrition and exercise habits of recipients were questioned by a

Baseline GFR were

67.3

(G5.2) and

70.2

(G5.0) ml/min/1.73 m²

with

survey. The 3-day dietary regimen of all patients was studied using the BEBISe

Manidipine and Amlodipine, respectively; at 6 months they were 68.6 (G5.6)

programme.

and 69.5 (G5.3), and at two years 66.9 (G4.7) and 65.5 (G5.0). During follow-

Results

up, patients treated with Manidipine lost 0.4 (G3.9) ml/min per 1.73 m² of FGR

Charateristics of groups similar. BMI, blood pressure, hip circumference,

vs 4.7

(G5.2) with Amlodipine. Point-to-point GFR were not significantly

suprailiac and suprascapular fold thicknesses of the groups were not different.

different between the groups, but GFR loss after two years was lower with

The waist (90.3 vs 98.2 cm, PZ0.01), mid-arm (27.2 vs 28.9 cm, P!0.05),

Manidipine (PZ0.032).

triceps

(16.1

11.8 cm, P!0.01) and neck (36.6 vs 41.5 cm, P!0.001)

Conclusions

circumferences in female recipients were lower than those of males. The body fat

The previously published data of AMANDHA showed a markedly greater

percentage of females (30.9 vs 23.8, P!0.01) were lower. HDL levels in males

albuminuria reduction (about 40% more) with Manidipine vs Amlodipine, which

are significantly lower among lipid and apolipoprotein levels. The ratios of eating

was attributed to efferential arteriole dilatation. The present post-hoc analysis also

at home, using oils and exercising in both groups were similar. When recipients’

shows a better preservation of renal function with Manidipine. These results

daily diets were evaluated, intake of fat in males was higher than that of females

strengthens the case for combined treatment with Manidipine and a renin-

(63.3G4.1 vs 70.1G3.1 g, P!0.05). There was no difference in total energy

angiotensin system blocker in hypertensive type 2 diabetic patients with persistent

(1645G68 vs 1681G62 kcal), water

(1590G79 vs 1665G76 ml), protein

microalbuminuria.

(70.4G4 vs 75.8G3.5 g), carbonhydrate (197.7G9 vs 191.8G11.4 g), fiber

(25.7G2.4 vs 24.1G1.7 g) and polyunsaturated fatty acid (12.8G1 vs 13.4G1)

DOI: 10.1530/endoabs.49.EP757

intakes between females and males, respectively. Also vitamin intake of both

groups were comparable except carotene intake of females (5.3G0.4 vs 4G0.3,

P!0.05).

Conclusion

We observed no difference in nutrition and exercise habits between male and

female recipients. Although the percentage of body fat in males was lower, the

amount of fat consume in their diets was higher. The waist and neck

circumferences, which is important for the risk of cardiovascular disease, were

EP758

higher in males.

Effects of calcineurin inhibitors on abdominal obesity in kidney

DOI: 10.1530/endoabs.49.EP759

transplant recipients

Emel Isiktas Sayilar¹, Alparslan Ersoy¹ & Canan Ersoy²

¹Department of Nephrology, Uludag University Medical Faculty, Bursa,

Turkey;²Endocrinology and Metabolism, Uludag University Medical

Faculty, Bursa, Turkey.

Calcineurin inhibitors (CNI, cyclosporine A: CsA and tacrolimus: Tac) cause

posttransplant diabetes mellitus, hypercholesterolemia and hypertension. Post-

transplant weight gain can be related to the type of CNIs. Distribution of obesity is

one of the major predictors of cardiovascular diseases. Several indices assessed

EP760

upper body obesity such as waist circumference (WC) and waist to hip ratio

Hyperglycemia as a factor changing the level of the patient’s

(WHR) are more accurate than whole body obesity (body mass index: BMI). This

rehabilitation after ischemic stroke

study aimed to compare the effects of CNIs on obesity after kidney

Irina Dzherieva, Natalia Volkova, Natalia Maslova & Nikolay Krivonosov

transplantation.

Rostov State medical University, Rostov on Don, Russia.

Methods

The 133 consecutive transplant patients were randomized into 2 groups: CsA

(nZ62) and Tac (nZ71) for two years. In all patients, BMI, body fat percentage,

The aim of the study was to defined the level of rehabilitation after the stroke

WC, hip circumference (HC) and WHR were measured.

depending on the type of hyperglycemia.

Results

Materials and methods

The weight, BMI, body fat percentage, WC and HC were significantly increased

The retrospective analysis of 122 (54 female and 68 men) cases of ischemic stroke

up to month 24 in both groups. There was no significant difference in increases of

(IS) has been done. The diagnosis of IS was confirmed by computer tomography.

BMI, WC, WHR and body fat percentage between both groups. The ratio of

According to the level of hyperglycemia at the debut of IS the patients were

diabetics in CsA group was higher than Tac group (21% vs 1.4%, P!0.001). The

divided into three groups. Group 1 (60 patients) - with normoglycemia, group 2

ratios of de novo diabetics (4.8% vs 12.7%) and hypertensives (29% vs 26.8%)

(27 patients) - with stress hyperglycemia and group 3 (35 patients) with chronic

were similar in the CsA and Tac groups, respectively. Although the abdominal

hyperglycemia. At the beginning and the end of hospitalization the level of

obesity ratios in the CsA and Tac groups increased, the ratios were comparable in

neurological deficit was determined according to NHSS scale. The comparison of

the preoperative (17.7% vs 23.9%), after 12 (37.3% vs 39.3%) and 24 (40% vs

averages was carried out using the Kruskal-Wallis test (a posteriori pairwise

45.9%) months of transplant, respectively. There was no significant difference in

comparisons were made using the method of Niemen), program R Foundation for

glucose and lipid profile between CsA and Tac groups.

Statistical Computing, Vienna, Austria (Version 3.2).

Conclusion

Results

The type of calcineurin inhibitor used did not affect anthropometrical

The patients with normoglycemia and stress hyperglycemia have had the same

measurements throughout two years although both of them caused weight gain

level of rehabilitation (50% (CI: 45-75%) and 50% (CI: 32-73%) respectively).

after transplant.

The statistical significant difference has been found between groups 1 and 3. In

DOI: 10.1530/endoabs.49.EP758

patients with chronic hyperglycemia the average relative level of rehabilitation

was 33% (CI: 22-50%, PZ0.023). The level of rehabilitation of patients 60 years

old was 57% and between 60-75 years old and older this level was 50%.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

woman without special history who was diagnosed to have autoimmune hepatitis,

The negative influence of chronic hyperglycemia has been revealed. The stress

celiac disease, autoimmune pancreatitis and sclerosing cholangitis. The patient

hyperglycemia does not influence on the level of rehabilitation The age exerts on

was put on a gluten-free diet, corticosteroid therapy, azathioprine and

the regress of neurological deficit regardless of the hyperglycemia kinds.

ursodeoxycholic acid. Observation 3: A 37-year-old man, with a history of

DOI: 10.1530/endoabs.49.EP760

vitiligo and Hashimoto’s thyroiditis, presented asthenia and normocytic

normochromic anemia. Biermer’s disease and celiac disease have been

diagnosed. Observation 4: A 41-year-old woman with a history of Hashimoto

thyroiditis presented a dry syndrome and asthenia and liver cytolysis. The anti-

nuclear, anti-SSA and anti-SSB antibodies were positive and labial biopsy

showed a lymphocytic sialadenitis stage III of Chisholm confirming the

EP761

association autoimmune hepatitis and syndrome of Gougerot Sjogren. Obser-

An investigation into role of circulating concentrations of vitamin D and

vation 5: A 29-year-old female patient with a history of Type 1 diabetes, Basedow

calcium in the development of hypertension and related cardiovascular

and Addison diseases was diagnosed to have a celiac disease revealed by diarrhea

diseases

and abdominal pain. Observation 6: A 31-year-old woman follwed for Systemic

Saba Nazir¹, Nadia Afzal¹, Maleeha Akram¹, Zubaria Iqbal¹, Abida Raza²,

erythematosus lupus and Gougerot Sjogren syndrome presented a persistent

Mazhar Qayyum¹, Afzaal Ahmed Naseem¹, Syed Ali Raza Kazmi³,

anemia. Anti-transglutaminase antibodies were positive and duodenal biopsies

Faheem Tahir⁴, Kiran Afshan⁵, Sarwat Jahan⁵ & Syed Shakeel Raza Rizvi¹

showed subtotal villous atrophy confirming celiac disease.

¹Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University

Conclusion

Rawalpindi, Rawalpindi/Punjab, Pakistan;²Department of Biophotonics,

Patients with autoimmune diseases have a tendency to develop additional

National Institute of Laser and Optrionics (NILOP), Nilore/Islamabad,

autoimmune disorders indicating the need for continued surveillance for the

Pakistan;³Aga Khan Health Centre, Rawalpindi/Punjab, Pakistan;

development of new autoimmune disease in predisposed patients.

⁴Reproductive Physiology, Public Health Laboratories Division, National

DOI: 10.1530/endoabs.49.EP762

Institute of Health (NIH), Islamabad, Pakistan;⁵Department of Animal

Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Vitamin D plays a key role in the control of cardiovascular diseases (CVDs), acting

as negative regulator of renin-angiotensin-aldosterone-system (RAAS), whereas

EP763

calcium directly affects central blood pressure (BP) control center, nucleus tractus

Endocrine complications in a female patient with b-thalassemia major

solitarus. We investigated associations between plasma concentrations of vitamin D

following bone marrow transplantation

and calcium and BP in 100 hypertensive CVDs patients and 100 normotensive

Luminita Nicoleta Cima¹, Ioana Maria Lambrescu¹, Lavinia Stejereanu¹,

subjects of 21-60 years. Vitamin D concentrations were measured using ECLIA

Anca Colita^1,3 & Simona Fica^1,2

system, whereas calcium concentrations were determined using spectrophotometric

¹Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;

system. Data were analyzed using Student’s t-test, ANOVA and Pearson correlation

²Endocrine Department, Elias Hospital, Bucharest, Romania;³Hematology

r. Out of 10 RAAS inhibitors (RAASi) treated patients, nine were vitamin D

Department, Fundeni Hospital, Bucharest, Romania.

deficient and one was vitamin D insufficient. Of 29 non-RAASi treated patients, 28

were vitamin D deficient and one was vitamin D insufficient. Among 36 patients

treated with combination of RAASi and non-RAASi, 35 were vitamin D deficient

We report the case of a 14-year-old female patient with b-thalassemia major (b-

and one was vitamin D insufficient. Out of 25 untreated patients, 22 were vitamin D

TM) that presented numerous endocrine complications following bone marrow

deficient and three were vitamin D insufficient. Ninety one control subjects were

transplantion (BMT). The patient was admitted in our department for endocrine

vitamin D deficient, eight were vitamin D insufficient and one was vitamin D

evaluation 3 years after BMT. She was diagnosed with b-TM at 1 year of age and

sufficient. In patients treated with RAASi, calcium concentrations were at lower

received chronic blood transfusions and oral chelating therapy until 2012 when

limit of normal range in 7 and at upper limit in 3. In non-RAASi treated patients,

BMT was performed. The patient developed acute skin and intestine graft-versus-

calcium concentrations were at lower limit in 13 and at upper limit in 16. In both

host-disease remitted with glucocorticoids and suffered severe convulsions as a

RAASi and non-RAASi treated patients, calcium concentrations were at lower limit

result of cyclosporine administration with two subsequent vertebral fractures

in 27 and at upper limit in 9. In untreated patients, calcium concentrations were at

appearance (T5-T6). At first admission in our department she complained of

lower limit in 15 and at upper limit in 10. In control subjects, calcium concentrations

irregular menses. The physical exam revealed HZ148.4 cm (K2.33 S.D.), BMIZ

were at upper limit in 21, at lower limit in 77 and below lower limit in 2. There were

20.17 kg/m², Tanner P5B5. The laboratory tests were normal, except for low

weak correlations between vitamin D and calcium concentrations and mean BP and

normal estradiol

(34.4 pg/ml) with elevated FSH

(57.9 mIU/ml), low

systolic and diastolic BP in all patients.

25-OH-vitamin D and high titre of thyroid antibodies with normal thyroid

DOI: 10.1530/endoabs.49.EP761

hormones level. The thyroid ultrasonography showed a hypoechoic, hetero-

geneous thyroid with increased vascularity. DXA whole-body revealed low bone

mineral density (Z scoreZK2.2 S.D.) and the vertebral MRI showed reduced

vertebral height at T6-T8 and L3-L5. She started treatment with Duphaston and

vitamin D. At 1 year follow-up, she presented normal menses, both FSH and

estradiol normalized

(FSHZ5.11 mUI/ml, E₂Z76.37 pg/ml) and no further

Clinical Case Reports - Thyroid/Others

fractures occurred.

EP762

Conclusion

Endocrinopathies are a common late effect of both b-TM and BMT, resulting in

Multiple autoimmune syndrome: about six observations

thyroid dysfunction, impaired growth, ovarian insufficiency and decreased bone

Soumaya Mrabet¹, Aya Hammami², Elleuch Nour², Jaziri Hanen²,

mineral density. Because of the possible endocrine complications, lifelong

Ben Slama Aida², Braham Ahlem², Ajmi Salem², Mehdi Ksiaa²,

endocrine follow-up is necessary in these patients.

Jmaa Ali² & Ben Jazia Elhem¹

¹Farhat Hached University Hospital, Sousse, Tunisia;²Sahloul University

DOI: 10.1530/endoabs.49.EP763

Hospital, Sousse, Tunisia.

Introduction

Autoimmune disorders are known to be more frequent in women and often

EP764

associated each others, but it is rare to see multiple autoimmune diseases in a

single patient. Multiple autoimmune syndrome

(MAS) is defined as the

Association of Basedow disease with pernicious anemia: a case report

combination of at least three autoimmune diseases in the same patient. The

Mihai Radu Diaconescu & Smaranda Diaconescu

pathogenesis of MAS is not known. Genetic, infectious, immunologic and

‘Gr T Popa’ University of Medicine and Pharmacy, Iasi, Romania.

psychological factors have all been implicated in its development.

Observations

Introduction

We report six new observations of MAS.

Immunologic background often present different association of two or more

Results

autoimmune diseases. However the coexistence of Basedow disease (BD) - the

Observation

1: A

24-year-old female patient followed for Hashimoto’s

prototype of these disorders - with pernicious anemia (PA), sometimes as a

thyroiditis, Addison disease and celiac disease. The patient was explored for

component of pancytopenia, is rarely described. Between 50 patients operated on

cytolysis. The diagnosis of autoimmune hepatitis was retained and the patient was

immunologic hyperthyroidism in a 20 years period only one case related this

treated with oral corticosteroid and azathioprine. Observation 2: A 61-year-old

uncommon combination.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Case report

Conclusion

AB, a 46-year-old woman with a long standing BD treated from 1 year with

Our case confirms that, Thiazides can induce hyponatremia, especially in elderly

antithyroid drugs

(propylthiouracil) and b-blockers

(propranolol) recorded a

female patients. Chronic hyponatremia, must be seriously evaluated, to find out

notable clinical improvement but with stationary or even increase size of her

the cause and to be corrected if possible. Correction of hyponatremia can improve

diffuse goiter. In addition she charged in the last three months palled skin,

cognitive performance and life quality. We must be careful while treating an older

giddiness, tiredness, anorexia and coldness of the extremities. Laboratory workup

female patient with Thiazides.

showed TSHZ4.6 mU/l, fT₄Z38 pmol/l, fT₃Z9 pmol/l, TRABZ1.8Z1.8 UI/l.

DOI: 10.1530/endoabs.49.EP765

Current thyroid scan and US objectifies a diffuse

8!6 cm homogeneous,

hypervascularised gland with uniform uptake. Though full blood count indicate

pancytopenia with normochromic, normocytic anemia (HbZ9 g/dl, MCVZ

88 fL, MHCHZ34 q/l). Also total white count was 3400 m/l, platelet count was

48 000 m/l and reticulocyte count was

1%. Peripheral smears show oval

macrocytes, hypersegmented granulocytes and anisopoikilocitosis so a diagnosis

EP766

of megaloblastic anemia secondary to Vitamin B12 deficiency was established.

Raynaud phenomenon in a young PCOS patient

The standard treatment with intramuscular cyanocobalamin obtained substantial

Martina Eva Leczycka¹, Johannes Ohrman¹ & Hisham Maksoud²

resolution of woman’s symptomatology. However maintained thyroidomegaly

¹Medical University of Gdansk, Gdansk, Poland;²Nottingham Woodthorpe

prompted our patient to undergo surgery. An adjusted near total thyroidectomy

Hospital, Nottingham, UK.

(Dunhill technique) was practiced followed by a smooth postoperative course.

Histological examination of the operative piece (150 g) showed all stygma of

Polycystic ovarian syndrome presents in 4-8% of women worldwide, making it

thyrotoxicosis. Astoningshly endocrine equilibration was obtained together with

the most common reproductive age endocrinopathy. Rheumatological concomi-

positive hematological response occuring gradually within few months and

tant diseases are extremely rare in PCOS patients, especially Raynaud’s

maintaining further.

phenomenon. Condition that, lowers the quality of life in patients, suggesting

Discussions and conclusion

hormonal imbalances despite years of treatment. Studies show that oestrogen

1-3% of patients with immunogenic hyperthyroidism (BD) have associated

plays a role in the vasculature, it is exogenous administration increases the

hematological disorders as single-cell lineage abnormalities like pernicious

endothelium dependent dilation. Treatment of the phenomenon is symptomatic,

anemia and related troubles or pancytopenias. In all cases BD precedes the blood

wearing gloves, avoiding triggering factors, and lastly pharmacotherapy or

disease. Causes of these pathologic coincidences reside unlikely as pure

sympathetic blockade in severe cases to avoid digital ischemia. We are presenting

coincidence but rather from reciprocal influence, immune-mediate effects,

a rare case of dermato-rheumatological involvement in a PCOS patient. 24-year-

outcomes of antithyroid therapy or vitamin B12

deficiency. Appropriate

old woman, diagnosed with PCOS in 2010 was treated with multi drug therapy

surveillance of all cases of untreated or treated BD is mandatory, recommended

including: Metformin up to 1500 mg daily, oral contraceptive pill, spironolactone

for early detection of pernicious anemia as for other autoimmune disorder.

up to

150 mg daily, Topiramate

50 mg daily for migraine headaches and

DOI: 10.1530/endoabs.49.EP764

Liraglutide 0.6 mg with varying regimens throughout the years. In winter 2014

she presented with the first symptom of Raynaud’s phenomenon (RP). However

that has been ignored until 2016; - 1 year after the discontinuation of oral

contraception, the patient reported; pain upon dishwashing, hand washing, and

increased frequency of the phenomenon despite wearing double winter gloves.

She was then referred to a rheumatology department, underwent capilaroscopy

exam, which revealed dilated capillary nail beds. The following laboratory tests;

EP765

ANA-HEp2 was elevated - 1:640 (!1:80 norm) of a granular type. Antibody

Chronic hyponatremia caused by Thiazide diuretic: A case report

panel characteristic for connective tissue diseases was all negative except for -

Marjeta Kermaj¹, Dorina Ylli¹, Anisa Zeqja⁴, Violeta Hoxha¹,

DFS 70 being mildly elevated. The antibody is typical for an autoimmune rather

Thanas Fureraj¹, Renta Sanxhaku¹, Ermira Muco², Adela Shkurta³,

than rheumatological ethology. No other abnormalities were found in the blood

Enalda Demaj⁵ & Agron Ylli¹

morphology, rheumatoid factor nor erythrocyte sedimentation rate. Syndrome as

¹UHC Mother Teresa, Endocrinology Department, Tirana, Albania;²UHC

common as PCOS should be of a concern across different hospital departments,

Mother Teresa, Department of Infectious Diseases, Tirana, Albania;³Vila

the complexity of the pathomechanism and treatment regime should alert us for

Maria Hospital, Endocrinology Department, Tirana, Albania;⁴UHC Mother

further clinical consequences.

Teresa, Department of Psychology, Oncologic Hospital, Tirana, Albania;

DOI: 10.1530/endoabs.49.EP766

⁵Kucova Hospital, Endocrinology Department, Tirana, Albania.

Introduction

Hyponatremia (defined as a serum sodium level !135 mmol/l), is seen in in 15-

30% in hospital setting, especially in intensive care units. Certain drugs

EP767

(e.g.Thiazides diuretics) used in everyday clinical practice, may induce

hyponatremia, more frequently in elder women.

Polyglandular autoimmune syndrome type III-case report

Case report

Jelena Malinovic Pancic^1,2 & Bojana Caric^1,2

A 76-year-old woman presented at emergency unit with complaints: physical

¹University Clinical Center of Republic of Srpska, Banja Luka, Bosnia and

weakness, nausea, vomiting, extreme fatigue and abdominal pain. She was under

Herzegovina;²Medical Faculty Banja Luka, Banja Luka, Bosnia and

arterial hypertension treatment with Valsartan/Hydroclortiazide

160/25 mg

Herzegovina.

2 pills/day for 4 years. She was presented many times at emergency unit, during

last 4 years with the same complaints, but she was never evaluated about the cause

The term polyglandular autoimmune syndrome (PAS) is used when there is a

of hyponatremia. Her life quality and cognitive performance were getting worse

dysfunction of two or more endocrine glands associated with circulating

during this time. Objective examination: Overall condition poor, pale face, stupor,

antibodies directed at organspecific included glands. Neufeld and Blizzard

incoherent answers to different questions, TA 170/80 mmHg, Fc 80/min, SO₂

classified PAS into two categories: type I and type II with the newly added

97%, lungs normal, abdomen soft, liver, spleen, kidneys were normal, legs free of

category, type III, which does not include the adrenal cortex. PAS III includes

edema. Laboratory examinations revealed: Severe hyponatremia, hypokalemia,

several autoimmune diseases

(autoimmune thyroiditis, immune-mediated

hypochloremia and metabolic alcalosis (NaC102 mmol/l; KC2.8 mmol/l; Cl-

diabetes mellitus, pernicious anemia, vitiligo, alopecia areata, and many others)

71 mmol/l,PhZ7.49), others biochemical blood test and hemograme were

and is divided into four sub-categories. We report a 44-year-old patient who was

normal. Urine analysis: density 1007,pH 7. Imagery examination: Head CT:

hospitalized in August 2016 at our department with suspected polyglandular

showed no acute lesions, hypodens areas, cortical subatrofi. Chest CT: normal.

autoimmune syndrome. In 2013 he was repeatedly evaluated at gastroenterology

EKG normal. She was treated for 2 days in Intensive unit care with 3% NaCl sol,

department where were established the diagnoses of primary hemochromatosis

KCl 7.5%, MgSO₄ 25%iv, correcting NaC, 10 mmol/l daily. After initial

(homozygous mutation in the gene p C282Y HFE), Crohn’s disease and celiac

improvement, she was transferred to Endocrinology Unit for further treatment.

disease, as well as candidiasis in May

2016. In our department, the

After normalization of blood electrolytes, we looked for the cause of

endocrinological testing establish the existence of autoimmune thyroiditis (anti

hyponatremia. In literature treatment with Hydrochlortiazide was reported as

-TG 207.1 IU/ml; antiTPO 141.0 IU/ml) without disorders of thyroid function and

the cause of hyponatremia and hypokalemia especially in elder women. She was

the presence of insulin resistance.

informed about the drug adverse effect and the importance of never using it again.

DOI: 10.1530/endoabs.49.EP767

She dehospitalized with overall improved conditions. During follow up, blood

electrolytes resulted normal and her life quality and cognitive performance were

improved.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP768

existence, because some may falsify the results

(underestimating or over-

estimating HbA1c, such as J-Camaguey). The use of alternative glycemic markers

Resistance of SIAD to tolvaptan despite initial control in progressive

may be helpful in these cases.

small cell lung cancer

Aoife Garrahy & Chris Thompson

DOI: 10.1530/endoabs.49.EP769

Academic Department of Endocrinology, Beaumont Hospital/ RCSI

Medical School, Dublin, Ireland.

A 58-year-old male was admitted through the emergency department with

symptomatic severe euvolemic hyponatremia. Biochemistry was consistent with

EP770

SIAD (plasma sodium (pNa) 107 mmol/l, plasma osmolality 230 mOsm/kg, urine

Myasthenia gravis associated with Graves’ disease and adrenal

sodium 36 mmol/l, urine osmolality (UOsm) 638 mOsm/kg, 0900 h plasma cortisol

insufficiency

484 nmol/l and thyroid function tests normal). Chest X-ray was normal but CT thorax

Mouna Elleuch, Hamza Elfekih, Faten Hadjkacem, Mahdi Kalthoum,

confirmed a lung mass suspicious for malignancy. As the patient had symptoms of

Mouna Ammar, Nabila Rekik, Wajdi Safi, Mouna Mnif & Mohamed Abid

cerebral irritation, including drowsiness and confusion, he was treated with

Hedi-Chaker University Hospital, Sfax, Tunisia.

hypertonic (3%) saline infusion; pNa rose by 13 mmmol/l over the 48 h and

symptoms resolved. Water deprivation caused no further rise in pNa so the patient

Introduction

underwent tolvaptan challenge; pNa rose from 121 to 125 mmol/l over 12 h,

Multiple autoimmune syndrome (MAS) is a rare condition, first described by

associated with a rise in plasma vasopressin (pAVP) from 4.4-9.3 pmol/l. Tolvaptan

Humbert and Dupond in 1988 and characterised by three or more autoimmune

7.5 mg daily was commenced on day 5 and pNa rose gradually to 130 mmol/l with an

disorders in the same individual.

eventual tolvaptan dose of 15 mg daily. Over 6 weeks, the patient developed

Case description

persistent hyponatremia despite escalating doses of tolvaptan to 60 mg daily. UOsm

Here we present a case of 14-year-old female patient diagnosed with ocular

while on tolvaptan was O800 mOsm/kg and AVP levels between 8 and 16 pmol/l

myasthenia gravis. The diagnosis of Graves’ disease was suspected on the basis

indicating unopposed action of AVP. Systemic chemotherapy led to temporary

of hyperthyroidism symptoms and confirmed by undetectable TSH level

improvement in plasma sodium and tolvaptan dose was reduced to 15 mg over the

(!0.01 mUI/l) with high FT₄ level (27.8 pmol/l). The adrenal insufficiency

subsequent three months. Six months after initial presentation, pNa fell again and

was suspected also clinically (extreme fatigue, weight loss, hyperpigmentation

tolvaptan dose was increased to 60 mg; noncompliance was excluded by supervised

and low blood pressure) and accepted with a low cortisol level (37.4 ng/ml). The

tolvaptan challenge, during which pAVP rose to 178 pmol/l, and UOsm remained

patient has improved after taking an anticholinesterase agent and corticosteroid

O909 mOsm/kg, suggesting renal resistance to tolvaptan. Imaging confirmed

replacement therapy. For the hyperthyroidism, a radical treatment is

progressive liver and bony metastases and the patient died 10 months after

recommended and the Beta-blockers should be avoided.

presentation, due to metastatic malignancy. This is the first report of escape of SIAD

Conclusion

from tolvaptan therapy, despite increasing doses. With progression of malignancy,

The MAS-3 in our case is characterized by the association of myasthenia gravis,

and rising pAVP conentrations tolvaptan may have been insufficient to compete with

Graves’ disease and adrenal insufficiency in which every condition has a different

tumour associated AVP for renal receptors.

treatment and prognosis in addition to a multidisciplinary care.

DOI: 10.1530/endoabs.49.EP768

DOI: 10.1530/endoabs.49.EP770

EP769

EP771

Overestimation of HbA1c by an unusual hemoglobin variant

Incidental asplenia in a patient with presumed type 2 autoimmune

Fernando García Pérez¹, Sandra Isabel Villanueva-Herraiz¹, José Ignacio

polyglandular syndrome (APS-2): misclassification or overlap?

Fernández Pen˜a1, Inés Camacho Benítez1, Juan Manuel García de Quirós1,

Thomas Georgiou, Fotini Adamidou, Gesthimani Mintziori & Marina Kita

Guillermo Martínez de Pinillos Gordillo¹, Antonio Moro Ortiz¹, Mariana

Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece.

Tomé Fernández-Ladreda² & María Victoria Cózar León¹

¹Hospital Universitario de Valme, Sevilla, Spain;²Hospital Punta de

Europa, Gibraltar, Spain.

Introduction

Asplenia has been reported in 10% of patients with type 1 APS (APS-1), but has

never been reported in APS-2. We describe a patient with presumed APS-2 and

Glycosylated haemoglobin (HbA1c) is considered the Gold Standard parameter

aplenia.

for evaluating long-term glycemic control in individuals with Diabetes Mellitus

Case report

(DM). The presence of hemoglobin variants or others conditions that modify its

A 69-year-old woman was diagnosed with B12 deficiency with severe anemia at

glycosylation, can affect the veracity of its measurement. The detection of these

age 21 and insulin dependent diabetes mellitus at age 33, following routine

hemoglobinopathies and his knowledge by the clinicians is very important for the

testing. At 59, she was hospitalized with salt wasting and a diagnosis of Addison’s

correct diagnosis and follow-up. We present the case of a patient who presented a

disease was made, which was subsequently confirmed by an inadequate response

hemoglobinopathy that interferes with the determination of HbA1c by HPLC, one

to tetracosactide stimulation. The diagnosis of subclinical Hashimoto’s thyroiditis

of the methods most used in laboratories. The case is about a man of 17 years old

was concurrently made. The patient had chronic onychomychosis of one

referred for evaluation by Endocrinology because in the context of a study of

fingernail and multiple toenails, but never of the mucous membranes and has

syncopal episodes and possible hypoglycaemia presents HbA1c of 6.5% with

never reported tetany. The diagnosis of APS-2 was made, based on the presence

repeated blood fasting glucose between 70 and 75 mg/dl. A new HbA1c with a

of the complete tri-glandular syndrome. The patient was under active surveillance

result of 7.0% and other exams were requested, which were normal: oral glucose

for other autoimmune manifestations, but none has so far been detected. Her past

tolerance test, negative autoantibodies

(GAD, IA-2

and insulin), plasma

history is negative for serious illnesses or infections and has never had abdominal

C-peptide and insulinemia. Blood count parameters were also normal. He had

surgery. Of note, she had never received a pneumococcal vaccine. Her family

no family history of DM to suspect Monogenic Diabetes. Levels of fructosamine

history is negative for autoimmune disorders. An abdominal CT scan was

(alternative marker for assessing glycemic control of the last 2-3 weeks, based on

requested for complaints of non-specific abdominal discomfort and an incidental

glycoproteins measurement) were requested, resulting in

240 mmol/l, which

observation regarding the absence of an orthotopic spleen was made. An

correlated with a calculated HbA1c of 5.6%. In addition to the incongruity

abdominal ultrasound found evidence of a hypoplastic splenic vessel. Functional

between the HbA1c values and the rest of the study, an abnormal peak in the

imaging of the spleen using 99mTC-colloid failed to reveal a functional spleen.

HbA1c chromatogram (HPLC assay) was observed. HbA1c was measured again

Relevant laboratory investigations including peripheral blood smear revealed

by a different method (boronate affinity chromatography) resulting in a very

Howell-Jolly bodies. Parathormone and electrolytes were normal. Quantitative

different result (HbA1c 5.3%). Due to the suspicion of hemoglobinopathy that

measurements of major immunoglobulin classes and T lymphocyte sub-

overestimates HbA1c, it was sent to the reference laboratory for molecular

populations were normal. HLA II haplotypes DQB1*05 and DQA1*01 were

characterization. Finally, the patient presented hemoglobin J-Camaguey

indentified. AIRE sequencing is pending.

heterozygous (ArgOGly; HBA1: c.424COG). The mother also presented the

Conclusion

same hemoglobinopathy in heterozygous.

Asplenia in the context of well-defined APS-2 and in the absence of clinical

Conclusions

immunodeficiency, is a novel finding that challenges our current understanding of

Many patients may present simultaneously a hemoglobinopathy and DM. Some

APS and needs to be further investigated.

hemoglobinopathies, without clinical repercussion are detected incidentally

during the measurement of HbA1c. It is important for clinicians to be aware of its

DOI: 10.1530/endoabs.49.EP771

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP772

thyroglobulin antibody (TgAb), negative peroxidase (TPOAb) and TSH-receptor

antibodies

(TRAb). He was treated with methimazole for 3.5 months. He

Immune checkpoint inhibitors related thyroiditis - a report of two cases

maintains normal thyroid function since antithyroid drug withdrawal. (iv) Male,

Sara Donato, Pedro Antunes, Joana Sim

˜es-Pereira & Hélder Sim

˜es

64-year-old, without previous thyroid disease, treated with nivolumab for

Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon,

metastatic lung adenocarcinoma. After 5 cycles, he developed thyrotoxicosis

Portugal.

with TSH 0.003 mUI/ml and normal FT₄ and FT₃. He had spontaneous remission

of thyrotoxicosis within 2 months and then developed hypothyroidism with TSH

Introduction

7.78 mUI/ml, FT₄ 0.48 ng/dl, FT₃ 2.19 pg/ml and positive TPOAb and TgAb.

Immune checkpoint inhibitors

(ICPIs) are recent approved drugs used in

Levothyroxine was initiated, compatible with the possible diagnosis of

malignant melanoma, non-small-cell lung cancer and renal cell cancer. They

nivolumab-associated thyroiditis.

act by activating host T cell against malignant antigens. Immune checkpoint

Conclusion

blockade can lead to breaking of immune self-tolerance, thereby inducing

Health providers must be aware of endocrine disorders that may be associated

autoimmune/autoinflammatory side effects, such as endocrinopathies. It may

with immunomodulatory therapies for a timely diagnosis and correct treatment.

affect thyroid, adrenal and pituitary. We present two ICPIs induced thyroiditis

DOI: 10.1530/endoabs.49.EP773

cases.

Case 1

Sixty-eight-year-old female diagnosed with a conjunctival malignant melanoma

at the age of 64. She was first surgery treated and then submitted to radiotherapy.

Due to bone, lung and hepatic metastasis she started Ipilimumab 3 mg/kg on

21-day cycle. Eleven days after the third Ipilimumab administration she was

EP774

asymptomatic but was found to have thyrotoxicosis (TSH 0.04 mUI/ml; FT₄

Meigs’ syndrome in a 63 year-old woman - case report

1.31 ng/dl). Thyroid peroxidase and thyroglobulin antibodies were elevated and

Alina Mihaela Pascu, Mircea Daniel Hogea, Marius Alexandru Moga,

thyroid stimulating immunoglobulin was low. Four months after suspension of

Lorena Dima, Petru Iulian Ifteni & Claudia Gavris

Ipilimumab a spontaneous recovery of the thyroid axis was seen.

Faculty of Medicine, Transilvania University of Brasov, Brasov, Romania.

Case 2

Sixty-two-year-old female diagnosed with a foot malignant melanoma one year

Introduction

before. She was first surgically treated. Due to lung, breast and lymph node

Meigs’ syndrome is defined as the presence of a benign ovarian tumour (fibroma),

metastases she started Nivolumab 3 mg/kg on 15-day cycle. Before starting this

in association with ascites and hydrothorax. The characteristic feature of this

drug she had a diffuse thyroid uptake on PET-scan with normal thyroid function.

condition is the resolution of the effusions once the tumour is surgically removed.

Twelve days after the first administration of Nivolumab she described a painless

Case report

increase of anterior cervical volume, fatigue and had thyrotoxicosis on the blood

A 63 year-old female patient was admitted to the Surgery Clinic with metroragia,

test (TSH 0.02 mUI/ml; FT₄ 2.50 ng/dl). One month after she was found to have

abdominal distention, and a recent history of minor breath shortness. Pulmonary

asymptomatic hypothyroidism

(TSH 9.96 mUI/ml; FT₄

0.49 ng/dl). Thyroid

clinical examination showed all the signs of right pleural effusion, which was also

ultrasound showed a thyroiditis pattern. She started levothyroxine therapy and

confirmed by the chest X-ray. The abdominal examination revealed a round

one month after stopping Nivolumab she was still on hypothyroidism.

irregular mass arising from the right pelvic cavity. Abdominal ultrasound showed

Conclusions

a large pelvic mass (23 cm in diameter) more on the right pelvic cavity, a

ICI may induce autoimmune thyroiditis or may worsen a pre-existing one. These

polyfibromatous uterus, and a small quantity of ascites. A complete blood count

patients should be monitored for signs and symptoms of thyroid dysfunction,

was carried out, with normal results. Surgical intervention was decided and the

since it can cause significant morbidity if not promptly recognized and treated.

laparotomy confirmed a large pelvic mass which was part of the left ovary,

DOI: 10.1530/endoabs.49.EP772

dislodged in the right side of the peritoneal cavity. Also, 100 ml of ascitic fluid

and a polyfibromatous uterus were found. The ovarian mass was removed and

also a hysterectomy with bilateral adnexectomy was performed. The macroscopic

appearance: giant polynodular tumoral mass (23 cm in diameter), with compact

structure, microcysts, and haemorrhagic areas. No residual ovarian tissue was

EP773

observed in the subcapsular portion of the tumour. Microscopically, a compact

tissue, consisting of pleomorphic fusiform cells, and discrete mitotic activity (less

Nivolumab-associated pituitary, adrenal and thyroid autoimmune

than 3 divisions/10 fields) was described. The cells were arranged in fascicles,

disorders

with hyaline and myxomatous areas. Dilated vessels with thrombotic material

Rita Bettencourt-Silva^1,2, Joana Oliveira^1,2, César Esteves^1,2,

were noted. The absence of malignancy of the tumour and of the ascitic and

Venceslau Hespanhol^2,3, Gabriela Fernandes³, Cláudia Caeiro⁴,

pleural effusions was confirmed by cytomorphologic study. In conclusion, the

Joana Queirós¹ & Davide Carvalho^1,2

histopathological examination demonstrated an ovarian tumour with a fibroma

¹Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-

aspect. Postoperative evolution was favorable and the patient was discharged after

talar São Joa˜o, E.P.E., Porto, Portugal;2Faculty of Medicine, University of

12 days. The controll chest X-ray revealed the resolution of the hydrothorax.

Porto, Porto, Portugal;³Department of Pulmonology, Centro Hospitalar São

Conclusion

Joa˜o, E.P.E., Porto, Portugal;4Department of Medical Oncology, Centro

Even though Meigs’ syndrome mimics an aggressive malignant ovarian tumour,

Hospitalar São Joa˜o, E.P.E., Porto, Portugal.

in the presence of pleural and peritoneal effusions, after surgical removal of the

tumour the patient has a good prognosis and the life expectancy is similar to

Background

normal healthy population, even if recurrence was also reported.

Nivolumab is a monoclonal antibody specific for human PD-1 (programmed cell

DOI: 10.1530/endoabs.49.EP774

death protein-1), a checkpoint molecule highly expressed in several cancers.

Nivolumab is an immunotherapeutic strategy for human cancer, but it can

interfere with endocrine system.

Case reports

We report four cases regarding nivolumab-associated endocrinopathies: (i) Male,

55-year-old, with previous normal cortisol and adrenocorticotropic hormone

Developmental Endocrinology

(ACTH) levels, treated with nivolumab for metastatic lung epidermoid

EP775

carcinoma. After

14 cycles, he developed asthenia, anorexia, weight loss,

GH influences plasma fasting adropin concentration in patients with

hypotension and hyponatremia, resulting in hospital admission. Adrenal

turner syndrome

insufficiency was confirmed by morning cortisol !1.0 mg/dl; hydrocortisone

Beata Wikiera¹, Magdalena Krawczyk², Anna Noczynska¹ &

treatment was started with clinical improvement. (ii) Male, 78-year-old, with

Jacek Daroszewski³

previous normal cortisol and ACTH levels, treated with nivolumab for stage 3B

¹Department of Endocrinology for Children and Adolescents, Medical

lung epidermoid carcinoma. After 15 cycles, he developed adrenal insufficiency

University, Wroclaw, Poland;²Cardiology Department, 4th Military

with morning cortisol!3.0 mg/dl and ACTH!5.0 ng/l. He had recent weight

Hospital, Wroclaw, Poland;³Department of Endocrinology, Diabetes and

loss, but was hemodynamically stable, without electrolyte imbalance. He started

Isotope Therapy, Wroclaw, Poland.

hydrocortisone with clinical improvement.

(iii) Male,

70-year-old, without

previous thyroid disease, treated with nivolumab for metastatic clear cell renal

carcinoma. After 2 cycles, he developed thyrotoxicosis with thyroid-stimulating

Background

hormone (TSH) 0.01 mUI/ml (ref:0.35-4.94), free thyroxine (FT₄) 1.82 ng/dl

Increased adiposity and insulin resistance are conditions frequently observed

(ref:0.70-1.48), free triiodothyronine (FT₃) 3.68 pg/ml (ref:1.71-3.71), positive

nowadays. Many hormones are involved in the pathogenesis of the condition but

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

therapeutic options we can offer to the patients are still scant. Each newly

EP777

discovered peptide give us hope. Adropin (Ad) is a newly discovered metabolic

Erk- and Akt-mediated osteocalcin signaling in human pancreatic

hormone involved in energy homeostasis. This homeostasis is frequently

b-cells does not directly involve GPRC6A activation

disturbed in patient with Turner Syndrome (TS). Patient with Turner syndrome

Silvia Perego¹, Veronica Sansoni¹, Martina Faraldi¹, Giuseppe Banfi^1,2 &

are unique model for studies of an effect of the treatment with supraphysiological

Giovanni Lombardi¹

doses of growth hormone (GH).

¹IRCCS Istituto Ortopedico Galeazzi, Milano, Italy;²Vita-Salute San

Objective and hypotheses

Raffaele University, Milano, Italy.

We studied adropin dependance and response in a group of TS patients treated

with supraphysiological doses of growth hormone (rGH).

Method

Osteocalcin (OC) is the main non-collagenous protein of the bone and it has a

The study group consisted of 36 TS patients aged 3.2-16.07 years (mean 8.2

regulatory role in mineralization. Extra-skeletal roles have been recently

years) diagnosed by karyotyping. The rGH was applied in a dose 0.05 mg/kg per

hypothesized for OC (e.g., modulation of glucose-induced insulin secretion by

day Prior to and following the treatment anthropometrical data were recorded as

interacting with GPRC6A in b-cells). However, OC-mediated GPRC6A activation

well as biochemical parameters were measured: adropin, OGTT, insulin, lipids,

has been demonstrated only in rodents and heterologous systems. In this study we

IGF-1, and IGFBP-3.

aimed at evaluating the dose-dependent response to OC and the eventual activation

Results

of the GPCR-dependent pathways in a physiologic-like model of human pancreatic

The increase of IGF-1 concentration at the end of observation was significant

b-cells. 1.1B4 cell line, derived from electrofusion of PANC-1 cell line and

(from 119.4G62.46 to 413.37G204.38 ng/ml, meanGS.D., PZ0.000). The GH

primary human b-cells, were treated for 5 and 30 min with different concentrations

treatment influenced insulin resistance revealed by increased HOMA values

of OC (20 to 100 ng/ml) either alone or in combination with 10 mM NPS2143, a

(median 0.64G0.45 before and 0.92G0.97 after, PZ0.02). rGH treatment cause

non-competitive antagonist of GPRC6A. mRNA and protein expression were

a significant rise in Ad level. The correlation between adropin and IGF-1 and IGF-

evaluated in order to assess the expression of GPRC6A and the activation profile of

1 SDS levels was not significant neither before nor on the treatment (rZ0.17 and

Erk and Akt pathways. As for human b-cells in vivo, which physiologically express

rZ0.004 respectively). Adropin concentration correlated with IGFBP3 level

nearly undetectable levels of GPRC6A, 1.1B4 cells displayed undetectable levels

before rGH treatment but not on rGH therapy. Ad also correlated with insulin

of GPRC6A protein. On the contrary, GPRC6A mRNA was slightly detectable. A

level before GH applying. Correlation with glucose levels at 30’ of OGTT was

slight increase (1.5 fold) of pErk/tErk was induced by OC 40 ng/ml at 30 min.

stable and even rise on GH treatment (PZ0.33 vs PZ0.48). Similar observation

Instead, pAkt was dose-dependently induced within 5 min with a 2-fold peak with

was noticed for lipids, but close correlations between Ad adropin and total

OC 80 ng/ml; at 30 min a residual activation was evident for OC 20 and 40 ng/ml.

cholesterol, LDL cholesterol, triglycerides (TG) before GH applying changed on

NPS2143 did not affect the activation profile of Erk and Akt if not for a slight peak

rGH therapy. The only correlation noticed in GH treated patients was between Ad

activation of both pathways with OC 60 ng/ml, instead of 40 ng/ml for Erk and

adropin and TG (PZ0.34).

80 ng/ml for Akt. In summary: i) GPRC6A is not expressed (or it is expressed at

Conclusion

very low levels) by human pancreatic b-cells; ii) the common OC signaling

Result of the study showed an increase in adropin level following rGH application

pathways, identified in heterologous expression systems, are only slightly induced

is not mediated by IGF-1. rGH treatment changes adropin influence on lipid

in human pancreatic b-cells; iii) the inhibition of GPRC6A do not affect the

metabolism, but ameliorates insulin action.

activation profile of Erk and Akt and, hence, GPRC6A may not be involved in

DOI: 10.1530/endoabs.49.EP775

physiological OC signaling in human b-cells.

DOI: 10.1530/endoabs.49.EP777

Diabetes (to include Epidemiology, Pathophysiology)

EP776

Diabetes Complications

Diagnosis of cystic fibrosis related diabetes

EP778

Ángel Rebollo-Román¹, Paloma Moreno-Moreno¹, Ana Barrera-Martín¹,

Aura-Dulcinea Herrera-Martínez¹, José-Manuel Vaquero-Barrios² &

The comparison of cardiovascular events in kidney transplant

Alfonso Calan˜ as-Continente1

recipients with and without type 2 diabetes mellitus

¹Endocrinology Service, Hospital Universitario Reina Sofía, Córdoba,

Alparslan Ersoy¹ & Canan Ersoy²

Spain;²Pneumology Service, Hospital Universitario Reina Sofía, Córdoba,

¹Department of Nephrology, Uludag University Medical Faculty, Bursa,

Spain.

Turkey;²Uludag University Medical Faculty, Endocrinology and Metab-

olism, Bursa, Turkey.

Aim

To describe the prevalence of abnormal glucose tolerance and diabetes in patients

Diabetes melliuts (DM) presents particular challenges after kidney transplant (KT).

with cystic fibrosis (CF) depending on the diagnostic criteria.

These challenges contribute to cardiovascular disesases among diabetic recipients.

Methods

We assessed frequency of posttransplant cardiovascular events in diabetic patients.

Observational, cross-sectional, clinical research on patients with CF evaluated at

Methods

Hospital Universitario Reina Sofía (Córdoba).

This retrospective study conducted in 399 kidney recipients at our center. The

Results

patients were divided into two groups: DM (n:59, 52.5% females) and non-DM

Twenty-eight patients were selected for the study. Age: 31.85G8.78 years, with a

(n:340, 46.5% females).

CF evolution time of 21.77G9.37 years. 64% women. 55.6% of the subjects

Results

presented with the deletion of phenylalanine in position 508 (DF508), known to

The median KT duration was 4 years. The median age and BMI of DM group were

be a severe one. Most patients (85.2%) suffered from pancreatic insufficiency. We

higher than those of non-DM group (51 vs 42 years and 28.6 vs 25.8 kg/m²,

compared the three ADA classical diabetes diagnostic criteria. With the fasting

respectively, P!0.001). The mean creatinine levels of both groups were similar.

plasma glucose 3.6% of patients were diagnosed with impaired glucose tolerance

Hypertension (76.3 vs 62.4%, PZ0.04), coronary artery disease (15.3 vs 4.1%,

(IGT) and 3.6% with cystic fibrosis-related diabetes (CFRD). Using the glycated

PZ0.001), obesity (39.7 vs 20.9%, PZ0.007) and dyslipidemia (32.3 vs 15.4%,

haemoglobin (HbA1c) 28.6% of patients had (IGT) and 3.6% CFRD. After the

PZ0.002) co-morbidities in DM were more frequent than those of non-DM groups.

oral 75g-glucose test (OGTT) with intermediate blood glucose measurements,

There was no significant difference between the ratios of myocardial infarction (3.4

25.1% were diagnosed with IGT and 7.1% with CFRD. We found different

vs 2.6%), cardiac arrhythmia (3.4 vs 9.4%), congestive heart failure (3.4 vs 1.2%),

prevalence of abnormal glucose tolerance depending on the diagnostic criteria

stroke (1.7 vs 0.6%), transient ischemic attack (1.7 vs 4.1%) and peripheral vascular

used. OGTT with intermediate blood glucose measurements is the most sensitive

disease (3.4 vs 0.6%) in DM and non-DM groups. The ratio of patients underwent

criteria for IGT and CFRD compared to fasting glucose (PZ0.002) and HbA1c

angioplasty was higher than that of non-DM group (23.7 vs 12.1%, PZ0.016)

(PZ0.289).

while the ratios of patients underwent coronary stenting (1.7 vs 1.8%) and coronary

Conclusions

by-pass operation (3.4 vs 1.2%) were similar. The graft loss and mortality rates in

- In our series, there are statistically significant differences among the criteria used

DM and non-DM groups did not differ (5.1 vs 5.6% and 5.1 vs 1.8%, respectively).

to diagnose the abnormal glucose tolerance and CFRD

Conclusion

- OGTT was the most sensitive test to establish the abnormal glucose tolerance

We observed that there was no difference in new cardiovascular events, graft loss

and CFRD in our series, in agreement with published evidence.

and mortality between recipients with or without DM after KT.

DOI: 10.1530/endoabs.49.EP776

DOI: 10.1530/endoabs.49.EP778

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Endocrine Disruptors

Conclusion

In the presence of autoimmune endocrinopathies the search of associated

EP779

autoimmune diseases in particular celiac disease is necessary in order to avoid any

The adrenal gland after diosgenin application in a rat model of the

therapeutic delay which can alter the prognosis of the patient.

menopause

DOI: 10.1530/endoabs.49.EP780

Vladimir Ajdzanovic¹, Ivana Jaric¹, Jasmina Zivanovic¹, Marko Miler¹,

Natasa Ristic¹, Dragana Miljic², Florina Percinic-Popovska³ &

Verica Milosevic¹

¹Institute for Biological Research “Sinisa Stankovic”, University of

Belgrade, Belgrade, Serbia;²Department of Neuroendocrinology, Clinic for

Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia,

EP781

Belgrade, Serbia;³Faculty of Veterinary Medicine, Ss. Cyril and Methodius

Characterization of murine Leydig cell lines as tools to study androgen

University in Skopje, Skopje, Macedonia.

synthesis disruption by xenobiotics

Roger Engeli, Cornelia Furstenberger, Denise Kratschmar & Alex Odermatt

University of Basel, Basel, Switzerland.

Diosgenin, a steroidal sapogenin of natural origin, demonstrated some

therapeutic effects when it comes to the treatment of cardiovascular issues,

malignancies and the menopausal symptoms. In this study, we have

Mammalian Leydig cells produce the majority of the systemic levels of the

investigated histological changes and corticosterone secretion of the adrenal

primary male sex hormone testosterone. Testosterone plays a crucial role

gland after diosgenin application in a rat model of the menopause. Middle-

during development of male reproductive tissues, onset of puberty, and

aged, acyclic female Wistar rats were divided into control (C; nZ6) and

maintaining health state. The final step of testosterone synthesis is catalyzed

diosgenin treated (D; nZ6) groups. Diosgenin (100 mg/kg b.w./day) was

17b-hydroxysteroid dehydrogenase

(17b-HSD3). Disruption of

orally applied for 4 weeks, while C group received the vehicle alone. Our

testosterone synthesis is associated with many diseases. Due to the lack of

approach considered using the design-based stereology, histochemistry and

a human Leydig cell line, two different murine Leydig cell lines (MA10,

the hormonal assay. The adrenal cortex volume decreased in D females by

BLTK1) were studied for their suitability as screening tools for testosterone

15% (P!0.05) while the volume of adrenal medulla increased (P!0.05) by

synthesis disruption by xenobiotics. The endogenous expression and activity

64%, compared to the same parameters in C group. Volume density of zona

of murine 17b-HSD3 was studied in both cell lines. Further, cells were

glomerulosa (expressed per absolute adrenal gland volume) in D rats

stimulated using br-8-cAMP and forskolin to study testosterone production.

increased (P!0.05) by 22% in comparison with C animals. Diosgenin

Cell supernatants were analyzed using LC-MS. Unstimulated cells showed

treatment decreased

(P!0.05) volume density of zona fasciculata

no or very low endogenous 17b-HSD3 activity. Stimulated MA10 cells

(expressed per volume of adrenal cortex) by 15% and caused vasodilatation

showed low but concentration-dependent increases of testosterone levels in

within this zone, when compared to C females. Circulating corticosterone

supernatants after 24 h. BLTK1 cells did not produce any testosterone. This

was also decreased by 16% compared to the C group. Absolute volume of

study emphasizes the necessity of analyzing steroid using sensitive

zona reticularis in D group decreased (P!0.05) by 38% in comparison with

MS-based methods and shows that MA10 and BLTK1 cells produce a

the same parameter in C rats. Also, after diosgenin application, volume

variety of steroids but only low amounts or no testosterone.

density of zona reticularis (expressed per absolute adrenal gland volume)

DOI: 10.1530/endoabs.49.EP781

and zona reticularis cell volume were decreased by 40% and 20% (P!0.05)

respectively, compared to C animals. Our results, reflecting a decrease of the

numerous adrenocortical stereological parameters, indicate that diosgenin

took over the role of corticosteroid precursors and got incorporated into the

steroidogenesis.

EP782

DOI: 10.1530/endoabs.49.EP779

Identification of chemicals disrupting adrenal steroid production by

steroid profiling in H295R cells

Petra Strajhar¹, David Tonoli², Fabienne Jeanneret², Raphaella Imhof¹,

Vanessa Malagnino¹, Melanie Patt¹, Denise Kratschmar¹, Julien Boccard²,

Serge Rudaz² & Alex Odermatt¹

University of Basel, Basel, Switzerland;²University of Geneva, Geneva,

Switzerland.

EP780

Association of autoimmune endocrinopathies and celiac disease

Human adrenal H295R cells are applied according to the validated OECD

Mrabet Soumaya¹, Akkari Imen¹, Ach Taieb², Ach Koussay² &

test guideline

456 to identify potential endocrine disrupting chemicals.

Ben Jazia Elhem

Testosterone and estradiol production serves as read-out although these are

¹Gastroenterology Department Farhat Hached University Hospital, Sousse,

not steroids typically produced by the adrenals. The current study attempted

Tunisia;²Endocrinology and Diabetology Department Farhat Hached

to optimize conditions for using H295R cells to detect chemicals disturbing

University Hospital, Sousse, Tunisia.

the synthesis of key adrenal steroids. Culture supernatants of H295R cells

were analysed by LC-MS-based steroid quantification. The impact of

experimental conditions including time and serum content on steroid

Introduction

profiles was assessed. Steroid profiles were measured before and after

Celiac disease (CD) is an immune-mediated small intestinal disorder that occurs

incubation with reference and test compounds for potential disruption of

in genetically susceptible people. It is significantly associated with other

adrenal steroidogenesis. The results revealed that H295R cells cultivated

autoimmune disorders represented mainly by type 1 diabetes and autoimmune

according to the OECD test guideline produced progestins, glucocorticoids,

dysthyroidism.

mineralocorticoids and adrenal androgens but only very low amounts of

Material and methods

testosterone. However, testosterone contained in Nu-serum was metabolized

We report 23 observations of patients with autoimmune endocrinopathies

during the 48 h incubation. Therefore, inclusion of positive and negative

associated with celiac disease.

controls and a steroid profile of the complete medium prior to the

Results

experiment was needed to characterize steroid synthesis and indicate

There are 23 patients with an average age of 31 years. All patients had chronic

changes occurring upon exposure to chemicals. Among the test chemicals,

diarrhea associated with abdominal pain in 15 cases and malabsorption syndrome

octyl methoxycinnamate and acetyl tributylcitrate resembled the corticos-

in five cases. The diagnosis of celiac disease was made on serological (Anti-

teroid induction pattern of the positive control torcetrapib. Gene expression

transglutaminase, anti-endomysium and anti-gliadin antibodies positive respect-

analysis revealed that octyl methoxycinnamate and acetyl tributylcitrate

ively in 20, 18 and 15 cases) and histological criteria (Partial villous atrophy in 13

enhanced CYP11B2 expression; however, less pronounced compared with

cases and total villous atrophy in

10 cases). Autoimmune endocrinopathies

torcetrapib. In conclusion, the extended profiling and appropriate controls

associated to celiac disease were: type

1 diabetes in

14 cases, Hashimoto

allow detecting chemicals that act on steroidogenesis and provide initial

thyroiditis in seven cases and Addison disease in one case. One patient had type 1

mechanistic evidence for prioritizing chemicals for further investigations.

diabetes, Basedow disease and Addison’s disease associated to celiac disease. All

DOI: 10.1530/endoabs.49.EP782

patients were treated with gluten-free diet and specific endocrinopathy treatment

with favorable evolution.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP783

diagnostic. When studying the relationship between the department of origin and

tumor type, we found a statistically significant difference between the cases

Endocrine dysfunctions associated with Hodgkin Lymphoma treatment

presented by the department of Endocrinology and the surgical departments

Daniela Dias, Joana Simo˜ es-Pereira, Sara Donato & Conceição Pereira

(General Surgery and Otolaryngology) and the remaining departments (c² 46.55;

Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa,

P!0.001). No significant association between the type of decision and tumor

Portugal.

type was found (c² 9.79; N.S.).

Conclusion

Introduction

Multidisciplinary teams are feasible and needed to make reliable, shared, patient-

Hodgkin lymphoma

(HL) survivors may develop a range of long-term

centered and evidence-based decisions. Endocrinology department remains the

complications that arise years after therapy. Among these, the endocrine

cornerstone that allows the flow of patients across the team.

dysfunctions are a major concern. Aim: To investigate the long-term endocrine

DOI: 10.1530/endoabs.49.EP784

effects of HL treatment.

Methods

Revision of the HL patients’ medical files who were followed at our Endocrine

Late-effects Clinics.

Results

We studied 178 patients (86 (48.3%) were female), whose mean age at HL

EP785

diagnosis was

18.07G10.79

(2-56) years. Chemotherapy was offered to

ER status heterogeneity in breast cancer: role in response to endocrine

177(99.4%) patients and radiotherapy to 157 (88.2%). Hypothyroidism was

treatment

identified in

76(42.7%) patients; women were not more affected than men

Teresa Gagliano, Angeliki Ditsiou, Arnhild Grothey & Georgios Giamas

(PZ0.083). Mean time between radiotherapy and hypothyroidism diagnosis was

Department of Biochemistry and Biomedicine, University of Sussex,

7.76G6.96 (1-39) years. Seven patients who developed hypothyroidism did not

Brighton, UK.

receive directed cervical radiotherapy and only 3 of them evidenced positive

thyroid antibodies. Thyroid nodules were present in 41 (23%) patients. Mean time

Tumor heterogeneity affects diagnosis, prognosis and response to therapy.

between radiotherapy and thyroid nodules development was 13.41G7.90 (1-35)

Heterogeneity is found in both normal and neoplastic human mammary gland. For

years. Although women were more affected (PZ0.01), they were not diagnosed

example, luminal estrogen receptor (ER)-negative cells can give rise to various

earlier (PZ0.842). Six (3.4%) patients developed thyroid cancer. Mean age at

phenotypes, including ER-negative and ER-positive mammary tumors,

thyroid cancer diagnosis was 24.4G8.36 (17-34) years. Patients who developed

suggesting that the cell-of-origin does not necessarily reflect the tumor type.

thyroid cancer were significantly younger when they underwent radiotherapy

Regarding ER status, heterogeneity can challenge endocrine therapies;

(10.2G2.9 vs 20.3G9.8/PZ0.024). Mean time between radiotherapy and thyroid

elimination of responsive clones can increase resistance of the survived ones

cancer diagnosis was 16.25G5.5 (11-21) years. Ten (11.63%) women developed

and ultimately reduce treatment efficacy leading to tumor relapse. The aim of our

breast cancer, 16.7G6.03 (7-25) years after HL therapy. Hypogonadism was

study is to investigate breast tumor heterogeneity and its role in endocrine

observed in 32 women and 12 men; mean age at hypogonadism diagnosis was

resistance onset. For this purpose, we co-cultured ER-positive (T47D, CAMA1)

28.07G8.92 (13-48) and 40.5G17.19 (14-66) years, respectively. Women

and triple negative breast cancer (TNBC) (MDA-MB231, HCC70) cell lines,

(P!0.001) and men (PZ0.001) who developed hypogonadism were older when

using 2D and 3D models. CAMA1 were sensitive to tamoxifen in term of cell

they received HL therapy. Median time between HL therapy and hypogonadism

viability, however this sensitivity was reduced when CAMA1 were co-cultured

was significantly shorter in women (1(0-18) vs 11.5 (3-39) years; (P!0.001)).

with TNBC cells. Interestingly, following co-culture with TNBC cells, the

Women who recovered their gonadic function were younger when they received

expression of ER in CAMA1 decreased while the anti-apoptotic protein Mcl-1

lymphoma therapy (17.5G7.0 vs 20.46G9.8/PZ0.026).

increased. On the other hand, T47D are slightly sensitive to tamoxifen; however,

Conclusion

this sensitivity was completely abolished when T47D were co-cultured with

Given the high relevance of endocrine dysfunctions in these patients, in order to

TNBC. In addition, the expression of ER in T47D was significantly increased

early identify and manage them, a long-term endocrine follow-up is needed, with

following co-culturing with TNBC cells, while the doubling-time of T47D was

adequate protocols.

significantly reduced, suggesting an increase in cell proliferation rate. Our results

DOI: 10.1530/endoabs.49.EP783

demonstrate that ER status appears to be modulated when ER positive cells are

co-cultured with TNBC cells, leading to a different response to endocrine therapy.

In addition, ER positive cells’ doubling time is modified after exposure to TNBC

cells. Further experiments are needed to fully understand the molecular

mechanisms behind these findings.

Endocrine Tumours and Neoplasia

DOI: 10.1530/endoabs.49.EP785

EP784

Multidisciplinary committee on endocrine tumors: an analysis of 6-year

experience

Juan J Díez^1,2, Pedro Iglesias¹, Teresa Alonso-Gordoa¹, Enrique Grande¹ &

Pablo Gajate¹

EP786

¹Hospital Universitario Ramón y Cajal, Madrid, Spain;²Universidad de

Potential role of vitamin D in restoring sensitivity to mTOR inhibitors

Alcalá de Henares, Madrid, Spain.

in hepatocellular carcinoma (HCC): 1,25(OH)vitamin D (VitD) reverts

everolimus (EVE) resistance in a hcc cell line

Claudia Pivonello¹, Donatella Paola Provvisiero¹, Mariarosaria Negri¹,

Aim

Gilda Di Gennaro¹, Cristina de Angelis², Chiara Simeoli¹,

Multidisciplinary approach is mandatory in the management of endocrine tumors.

Giacomo Galdiero¹, Maria Cristina De Martino¹, Annamaria Colao¹ &

Herein, we summarize the healthcare activity performed during the last 6 years at

Rosario Pivonello¹

the multidisciplinary committee for endocrine tumors of a tertiary and University

¹Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia,

Hospital.

Università Federico II di Napoli, Naples, Italy;²I.O.S. and COLEMAN

Methods

S.r.l., Naples, Italy.

A search of clinical-care activity of the endocrine tumors committee of our

hospital from 2011 to 2016 was performed. Clinical and demographic data of all

patients were recorded. The committee’s decisions were analyzed by tumor type

HCC is a difficult-to-treat- cancer with poor prognosis. Despite EVOLVE-1 trial

and the type of decision (diagnostic or therapeutic). Clinical protocols approved

demonstrated that EVE did not improve overall survival in molecularly and

by the committee were quantified.

clinically unselected patients with advanced sorafenib resistant HCC, in selected

Results

patients, the established antitumor effect of EVE could make this drug a potential

Two hundred and sixty seven decisions, affecting 205 patients (72.2% women,

adjuvant therapy. Unfortunately, the acquired EVE resistance due to the tumour

mean age 53.3G16.9 years) with endocrine tumors, were made. Thyroid tumors

adaptation to chronic drug use is a current challenge. VitD has been deemed as

accounted for the main workload of the committee, with 61.8% of all decisions, a

potential regimen to treat a variety of cancers alone or in combination with other

percentage that has not substantially changed over the years. The rest of decisions

drugs. The aim of this study was to assess the antiproliferative effect of the

dealt with neuroendocrine

(14.6%), pituitary

(13.5%), adrenal

(6.0%) and

combined treatment with EVE and VitD in JHH-6, a model of HCC cell line, and

parathyroid tumors

(4.1%). Most cases came from the Departments of

to explore the role of VitD pre-treatment in the re-sensitization to EVE in JHH-6

Endocrinology (52.8%) and General Surgery (18.0%). 75.7% of the committee’s

cell line resistant to EVE

(JHH-6 EveR). JHH-6 EveR were obtained after

decisions were therapeutic and 15.7% diagnostic. The committee developed 29

4 months of EVE 10-8M treatment. Messenger and protein VitD receptor (VDR)

clinical protocols for local use. 65.5% of them were therapeutic and 34.5%

expression was confirmed by RT-qPCR and immunofluorescence. DNA assay

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

was established to evaluate the proliferation rate in parental and EveR cells after

Objective

EVE treatment (from 10-14 M to 10-8 M) alone or in combination with VitD

The objective of the study was to describe the endocrine outcomes of 764 patients

(10-7 M). In parental cells, EVE significantly reduced the proliferation index in a

followed during a 20 years period in our out-patient clinic.

dose-dependent manner after 6 days of treatment and VitD did not improve EVE

Design

effect. JHH-6 EveR cells no longer responded to EVE treatment but 12h and 24h

The design was a retrospective medical records review.

of VitD pre-treatment was sufficient to significantly restore the efficacy of EVE at

Patients

concentration ranging from 10-14 M to 10-8 M with a maximum effect of 3.3%

The study included 764 patients whose oncological or hematological dangerous

10-8 M (P!0.001). Moreover, the liver miRNA PCR Array study

diseases appeared before

18 years old. Larger groups were constituted by

demonstrated that VitD treated JHH-6 EveR showed an increased expression of

Leukaemias, Central Nervous Tumors and Lymphomas.

miR-375 compared to JHH-6 EveR, suggesting a role of miR-375 in EVE

Outcome measures

re-sensitization. These preliminary data suggested the use of VitD to overcome

The frequency and types of endocrine conditions were measured.

the acquired resistance to EVE in HCC.

Results

DOI: 10.1530/endoabs.49.EP786

One thousand and ninety one endocrine conditions were observed in all groups.

The most common types of endocrine conditions were problems with growth and

thyroid. We found puberty abnormalities and bone problems in third and fourth

places of frequency. ACTH insufficiency was found in seventh place.

Conclusion

Endocrine dysfunctions are very common in survivor’s population. Endocrinol-

EP787

ogists should be aware of international guidelines and to make an effort to

Comparisson of subtraction and two-phase parathyroid scintigraphy

optimize screening and treatment of endocrine effects of cancer therapy. The

conserning histological type of hyperfunctioning parathyroid tissue

crucial period is the pubertal with growth spurt failure and acceleration puberty

Sanja Dugonjic¹, Boris Ajdinovic², Snezana Cerovic³ & Zoran Hajdukovic⁴

maturity wisch of them can bring future social and professional difficulties.

¹Military Medical Academy, Institute of Nuclear Medicine, Belgrade,

DOI: 10.1530/endoabs.49.EP788

Serbia;²Military Medical Academy, Institute of Nuclear Medicine,

Belgrade, Serbia;³Military Medical Academy,Institute of Pathology and

Forensic Medicine, Belgrade, Serbia;⁴Military Medical Academy,

Clinic of Endocrinology, Belgrade, Serbia.

The aim of this study was comparison of sensitivity of subtraction parathyroid

scintigraphy (SBPS), vs. two-phase parathyroid scintigraphy (2FPS), related to

EP789

histological type of hyperfunctioning parathyroid tissue.

Magmas modulates chemoresistance in endocrine-related cancers

Materials and methods

Eleonora Riva¹, Federico Tagliati¹, Teresa Gagliano¹, Claudio Trapella²,

Fifty patients, thirty with primary hyperparathyroidism and twenty on dialysis and

Sonia Missiroli³, Paolo Pinton³, Cristiano Bertolucci⁴, Ettore degli Uberti¹

secondary hyperparathyroidism underwent parathyroid scintigraphy (PS) before

& Maria Chiara Zatelli¹

surgery. Static scintigrams of neck and chest were performed, fifteen minutes and

¹Section of Endocrinology, Department of Medical Sciences, University of

two hours after iv. injection of 740 MBq of Tc99m-MIBI. Four hours latter, after

Ferrara, Ferrara, Italy;²Department of Chemical and Pharmaceutical

iv. injection of 185 MBq Tc99m, thyroid scintigraphy was performed. After

Sciences, University of Ferrara, Ferrara, Italy;³Department of Morphology,

normalization and motion correction, subtraction Tc99m from Tc99m-MIBI

Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy;

scintigrams was done. Scintigraphic results of both PS methods were graded from

⁴Department of Life Sciences and Biotechnologies, University of Ferrara,

one to five: grade 1-normal finding, grade 2-probably normal finding, grade

Ferrara, Italy.

3-suspicious finding, grade 4-probably abnormal finding and grade 5-abnormal

finding. Scintigraphic findings graded 3, 4 and 5 were considered as pathologic.

Pathohistological analyses were done microscopically on standard haematoxylin-

eosin stained slides to determine the substrate: adenoma and type of hyperplasia.

Magmas, a gene encoding for the mitochondrial import inner membrane

Results

translocase subunit, Tim16, protects different cell lines from the antitumoral

Postoperatively 96 hyperfunctioning paratiroid glands (PG): 24% adenomas,

effects of several pro-apoptotic stimuli (i.e. chemicals and chemotherapeutic

62.5% with nodular hyperplasia (NHPL) and 13.5% with diffuse hyperplasia

agents). The synthetic Compound 5 is capable of sensitizing chemoresistant

(DHPL), were found. Overall sensitivity of SBPS was 74%; 91.3% for adenoma,

tumor cells overexpressing Magmas to proapoptotic stimuli, indicating that this

molecule may be useful to overcome tumor chemoresistance. The aim of our

70% for NHPL and 61.5% for DHPL, with no statistically significant difference in

sensitivity between groups of PG. Overall sensitivity of 2FPS was 67.7%; 100%

study was to evaluate whether Compound 5 targets Tim16 and is cytotoxic

for adenoma, 61.5% for NHPL, and 38.5% for DHPL. Statistically significant

in vivo. We found that Compound 5 enhances the antiproliferative effects of

difference was found in sensitivity of 2FPS findings between these three groups,

doxorubicin in MCF7 cells, while it fails to do so in two independent MCF7 cell

P!0.0001. SBPS had statistically significantly higher sensitivity of 61.5% for

clones where Magmas was silenced by specific shRNA. Then, the normal breast

diffuse hyperplasia, comparing to 2FPS, with sensitivity of 38.5%, P!0.0001.

MCF12 cells were transfected with two differently tagged vectors, tim16-ddktag

Conclusion

encoding for Tim16 and tim14-hatag, encoding for its partner Tim14. We found

SBPS and 2FPS showed similar sensitivity in detection of PG adenoma and

that Tim16 co-immunoprecipitates with Tim14 and that their interaction is

nodular hyperplasia of parathyroid glands. Superiority of subtraction parathyroid

reduced in the presence of Compound 5. However, Tim16 levels appear to be

scintigraphy in detection of PG with diffuse hyperplasia is important finding,

reduced in cells treated with Compound 5. The toxicity of this molecule was then

knowing that these glands are the smallest one and often remain undetected prior

tested in vivo by the Fish Embryo toxicity assay, employing Zebrafish eggs:

surgery, both in secondary, and importantly in primary hyperplasia.

Compound 5 is not toxic in vivo at the concentrations employed in vitro (5 and

10 mM), while its toxicity increases dose-dependently at higher concentrations.

DOI: 10.1530/endoabs.49.EP787

These data support the hypothesis that Compound 5 targets Tim16 and that Tim16

levels modulate the chemosensitizing effects of Compound 5, that need to be

confirmed by in vivo studies.

DOI: 10.1530/endoabs.49.EP789

EP788

Endocrine health problems detected in 764 patients evaluated in a late

effects clinic

Conceiçao Pereira, Joana Pereira, Daniela Dias, Sara Donato &

EP790

Dauarte Salgado

Portuguese Cncer Institute, Lisbon, Portugal.

Altered expression of the components of the splicing machinery is

associated to increased malignancy and expression of aberrant splicing

variants in prostate cancer

Context

Juan M Jiménez-Vacas¹, Manuel D Gahete¹, Sergio Pedraza-Arévalo¹,

Many pediatric cancer survivors have endocrine conditions. After alkylating

Mercedes del Río-Moreno¹, Daniel Hormaechea-Agulla¹,

agents, steroids, methotrexate and radiation, several endocrine dysfunctions may

Enrique Gómez-Gómez^1,2, Julia Carrasco-Valiente², María del Mar

appear. Surveillance for late effects is recommended by worldwide guidelines.

Moreno³, María José Requena-Tapia², Justo P Castan˜o1 & Raúl M Luque1

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Maimonides Institute of Biomedical Research of Cordoba (IMIBIC); Reina

EP792

Sofia University Hospital (HURS); Department of Cell Biology, Physiology

Chronic stress and somatotroph axis in breast cancer more than a

and Immunology, University of Cordoba (UCO); CIBER Physi, Cordoba,

simple association

Spain;²Service of Urology, HURS/IMIBIC, Cordoba, Spain;³Service of

Iulia Crumpei^1,2, Ioana Armasu^1,2, Mihai Danciu^1,5, Mariana Tofan³,

Anatomical Pathology, HURS/IMIBIC, Cordoba, Spain.

Constantin Volovat³, Alina Belceanu^1,2, Felicia Crumpei⁴,

Valentina Adomnicai² & Carmen Vulpoi^1,2

University of Medicine and Pharmacy, Iasi, Romania;²Department of

Endocrinology, Sf. Spiridon Hospital, Iasi, Romania;³Department of

Prostate cancer (PCa) is the most common cancer among men in developed

Onclogy, Victoria Hospital, Iasi, Romania;⁴Department of Radiology,

countries. Unfortunately, the heterogeneity of this malignancy hinders the finding

of new biomarkers and therapeutic tools. A potential factor contributing to PCa is

Sf. Spiridon Hospital, Iasi, Romania;⁵Department of Morphopathology,

alternative splicing, which can generate the appearance of oncogenic variants

Sf. Spiridon Hospital, Iasi, Romania.

involved in PCa aggressiveness. Thus, we hypothesized that the alteration of the

splicing machinery (spliceosome components and splicing factors (SFs)) could be

Introduction

associated to the expression of tumorigenic splicing variants and malignancy of

Epidemiological and clinical studies have proven direct correlations between

PCa. Accordingly, we characterized the expression pattern of key components of

chronic stress, inflammation and cancer progression. The inflammatory

the major (nZ13) and minor spliceosome (nZ4) and associated SFs (nZ28) in

environment preexisting the malignant change and elevated IGF-1 levels are

51 PCa biopsies and 15 normal prostates, by using a microfluidic-based qPCR-

associated with higher cancer risk, especially through GH effects on cell

array. The results revealed a downregulation of two key components of the

proliferation and inhibition of apoptosis.

spliceosome responsible for the recognition of and binding to the branching site of

Aim

the target introns (RNU2 and RNU12) in PCa samples compared to controls,

To evaluate the relationship between biological and hormonal stress markers,

which might explain the prevalence of intron retention events found in PCa. In

growth factors and breast cancer (BC).

addition, expression of other components of the minor spliceosome (i.e. RNU11,

Patients and Methods

RNU4atac or PRPF8) was also significantly reduced in PCa, suggesting a

Biological markers (fibrinogen, C-reactive protein (CRP), ESR), endocrine stress

profound dysregulation of the minor spliceosome function and a consequent

markers

(urinary free cortisol, ACTH and urinary metanephrines) and

alteration in the processing of U12-introns. Furthermore, this analysis also

somatotroph axis: growth hormone (GH), insulin-like growth factor-1 (IGF1)

revealed a marked alteration of certain SFs (i.e. SRSF5, SRSF9, MAGOH or

were determined in a population-based sample of 79 female patients diagnosed

TIA1) in PCa, whose expression was associated with the expression of relevant

and treated for breast cancer.

splicing variants

(i.e. In1-ghrelin variant) and with malignancy features

Results

(metastasis, PSA levels, etc.). Finally, functional assays (proliferation, migration,

Among the inflammatory markers the increase of fibrinogen has been connected

etc.) with PCa cell lines confirmed the pathophysiological role of some of these

to high levels of IGF1 (rZ0.231, PZ0.045), low GH (rZK0.220, PZ0.062) and

SFs. Altogether, these results indicate that the splicing machinery is drastically

low cortisol (rZK0.226, PZ0.058); elevated ESR correlates with the increase in

dysregulated in PCa, which could help to explain the predominance of intron

GH secretion (rZ0.243, PZ0.039) and high CRP was directly linked to higher

retention events and the appearance of tumorigenic splicing variants in this

values of ACTH (rZ0.417, PZ0.00). Both cortisol (rZK0.265, PZ0.025) and

pathology, providing novel tools to develop diagnostic markers or therapeutic

urinary metanephrines

(rZK0.311, PZ0.016) have proven to negatively

targets.

correlate to IGF-1. While advancing in age, both ACTH levels (rZK0.225,

DOI: 10.1530/endoabs.49.EP790

PZ0.052) and IGF1 (rZK0.223, PZ0.051) tend to decrease.

Conclusion

The chronic inflammatory status, frequently found in patients suffering from

breast cancer, seems to be linked to the increase of the endocrine stress and

growth markers. This augmentation of IGF1 levels could be a negative predictive

factor for the further evolution and prognostic for the disease. However, our study

EP791

has shown that high levels of stress hormones correlate to lower IGF1.

Polyglandular autoimmune syndrome type III b

DOI: 10.1530/endoabs.49.EP792

Raquel Vaz de Castro¹, José Maria Aragués², Florbela Ferreira¹,

Vânia Gomes¹, Ana Wessling¹, Lurdes Tavares¹, Joana Ribeiro¹,

Irina Alves¹, Afonso Camilo Fernandes¹ & Maria Joa˜o Bugalho1

¹Santa Maria Hospital, Lisbon, Portugal;²Beatriz Ângelo Hospital, Lisbon,

Portugal.

Female Reproduction

EP793

We report the case of a 57-year-old female diagnosed with Grave’s disease fifteen

years before (TSH !0.001 U/ml; FT4 2.3 ng/dl; FT3 7.2 ng/dl, TSAbs 17 U/l).

Cynicism and common endocrine diseases in pregnancy

Persistency of hyperthyroidism despite antithyroid therapy led to total

Ioannis Ilias¹, Anastasia Linardi¹, Charalambos Milionis¹,

thyroidectomy three years after the diagnosis. Thereafter, thyroid function

Evangelia Venaki¹, Athanasios Tselebis², Stamatina Nikopoulou¹ &

remained normal under hormonal replacement with levothyroxine. The patient

Eftychia Koukkou¹

had also been diagnosed with Pernicious Anemia at 47 years of age after

¹Department of Endocrinology, Diabetes & Metabolism, El. Venizelou

investigation for complaints like fatigue and shortage of breath. Hemoglobin

Hospital, Athens, Greece;²Department of Psychiatry, Sotiria Hospital,

levels were 10.2 g/dl and Intrinsic Factor antibody titer was positive. She was

Athens, Greece.

treated with cobalamin and folic acid and hemoglobin levels became stable in the

low-normal range. A year ago, the patient presented with left upper quadrant

Introduction

abdominal pain and asthenia, raising the suspicion of gastric disease. Specific

Cynicism (or cynical distrust) is described as a state of mind and belief that most

blood tests were performed and the presence of high titers of gastric parietal cells

people are selfish. Cynicism is an attitude characterized by general distrust of the

antibodies (PCA), elevated gastrin (O1000 pg/ml; normal range: 13-115 pg/ml)

motives of others, and some experts describe it as a form of chronic anger.

and chromogranin A (936 ng/ml; normal range !102 ng/ml) confirmed the

Negative emotions, especially cynicism, may be harmful to physical health.

hypothesis of autoimmune gastritis. Furthermore, an elevated NSE level of

Aim

13.2 ug/l was detected. Endoscopy of the gastrointestinal tract found a

The assessment of cynicism in pregnant women with common endocrine diseases.

pedunculated polypoid lesion in the stomach fundus which was resected.

Subjects - Methods

Histological results revealed a well differentiated neuroendocrine tumor (NET)

We examined 54 Greek pregnant women (mean age C S.D.: 35C5 years), 18

with no evidence of vascular invasion or necrosis and Ki-67 index !2%;

with hypothyroidism diagnosed during pregnancy (HT), 18 with gestational

immunohistochemical studies for gastrin, somatostatin and serotonine were

diabetes mellitus (GDM) treated with medical nutrition therapy and 18 with HTC

negative; atrophic gastritis was also documented. The association of Graves’

GDM. They all responded to the validated Greek version of the Cook-Medley

disease, pernicious anemia and gastrointestinal neuroendocrine tumor suggests

questionnaire (by T Anagnostopoulou & G Kioseoglou) (minimum possible

the diagnosis of the very rare type IIIb polyglandular autoimmune syndrome.

score: 8, maximum: 40). The validity of the responses was assessed by calculating

Gastric NETs associated to chronic atrophic gastritis (Type 1) are often small

Cronbach’s alpha and the differences between the three groups of women, taking

(!1-2 cm) multiple in 65% of cases and polypoid in 78% of cases, often G1 and

into account their age, were assessed with analysis of covariance (ANCOVA).

with an excellent prognosis.

Results

DOI: 10.1530/endoabs.49.EP791

The validity of the questionnaire was satisfactory (Cronbach alpha Z0.77).

Women with HT had mean cynicism scoreCSE: 19.4C1.3, with GDM: 21.6C

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

1.3 and HTCGDM; 24.7C1.3 (PZ0.02 for HT vs HTCGDM). The cynicism

score had no correlation with age (PZ0.34).

Age

Agreement Disagreement

% concordance

Discussion

Female

16-73

In our study we found that coexistence of HTCGDM acted cumulatively in

Male

13-60

73.1

cynicism score. It has been found that cynicism raises the risk of developing DM

type 2, and so does GDM. Given such negative consequences, we discern the need

of women with GDM to reassess their life attitudes and possibly to seek help to

improve their life and their prognosis.

Conclusion

There is a good agreement between the two methods. The absence of age-

DOI: 10.1530/endoabs.49.EP793

stratified reference values by CLIA’ method may explain the discordant results.

Despite the small sample size, Maglumi free testosterone may be considered a

good alternative to the RIA assay, although it is fundamental to have reference

values according to age and gender since the concentration of free testosterone

varies throughout life from childhood to adulthood.

EP794

DOI: 10.1530/endoabs.49.EP795

Thyroid ultrasonography findings in patients with polycystic ovary

syndrome

Anice Bergamim, Cristiane Perazo, Ivan Cruz, Simone Austgulen,

Patricia das Oliveiras, Roberto Perrotta & Flávia Concei

˜o

Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Growth Hormone IGF Axis - Basic

Polycystic ovarian syndrome (PCOS) affects 6-10% of women of childbearing

EP796

age. The pathophysiology of PCOS is related to increased insulin resistance (IR).

Impact of new standardization on IGF-I assay IMMULITE 2000

Obesity, the leading cause of high IR, is present in 50% of women with PCOS, but

Isaura Rodrigues & Conceicao Godinho

lean women with PCOS also have higher IR than women with the same BMI

Centro Hospitalar Lisboa Central, Lisbon, Portugal.

without PCOS. Recent studies have correlated high IR with presence of thyroid

nodules (TN), which motivated us to evaluate the occurrence of TN in patients

with PCOS. 50 women with 18-45 years with PCOS according to the Rotterdam

Introduction

criteria were submitted to: evaluation of BMI and presence of acanthosis nigricas

IGF-I is a clinically relevant protein in the diagnosis and monitoring of treatment

(AN): laboratory tests for blood glucose and thyroid hormones; and thyroid

of growth disorders. The Growth Hormone Research Society and the International

ultrasound (made by the same examiner with the same device). Laboratory and

IGF Research Society have encouraged the adoption of a universal calibration for

imaging results were compared between patients with (group 1) and without

immunoassays to improve standardization of IGF-I measurements.

(group 2) TN through the Student’s T-test. The prevalence of TN was 36%. We

Objectives

observed that weight, BMI and glycemia were significantly higher in group 1 with

Comparison of new standardization IGF-I assay with IGF-I assay currently used

the following p-values, respectively: 0.003; 0.01; and 0.028. The prevalence of

in CHLC, Lisbon; To study whether the introduction of the new assay would lead

AN was also higher in group 1 (50!37.5%). Among patients with TN, 13 had a

to different clinical interpretations, verifying the concordance of results.

single nodule and only 5 had multinodular disease (2 patients with 4 and 3 with 3),

Material and Methods

totalizing 30 nodules identified. 13 of these were %1 cm and 7 were suspicious,

A random sample of 186 patients regularly assisted at CHLC, mostly in

indicating that further investigation would be necessary. Our prevalence of TN

Endocrinology Departments, comprising both genders, ages 2 months-85 years.

was higher than that found by other authors in obese women at the same age

Determinations on IMMULITE 2000 (Siemens). Chemiluminescent assays: new

without PCOS (21.4%). Although prevalence of TN increases with age, a Finnish

standardization (1st IS WHO, 02/254 NIBSC) and old (1st IRR WHO, 87/518

study evaluating healthy middle-aged women (49-58 years) also showed a lower

NIBSC); An Excel tool was used for statistical treatment. For comparison

prevalence (30.69%). These data suggest that patients with PCOS have a higher

statistics we excluded 9 patients.

risk of developing TN.

Results

Comparison statistics: rZ0.994; SlopeZ0.63; interception

(ng/ml)Z22.4;

DOI: 10.1530/endoabs.49.EP794

nZ177; range 27.2-938.0 ng/ml. According to assay and age-specific reference

values specified by the manufacturer, we found concordance between 78.3 and

90.4%, regardless of gender, with the exception of 0-3 year age group, in which

concordance fell below 33.3 and 50%.

Conclusions

Comparison statistics revealed data overlapping with those of the manufacturer.

Although there was a good agreement between assays results, caution should be

EP795

exercised in the interpretation of a single IGF-I value and of the impact of the new

Comparison of free testosterone results by a radioimmunoassay and a

standardization. Discrepancies require posterior evaluation in the evolution of the

chemiluminescent assay

disease, mainly in group 0-3 years. Clinicians should be aware of the tendency to

Conceicao Godinho & Isaura Rodrigues

reduce IGF-I values with the new calibration, so that they do not attribute it to a

Centro Hospitalar Lisboa Central, Lisboa, Portugal.

change in patient status.

DOI: 10.1530/endoabs.49.EP796

Introduction

Radioactive assays are widely used in clinical laboratories for measuring free

testosterone. The appearance of a non-isotopic, chemiluminescent automatic

assay, may be an interesting alternative if the performance of the assay remains

the same or higher.

Objective

To compare the free testosterone results by radioimmunoassay

(RIA) and

Male Reproduction

chemiluminescent assay (CLIA) and to analyze the clinical impact taking into

EP797

account the % concordance.

Rare case of manifestation of erectile dysfunction soon after

Material and Methods

thyroidectomy because of thyroid cancer in 56-year-old man with

We studied 76 patients, aged 13-73 years old, and observed at CHLC medical

diabetes mellitus type 2 and diabetic neuropathy

appointments, in Lisbon. The serum samples were analyzed by “Free TESTO-

Natia Katamadze & Zurab Marshania

RIA-CT”, DIASource (0.2-22.1 pg/ml) and “Maglumi Free Testosterone (CLIA)”

V.Iverieli Endocrinology, Metabology, Dietology Center, “ENMEDIC”,

Snibe (1.52-40.62 pg/ml). An excel tool was used for statistical treatment and the

Tbilisi, Georgia.

clinical concordance of the results were analyzed according to the reference

values of both.

Results

Introduction

A strong correlation was observed rZ0.95 and linear regression was calculated:

Erectile dysfunction (ED) is common among men with diabetes mellitus (DM).

yZ1.51xC0.072. The % concordance found was:

Early diagnosis for such patients is essential in case of other multiple serious

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

endocrine disorders like thyroid cancer (TC). The aim of our presentation is to

EP799

demonstrate the case of

56-year-old male with DM and TC when the

Epileptic seizures in patients with large and giant prolactinomas

manifestation of ED had been observed only after thyroidectomy.

Yuliya Sidneva, Luidmila Astafieva, Maksim Kutin & Pavel Kalinin

Clinical presentation

The Burdenko Neurosurgical Institute, Moscow, Russia.

A 56-year-old man attended our clinic with complains of ED and loss of libido.

He also represented the complains characteristic to diabetic neuropathy. The

symptoms of diabetic neuropathy appeared approximately 10 years ago. The

Objective

patient is diagnosed with diabetes mellitus type 2 since the age of 46. So diabetes

To study epileptic seizures in patients with large and giant prolactinomas.

mellitus and diabetic neuropathy was diagnosed at the same time. In November

Patients and methods

2016, total thyroidectomy was performed because of papillary microcarcinoma.

The study group included 45 patients with large prolactinoma (more 36 mm in

After several days of surgical intervention the patient represented complaints of

diameter) and 23 patients with giant prolactinoma (more than 60 mm in diameter).

ED. Laboratory investigations were performed: HbA1c-6.0%, prolactin and total

55 men and 13 women aged 16-67 years (mean 39). Patients were followed by

testosterone within normal range. It had carried out a comprehensive, phased

hormone measurements, magnetic resonance imaging (MRI), electroencephalo-

treatment, which included treatment of diabetic neuropathy and hypothyroidism

gram (EEG) and endocrinological, psychopathological, neurologic examinations.

with carrying out non-specific stimulation

(Yohimbin Hydrochlorid and

Results

L-arginin) as well as the therapy by PDE-5 inhibitor. Above-mentioned treatment

Mean serum prolactin level ranged between 12 990 and 1 038 000 mU/l (mean

led positive results because the treatment of ED was initiated in a timely manner.

198 000 mU/l). Epileptic syndrome was revealed in 14 patients (21%): partial

In our clinical case DM and DN was diagnosed at the same time. It is interesting

seizures with secondary generalization (64%), complex (28%) and simple (14%)

that the patient underwent to thyroidectomy and soon after he attended our Clinic.

seizures or their combinations. Seizures differed in structure depending on growth

The question is: does thyroidectomy and high level of TSH could be the reason of

of the tumor. Partial seizures with secondary generalization were mostly revealed

early manifestation of ED?

in patients with growth of adenoma to temporal region on left (50%) and right

Conclusion

(14%). Complex partial seizures were revealed in patients with growth of the

The early diagnosis of ED is important for successful treatment especially among

adenoma to temporal region on left (21%) and into the III ventricle (7%). Simple

man who had ED and multiple serious endocrine disorders. So it is important to

partial (psychosensory) seizures were in patients with growth of adenoma into

reveal it in the early stage. The easiest way not to miss ED in diabetic patients is

diencephalic region (14%). Diagnosis of epileptic seizures was based on the

the questionnaires, which we use successfully in our clinic.

detection of typical pathological patterns in EEG.

DOI: 10.1530/endoabs.49.EP797

Conclusion

21% patients with large and giant prolactinomas have epileptic syndrome.

Structure of epileptic seizures depends on extension of the adenoma and intrusion

in different regions of the brain.

DOI: 10.1530/endoabs.49.EP799

Neuroendocrinology

EP798

EP800

Dissecting the androgen excess phenotype of women with idiopathic

Prednisolone reinforces the food reward system by bilateral amygdala

intracranial hypertension

activation - an fMRI study

Michael O’Reilly¹, Catherine Hornby¹, Connar Westgate¹,

Georg Serfling¹, Macià Buades-Rotger^2,3, Birgit Harbeck¹, Ulrike Kramer^2,3

Hannah Botfield¹, Keira Markey¹, Carl Jenkinson¹, Lorna Gilligan¹,

& Georg Brabant¹

Mark Sherlock², James Gibney², Jeremy Tomlinson³, Wiebke Arlt¹ &

¹Department of Internal Medicine I, University of Lubeck, Lubeck,

Alexandra Sinclair¹

Germany;²Institute of Psychology II, University of Lubeck, Lubeck,

¹University of Birmingham, Birmingham, UK;²Tallaght Hospital and

Germany;³Department of Neurology, University of Lubeck, Lubeck,

Trinity College, Dublin, Ireland;³University of Oxford, Oxford, UK.

Germany.

Abstract

Introduction

Idiopathic intracranial hypertension (IIH) is a devastating neurological condition,

A well known side effect of glucocorticoid treatment is abdominally centred

with elevated intracranial pressure of unknown aetiology. IIH is largely a disease

weight gain due to increased sensation of hunger but the underlying mechanism is

of obese females of reproductive age. The clinical phenotype of IIH overlaps with

still only incompletely clarified. To elucidate whether the brain reward system is

polycystic ovary syndrome (PCOS), with prevalent obesity, hyperandrogenism

involved in this regulation we studied here the effects of an acute prednisolone

and anovulation. In this study, we aimed to delineate the androgen excess

infusion on brain centres responding to food stimulation by fMRI in healthy males

phenotype of IIH women compared to those with PCOS and simple obesity.

and correlated these findings to the 24 h food intake of the subjects.

Women with IIH (nZ70), alongside age- and BMI-matched cohorts with PCOS

Methods:

(nZ60) and simple obesity (nZ40), were recruited to an in vivo study. Serum

20 healthy normal-weight men were tested in a prospective randomized cross-

classic and 11-oxygenated androgens were measured by liquid chromatography-

over setting after an overnight fast respectively. They were either infused for

tandem mass spectrometry (LC-MS/MS) and urinary steroid excretion by gas

30 min with 250 mg prednisolone or placebo. fMRI scans were taken 4 h later

chromatography-mass spectrometry. Cerebrospinal fluid (CSF) androgens were

while presenting food and object pictures. At the following morning participants

quantified by LC-MS/MS in IIH women (nZ49) and a female cohort with non-

had a supervised breakfast at a standardized buffet. All were restricted from eating

IIH neurological disease (nZ30). PCOS patients had increased insulin resistance,

during the four hours until fMRI and kept a food diary until the next morning.

as measured by HOMA-IR (P!0.05), while HOMA-IR in IIH and controls did

Results

not differ. Serum testosterone was higher in IIH compared to both PCOS and

When presenting palatable food pictures in contrast to object pictures we obtained

control women (P!0.001 for both); conversely, serum androstenedione was

a significant activation in brain regions known to be part of the food reward

higher in PCOS women than in IIH (P!0.001) and controls (P!0.01). Serum

system like the hippocampus, anterior cingulate cortex, bilateral amygdala and

levels of the 11-oxygenated androgen precursors 11b-hydroxyandrostenedione

insula. Application of prednisolone significantly increased the activity in the

and 11-ketoandrostenedione were increased in PCOS (P!0.0001), while levels

bilateral amygdala and right insula in contrast to placebo. The buffet test did not

in IIH patients did not differ from controls. Systemic 5a-reductase activity, as

reveal any significant difference in calorie intake or preferences of different

measured by the ratio of 5a-tetrahydrocortisol/tetrahydrocortisol, was higher in

macronutrients nor did the food diary.

IIH women compared to both PCOS and controls (P!0.05 for both). IIH women

Discussion

had increased CSF androstenedione and testosterone compared to controls (all

The present imaging results support a direct stimulatory, prednisolone specific

P!0.0001). Using mass spectrometry-based analysis, we show that women with

effect on food reward centres in the bilateral amygdala and the right insula. This

IIH have a distinct androgen excess phenotype compared to PCOS and simple

interaction may represent an increased anticipated reward value of high calorie

obesity, with higher active serum androgens, 5a-reductase activity and increased

food mediated by glucocorticoids, an effect which most likely needs to be present

CSF androgens. Further studies are needed to understand the role of androgen

for a prolonged period of time to relate to a measurably increased food intake

excess in the pathogenesis of IIH.

(supported by DFG).

DOI: 10.1530/endoabs.49.EP798

DOI: 10.1530/endoabs.49.EP800

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Nuclear Receptors and Signal Transduction

peptides, whereas 5aTHB induced weak changes with only 3. Interestingly,

interactions between the MR LBD and its co-regulator peptides were altered

EP801

to a comparable extent by F and 5aTHB treatment (76 vs 41 interactions

18b-glycyrrhetinic acid reduces VLDL secretion as a modulator for

altered, respectively). In addition, both aldosterone (10 nM) and 5aTHB

HNF4a

(5 mM) increased transcriptional activity of a luciferase tagged MR reporter

Qingli Liu, Meng Yang, Minyi Zhang & Min Guan

construct in HEK293 cells (13.50G1.09 fold and 11.20G1.24 fold vs

Shenzhen Institutes of Advanced Technology, Chinese Academy of

vehicle, respectively, both P!0.0001, nZ4). Both effects were antagonised

Sciences, Shenzhen, Guangdong, China.

by spironolactone. In conclusion, the mechanisms underlying the action of

5aTHB differ from those of classical GCs, consistent with its reduced side-

effect profile, and may involve MR as much as GR.

Glycyrrhizin (GL) is a major bioactive triterpene glycoside of licorice root,

DOI: 10.1530/endoabs.49.EP802

a traditional Chinese herbal medicine. GL and primary metabolite 18b-

glycyrrhetinic acid (GA) have been developed as anti-inflammatory and

antiviral drugs for liver diseases in China and Japan. Hepatic VLDL

secretory pathway is not only responsible for lipid homeostasis but also

associated with viral particles assembly and secretion. Hepatocyte nuclear

factor 4a (HNF4a) together with its downstream targets, namely, secreted

phospholipase A2 G12B (PLA2G12B) and microsomal triglyceride transfer

EP803

protein (MTP), regulate VLDL production and secretion. We hypothesized

Development of novel human stable reporter cell line for the assessment

that GA may act through HNF4a to mediate some of its beneficial effects.

of PPARg transcriptional activity

We found that GA inhibits the transcriptional activity of HNF4a.

Peter Illes, Aneta Grycova & Hana Prichystalova

Specifically, promoter reporter expression of PLA2G12B, MTP and ApoB

Department of Cell Biology and Genetics, Faculty of Science, Palacky

activated by HNF4a are dose-dependently suppressed by GA. Through lipid

University, Slechtitelu 27, 783 71 Olomouc, Czech Republic.

droplet analysis in vitro, we further found that GA trended to elevate

intracellular triglycerides levels in a dose dependent manner in Huh7 cells,

indicating that VLDL production and secretion is suppressed. To investigate

GA effects in vivo, we fed mice a high-fat diet for 19 weeks. These mice

Endocrine disrupting chemicals (EDCs) are exogenous compounds that

were then gavaged with GA 60 mg/kg (HFD-GA) or vehicle (HFD-ctrl)

affect the endocrine system, disrupt the hormonal balance and consequently

every day for 6 weeks. We found that VLDL secretion rate was lowered

cause the adverse health effects in humans. These compounds persist and

significantly by GA treatment in HFD mice compared to HFD-ctrl mice.

accumulate in the environment and can easily gain entry to the food chain.

Data from blood biochemistry analysis revealed that treatment with GA

Peroxisome proliferator-activated receptor gamma

(PPARg) and its

significantly reduced blood TG, TC, ALT, AST, and glucose. While hepatic

heterodimeric partner retinoid X receptor alpha (RXRa) are very often

TG and TC levels were increased by HFD feeding, GA blunted the amount

targets of EDCs. PPARg play crucial role in lipid and glucose metabolism

elevated by HFD. Oil red O staining showed that the amount of fat droplets

and disturbing of PPARg signaling leads to serious diseases such as obesity,

in HFD-GA hepatocytes were reduced noticeably compared to HFD-ctrl,

diabetes, insulin resistance and cardiovascular diseases. Therefore, it is of

indicating that GA treatment reduced neutral lipid accumulation in the liver.

topical interest to develop reliable, high throughput in vitro system allowing

These evidence collectively suggested that GA acts as a modulator of

screening and identification of compounds affecting PPARg activity. In the

HNF4a, not only alleviating hepatosteatosis but also reducing hepatic

current work, we developed the unique stably transfected human reporter

secretion of TG-rich VLDL implying an underlying mechanism for antiviral

cell line T24/83-PPARgamma for the assessment of PPARg transcriptional

and hepatoprotective properties.

activity. Reporter cell line was prepared by transfecting the human bladder

carcinoma cell line T24/83 with reporter plasmid pNL2.1[Nluc/Hygro]

DOI: 10.1530/endoabs.49.EP801

containing three copies of PPARg response element, coupled with minimal

promoter. Design of response element was based on the sequences of

promoter region of human acyl-CoA-oxidase. In the cells treated with

PPARg ligand 15-deoxy-d12,14-prostaglandin J2 and prostaglandin D2 for

24 h, luciferase activity ranged from 40-fold to 50-fold and from 70-fold to

80-fold, respectively

(RLU 10⁴-10⁵). Application of PPARg selective

antagonist T0070907 resulted in inhibition of luciferase activity, indicating

EP802

specific response of T24/83-PPARgamma cell line. The inducibility of

5a-THB as a novel anti-inflammatory drug: The roles of the

luciferase activity remained unaffected after cryopreservation and even after

glucocorticoid and mineralocorticoid receptors

prolonged cultivation for more than 2 months. Based on these results, the

Amber Abernethie¹, A Gastaldello¹, RA Morgan¹, C Mitchell¹,

novel human reporter cell line T24/83-PPARgamma can be considered as a

KJ McInnes¹, K Beck⁴, A Odermatt⁴, R Houtman³, D Melchars³,

potential tool for screening of compounds affecting PPARg activity,

OC Meijer², PWF Hadoke¹, DEW Livingstone¹, BR Walker¹ & R Andrew¹

applicable in various toxicological and environmental studies.

¹University of Edinburgh, Edinburgh, UK;²University of Amsterdam,

DOI: 10.1530/endoabs.49.EP803

Amsterdam, The Netherlands;³PamGene International, Den Bosch,

The Netherlands;⁴University of Basel, Basel, Switzerland.

Glucocorticoids

(GC) are potent anti-inflammatory compounds, acting

mainly through the glucocorticoid receptor (GR). GC therapy, however, has

debilitating side-effects, necessitating safer new alternative therapies. The

EP804

natural GC metabolite

5a-Tetrahydrocorticosterone

(5aTHB) is anti-

Functional characterization of inherited S127F substitution in V2

inflammatory in vivo in mice, but with fewer side-effects. Its mechanism

vasopressin receptor revealed a loss-of-function mutation leading to

of action is unknown, and here we test signalling via GR and the

nephrogenic diabetes insipidus

mineralocorticoid receptor (MR). 5aTHB displaced dexamethasone (Dex)

László Erdélyi¹, András Balla^1,2 & László Hunyady^1,2

from primary rat hepatocytes (nZ6, Kd (nM): Dex 37G8, corticosterone

¹Department of Physiology, Semmelweis University, Budapest, Hungary;

153G59, 5aTHB 268G78) but only negligibly from isolated human GR

²MTA-SE Laboratory of Molecular Physiology, Hungarian Academy of

(nZ3, EC₅₀ (mM): Dex 0.004, cortisol 0.019, 5aTHB 480). GR nuclear

Sciences and Semmelweis University, Budapest, Hungary.

translocation was quantified by western blot after nuclear

(N) and

cytoplasmic (C) separation of steroid-treated A549 cells. Dex (100 nM)

increased the N/C GR ratio, after 30 minutes (0.59G0.26 to 2.97G0.50,

P!0.0001) and 24 h (0.47G0.29 to 2.23G0.72, P!0.05). In contrast, GR

The V2 vasopressin receptor (V2-R) mediates the effect of vasopressin on

translocation was not observed with 5aTHB (1, 3 or 10 mM) at either time

the water reabsorption in the kidney and several mutations in the V2-R have

(nZ6). Similarly, GR Ser211 phosphorylation was increased by (1 mM)

been identified causing nephrogenic diabetes insipidus (NDI). In this study,

corticosterone

(B;

5.00G1.05 fold vs vehicle, P!0.0001) but not by

we investigated a previously not characterized mutation of the. We obtained

(10 mM) 5aTHB (2.74G0.35 fold vs vehicle, not significant). MARCoNI

genomic DNA of a young male patient with NDI, the AVPR2 gene was

(Pamgene) peptide array analysis (nZ3) demonstrated that Dex altered the

amplified with PCR and a missense mutation (S127F) was identified. We

interaction of GR ligand binding domain (LBD) with 75 co-regulator

monitored the cellular localization of the S127F mutant V2 receptor using

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

HA-tagged receptors in confocal microscopy experiments. The S127F V2

¹Klinik fur Augenheilkunde - Charité Universitatsmedizin Berlin, Berlin,

receptor was detected only in the endoplasmic reticulum but not in the

Germany;²Institut fur Experimentelle Pädiatrische Endokrinologie, Charité

plasma membrane. We also measured the cAMP signaling capability of the

- Universitatsmedizin Berlin, Berlin, Germany; ³Institute of Anatomy,

mutant receptor with BRET measurements. The S127F receptor was not

Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.

able to increase the intracellular cAMP levels in response to vasopressin

stimulation. Certain ER retention mutations can be rescued by pharma-

cological chaperones, which cause misfolded mutant receptors to present in

3-Iodothyronamine

(3-T₁AM) is an endogenous metabolite of thyroid

the plasma membrane. We examined the effect of tolvaptan

(V2R

hormone (TH) for which was shown to have various effects. One of the

antagonist) on the S127F V2 receptor. HEK293 cells were transiently

effects is body temperature decline, which may be related with menthol

transfected with the plasmid of the mutant receptor and after one day the

receptor TRPM8. Normally, this ion channel is expressed in neuronal tissue,

cells were incubated for 18 hours with tolvaptan. After the pretreatment, the

where it has a nociceptive role. Functional TRPM8 expression has also been

cells were exposed to vasopressin, and we were able to detect cAMP signal

shown in non-neuronal cells of the eye such as corneal and conjunctival

generation of the mutant receptor. We checked whether the result after

epithelial cells, corneal endothelial cells as well as human corneal

tolvaptan pretreatment was due to restored plasma membrane location of the

keratocytes. Furthermore, we could demonstrate in previous studies that

receptor. We were able to demonstrate significant increase of the mutant

3-T₁AM acts as a cooling agent in human corneal epithelial and conjunctival

receptors in the plasma membrane using flow cytometry. Since the tolvaptan

epithelial cells and that it is suppressing TRPV1

channel

(capsaicin

is already used in the treatment of multiple diseases, we plan to carry out

receptor), which plays an important role in dry eye disease. Here, we

clinical studies to assess the potential therapeutic usage of this drug in the

determined in a human corneal endothelial cell line (HCEC-12) and a human

NDI patients with S127F V2R mutation. This work was supported by

corneal keratocyte cell line (HCK) if 3-T₁AM also acts as a cooling agent to

National Research, Development and Innovation Fund (NKFI K116954).

directly affect TRPM8 at a constant temperature. Functional activity was

DOI: 10.1530/endoabs.49.EP804

evaluated by comparing the effects of 3-T₁AM with those of TRPM8 known

agonists on intracellular Ca^2C currents and whole-cell currents using

fluorescent Ca^2C-imaging and planar patch-clamping. Menthol (500 mM), a

specific TRPM8 activator, evoked a Ca^2C influx as well as an increase of

whole-cell currents. This effect could be blocked by BCTC (20 mM) and

AMTB (20 mM), both selective TRPM8 antagonists. Notably, comparable

effects were observed with 1 mM 3-T₁AM. Overall, this study completes our

EP805

previous studies of human corneal and conjunctival epithelial cells.

Effects of human interleukins on transcriptional activity of vitamin D

Interestingly, the effect of 3-T₁AM has a similar Ca^2C response pattern

receptor in transgenic gene reporter cell lines IZ-VDRE and IZ-CYP24

and similar whole-cell current pattern in all three layers of the cornea.

Iveta Bartonkova, Aneta Grycova & Zdenek Dvorak

Therefore, this might represent a general biological phenomenon. Further

Department of Cell Biology and Genetics, Faculty of Science, Palacky

investigation of 3-T₁AM effects on the cornea should be performed in order

University, Slechtitelu 27, 783 71 Olomouc, Czech Republic.

to better characterize a potential benefit of 3-T₁AM on the treatment of dry

eye disease.

DOI: 10.1530/endoabs.49.EP806

Vitamin D receptor (VDR) signalling can be affected with a variety of

compounds, both endo- or exogenous. However, any disruption of VDR

transcriptional activity can exert severe physiological or pathophysiological

outcomes. It is therefore of a great importance to have a reliable in vitro

screening technique that would provide a tool for efficient identification of

agonists and activators of human VDR. In the current work, we described

two novel human reporter cell lines IZ-CYP24 and IZ-VDRE, constructed

EP807

for the purpose of VDR transcriptional activity detection. Parental human

Cytotoxic activity of plant extracts from Brazilian biome in prostate

adenocarcinoma cell line LS 180 was stably transfected with a reporter

cancer cell lines

construct CYP24_minP-pNL2.1[Nluc/Hygro] containing a sequence from

Sarah Cardoso, Matheus Andrade, Vinicius Cunha, Cristian Silva,

the promoter region of human CYP24A1

gene

(IZ-CYP24), or

Patrícia Rodrigues, Mayra Leão, Christopher Fagg, Eliete Guerra,

VDREI3_SV40-pNL2.1[Nluc/Hygro] containing three copies of VDREI

Francisco Neves, Luiz Simeoni, Dâmaris Silveira & Adriana Lofrano-Porto

from the promoter region of human CYP24A1

gene

(IZ-VDRE),

University of Brasilia, Brasilia, Brazil.

respectively. Both our cell lines remained fully functional in the cell culture

for more than 2 months (corresponding to 30 passages) and even after

Introduction

cryopreservation. Luciferase inductions ranged from 10-fold to 25-fold

Prostate cancer is a public health problem worldwide. The cure is unlikely and

(RLU 10⁶-10⁷) and from 30-fold to 80-fold (RLU 10³-10⁴) in IZ-VDRE and

therapeutic alternatives are limited. The Brazilian biodiversity represents a huge

IZ-CYP24 cells, respectively. Time-course analyses revealed the possibility

source of potential discovery of new drugs derived from plants. We therefore

to detect VDR activators as soon as after 8 hours of incubation. Both our cell

aimed to conduct a biomonitoring chemical study of plant extracts from Pouteria

lines were highly selective towards VDR agonists, no cross-talk with

sp. previously shown to be cytotoxic in androgen-sensitive

(LNCaP) and

retinoids, thyroids or steroid was observed. As a proof of concept, the effect

androgen-resistant (PC3) human prostate cancer cell lines.

of 13 human interleukins on VDR transcriptional activity was examined.

Methods

Luciferase assays showed an inhibition of VDR transcriptional activity by

The crude ethanolic extract of Pouteria caimito leaves and hexanic extract of

interleukin-4 and interleukin-13, reaching approximately 60% of calcitriol-

Pouteria ramiflora were tested in PC3 and LNCap human prostate adenocarci-

induced luciferase signal in concentrations about 1 ng/ml after 24 h of

noma cells. The crude extract of P. ramiflora branches and stem was then pre-

incubation in IZ-CYP24 cell line. Similar results were obtained from

fractionated through sintered funnel. The pre-fraction hexane: ethyl acetate 1:1

expression analyses of human CYP24A1 mRNA. Taken together, both of

was fractionated by column chromatography into

649

fractions, grouped

these cell lines provide a tool for reliable, high-throughput and selective

according to the profile in thin layer chromatography into 49 samples. Among

identification of VDR ligands, with possible implications in toxicological

those, four samples were selected for Nuclear Magnetic Resonance (NMR)

and environmental studies.

spectroscopy, based on their abundance and cytotoxicity biomonitored by MTT.

DOI: 10.1530/endoabs.49.EP805

Results

The ethanolic extract of P. caimito showed a dose-dependent cytotoxic effect in

PC3 cells (O50%), with a statistically significant inhibitory effect on the cell

cycle. The hexanic extract of P. ramiflora showed a dose-dependent cytotoxic

effect in LNCaP, with a high selectivity index (5.5 after 48 h of treatment), as

compared to a non-cancerous human cell line (HaCat). Among the 49 samples

obtained from this extract, fraction “8” was purified and the compound epi-

EP806

friedelanol was isolated, whose bioactivity is under evaluation in prostate cancer

3-Iodothyronamine induces transient receptor potential melastatin 8

cell lines.

(TRPM8) channel activation in human corneal endothelial cells and

Conclusion

human corneal keratocytes

Our biomonitored analysis of Pouteria sp. extracts has provided the purification

Nina Ljubojevic¹, Noushafarin Khajavi², Katharina Lohse¹,

of a number of cytotoxic fractions. Among those, a triterpenic bioactive

Monika Valtink³ & Stefan Mergler¹

compound (epi-friedelanol) was identified by RMN spectroscopy, and deserve

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

further studies regarding its specific cytotoxicity. Triterpens have been shown to

unique gut-derived peptide that has major impact in energy homeostasis and

exert cytotoxic effects on different types of cancer at low activity towards normal

weight regulation, with new emerging implications in tumorigenesis process,

cells, including prostate cancer.

especially in hormone-dependent cancers.

DOI: 10.1530/endoabs.49.EP807

Aim

To evaluate the relationship between ghrelin, clinico-biological parameters of

obesity and gonadotropic axis in breast cancer patients.

Patients and Methods

We assessed the relationship between fasting ghrelin and anthropometric

measures, insulin-resistance, lipid and glucose metabolism parameters, hypo-

thalamic-pituitary-gonadal axis (HPG): FSH, testosterone/estradiol-ratio, SHBG,

and body composition (evaluated by dual-energy X-ray absorptiometry) in 64

Obesity

breast cancer patients. Both acyl-ghrelin (AG) and des-acyl-ghrelin (DAG) were

EP808

evaluated through ELISA; total ghrelin (TG) was calculated as the sum of the two.

Evolution of patients with amyotrophic lateral sclerosis followed in a

Results

nutrition and endocrinology specific unit during 3 years

DAG, but not AG, negatively correlates with BMI (rZK0.280, PZ0.013), waist

Inmaculada Gonzalez-Molero, Monserrat Gonzalo, Viyu Doulatram,

circumference

(rZK0.335, PZ0.006) and waist/hip ratio

(rZK0.302,

Jose Abuin, Francisco Tinahones & Gabriel Olveira

PZ0.015). Concerning body fat distribution, DAG negatively correlates with

Hospital REgional de Málaga, Malaga, Spain.

sub-total (rZK0.326, PZ0.005) and truncal fat mass (rZK0.273, PZ0.02).

Even stronger association of these parameters was observed with TG. Also, DAG

negatively correlates with insulin l

(rZK0.354, PZ0.003) and HOMA-IR

Introduction

(rZK0.343, PZ0.004). Concerning HPG, AG, but especially AG/TG-ratio were

A high percentage of patients diagnosed with Amyotrophic Lateral Sclerosis

positively correlated with FSH (rZ0.354, PZ0.004) and SHBG (rZ0.272,

(ALS) have malnutrition. The nutritional treatment in ALS is essential, affecting

PZ0.03). Even though no direct correlations were found between ghrelin and

muscle strength, quality of life and survival.

HPG, we observed that insulin positively correlates with testosterone/estradiol-

Objective

ratio (rZ0.247, PZ0.039), as with SHBG (PZ0.341, PZ0.004), and that the hip

To describe the nutritional characteristics of patients evaluated in a specific

circumference was positively correlated with free-testosterone levels (rZ0.251,

nutritional Unit in patients with ALS during 3 years.

PZ0.044).

Material and methods

Conclusions

A descriptive study of all patients diagnosed with ALS and evaluated in this

Ghrelin has definitely indirect effects in breast cancer through its roles in obesity

specific consultation since October 2013. The nutritional status is assessed by

and insulin-resistance. We described different connections between ghrelin-

anamnesis, 24-h ingestión count, physical examination (BMI, % lost weight,

obesity-gonadotropic axis in these patients, underlying discreet metabolic and

Plicometry, dynamometry), evaluation of dysphagia by EAT-10 (if positive,

hormonal modifications. However, ghrelin may also play a direct role in breast

volume viscosity test) and analytical tests.

cancer pathogenesis due to its recently discovered anti-aromatase effect in

Results

adipocytes.

Data were obtained from 60 patients. Mean age at diagnosis: 57.5 years (26-79

DOI: 10.1530/endoabs.49.EP809

years),

65% male. Bulbar: 28.6%, spinal: 61.2%. The mean time until the

evaluation in nutrition Unit was 22.1 month (12.6 in bulbar vs 24.7 in spinal,

P!0.05). The initial BMI: 26.4 (18.1 to 36.2), in 78.3%O 25. The nutritional

status in the first consultation was

(VSG): 23% of patients with moderate

malnutrition, 17.1% of severe malnutrition (30.8% of bulbars vs 5.9% of spinal,

P!0.05). The most frequent analytical alterations were vitamin D insufficien-

cy/deficiency

(58.3%) and hypercholesterolemia

(50%). The most frequent

analytical disorders were vitamin D deficiency/insufficiency

(58.3%) and

EP810

hypercholesterolemia

(22.5%). Nutritional intervention at the first visit was

Differences in calcium and thyroid homeostasis and thyroid volume

only diet in 46% (7.1% bulbar vs 69% in spinal, P!0.05), thickening prescription

after bariatric surgery

in 34%, nutritional supplements in seven patients, gastrostomy in three patients

İffet Dagdelen Duran¹, Nese Ersoz Gulc¸elik2, Dilek Berker1 &

(all of them bulbar). Of the patients who were offered gastrostomy during follow-

Serdar Guler¹

up (56.8%), 68.4% accepted. The main reason for this was weight loss (83%). The

¹Ankara Numune Education and Research Hospital, Department of

FVC (Forced vital capacity) at this time was: 58% (23 to 97%) and 100% were

Endocrinology and Metabolic Diseases, Ankara, Turkey;²Ankara

endoscopic. As complications of gastrostomy: three patients had accidental

Education and Research Hospital, Department of Endocrinology and

withdrawal. The mean survival time after gastrostomy was 14 months (2-25

Metabolic Diseases, Ankara, Turkey.

months).

Conclusions

- 40.1% of patients with ALS present moderate/severe malnutrition in the first

Introduction

assessment.

Bariatric surgery would end up with great alterations in homeostatic measures

- BMI and analytical parameters are not early markers of malnutrition, being

such as glucose and lipid metabolism and hormonal regulation, which of all are

weight loss the best marker.

interweaved with some number of ways to each other. The hormonal modulation

- Patients with bulbar ALS present malnutrition more frequently than spinal

extands along a wide span starting from the change in gastrointestinal peptides, to

forms and require an earlier and more aggressive nutritional intervention.

the effect in insulin and other nutrient metabolism regulatory hormones and even

DOI: 10.1530/endoabs.49.EP808

the hormones establishing thyroid and calcium homeostasis. Secondary

hyperparathyroidism is a common finding associated with decreased nutrient,

mineral and vitamin D absorption after gut lumenal loss due to bariatric surgery.

Meanwhile when the adaptation of thyrotropin (TSH) and free t4 (fT4) level

shows variance among studies, in fact TSH frequently was reported to decrease.

Free t3 (fT3) was constantly shown to decrease, used to be correlated with

dysfunction in deiodination. The thyroid volume would also be a candidate of

other parameter that is expected to change over postsurgical period.

EP809

Materials and Methods

Obesity, gonadotropic axis and breast cancer - is ghrelin the

We recruited 67 morbidly obese patients planned to have bariatric surgery. All the

connexion?

subjects were recorded for their body weight, BMI, metformin, insulin and

Ioana Armasu^1,2, Iulia Crumpei^1,2, Constantin Volovat³, Mariana Tofan³,

levothyroxine(LT4) usage and if used dosage of the drug before the operation.

Valentin Zaharia², Adrian Aancutei², Ioana Vasiliu¹, Ionela Lacramioara

The patients were examined with hormonal [parathormon(PTH), 25-oh-vitamin

Serban¹ & Carmen Vulpoi^1,2

d3(25vitD3), TSH, fT3, fT4 and biochemical tests [calcium(Ca), ionized Ca(iCa),

¹University of Medicine and Pharmacy, “Gr.T. Popa”, Iasi, Romania;

phosphorus(P), 24 hour(h) urinary Ca]. Thyroid ultrasonography (USG) were

²County Emergency Hospital, “Sf. Spiridon”, Iasi, Romania;³Victoria

performed by one same practitioner and the diameters of each lobe was given as

Hospital, Iasi, Romania.

axbxc(cm). The volume of each lobe was calculated with axbxcx0.524 (cm³), and

total thyroid volume with addition of right to left lobe volume. The number of

Introduction

nodules and the size of largest nodule were also recorded. The antropometric

Obesity and insulin resistance have been identified as risk factors for breast cancer

measures, drug consumption data, laboratory tests and thyroid USG were repeated

and are associated with late-stage diagnosis and poor prognosis. Ghrelin is a

after 12 month of surgery.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

Aim

The mean age of patients was 41.5G9.6 year. 58 (86.5%) subjects were female,

To report the clinical findings in a third case with overgrowth related to a small

while 9(13.5%) were male. After 12 month of surgical approach, mean body

microduplication of 15q26.3 not including the IGF1R region.

weight decreased from 120.3G4.1 kg to 85.4G3.3 kg (P:0.00), BMI from 47.8G

Methods

1.4 kg/m² to 34.0G1.2 kg/m² (P:0.00), TSH from 2.3G0.2 to 1.1G0.2 mIU/ml

Comparative genome hybridization was done using an Agilent 180k microarray

(P:0.00), fT4 from 1.0G0.0 to 0.5G0.0 ng/dl (P:0.00), fT3 from 2.5G0.1 to

platform.

1.3G0.1 pg/ml (P:0.00), PTH from 48.6G4.7 to 24.4G4.4 pg/ml (P:0.00), Ca

Results

from 8.0G0.4 to 5.0G0.6 mg/dl (P:0.00), and thyroid volume from 9.6G2.2 to

Accelerated linear growth was observed after the first 3 months with a normal

4.0G0.8 cm³ (P:0.022) significantly. Levothyroxine and insulin requirement

weight increase in a female patient, born at 36 weeks of gestation by normal

decreased after operation nonsignificantly. 25vitD3 increased, 24 h urinary Ca

delivery. At birth weight was 3200 g (O97th centile), length 52 cm (O97th

decreased again nonsignificantly.

centile) and head circumference (HC) 35.5 cm (97th centile). Mother’s and

DOI: 10.1530/endoabs.49.EP810

father’s height was 182 cm. She had transient feeding problems, necessitating

nasogastric feeding in the first week of life. She presented with delayed motor

development. Teeth erupted prematurely. At the age of 2 years, her length was

96 cm (O 97th centile), weight 16 kg (97th centile), HC 51 cm (97th centile) and

armspan 96 cm. She showed a high forehead, mild synophris, epicanthal folds,

deep-set eyes, a flat nasal bridge, mid face flattening, a prominent chin, and

tapering fingers. Ultrasound of the abdomen and heart were normal. Bone

maturation and serum IGF-1 were normal. ArrayCGH analysis showed a de novo

Paediatric Endocrinology

1.6 Mb duplication of 15q26.3 (arr

15q26.3q26.3 (98386658 99753407)x3).

EP811

Speech delay and mild coordination and motor problems were noted later on,

Sebaceous hyperplasia and androgen levels-still controversial

whereas height and weight progressed normally but above the 97th percentile. At

Anca E Chiriac¹, Anca Chiriac^2,3 & Doina Azoicai¹

the age of 4 year, mitral valve insufficiency developed, necessitating a surgical

¹University of Medicine and Pharmacy, “Grigore T Popa”, Iasi, Romania;

repair.

²Apollonia University, Iasi, Romania;³Nicolina Medical Center, Iasi,

Conclusions

Romania;⁴“P Poni” Research Institute, Iasi, Romania.

The previous and this case report highlight the possible involvement of the distal

region of 15q in infantile overgrowth, independent of IFGR1 duplication. Delayed

speech development, tall stature and macrocephaly with a prominent chin appear

constant findings, while cardiac manifestations may be variably present.

Sebaceous glands are very sensitive to androgens which can modify the size but

DOI: 10.1530/endoabs.49.EP812

not the number of sebaceous glands. Sebaceous hyperplasia is a common benign

proliferation of the sebaceous glands seen during the first weeks of life, being

reported in 89.4% of 1000 newborns enrolled in across-sectional prospective

study in the period of November 2007 to May 2009 in India [1] or in 35% of 2938

neonates aged up to three days of life hospitalized in a Brazilian city [2]. Sebum

secretion is high in neonates probably induced by maternal androgen:

dehydroepiandrosterone transferred trans-placental. [3] It is also named “the

miniature puberty of the newborn” along with vaginal bleeding in infant girls and

neonatal acne. Reduced androgen levels in elderly could explain hyperplasia of

sebaceous glands

(slower cell turnover), especially in women while high

androgen-dependent sebum secretion in neonates results in neonatal sebaceous

hyperplasia. The association between sebaceous hyperplasia and androgens has

EP813

been demonstrated in animal models [5], but no correlation was found between

A very rare case of 48, XXYY syndrome

serum androgen levels and the appearance of sebaceous hyperplasia lesions in

Ioana Alexandra Ambarus Popovici¹, Cristina Rusu^2,3, Alina Andreea

women [6].Controversial data exist and further clinical studies are required.

Oprea¹, Laura Feraru¹, Raluca Balaceanu¹ & Cristina Preda^1,3

¹University Hospital, “St. Spiridon” Iasi, Iasi, Romania;²University

Hospital for Children “St. Maria” Iasi, Iasi, Romania;³University Of

Table 1 Differences between neonatal and adult form of sebaceous

Medicine and Pharmacy, “Gr. T. Popa”, Iasi, Iasi, Romania.

hyperplasia [4].

Neonatal sebaceous

Adult sebaceous gland

Introduction

gland hyperplasia

hyperplasia

48, XXYY is a rare sex chromosome aneuploidy, being estimated to occur in

1:18000-1:40000 male births. Phenotypically it was considered a variant of

Age of onset

First weeks of life

Middle age-elderly

Klinefelter syndrome (47,XXY), but currently, due to mental deficiency and

persons

behavioural characteristics associated, it’s considered to be a separated genetic

Gender: males/females

1.08/1

condition.

Sites of skin lesions

nose

forehead,genitalia,

Case report

areola, chest

We report a case of a 8-year-old boy, first child of a young non-consanguineous

Androgen levels

high

low/normal

couple, born at term. Due to minor dysmorphic facial features, hypospadias and

(hyper-receptivity)

bilateral talus valgus, a genetic test was conducted and the karyotype identified

Evolution

Spontaneously

progressive evolution

was 48,XXYY. He was frequently hospitalized for upper respiratory infections,

remission within

without treatment

gastro-enteritis, recurrent otitis. He was diagnosed with viral induced asthma and

weeks

IgA and IgG subclass deficiencies, developing food and medication allergies.

Physical examination revealed normal height and weight, dysmorphic facial

features (thick eyebrows, hypertelorism, mongoloid slant of the eyes, convergent

DOI: 10.1530/endoabs.49.EP811

strabismus, thin lips, dental problems), bifid scrotum, hypospadias, sacral sinus,

clinodactyly of the fifth finger, bilateral talus valgus surgically corrected.

Neuropsychiatric evaluation revealed borderline mental retardation, delayed

speaking, aggressive behaviour, learning difficulties. The endocrinologic consult

showed a normal thyroid axe, with a normal-low testosterone level

EP812

(!0.025 ng/ml) associated with a FSH level of 0.98 mUI/ml (0.4-3.8) and LH

Microduplication of 15q26.3 not including IGF1R as a novel genetic

level !0.1 mUI/ml (0-3,8). Thyroid ultrasound was normal, testicular ultrasound

cause of infantile overgrowth

revealed hypoechoic testis, the X-ray of the hand revealed delayed bone age.

Jean De Schepper^1,2, Denis Libeert² & Bert Callewaert²

Conclusions

¹UZ Brussel, Brussels, Belgium;²UZ Gent, Ghent, Belgium.

48,XXYY was described as a variant of 47,XXY syndrome. It is very important to

distinguish the two syndromes regarding the associated medical conditions (as in

our case - asthma, food allergies, dental problems, strabismus, recurrent otitis,

Introduction

frequent upper respiratory infections), cognitive and behavioural problems,

Recently, a microduplication of 15q26.3 not including IGF1R was reported in

learning difficulties which are more frequently correlated with

48,XXYY

subjects of two families with overgrowth and variable intellectual disability

syndrome. Due to complexity and specific features of this particular syndrome,

(Leffler M. et al., Eur J Med Gen, 2016).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

it is recommended a thorough evaluation and a different therapeutic attitude for

which was noted to have started in the first few days of life. He had normal serum

each case.

sodium concentration (142 mmol/l), high serum osmolality (311 mOsm/l), low

DOI: 10.1530/endoabs.49.EP813

urinary osmolality (129 mOsm/kg), and hyponatriuria (15 mmol/l) on admission.

The water deprivation test was stopped due to weight loss higher than %3 at 3.5th

hour of the test. The plasma vasopressin (16.75 pmol/l, range:0-13) drawn at the

conclusion of the dehydration test was high, and the urine parameters showed

little insignificant changes. The desmopressin challenge test did not affect the

urine parameters, either. There was a continuous high urine output, low urine

osmolality and impaired ability to increase urine osmolality to normal levels after

ADH administration. The AVPR2 gene of this patient was sequenced with

ABI310 and revealed a novel hemizygous missense mutation causing a

conversion of the histidine residue to tyrosine in the protein sequence, at the

EP814

position 80th in exon 2. We suggest that bioinformatical analysis and functional

Clinical case of early manifestation of autoimmune polyglandular

characterization studies will enlight the function of the mutant AVPR2 protein.

syndrome type 3 A in children

This research was funded by The Scientific and Technological Research Council

Julia Volk & Anzhalika Solntsava

of Turkey (SBAG Project Numbers: 112S513 and 115S499).

Belarusian State Medical University, Minsk, Belarus.

DOI: 10.1530/endoabs.49.EP815

Autoimmune polyglandular syndrome (APS) type 3 - is a rare orphan disease,

which is a combination of autoimmune thyroid disease and diabetes mellitus

(DM) type 1 and/or pernicious anemia, vitiligo, alopecia. Due to the rare

occurrence in pediatric patients we give our own observation of early

manifestation of APS type 3 A in a girl 10 years. Complaints in the primary

treatment: sweating, irritability, cardiopalmus, weight loss. Survey results:

ultrasound examination of the thyroid gland: expressed diffuse changes, the

EP816

increase in volume K22.0 cm³

(normal

2.74-6.76). Indicators: thyroid-

Type 1-like diabetes mellitus in an oncological endocrinology unit

stimulating hormone (TSH) 0.05 mkIE/ml (normal 0.27-4.2), free thyroxine

Sara Donato, Sónia Andrade, Daniela Dias, Joana Simo˜es-Pereira &

(T4) O100.0 pmol/l (normal 12.0-22.0), free triiodothyronine (T3) 43.1 pmol/l

Maria da Concei

¸a˜o Pereira

(normal

3.1-6.8), TSH receptor antibodies

18.0 IU/l

(normal

0-1.75).

Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon,

Ophthalmologist: ophthalmopathy low degree of both eyes. Primary diagnosis:

Portugal.

Graves’ disease

(GD), goiter grade

2, thyrotoxicosis of medium gravity,

decompensation. Autoimmune ophthalmopathy. Starting treatment: tiamazol

20 mg/day; metoprolol 25 mg/day. 6 months later the patient was hospitalized

Introduction

with complaints during the month of thirst, frequent urination, weight loss of

Asparaginase is a component of chemotherapy regimens used to treat paediatric

4.5 kg, weakness. Survey results: blood glucose level 34.1 mmol/l. Acid-base

acute lymphoblastic leukaemia (ALL). One of its well-known side effects is

balance: metabolic acidosis. Indicators: C-peptide 155.6 pmol/l (normal 160-

hyperglycaemia which is probably related to hypoinsulinemia. Its incidence rises

1100), antibody titer to glutamic acid decarboxylase 93.2 U/ml (normal 0-1.0),

significantly when associated with corticotherapy. We present two cases of

glycated hemoglobin 9.5%. The metabolic compensation of thyrotoxicosis was

diabetes related to asparaginase and corticoid administration.

observed on maintenance therapy (tiamazol 5 mg/day): T4 17.16 pmol/l, TSH

Case 1

!0.05 mkIE/ml. There was a volume reduction 16.2 cm³ on thyroid ultrasound.

Eleven-year-old girl diagnosed with an ALL. Before treatment she had a normal

Final diagnosis: APS type 3 A: DM, type 1, decompensation. GD, medical

body weight and was normoglycaemic. She started the DFCI-2011 protocol and

euthyroidism. Autoimmune ophthalmopathy. Treatment: insulin therapy

on the day of the first peg-asparaginase administration she was found to have

U/day; tiamazol 5 mg/day. 2 months later a child was hospitalized due to

polydipsia, polyuria and a glycaemia of 700 mg/dl with no clinical evidence of

worsening indicators of thyroid hormones and severe fluctuations in blood

pancreatitis. She started an intensive insulin scheme of therapy with an average

glucose on the treatment of human genetic engineering insulins. Survey results:

dose of 0.6 U/kg/day. On the 16th day insulin dose started to be reduced. Despite

thyroid ultrasound: negative dynamics - increase to 21.08 cm³. Indicators: TSH

the higher doses of corticosteroids in the following asparaginase infusions she

0.009 mkIE/ml, T4

24.8 pmol/l, T3

10.06 pmol/l. Correction of therapy:

needed lower doses of insulin to maintain euglycaemia.

increasing the dose of tiamazol to 20 mg/day and using insulin analogs. The

Case 2

simultaneous presence of two or more autoimmune diseases of the endocrine

Six-year-old boy diagnosed with an ALL at the age of three. He was first treated

glands (thyroid and DM) aggravates the symptoms of each of them, leads to the

with DFCI-2005 protocol without evidence of hyperglycaemia. A remission

decompensation of patients.

lasting 10 months was achieved with recurrence diagnosed at the age of six. He

DOI: 10.1530/endoabs.49.EP814

started the IntReALL-SR-2010 protocol and before this treatment his body weight

was between P25-50 and he was normoglycaemic. Seven days after the first peg-

asparaginase administration he was found to have a glycaemia of 519 mg/dl with

ketonuria of 5 mg/dl, without clinical evidence of pancreatitis. He started an

intensive insulin scheme with an average dose of 1.5 U/kg/day. Eleven days after

the second peg-asparaginase administration insulin dose started to be reduced and

at the end of induction course was stopped. Peg-asparaginase was administered

one last time without hyperglycaemia.

EP815

Conclusion

A novel p.H80Y mutation in the AVPR2 gene causing congenital

Asparaginase-induced hyperglycaemia may cause diabetic ketoacidosis or

nephrogenic diabetes insipidus

hyperosmolar hyperglycaemic nonketotic syndrome which can be fatal. It is

Tugce Karaduman¹, Merve Ozcan¹, Aslı Celebi Tayfur², Emel Saglar¹,

recommended a frequent assessment of glycaemia in these patients. Its occurrence

Beril Erdem¹, Dilara Sahin¹, Aysun Caltık Yılmaz², Bahar Buyukkaragoz²,

usually does not lead to suspension of therapy. Hyperglycaemia frequently gets

Ayse Derya Bulus³ & Hatice Mergen¹

better despite continuous use of asparaginase.

¹Hacettepe University, Faculty of Science, Department of Biology, Ankara,

DOI: 10.1530/endoabs.49.EP816

Turkey;²Kecioren Training and Research Hospital, Pediatric Nephrology,

Ankara, Turkey;³Kecioren Training and Research Hospital,

Infant Endocrinology Clinic, Ankara, Turkey.

X-linked nephrogenic diabetes insipidus (NDI) is a rare disease caused by a defect

in the vasopressin V2 receptor in renal collecting duct cells which is encoded by

EP817

the AVPR2 gene (Xq28). More than 200 mutations have been found comprising

P3NP has high-normal values in GHD children and correlates

missense, nonsense, small insertions and deletions, large deletions and complex

negatively with IGF1

rearrangements in AVPR2 gene to date. In this study, a 6-year-old boy was

Mariana Costache Outas^1,2, Camelia Procopiuc³, Andra Caragheorgheopol³

referred to the Pediatric Nephrology Department of Kecioren Research and

1,4

& Simona Fica

Training Hospital for abnormal fluid intake (5 l/day) and diuresis (4.3 l/day)

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;

congenital heart defects

(29%), renal malformations

(26%), autoimmune

²Coltea Clinical Hospital, Bucharest, Romania;³CI Parhon National

thyroiditis (17%) and celiac disease in one patient. Sixty-nine percent (nZ24)

Institute of Endocrinology, Bucharest, Romania;⁴Elias Emergency

were eligible for growth hormone (GH) treatment. Among these, 13 reached their

Hospital, Endocrinology Department, Bucharest, Romania.

final stature with a variation of the mean z-score from K2.78 (K4.38-K1.31)

before to K2.16 (K3.85 to 0.00) after treatment. Among patients older than 12

years (nZ21), in 62% puberty was induced by transdermal oestrogens. One

Aim

patient had two spontaneous pregnancies.

Procollagen type III N-terminal peptide (P3NP) occurs during type III collagen

Conclusions

synthesis. Previous studies about the GH misuse in athletes proved the P3NP as a

In our study treatment with GH showed improvement of the height z-score. Some

growth hormone (GH) responsive biomarker. We evaluate the P3NP levels and

girls were diagnosed very late and some of them after attended final height

correlate with IGF1 depending on GH status.

without GH treatment. It is essential to be alert to the main clinical manifestations

Subjects and Methods

of the syndrome and provide an earlier diagnosis to optimize the treatment.

We determined P3NP levels in 81 prepubertal children (35 girls) with a mean age

DOI: 10.1530/endoabs.49.EP818

of 6.2 y.o [3.37-9.95]. The group consists of 37 subjects with normal height, 18

subjects with growth hormone deficiency (GHD) and 26 subjects with non-GHD

short stature. We measured P3NP with a commercially available (for research

purpose) ELISA kit (catalog code: DL-PIIINP-Hu) with the detection range 62.5-

4000 pg/ml.

Results

In 50 subjects with values of IGF1 below 0 SDS, we found a negative correlation

of P3NP and IGF1 (rsZK0.292, PZ0.039). Even not statistically significant,

P3NP correlate negatively with height-SDS (rsZK0.210, PZ0.144). 26 values

of P3NP were out of the reference range for this biomarker. Five of these records

belongs to GHD subjects with conditions that can explain high P3NP levels

Pituitary - Basic

(hypothyroidism in the context of multiple pituitary deficiencies, trauma or

inflammation). We analyzed 55 registrations with P3NP in the normal range

EP819

available for the whole group, according to GH status. We found higher P3NP

Non-functioning pituitary adenomas: association between

levels, expressed as median of SD in the GHD group compared to normal stature

clinical-pathological and molecular parameters

children

(MZ0.7, nZ9 vs MZK0.17, nZ28) and this difference was

Ana Barrera-Martín¹, María-Carmen Vázquez-Borrego², Ángel Rebollo-

statistically significant UZ70.5, zZ1.96, PZ0.049).

Román¹, Pedro-Blas García-Jurado³, Paloma Moreno-Moreno¹,

Conclusion

María-Rosa Alhambra-Expósito¹, Álvaro Toledano-Delgado⁴,

The lack of GH-IGF1 effect in GHD children could lead to normal -high levels of

Justo-P Castan˜o2, María-Ángeles Galvez-Moreno1 & Raúl-M Luque2

P3NP because this biomarker of collagen synthesis is not effectively incorporated

¹Endocrinology Service, Hospital Universitario Reina Sofia, Córdoba,

into collagen supportive tissues.

Spain;²IMIBIC/HURS, Department of Cell Biology, Physiology and

DOI: 10.1530/endoabs.49.EP817

Immunology, University of Cordoba; CIBER Fisiopatología de la Obesidad

y Nutrición (CIBERobn); Campus de Excelencia Internacional Agroali-

mentari, Córdoba, Spain;³Radiology Service. Hospital Universitario Reina

Sofia, Córdoba, Spain;⁴Neurosurgery Service. Hospital Universitario Reina

Sofia, Córdoba, Spain.

Non-functioning pituitary-adenomas

(NFPAs) represent the most common

pituitary tumor-type. To date, there are not clinical, biochemical, anatomo-

pathological, immuno-histochemical or molecular parameters useful to predict

their remission. Therefore, the aim of this study was to evaluate the potential

EP818

relationship between the clinical, biochemical and pathological characteristics of

patients with NFPAs, the expression profile of these tumours and the clinical

Turner Syndrome (TS): overview of surveillance in a tertiary care

outcomes during their follow-up. An observational/retrospective-study of patients

hospital

with NFPAs evaluated between January 2002-December 2015 was implemented

Ekaterina Popik, Catarina Matos de Figueiredo, Joana Freitas,

at our hospital, by collecting a complete set of clinical/biochemical/radiological-

Helena Cardoso, Maria João Oliveira & Teresa Borges

data from patients

(nZ34; 50% women; age: 56.2G11.9 years-old), and

Centro Materno-Infantil do Norte, Centro Hospitalar do Porto, Oporto,

anatomopathological and molecular (26 genes measured by qPCR) data from the

Portugal.

tumours. Mean follow-up of patients: 5.2G3.9 years. Symptomatology: 38.2%

campimetric alterations, 35.3% headache and 11.8% symptoms derived from

Introduction

hormonal deficits. A predominant expression of Dopamine-receptor 2 (DRD2)

Turner syndrome is one of the most common human chromosomopathy and

followed by somatostatin-receptors (sst) 3 and 2 was found. Furthermore, a

represents an important cause of short stature and ovarian insufficiency. It is

consistent increase in the expression of the majority of receptors analyzed

caused by total or partial loss of X-chromosome and its prevalence is about 1 in

between first and second surgery of the patients was observed. Interestingly,

2000-2500 live female births.

lower expression-levels of sst1 and sst3 were found in patients pre-treated with

Objectives

statins. Correlations between receptors and/or molecular markers (i.e. DRD2 with

To review the patients with TS followed in a Paediatric Endocrinology Unit since

AVPR1b, sst5TMD5 with serum testosterone-levels or sst5TMD4 with p53-

1999.

levels) were observed. Additionally, male sex, lower levels of pre-surgery cortisol

Methods

and testosterone and low sst5, AVPR1b and PTTG1 expression were associated

A retrospective study regarding diagnosis, course, treatment and current status of

with a higher curation of patients. Although further studies with a larger cohort of

patients with TS was performed, based on medical records’ review.

well-characterized patients are needed, our molecular and clinical data suggest

Results

that a putative pharmacological treatment for this pathology might be

Thirty-five female patients were included; 62.9% showed mosaic karyotype;

somatostatin-analogues with affinity for sst3

or dopamine agonists

(e.g.

5 patients had a prenatal diagnosis and 3 during the neonatal period and in the

pasireotide or cabergoline), that statin-treatment might influence the expression

others (nZ27) the mean age of diagnosis was 7.83 years (0.40-16.11). The main

levels of some sst-subtypes (e.g. sst3), and that some clinical/molecular markers

reason for investigation was short stature

(46%); other less frequent and

(i.e. sex, pre-surgery cortisol and testosterone levels and sst5/AVPR1b/PTTG1-

sometimes combined included failure to thrive (nZ5), primary amenorrhea

expression) could be associated with the curation of patients with NFPAs.

(nZ2), foot oedema at birth (nZ2), dysmorphic features (nZ6), cardiomyopathy

DOI: 10.1530/endoabs.49.EP819

(nZ1) and hepatitis (nZ1). The main associated morbidities were: learning

disabilities

(31%), hearing and visual problems (40 and 29%, respectively),

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Steroid Metabolism C Action

260.64G114.81 and 211.44G91.67, respectively, on chorus working day (Group

II) at similar hours. Saliva cortisol levels showed a 33% decrease in Group II

EP820

while an increase of 21% was detected in Group I (P!0.02). Also a reduction

Reference values for the urinary steroid metabolome: the impact of sex

14% in stres scores was observed in Group II (P!0.04); especially remarkable in

and age on human adult steroidogenesis

women, individuals with non-alcoholic, but smokers, active employeers and

Daniel Ackermann¹, Belen Ponte², Menno Pruijm³, Claudia H. d’Uscio¹,

people who have less time engaged in music.

Idris Guessous⁴, Georg Ehret⁵, Fred Paccaud⁷, Antoinette Pechére-

Conclusion

Bertschi⁶, Pierre-Yves Martin², Michel Burnier³, Bernhard Dick¹,

We can say that individuals who perform a two-hour Turkish art music per week,

Bruno Vogt¹, Murielle Bochud⁷ & Nasser A. Dhayat¹

are affected positively by music different from the day of their normal life.

¹Department of Nephrology and Hypertension, Bern University Hospital,

Particularly due to fact that mucic is very popular, cheap and easly applicable in

University of Bern, Bern, Switzerland and Department of Clinical Research,

daily life, it seems promising to use music in daily life as strategy for stress

University of Bern, Bern, Switzerland;²Nephrology Service, Department of

reduction.

Specialties of Internal Medicine, University Hospital of Geneva, Geneva,

DOI: 10.1530/endoabs.49.EP821

Switzerland;³Nephrology Service, University Hospital of Lausanne,

Lausanne, Switzerland;⁴Department of Community Medicine, Primary

Care and Emergency Medicine, University Hospital of Geneva, Geneva,

Switzerland;⁵Cardiology Service, Department of Specialties of Internal

Medicine, University Hospital of Geneva, Geneva, Switzerland;

⁶Endocrinology Service, Department of Internal Medicine Specialties,

EP822

University Hospital of Geneva, Geneva, Switzerland;⁷Institute of Social

Inhibition of 11b-hydroxysteroid dehydrogenase 2 by the fungicides

and Preventive Medicine, University Hospital of Lausanne, Lausanne,

itraconazole and posaconazole

Switzerland.

Katharina Beck¹, Denise Kratschmar¹, Arne Meyer¹, Daniela Schuster² &

Alex Odermatt¹

Division of Molecular and Systems Toxicology, Department of Pharma-

Background

ceutical Sciences, Pharmazentrum, University of Basel, Basel, Switzerland;

Urinary steroid metabolomics by GC-MS is an established method in clinic and

²Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular

research to describe steroidogenic disorders, but normative data are scarce.

Biosciences Innsbruck (CMBI), Computer Aided Molecular Design Group,

Methods

University of Innsbruck, Innsbruck, Austria.

The 24-hour urinary excretion of 40 steroid metabolites was measured by GC-MS

in 1128 adult participants of the Swiss Kidney Project on Genes in Hypertension

(SKIPOGH), a multicenter, family-based, cross-sectional study. Sex- and age-

Impaired

11b-hydroxysteroid dehydrogenase type

(11b-HSD2)-dependent

specific reference ranges were created in the units mg/mol Creatinine and

cortisol inactivation can lead to electrolyte dysbalance, hypertension and

mg/24 hours.

cardiometabolic disease. Furthermore, placental 11b-HSD2 essentially protects

Results

the fetus from high maternal glucocorticoid levels, and its impaired function has

Most urinary steroids showed an age- and sex-specificity. An age- but no sex-

been associated with altered fetal growth and a higher risk for cardio-metabolic

specificity was found for etiocholanolone, 18-OH-11-dehydro-TH-corticosterone,

diseases in later life. Despite its important role, 11b-HSD2 is not included in

TH-cortisol, a-cortol, and b-cortol in the unit mg/mol Creatinine. No sex- but an

current off-target screening approaches. To identify potential 11b-HSD inhibitors

age-specificity was found for 20a-DH-cortisol in mg/24 hours and neither a sex-

amongst approved drugs, a pharmacophore model was used for virtual screening,

nor an age-specificity was found for TH-corticosterone and 18-OH-cortisol in

followed by biological assessment of selected hits. This led to the identification of

mg/24 hours.

several azole fungicides as 11b-HSD inhibitors, showing a significant structure-

Conclusions

activity relationship between azole scaffold size, 11b-HSD enzyme selectivity

Sex- and age-specific reference ranges for 40 steroid metabolites measured by

and inhibitory potency. A hydrophobic linker connecting the azole ring to the

GC-MS were established in a thoroughly characterized general Caucasian

other, more polar end of the molecule was observed to be favourable for 11b-

population and can be used in routine clinical work.

HSD2 inhibition and selectivity over 11b-HSD1. The most potent 11b-HSD2

DOI: 10.1530/endoabs.49.EP820

inhibition, using cell lysates expressing recombinant human 11b-HSD2, was

obtained for itraconazole (IC₅₀ 139G14 nM), its active metabolite hydroxyi-

traconazole (IC₅₀ 223G31 nM) and posaconazole (IC₅₀ 460G98 nM). Interest-

ingly, experiments with mouse and rat kidney homogenates showed considerably

lower inhibitory activity of these compounds toward

11b-HSD2, indicating

important species-specific differences. Thus,

11b-HSD2 inhibition by these

EP821

compounds are likely to be overlooked in preclinical rodent studies. Inhibition of

Does music effect the stress of daily life?

placental 11b-HSD2 by these compounds, in addition to the known inhibition of

Nevin Dinccag¹, Coskun Oruc², Sevim Oncul³, Sevda Ozel Yildiz⁴ &

cytochrome P450 enzymes and P-glycoprotein efflux transport, might contribute

Cengizhan Sonmez⁵

to elevated local cortisol levels, thereby affecting fetal programming.

¹Istanbul University, Istanbul Faculty of Medicine, Endocrinology and

DOI: 10.1530/endoabs.49.EP822

Metabolism Division, Istanbul, Turkey;²Istanbul University, Istanbul

Faculty of Medicine, Biochemistry Division, Istanbul, Turkey;³Istanbul

University, Istanbul Faculty of Medicine, Physciatry Department, Istanbul,

Turkey;⁴Istanbul University, Istanbul Faculty of Medicine, Bioistatistics

and Medical Informatics Department, Istanbul, Turkey;⁵Bahcesehir Music

Society, Istanbul, Turkey.

EP823

Cortisol levels and thyroid hormones in surgical patients with different

sensitivity to pain

Introduction

Anatoli Zhudro

It’s assumed that music has health beneficial effects by its potential stres-reducing

Republican Clinic Medical Center of the Presidential Administration,

life. There are some reports that chorists in choral soceity are influenced by music

Minsk, Belarus.

positively during their activities.

Research design and methods

37 healthy volunteers who perform Turkish art music in Bahcesehir Music

Objective

Society with mean age 50.3G10.3yrs, were included into this study. The state and

To determine the intraoperative levels of cortisol and thyroid hormones in

trait anxiety status of chorists was evaluated by using a Likertscale at the time of

surgical patients with different sensitivity to pain.

beginning (19.00) and the end (21.00) of choir, on chorus working day. After each

Material and methods

assesments, chorists were asked to collect saliva samples for cortisol levels to be

We analyzed the individual sensitivity to pain in 94 people the day before surgery.

measured later by using electrochemiluminescence immunoassay. Participants

Patients were ASA 1-2. Age 46G10.2 years. We used a mechanical stimulus (1!5

were requested to repeat the same procedure at similar times of any day in their

mm wire with stop) and the visual analogue scale of 10 points (color, grayscale,

normal lives. All data was evaluated with SPSS 20 version.

10 fields, from light to black). Incentives applied to the base of the thumb. Patients

Findings

divided into 2 groups, first group - low sensitivity to pain (VAS 1-5). 2nd group -

Although results were within normal limits in all subjects, differences were

high sensitivity to pain

(VAS 6-10). All patients underwent laparoscopic

observed on normal and chorus activity days. While mean cortisol levels (ng/dL)

cholecystectomy under general anesthesia. Anesthesia consisted of premedica-

were detected as 248.69G140.50 and 286.11G179.50, respectively, at hours

tion, induction, myoplegia, intubation, ventilation with a mixture of oxygen

19.00 and 21.00 on the normal day of life (Group I); the levels were observed as

supply, nitrous oxide and sevoflurane, anodyne - fentanyl, paracetamol. We used

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

hemodynamic monitoring and ventilation system. Control thyroid hormones (T3,

oxidation substrate. Aim of this project was to understand whether T3 influence

T4, TSH) and cortisol before operation, 3 times during surgery and after surgery.

skeletal muscle metabolism during fasting.

Statistical analysis was performed using the software package Statistica 7.0

Methods

Results

Adult male BALB/C mice were food deprived for 48h (STV), and daily treated

In all patients, the level of thyroid hormones remained normal throughout the

with intraperitoneal injections of T3 (100 mg/Kg BW) (STVT3) or vehicle as

study period. Not observed any changes of thyroid hormone levels in patients with

controls. At the end of the experiments, Tibilias anteriors were collected and

both high and low sensitivity to pain. Plasma cortisol levels remained within the

firstly laminin stained sections were analyzed for myofiber sizes by IF

normal range in 92% of patients. In 8% of the patients (all patients in the second

microscopy. Secondly, the number of glycolytic, intermediate or oxidative fibers

group, the high sensitivity to pain) noted the excess of normal levels of cortisol.

per cross section area on NADH stained histological sections was analyzed.

After the start of operation of cortisol level was higher than baseline.

Mitochondria content, indicative of a more oxidative metabolism, was then

Intraoperatively, in patients with high sensitivity to pain of the plasma cortisol

analyzed by qRT Syber Green PCR for PGC-1a mRNA.

level was higher than in patients with low sensitivity to pain.

Results

Conclusion

As expected, laminin staining evidenced a reduction in Cross Sectional Area of

Perioperative levels of thyroid hormones and cortisol most surgical patients

the myofibers induced by fasting (STV), as a sign of atrophy. The cited reduction

remains within the normal range. Patients with high sensitivity to pain was higher

was significantly hampered by the presence of T3 in the STVT3 group. Secondly,

cortisol levels after starting operation as compared to the level of cortisol in

T3 was able to significantly reduce the shift in the metabolism towards a more

patients with low sensitivity to pain.

oxidative state (P!0.05) and a less glycolytic one (P!0.01) induced by fasting.

DOI: 10.1530/endoabs.49.EP823

Coherently, T3 reduced the increase in PGC-1a mRNA level induced by fasting in

the STV group (P!0.05).

Conclusions

The decrease of the amount in oxidative muscle fibers during T3 treatment in STV

agrees with a less expression of PGC-1a, a molecular marker of mitochon-

driogenesis and fatty acid oxidation. Therefore, T3 treatment during fasting seems

EP824

to exert a protective role on the metabolism of muscle fibers.

Ritonavir induced Cushing’s Syndrome in a patient under inhaled

DOI: 10.1530/endoabs.49.EP825

corticosteroids

Teresa Alves Pereira¹, Inês Furtado², Ana M Lopes¹, Liliana Fonseca¹ &

Isabel Palma¹

¹Endocrinology Department, Centro Hospitalar e Universitário do Porto,

Porto, Portugal;²Internal Medicine Department, Centro Hospitalar e

Universitário do Porto, Porto, Portugal.

EP826

Introduction

False memory in elderly patients with thyroid disease

Cushing’s Syndrome secondary to inhaled or topic corticosteroids is very rare,

Anna Golda¹, Agnieszka Sawicka¹, Agata Bielecka¹ &

although there are reports of a link to cytochrome inhibitors. Ritonavir, a protease

Krzysztof Marczewski^1,2

inhibitor used for treatment in human immunodeficiency virus (HIV) infection, is

¹Department of Nephrology and Endocrinology Pope John Paul II Regional

a potent inhibitor of cytochrome P450 3A4.

Hospital, Zamosc, Poland;²Faculty of Health Sciences Lublin University of

The case

Economy and Innovation, Lublin, Poland.

A 41 years old man - with personal history of asthma, HIV infection diagnosed in

2002 and hepatitis C infection since 1999 - was sent to an endocrinology consult

in January/2015 for obesity investigation and orientation. The patient presents

Introduction

with a one-year history of truncal and facial obesity and global weakness of the

The phenomenon of false memory is quite prevalent among people with cognitive

lower limbs. Moreover, the patient presented with cushingoid facies, facial

impairment. Cognitive dysfunction and its relationship with the thyroid gland has

plethora, centripetal obesity and hypotrophic upper limbs. At that time, the patient

been described. In contrast, little is known about the phenomenon of false

was under therapy with ritonavir 100mg/day, salmeterol/fluticasone 50/250 mg

memory in patients with thyroid diseases. That is why we want to introduce our

two inhalations per day and a topic betamethasone lotion 0,5mg/g twice a week.

preliminary observation.

Morning total plasma cortisol levels were low

(0,6 mg/dl) and ACTH was

Method

suppressed

(5 pg/ml). Cosyntropin stimulation test confirmed a suppressed

Patients aged 64 to 90 years (average 77) with endocrine disorders were subjected

to tests for typical geriatric assessment and tests investigating the so-called. false

pituitary-adrenal axis. Consequently, ritonavir was concluded and the clinical

picture resolved progressively.

memory, that is. “remembering” the words that were not spoken, according to the

Conclusion

method Roediger and McDermott’s

The present case underlines the importance of cytochrome inhibitors in the

Results

modification of corticosteroid metabolism and their extended effect - as in

We investigated 31 patients, of which 17 had thyroid disease. All patients with

Cushing’s Syndrome.

thyroid diseases, “remembered the” unspoken words. The best result was only 6%

of the words false “recalled”, the worst result was 75%, on average, about 35%.

DOI: 10.1530/endoabs.49.EP824

This result did not differ significantly on the outcome of patients with other

endocrine disorders, but among them were two people without the presence of

false memory. We found a negative correlation between the results of the test of

false memory and mini mental status (P!0,01). We did not find significant

correlations between the results of the tests and TSH.

Conclusion

False memory may prove to be an important problem among older people with

Thyroid (non-cancer)

thyroid disease. Although its clinical significance needs further study.

EP825

DOI: 10.1530/endoabs.49.EP826

Thyroid hormone T3 protects skeletal muscle metabolism during

fasting in mice

Valentina Russi¹, Sarassunta Ucci¹, Camilla Virili², Marco Centanni²,

Viviana Moresi³ & Cecilia Verga Falzacappa^1,2

¹Pasteur Institute, Rome, Italy;²Sapienza, University of Rome, Medical

surgical Sciences and Biotechnologies Department, Rome, Italy;³Sapienza,

University of Rome, Department of Anatomy, Histology, Forensic Medicine

and Orthopedic, Section of Histology, Rome, Italy.

EP827

Orbital disease primer for Endocrinologists-not always thyroid

Background

associated orbitopathy (TAO): a case vignette

Skeletal muscle is known to be a target of THs, regulating oxygen consumption,

Fotini Adamidou¹, Christina Manani¹, Panagiotis Anagnostis¹,

fiber composition, calcium mobilization and glucose uptake. However, a possible

Thomas Georgiou¹ & Kostas Boboridis²

role for THs in muscle homeostasis and cellular metabolism under pathological

¹Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece;

has never been investigated. Food deprivation induces skeletal muscle atrophy,

²Aristotle University of Thessaloniki, Ophthalmology Department,

causing metabolic changes, and forcing the tissue to utilize fatty acid as the main

Thessaloniki, Greece.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

“hand motion”, necessitating two cycles of rituximab at 375 mg/m² each, two

TAO is a rare disease, seriously involving 5% of patients with autoimmune

weeks apart. Lymphocyte depletion was immediate and sustained and visual

thyroid disease. The clinical presentation may be difficult to distinguish from

acuity improved to 4/10 bilaterally. Three years later CASZ0 and the patient

other orbital conditions.

maintains a visual acuity of 2/10.

Case 1

Case 2

A 63-year-old woman was admitted to the Neurology Service for worsening

A 78-year-old male non-smoker presented with hyperthyroidism initially thought

diplopia over the previous six months, with a working diagnosis of myasthenia

to be due to toxic multinodular goiter and had thyroidectomy four months later.

gravis or multiple sclerosis. The Endocrine Service was consulted because of a

An incidental papillary thyroid carcinoma measuring 1.05 cm, insular type, was

long history of Hashimoto’s thyroiditis. The patient was euthyroid on thyroxine

found at histology in the right lobe. He was referred for management of GO one

replacement. Clinical activity score was 0, but there was restriction in elevation of

month postoperatively, characterized by retrobulbar pain, chemosis and diplopia,

the right eye. Orbital MRI demonstrated thickening of the right inferior rectus.

CASR7, loss of color vision and visual acuity of 1/10 bilaterally. He received

The diagnosis of TAO was made and the patient received intravenous

pulsed methylprednisolone to a cumulative dose of 8 g and orbital radiotherapy,

methylprednisolone with symptomatic improvement.

resulting in mild improvement in inflammation, but worsening of the acuity to

Case 2

light perception on the right only, with relative afferent pupillary defect on the left

A 48-year-old man with a history of Crohn’s disease, was referred for presumed

and fixed globes. The patient then received two infusions of rituximab of 500 mg

TAO, with severe diplopia, right retrobulbar pain and exophthalmos. He was

two weeks apart. He recovered vision to 2.5/10 in the right eye, which allowed his

euthyroid, with negative thyroid antibodies. Orbital MRI demonstrated

return to independent living. He subsequently received 100mCi¹³¹I without GO

thickening of all extraocular muscles of the right eye. A diagnosis of orbital

relapse.

myositis was made. The patient received 1.5g intravenous methylprednisolone

Conclusion

with marked improvement, but a month later presented with a red left eye and

Rituximab therapy can benefit vision and quality of life in refractory, severe GO.

diplopia. Orbital CT demonstrated thickening of the superior oblique and the

DOI: 10.1530/endoabs.49.EP828

medial rectus. The patient again received intravenous methylprednisolone with

complete remission and remains asymptomatic from his orbital and bowel disease

one year later.

Case 3

A 45-year-old woman was referred to the Endocrine Service with right sided

EP829

ptosis, for presumed TAO. She was euthyroid, with negative thyroid antibodies.

Evaluation of clinical performance of a new immunoassay in the

Eye exam was normal except for right-sided ptosis. Orbital MRI was normal. On

determination of thyroid stimulating immunoglobulins (TSI)

further questioning, the patient admitted having had botulinum toxin injections on

Isaura Rodrigues & Conceicao Godinho

the forehead and right brow a week before.

Centro Hospitalar Lisboa Central, Lisbon, Portugal.

Conclusion

The differential diagnosis and management of orbitopathy often relies on the

Endocrinologist and spans the spectrum of divergent medical specialties.

Introduction

DOI: 10.1530/endoabs.49.EP827

Anti-TSH receptors (TRAb) are an important marker in the differential diagnosis

of the etiologies of hyperthyroidism. They detect serum TSH receptor

immunoglobulins that interact with the TSH receptor without the functional

discrimination of stimulating from blocking antibodies. A new assay has recently

been released, that utilizes recombinant human TSH receptors (hTSHR) for the

specific detection and quantification of thyroid stimulating autoantibodies (TSI).

Objective

EP828

To evaluate the agreement of a new TSI test by method comparison with a TRAb

RIA, in the assessment of Graves disease (GD) in clinically well defined patients.

Management of very severe Graves’ orbitopathy with low dose

Material and methods

rituximab: report of two cases

We studied 162 patients regularly assisted at CHLC, Lisbon: 104 clinically

Fotini Adamidou¹, Christina Manani¹, Panagiotis Anagnostis¹,

documented GD, 29 with other thyroid diseases and

29 with non-thyroid

Thomas Georgiou¹, Kostas Boboridis² & Marina Kita¹

autoimmune disease. The serum samples were analyzed by a RiaRSR TRAb CT,

¹Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece;

traceable to WHO standard 90/672, and a new automatic chemiluminescent

²Aristotle University of Thessaloniki, Ophthalmology Department,

immunoassay, Immulite 2000 TSI (Siemens), traceable to WHO 2nd IS, NIBSC

Thessaloniki, Greece.

08/204.

Results

Introduction

At manufacturer TSI cut-off (0.55 IU/l), the clinical sensivity and specificity

Although Graves’ orbitopathy (GO) is common in the course of Graves’ disease,

were:

97.1

and

91.4% and at TRAb cut-off

(1.5 IU/l),

80.7

and

94.8%

dysthyroid optic neuropathy and corneal breakdown are rare. We describe two

respectively. The agreement of the results in the range of 0-1.5 IU/l revealed

cases of severe GO treated successfully with rituximab.

the occurrence of 17 positive results in TSI that were negative or gray in RIA.

Case 1

Conclusions

A 50-year-old female smoker with Graves’disease, presented with disfiguring

TSI may prove to be a useful method in clinical practice, by automating and

eyelid edema, exophthalmos and diplopia, preserved visual acuity and clinical

discriminating the functional activity of the TRAb.The high sensitivity of TSI

activity score (CAS) R 5. She received pulsed medroxyprednisolone to a total of

may be of great value in the diagnosis and follow up of GD and a good alternative

6 gr and standard orbital radiotherapy 3 months later with minor improvement.

to the RIA assay.

Thyroid status stabilized on methimazole combined with lithium and an

DOI: 10.1530/endoabs.49.EP829

uncomplicated thyroidectomy followed. However, visual acuity declined to

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Adrenal Cortex (to include Cushing’s)

Clinical Case Reports - Pituitary/Adrenal

EP830

EP832

The metabolic impact of ACTH-dependent versus ACTH-independent

Coexistence of TSH-secreting pituitary adenoma, primary

Cushing’s syndrome: a retrospective study of 99 patients

hyperparathyroidism and vitamin D deficiency

Mirela Diana Ilie¹ & Corin Badiu^1,2

Ibtissem Oueslati, Nadia Mchirgui, Karima Khiari & Néjib Ben Abdallah

¹‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;

Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.

²‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania.

Introduction

The simultaneous occurrence of central hyperthyroidism and primary hyperpar-

Although the metabolic impact of Cushing’s syndrome and hypercortisolemia are

athyroidism is extremely rare. Few cases of TSH pituitary adenoma in the setting

well known, the metabolic impact of ACTH is less established.

of multiple endocrine neoplasia type 1-associated syndrome were reported in

Objective

literature. Herein, we report a new case of TSH secreting pituitary adenoma

To identify differences in the glucidic, lipid and bone metabolism in ACTH-

particular by the coexisting of primary hyperparathyroidism and vitamin D

dependent versus ACTH-independent Cushing’s syndrome.

deficiency.

Methods

Observation

Retrospective, cross-sectional study of 99 patients with Cushing’s syndrome (54

A 76-year-old woman was referred to our Department with thyrotoxicosis and

with ACTH-dependent Cushing’s syndrome and 45 with ACTH-independent

elevated TSH levels. She presented with an important weight loss, intolerance to

Cushing’s syndrome) admitted to

‘C.I.Parhon’ National Institute of Endo-

heat, restlessness, flapping tremor, diarrhea and vomiting. On examination, she

crinology during 1998-2016. Clinical and paraclinical data were analyzed.

had a body mass index of 19 kg/m², a clinical signs of dehydration, a blood

Results

pressure of 120/60 mmHg and an irregular pulse of 120 beats/min. Thyroid gland

Type 2 diabetes was found in 39% and prediabetes was found in 31% of the

was asymmetrically enlarged. No proptosis was observed. Electrocardiogram

patients in the ACTH-dependent group; in the ACTH-independent group 31% of

showed an arythmic tachycardia (120/min). Echocardiography revealed moder-

the patients had diabetes and 27% had prediabetes. Regarding lipid metabolism,

ate, asymmetric hypertrophy of the left ventricle. Systolic and diastolic functions

15% of the patients in the ACTH-dependent group were already on lipid-lowering

were preserved. Laboratory tests revealed central hyperthyroidism and primary

drugs compared with 29% in the ACTH-independent group; of the remaining

hyperparathyroidism. The 25 OH vitamin D was 4.6 mg/l (nr: 30-100 mg/l).

patients, who were not on lipid-lowering drugs, 63% had hypercholesterolemia

Serum creatinine was

131 mmol/l and creatinine clearance was

59 ml/min.

and 46% had hypertriglyceridemia in the ACTH-dependent group, compared with

Pituitary hormone explorations revealed hypogonadotropic hypogonadism with

75% having hypercholesterolemia and 50% having hypertriglyceridemia in the

normal lactotropin and corticotropin functions. Pituitary MRI scan showed an

ACTH-independent group. Osteoporosis was found in 31% of the tested patients

invasive pituitary adenoma measuring

21!15!17 mm and causing right

in the ACTH-dependent group and in 60% of the tested patients in the ACTH-

cavernous sinus invasion. Sestamibi parathyroid scintigraphy, cervical and

independent group.

thoracic magnetic resonance imaging were normal. Bone densitometry revealed

Conclusions

osteopenia. The patient was symptomatically treated with intravenous fluid

Lipid and bone metabolism were more affected in the ACTH-independent group,

replacement therapy, antithyroid drugs and beta blockers. Due to the patient’s

while glucidic metabolism was more affected in the ACTH-dependent group.

poor general condition, surgical approach of the TSH-oma was contraindicated

DOI: 10.1530/endoabs.49.EP830

and pituitary radiotherapy was considered.

Conclusion

Although vitamin D deficiency and primary hyperparathyroidism are common

disorders in the elderly population, their association to TSH pituitary adenoma is a

rare condition.

DOI: 10.1530/endoabs.49.EP832

EP831

ACTH-independent subclinical Cushing’s syndrome in patient with

acromegaly and adrenal incidentaloma

Maria Kurowska, Joanna Malicka & Jerzy Tarach

Department of Endocrinology, Medical University, Lublin, Poland.

EP833

Central diabetes insipidus in children: about eight cases

Introduction

Najoua Lassoued, Selmene Ouannes, Afef Jguirim & Mohamed Taher Sfar

It is well established that acromegaly is associated with increased risk of cancer.

Department of Pediatrics, CHU Taher Sfar, Mahdia, Tunisia.

However, it is currently unclear whether patients with acromegaly are at increased

risk of developing adrenal tumors and little is known about the association

between acromegaly and adrenal adenomas. The simultaneous occurrence of

Introduction

preclinical Cushing’s syndrome in patients with acromegaly and adrenal adenoma

Central diabetes insipidus (CDI) is a rare but potentially dangerous dysregulation

is extremely rare, and to our knowledge, so far only 5 such cases have been

of the water balance secondary to an arginine vasopressin (AVP) deficiency.

reported in literature.

Diabetes insipidus may have different manifestations in children compared to

Case report

adults. CDI is more common in children than nephrogenic diabetes insipidus.

73-year-old female with typical acromegalic appearance and acromegaly

Methods

suspected

34 years ago and recognized 16 years ago. She underwent non

A retrospective study of eight patients collected in the pediatric department of

complete transsphenoidal resection of somatotroph macroadenoma 15 years ago.

Mahdia.

Since neurosurgery she is chronically treated with long-acting somatostatin

Results

analogue, currently with lanreotide autogel 120 mg every 28 days. The current

The average age of patients was 2.8 years. The reason for hospitalization was a

GH level is 2.59 ng/ml [n:0.126-9.88] and IGF-1

252.2 ng/ml

[n:29-204].

prolonged fever in three patients, weight stagnation in three patients, severe

Approximately 3 years ago, a focal lesion 22!17 mm was detected in left adrenal

dehydration in one patient and headache and decreased visual acuity in one

gland, with a basal density (K)12HU (tumor density in the adrenal protocol:

patient. A history of polyuropolydypsic syndrome was found in five patients only.

Diuresis was quantified at 9 ml/kg per hour on average. In biology, the plasma

had long-term arterial hypertension with no cushingoid features. An examination

osmolarity was

296.8 mosmol/Kg and the urinary osmolarity was

95.8

of pituitary-adrenal axis showed lowered ACTH levelZ4,76 pg/ml [n:7.2-63.6],

mosmol/kg with a urinary density at 1001 on average.Water deprivation test

a tendency to lose a circadian rhythm of cortisol [19.6-10.3 mg/dl] and the lack of

was carried out in four patients only confirming the diagnosis of CDI while the

cortisol secretion inhibition by 1 and 2 mg of dexamethasone [8.5 and 5.3 mg/ml,

four remaining patients had underwent directly a Desmopressin stimulation test.

respectively]. Daily excretion of urine cortisol was normal [172.5 and 123.6 mg;

The etiological assessment revealed a cerebral malformation in 4 patients, a

n:55.5-286.0].

Langerhans cell histiocytosis in three patients and a craniopharyngioma in one

Conclusion

patient. Hormonal assessment revealed adrenal insufficiency in one patient and

In order to determine the incidence and the relationship between the adrenal

thyrotropic insufficiency in two patients. Treatment with intranasal Desmopressin

tumors and acromegaly, standard evaluating of the adrenal glands is indicated in

was started at the mean dose of 0.125 ml/day in combination with the etiological

patients with acromegaly.

treatment. The evolution was favorable in most of our patients.

DOI: 10.1530/endoabs.49.EP831

Conclusion

The discovery of a CDI in children leads to an etiological investigation with an

urgent need to identify tumor pathologies (craniopharyngioma, dysgerminoma).

Infiltrative pathologies may be already known or reveal the disease (histiocytosis,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

and more rarely sarcoidosis). The objective of the management is to ensure a

EP835

normal water balance by normalizing the diuresis by the administration of

Pachydermoperiostitis associated with non secrettory pituitary

Desmopressin, to prevent any water retention and therefore any hyponatremia. It

macroadenoma in patient with toxic multinodular goitre

is associated with the treatment of the etiology of the CDI and the hormone

Ramazan Gen

replacement therapy of the associated anterior pituitary insufficiency.

Mersin University, Mersin, Turkey.

DOI: 10.1530/endoabs.49.EP833

Pseudoacromegaly is associated with acromegalic phenotype but normal insulin

like growth factor-1

(IGF-1) levels and suppressed growth hormone levels.

The reasons of this condition may be pachydermoperiostitis insulin resistance,

drug intake such as minoxidil and hypothyroidism (4). We describe pachy-

EP834

dermoperiostitis in a patient with hyperthyroidism and non-secretory pituitary

A hpothyroid case with pituitary hyperplasia mimicking TSHoma

macroadenomas.

H Sebile Dokmetas, Oguzcan Kinikoglu, Y Emre Altintas, Murat Atmaca &

Clinical case

Fatih Kilicli

A 62 year old man presented with palpitation, sweating and weight loss. Physical

Department of Endocrinology, Istanbul Medipol University, Istanbul,

examination revealed that’s multi nodular goitre, acral enlargement, gigantism,

Turkey.

fall in the left eye lid and thickening of the skin (heel-pad thickness was 27 mm on

right foot and 28 mm on left foot) Laboraory results revealed that serum st4

37.7 pmol/l

(12.8!n!20,4), TSH

!0.006 mIU/ml

(0.47!n!4.2), IGF-1

A 36-year-old female patient was referred to endocrinology outpatient clinic due

91.8 ng/ml (75(n(212). We re-evaluated GH-IGF-1 levels after treatment of

to increased TSH levels. Two years ago, she had been diagnosed and treated as

hyperthyroidism. After being euthyroid, GH level 0.379 ng/ml (1!n!9), IGF-1

Graves’ disease with propylthiouracil. Total thyroidectomy was performed in

88 ng/ml (75!n!212). GH level was suppressed after 100 gr oral glucose load.

another center due to ineffective medical treatment and oral levothyroxine sodium

Pituitary magnetic resonance imaging revealed 10.5 mm macroadenoma. All

(LT4) was started. During the follow-up her TSH levels were normal. Thirteen

pituitary hormone levels of patient was normal. Advanced investigation for

months after the last normal TSH value, she consulted the endocrinology

hyperinsulinemia, hypothyroidism and drug use revealed nothing. In contrast

outpatient clinic due to high levels of TSH (23 uIU/ml). She was questioned about

patient has hyperthyroidism. Two sons of the patients physical exam revealed

the proper usage of medication and the LT4 dose was increased. Despite the

acral enlargement, gigantism and thickening of the skin as a patient. GH levels,

higher dose of LT4

(400 mg/day), her TSH level was still increased at

IGF-1 levels and pituitary MRI of the sons of patient was normal. We considered

O100 uIU/ml. Although pituitary function test were normal, pituitary MRI

patient and two sons have autosomal dominant inheritance pachydermoperiostitis.

showed a macroadenoma with suprasellar extension. TSH a-subunit was

Conclusion

4.25 ng/ml (0-0.90 ng/ml). She was hospitalized for operation of TSHoma by

This is a very rare case of pseudacromegaly due to pachydermoperiostitis with

brain surgery department. After endocrinological evaluation request, we advised

nonfunctioning pituitary adenoma in patient with toxic multinodular goitre.

medical treatment because of more likely pituitary hyperplasia. She re-checked

up for ruling out possible malabsorption due to Celiac disease, but symptoms of

DOI: 10.1530/endoabs.49.EP835

malabsorption and Anti- Gliadin antibody (IgA) was negative. Also 200 mg oral

LT4 treatment was given and 2 hours later plasma free T4 level was measured due

to incompliance the medical treatment was not successful and it was found

increased levels of free T4. Intramuscular (i.m) LT4 200 mg/day treatment was

started. Ten days later her TSH level had decreased to 27 uIU/ml. After another

10 days of i.m LT4 treatment every other day, her TSH level decreased to

0.35 uIU/ml, while her fT4 and fT3 rose to slightly above the upper limit. A

control pituitary MRI showed significant regression of hyperplasia. During the

i.m LT4 treatment period the patient was consulted by a psychiatrist to explore

EP836

possible underlying psychiatric causes that could account for the previously

unsuccessful oral treatment and she was convinced to take oral LT4 properly.

Successful management of macroprolactinoma with aromatase

inhibitor in a patient with hypogonadotropic hypogonadism

Feyza Yener Ozturk, Esra Cil Sen, R Selvinaz Erol, Sezin Dogan Cakir,

Seda Erem Basmaz, Emre Sedar Saygili, Adnan Batman & Yuksel Altuntas

Department of Endocrinology and Metabolism, Sisli Hamidiye Etfal

Training and Research Hospital, Istanbul, Turkey.

Introduction

Hypogonadism persisting in man with macroprolactinoma requires exogenous

testosterone replacement therapy (TRT). But TRT may cause secondary elevations

of prolactin. We report here a case of macroprolactinoma and hypogonadotropic

hypogonadism with persistently high prolactin level after initiating TRT.

Case report

A 28 year-old male was admitted to outpatient clinic with complaints of

headache, low libido and blurred vision on left eye for three years. Magnetic

Figure 1 Pretreatment pituitary MRI image.

resonance imaging

(MRI) revealed a pituitary mass

(3.6!3.5!2.3 cm)

occupying entire sella, extending to sphenoid sinus, internal carotid arteries

(ICA), encasing right ICA and deviating stalk to left. Tumor compressed optic

chiasm causing bitemporal hemianopsia. Laboratory tests: prolactin: 133 ng/ml

(1/100 diluted prolactin: 77 ng/ml), cortisol:6.75 mg/dl (unresponsive to low dose

ACTH stimulation test), TSH:2.31 uIU/ml, fT4:0.47 ng/dl, fT3:1.06 pg/ml,

FSH:0.43 mIU/ml, LH:0.29 mIU/ml, t.testosteron!20 ng/dl, GH!0.05 ng/ml,

IGF-1:86.9 ng/ml (n:117-329). Nonfunctional adenoma and panhypopituitarism

was the diagnosis. Transnasal transsphenoidal adenomectomy was performed

after hormone replacement. Pathology revealed prolactin-secreting pituitary

adenoma with Ki67:1-2%. Cabergoline therapy (1 mg/week) was started on

postoperative

15th-day as prolactin was

323 ng/ml. Prolactin decreased to

80 ng/ml on the 2nd-month of therapy but t.testosteron was still low. TRT was

started intramuscularly per 3 weeks for complainment of low libido. After then,

prolactin level increased abruptly to 470 ng/ml. Despite gradual increament of

dosage to 4 mg/week, prolactin remained elevated (451 ng/ml). No enlargement

Figure 2 Pituitary MRI image after 3 weeks i.m LT4 treatment.

of residual mass was noted on new MRI. When TRT was quitted for 3 months,

prolactin decreased to 93 ng/ml. Then TRT was started with selective aromatase-

inhibitor anastrozole 1 mg/day. With cabergoline dosage decreased gradually to

DOI: 10.1530/endoabs.49.EP834

3 mg/week, prolactin decreased to 18.8 ng/ml and t.testosterone was normal

(300 ng/dl).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

asthenic patient with limited lesions of vitiligo and loss of libido. Water

Aromatisation of exogenous testosterone to estradiol and subsequent estrogen-

deprivation test showed the persistence of excretion of highly diluted amounts of

stimulated prolactin release may complicate the control of hyperprolactinemia.

urine, confirming the diagnosis of diabetes insipidus. The patient responded

Aromatase-inhibitor added to therapy may facilitate successful TRT for patients

spectacularly to therapy with sublingual desmopressin, with a decrease of diuresis

with macroprolactinoma.

to under 2500 ml/24 hours and an increase of urine gravity to 1010 under a dose

DOI: 10.1530/endoabs.49.EP836

of 60 mg!3/day, supporting the diagnosis of central diabetes insipidus. Serum

testosterone was of 1.01 ng/ml (normal range - between 2.6 and 10 ng/ml) and

low-normal LH and FSH (LHZ1.5 mU/l and FSHZ2 mU/l) suggesting the

presence of central hypogonadism. Serum fT4 was of 0.545 ng/ml (normal range

- between 0.9 and 1.9 ng/ml) with ‘normal’ TSH (1.6 mIU/l) suggestive for

central hypothyroidism. Corticotroph axis was undamaged (morning plasma

cortisol of 15.5 mg/dl and ACTH of 38.9 pg/ml). Osteodensitometry revealed

osteopenia. MRI investigation of the hypothalamo-pituitary region showed a

small pituitary gland (7/3/6 mm) accompanied by partial empty sella without

images of pituitary adenomas and absence of the native hypersignal of the

EP837

neurohypophysis. The pituitary stalk was deformed, taking a nodular shape with

dimensions of 4/5/6 mm. This image was highly suggestive for neuroinfundibular

Multifocal multisystem langerhans cell histiocytosis - a rare cause of

hypophysitis, most probably of autoimmune origin. Injections with testosterone

panhypopituitarism and diabetes insipidus - a case report

undecanoate every three months and daily oral supplementation of thyroid

Filip Gabalec^1,2, Martin Simkovic^1,2, Petra Kasparova^2,3, Pavel Zak^1,2 &

hormones added to desmopressin therapy significantly improved patient’s quality

Jan Cap^1,2

of life. Autoimmune associations of the anterior and posterior pituitary are very

¹4th Department of Internal Medicine, University Hospital Hradec Kralove,

rare and may raise difficulties of diagnosis and therapeutic decisions.

Hradec Kralove, Czech Republic;²Faculty of Medicine Hradec Kralove,

Charles University, Hradec Kralove, Czech Republic;³The Fingerland

DOI: 10.1530/endoabs.49.EP838

Department of Pathology, Hradec Kralove, Czech Republic.

Introduction

Langerhans cell histiocytosis (LCH) is a very rare disease in adults and as well a

very rare cause of sellar expansion. The clinical presentation can be

heterogeneous, from a single bone lesion to potentially fatal, widespread disease.

We describe the difficulties with the evaluation and the treatment of LCH.

Case

EP839

39 years old woman has had amenorrhea for 2 years and higher intake of fluids

Pituitary apoplexy while treating recurrence of Cushing’s disease with

(5-7 l/day) for 6 years. Non-functioning pituitary expansion with pituicytoma

Pasireotide

appearance was found on MRI. She was followed up for almost 3 years.

Birute Zilaitiene^1,2, Aiste Kondrotiene³, Rasa Verkauskiene^1,2,

Panhypopituitarism developed during the follow-up and replacement therapy

Lina Barsiene², Robertas Knispelis², Valdas Sarauskas⁴ &

with adiuretin, thyroxin and hydrocortisone was initiated. Finally, she underwent

Annamaria Colao⁵

biopsy for slow progression of sellar expansion - Langerhans cell histiocytosis

¹Institute of Endocrinology, Lithuanian University of Health Sciences,

was confirmed histologically, with S100 a CD1a protein immunohistochemical

Kaunas, Lithuania;²Department of Endocrinology, Hospital of Lithuanian

positivity. Staging of the disease revealed suprasellar expansion, skeletal and

University of Health Sciences Kauno Klinikos, Kaunas, Lithuania;

retrobulbar infiltration, lymphadenopathy along the right internal carotid artery

³Lithuanian University of Health Sciences, Medical Academy, Kaunas,

and retroperitoneal and mediastinal lymphadenopathy with FDG avidity on

Lithuania;⁴Department of Pathological Anatomy, Lithuanian University of

18-FDG-PET/CT. She received five cycles of cladribine monotherapy with

Health Sciences, Kaunas, Lithuania;⁵Department of Molecular and Clinic

subsequent PET/CT restaging.

Endocrinology and Oncology, University of Naples Frederico 2,

Discussion

Endocrinology Sector, Naples, Italy.

Hypothalamus-pituitary-adrenal axis infiltration is present in up to 50% of LCH;

the most common disorder is diabetes insipidus (DI). The frequency of DI is 30-

Introduction

40% and 94% if other pituitary hormone deficiencies exist. The diagnosis can be

ACTH producing macroadenoma and pituitary apoplexy are rare in Cushing’s

tricky. The primary treatment modalities for LCH include local excision of the

disease. Somatostatin receptor agonist Pasireotide is indicated for the treatment of

lesion, corticotherapy, chemotherapy, radiotherapy, and imunnotherapy with anti-

patients with Cushing’s disease for whom surgery is not an option or has failed.

CD1a monoclonal antibodies. The data regarding the treatment of the central

We present a case of pituitary apoplexy in patient with recurrence of Cushing’s

nervous system involvement with LCH are very limited. Cladribine (2-CdA) is a

disease treated with Pasireotide.

promising agent in this setting as previously reported. Cladribine has good

Case

bioavailability in the CNS. A total of six cycles of cladribine monotherapy can be

38 years old female presented with quick weight gain, weakness, irregular

administered with respect to the good profile of toxicity in this indication.

menstruation, hirsutism, hypertension, newly diagnosed diabetes mellitus. High

However, prolonged neutropenia and respiratory infections led to premature

levels of blood cortisol and ACTH were observed. Cortisol was not suppressed

termination of the treatment in our case.

after 1 mg overnight dexamethasone suppression test (DST) and after low-dose

DST. High-dose DST suppressed cortisol secretion. Pituitary macroadenoma with

DOI: 10.1530/endoabs.49.EP837

diameter of 12!9 mm was diagnosed on MRI. Patient underwent transsphenoi-

dal surgery in January, 2012. In 2014 recurrence of Cushing’s disease was

diagnosed and second transsphenoidal surgery was performed in January, 2015.

In November, 2015 recurrent pituitary adenoma with diameter of 15!11 mm was

identified on MRI and hormonal tests confirmed hypercortisolemia with elevated

ACTH again. Therapy with Pasireotide was started in January, 2016. After 9

months of successful use of this medication patient was emergently hospitalized

to the Department of Endocrinology with an episode of an acute headache,

nausea, vomiting. Ptosis of a right eyelid and blurred vision occurred. Head MRI

EP838

demonstrated pituitary apoplexy and tumor spreading around right optical nerve

A rare association of autoimmune diabetes insipidus and hypophysitis

and optic chiasm. Pituitary apoplexy led to hypocortisolemia and need of

with partial pituitary insufficiency

hydrocortisone for several days. Two weeks later normal cortisol levels were

Livia Matei¹, Corina Stefaroi¹, Simona Mogos^1,2 & Dumitru Branisteanu^1,2

observed, hydrocortisone discontinued. Further treatment with Pasireotide 0.6 mg

¹Endocrinology Clinic, ‘Sf. Spiridon’ Clinical Emergency Hospital, Iasi,

b.i.d. was continued. 4 months after pituitary apoplexy and further treatment with

Romania;²Department of Endocrinology, University of Medicine and

Pasireotide, ptosis and blurred vision regressed, eucortisolemia was achieved.

Pharmacy “Gr. T. Popa”, Iasi, Romania.

Conclusion

To our knowledge we report the first case of pituitary apoplexy in patient with

Cushing’s disease treated with Pasireotide. This complication might be related to

We present the case of a 40 year old man presenting at first consultation an

Pasireotide effect on tumorogenesis mechanisms.

‘idiopathic’ fast-onset and severe polyuro-polydipsic syndrome

(diuresis of

10 l/24 hours, with urine osmolality of less than 50 mOsm/kg and urine gravity

DOI: 10.1530/endoabs.49.EP839

lower than 1001). Clinical examination showed pallor and decreased pilosity at an

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP840

EP842

Hemodialysis patient with metastatic renal cell carcinoma to the

A hypopituitarism case diagnosed after sphenoid sinus mucocele

pituitary stalk presenting as hypopituitarism: an autopsy case

operation

Hisashi Sugano¹, Riku Ino¹, Yuko Dehara² & Yoshinori Tuchiyama²

Betul Ekiz-Bilir¹, Bulent Bilir², Aysel Oz³, Halide Gunes-Ciftci⁴,

¹Department of Diabetes and Endocrinology, Kochi Health Sciences Center,

Neslihan Soysal-Atile¹ & Gulsah Elbuken⁵

Kochi, Japan;²Department of Clinical Nephrology, Kochi Health Sciences

¹Endocrinology and Metabolic Diseases Division, Tekirdag State Hospital,

Center, Kochi, Japan.

Tekirdag, Turkey;²Internal Medicine Department, Medical Faulty, Namik

Kemal University, Tekirdag, Turkey;³Radiology Department, Tekirdag

State Hospital, Tekirdag, Turkey;⁴Department of Otolaryngology and Head

Introduction

and Neck Surgery, Tekirdag State Hospital, Tekirdag, Turkey;⁵Internal

Pituitary metastases occur in 1% to 4% of cancer patients in autopsy studies. The

Medicine Department, Endocrinology and Metabolic Diseases Division,

most frequent primary tumors are breast and lung tumors. Renal cell carcinoma

Medical Faculty, Namik Kemal University, Tekirdag, Turkey.

(RCC) is a rare cause of pituitary metastases, with only 25 previously reported

cases.

Case report

Introduction

A 77-year-old-man was admitted to our hospital because of acute progression of

Mucoceles-mucus containing benign cysts of paranasal sinuses- are common with

chronic renal failure presenting with appetite and weight loss in August 2014. He

an incidence of 1% but involvement of sphenoid sinus is much less common. In

underwent hemodialysis. His fasting blood glucose was low without any

this case report, we reported a patient presented with hypopituitarism after

symptoms. In 1998, he had undergone left nephrectomy and adrenalectomy,

sphenoid mucocele drainage operation.

and was diagnosed with a clear cell RCC. In 2001, lung metastasis was diagnosed

Case report

and he was treated with interferon therapy, which led to remission. In 2009, lung

A 59- year-old woman was admitted to our endocrinology out-patient clinics with

metastasis was observed again, but he declined treatment. He had hyperprolacti-

a complaint of fatigue over the past 2 months. One month prior to admission, she

nemia and hypopituitarism; levels of PRL: 292.8 ng/ml, free T4: 0.56 ng/ml,

had been internalized for about 10 days in our hospital’s infectious diseases

TSH: 0.953 mIU/ml, cortisol:

2.0 mg/ml, ACTH: 5.4 pg/ml, IGF1: 42 ng/ml.

clinics for fever of unknown origin. After extensive medical investigation, a

Magnetic resonance imaging revealed a 7!8!9 mm mass with a pituitary stalk

sphenoid sinus mucocele and pansinusitis had been diagnosed. An operation for

that compressed the optic chiasm without visual disturbance. Dynamic tests

drainage of the mucocele with endonasal surgical approach had been performed

showed hyporesponses of cortisol, LH, FSH, TSH, and GH. We considered pan-

and she had been externalized for follow-up with an attention card indicating that

hypopituitarism due to pituitary stalk metastasis from RCC but could not diagnose

her nasal cavity was in direct contiguity with the optic nerve. Three weeks after

it histologically. Diabetes insipidus was not recognized, probably owing to renal

the operation, she admitted to our clinics. The physical examination revealed that

failure. Hormone replacement was started with hydrocortisone and L-thyroxine;

her arterial blood pressure was 90/50 mmHg, heart rate was 108 bpm, respiratory,

his hypoglycemia and anorexia improved. In September

2015, he died of

abdominal, cardiac examinations were normal. Her skin was pale and minimal

pneumonia. The autopsy showed that the clear cell RCC had spread to the thyroid

pitting edema was detected. In her repeated laboratory examination, serum

gland, right lung, and pancreas in addition to the pituitary stalk.

cortisol levels were found to be less than

1 mg/dl. Coexisting secondary

Conclusion

hypothyroidism and GH deficiency were detected. The magnetic resonance

We reported a case of a hemodialysis patient presenting with a symptomatic

imaging of the pituitary region was revealed no tissue corresponding to the

pituitary metastasis from RCC. It is difficult to distinguish symptoms of

adenohypophysis. Following adequate replacement therapy with methyl-

hypopituitarism from nonspecific symptoms in a hemodialysis patient. In this

prednisolone and levo-thyroxine, her fatigue relieved. GH replacement therapy

case, we diagnosed an extremely rare pituitary stalk metastasis by autopsy.

was refused by the patient for its administration difficulty.

DOI: 10.1530/endoabs.49.EP840

Conclusion

For mucoceles involving sphenoid sinus, pre-operative and post-operative

endocrinological evaluation is essential.

DOI: 10.1530/endoabs.49.EP842

EP841

Effect of the addition of lanreotide autogel to the treatment of an

aggressive prolactinoma - a case report

Lucio Vilar^1,2, Clarice Vilar², José Luciano Albuquerque¹,

Patricia Gadelha¹, Ana Carolina Thé¹, Erik Trovão¹, Izabela Cardoso¹,

EP843

Thaíse Cardoso¹ & Ruy Lyra¹

¹Division of Endocrinology, Hospital das Clinicas, Federal University of

Coexistence of acromegaly and rheumatoid arthritis: presentation of

Pernambuco, Recife (Pernambuco), Brazil;²Endocrine Research Center of

three cases

Pernambuco, Recife (Pernambuco), Brazil.

Reyhan Ersoy¹, Nagihan Bestepe², Sevgul Faki¹, Cuneyt Bilginer¹,

Didem Ozdemir¹, Sukran Erten³ & Bekir Cakir¹

¹Department of Endocrinology and Metabolism, School of Medicine,

Case report

Ankara Yildirim Beyazıt University, Ankara, Turkey;²Department of

A giant prolactinoma

(sizeZ5.2!4.1!3.2 cm; PRLZ6 400 ng/mL) was

Endocrinology and Metabolism, Ankara Ataturk Education and Research

diagnosed in an amenorrheic 19-year old girl who presented to the emergency

Hospital, Ankara, Turkey;³Department of Rheumatology, School of

room complaining of headaches and bilateral decrease in visual acuity for

Medicine, Ankara Yildirim Beyazıt University, Ankara, Turkey.

10 days. The patient was started on cabergoline (CAB) in progressive doses up to

3 mg/week. PRL levels decreased from 6 400 to 4 600 ng/dl within 60 days, with

improvement of visual complaints and visual fields defects. The dose was

Introduction

subsequently increased up to 6 mg/week over the next 6 months but PRL did not

Musculoskeletal system is widely affected in acromegalic patients which might

normalize (1 840 ng/dl) and amenorrhea persisted. A new pituitary MRI was

cause difficulties in the diagnosis and treatment of inflammatory rheumatological

performed revealed a w50% tumor reduction. Six months later, worsening of

diseases. Here, we report coexistent rheumatoid arthritis

(RA) in three

visual fields and a 20% increase in tumor volume were detected, whereas PRL

acromegalic patients presenting with continuing joint and back pain although

levels increased to 2 270 ng/ml. A transsphenoidal surgery (TSS) was therefore

acromegalic state was in remission.

undertaken (Ki-67 expressionZ8%), which led to a w30% reduction of tumor

Case 1

volume whereas PRL levels decreased from 2 270 to 1 210 ng/dl within 4 months.

A 64 years old female patient with acromegaly and macroadenoma had undergone

CAB was restarted but PRL did not normalize (520 ng/dl), despite the use of

transsphenoidal surgery 11 years ago and radiosurgery 7 years ago because of

doses up to 4 mg/week (maximal tolerated dose) for 6 months, and amenorrhea

clinical and laboratory evidence of disease. The patient got into remission 3 years

persisted. Lanreotide autogel

(120 mg every 28 days) was added to CAB

after radiosurgery. Because she had morning stiffness and symmetrical pain and

(4 mg/week). The combined treatment was well tolerated and lead to decrease of

swelling in interphalangeal joints, she was consultated with rheumatology and

PRL levels to 91 ng/ml (NR: 2.8-29.2) within 8 months, as well as to resumption

diagnosed as seronegative RA. Her complaints improved dramatically at the

of a regular menstrual cycle.Moreover, the combination of CABClanreotide

second month of methotrexate, prednisolone and indomethacin treatment.

autogel enabled further tumor shrinkage but invasion of both cavernous sinuses

Case 2

persisted. CAB dose could be subsequently reduced to 3 mg/week.

A 62 years old female had undergone transsphenoidal surgery for acromegaly 12

years ago. She had been treated with conventional radiotherapy and radiosurgery

DOI: 10.1530/endoabs.49.EP841

4 and 10 years after diagnosis, respectively because remission could not be

achieved by medical treatment which had been stopped about a year after

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

radiosurgery. She had symmetrical pain, swelling and deformities in inter-

Introduction

phalangeal and metacarpal joints. Seronegative RA was diagnosed and

Cyclic Cushing’s syndrome is a rare disorder, characterized by repeated episodes

methotrexate and prednisolone were started.

of cortisol excess interspersed by periods of normal cortisol secretion ranging

Case 3

from days to years. It remains a difficult diagnostic challenge in endocrinology,

Acromegaly had been detected 13 years ago in a 57 years old female. Because she

we report a case.

had refused surgery, she had been treated with conventional radiotherapy and cure

A case report

had been achieved in a year. She complained morning stiffness, back pain and

The patient was 41 years old woman, she presented in 2012 a period of

pain and swelling in hand joints. She was diagnosed to have seropositive RA and

symptomatic hypercortisolism. Urinary free cortisol was elevated to 113 mg/24,

treated with methotrexate, sulfosalazine and indomethasine.

Low-dose dexamethasone testing was negative, ACTH was elevated to

Conclusion

20.2 pmol/l, the high-dose dexamethasone suppression test was positive, a

Symptoms related with RA might be confused with musculoskeletal symptoms

pituitary MRI and a thoraco pancreatic scanner were normal; These finding led us

seen in acromegaly. Detailed rheumatological physical examination and

to an ACTH-dependent Cushing’s syndrome. The patient was revaluated 5

immunological evaluation might be helpful to display concomitant rheumatolo-

months later and she was clinically and biochemically better. Six months later she

gical disease in acromegalic patients with ongoing musculoskeletal complaints

presented relapsed symptoms and a biochemical recurrence of hypercortisilosm

despite achievement of treatment targets.

(high urinary cortisol:

125.7 mg/24

and negative Low-dose dexamethasone

DOI: 10.1530/endoabs.49.EP843

testing). In 2015 the patient presented a sudden tumor syndrome, pituitary MRI

revealed an intrasellar arachnoidocele that was in favour of the apoplexy of an

adrenocorticotropic pytuitary adenoma. The patient was revaluated 9 months later

and she was clinically better, The Urinary free cortisol was normal (20 mg/24).

Discussion

Cyclic Cushing’s syndrome is characterized by rhythmic fluctuations in

EP844

glucocorticoid production, both clinical and biochemical spontaneous remissions

Case of TSH secreating pituitary adenoma (TSHOMA) where course

may occur in patients with this disorder. Our patient presented two periods of

was modified by coexistant autoimmune hypothyroidism

normal glucocorticoid production and two periods of hypercortisolism. Causes of

Ameya Joshi¹, Rajesh Ghagre², Premlata Varthakavi³, Pradeep Dalwadi³ &

cyclic Cushing’s syndrome are multiple dominated by pituitary adenoma. The

Nikhil Bhagwat³

biological and radiological investigations in this case and therfore the subsequent

¹Bhaktivedanta Hospital and Research Institute, Mira Road, Thane,

evolution enabled a diagnosis of a Cushing’s syndrome spontaneously regressive

Maharashtra, India;²Ashtavinayak Hospital, Borivali, Mumbai,

by the apoplexy of pytiutary adrenocorticotropic adenoma. Clinicians should be

Maharashtra, India;³Topiwala National Medical College and BYL Nair

aware that hypercortisolism may occur periodically and the duration of the

Charitable Hospital, Mumbai Central, Mumbai, India.

periods of normal and abnormal cortisol secretion can vary significantly, so the

correct diagnosis can be a challenge in clinical practice.

DOI: 10.1530/endoabs.49.EP845

Introduction

TSHOMAs are rare pituitary tumors with prevalence of 1-2 cases per million.

We present a case of of TSHoma where the course was complicated by the

coexistence of autoimmune hypothyroidism.

Case

41 year old male presented with fatigue, lethargy and palpitations. On screening

was found to have raised t3 - 216.30 ng/dl (N-70-204 ng/dl), t4 - 12.10 mg/dl(N-

4.2-11.6 mg/dl) and TSH - 27.55 uIU/ml (0.2-5.7 uIU/ml). Further evaluation

revealed raised free t3 (FT3), free t4 (FT4) and TSH (column 1, Table 1), raised

anti thyroid peroxidase antibodies and negative TSH receptor antibody, normal

cortisol - 10.8 mg/dl (N-5-25), testosterone - 769.73 ng/dl (N-275-900), prolactin

EP846

- 18.89 ng/ml (5-25), IGF1 - 124 ng/ml (64-210) levels. Thyroid function of first

Breast cancer and newly discovered non-secretor pituitary mass- as risk

degree relations was normal. SHBG - 78.20 nmol/l (N-11.2-78.1) and alpha

of metastases?

subunit levels - 3.8 ng/ml (0.1-0.5) were raised. TSH concentration significantly

Ana Valea¹, Iulia Oprisor², Mara Carsote³, Dan Dumitru Pop⁴,

reduced 5 hours after single octride dose as well as after three doses of 100 mg

Andra Morar⁵, Cristina Ghervan¹ & Carmen Emanuela Georgescu¹

octride over 24 h. MRI confirmed presence of pituitary macroadenoma 2.4!

¹I.Hatieganu UMPh & Clinical County Hospital, Cluj-Napoca, Romania;

1.2!1.2 cm abutting the chiasma (visual fields normal). Patient was subjected to

²Clinical County Hospital, Cluj-Napoca, Romania;³C.Davila UMPh &

transsphenoidal surgery. The adenoma immunostained positive for TSH, was also

I.Parhon National Institute of Endocrinology, Bucharest, Romania;

positive for p53 with MIB index 3-5%. Patient FT3, FT4 and TSH was low 2

⁴Oncology Institute, Cluj-Napoca, Romania;⁵Clinical Hospital of Infectious

weeks post surgery and 25 mg thyroxine was started. Follow up report at 6 weeks

Diseases, Cluj-Napoca, Romania.

showed low FT3, FT4 and raised TSH levels after which thyroxine was stepped

up. Patient did not need any other hormone replacement.

Introduction

Even if breast cancer is rare cause of pituitary metastases, the diagnosis of a

pituitary adenoma, shortly after surgery for breast cancer, raises suspicion of a

Table 1 Serial free t3 free t4 and TSH levels.

possible secondary determinations.

Material and method

After 3

Post

This is a case report revealing the medical history and endocrine profile of a

After

doses of

Post

surgery

female with breast cancer and pituitary macroadenoma.

5 h of

100 mg

surgery

Baseline octride

octride

2 weeks

6 weeks

weeks

Case data

A 64-year old non-smoking female (with menopause at age of 52), who had

Free t3

4.86

1.19

1.1

2.7

undergone treatment for breast cancer (diagnosed at the age of 60), with left

(1.7-3.7 pg/ml)

radical mastectomy pT2N0M0 L0 V0 Pn0 R0, followed by adjuvant radiation

Free

1.83

0.53

0.62

1.12

treatment and aromatase inhibitor hormonal treatment, was admitted for

t4 (0.7-1.8 ng/ml)

TSH

25.5

13.8

7.6

0.1

3.82

headache, dizziness, diplopia, and narrowed visual field. Pituitary MRI performed

(0.2-5.7 uIU/ml)

pointed a 40/26/36 mm-sized mass of oval shape, with intra and extra-sellar

expansion. Endocrine evaluation indicated low levels of serum gonadotropins

(FSH of 10.5 U/l, normal: 30-150 U/L and LH of 1.6 U/l, normal of 8.2-41 U/l),

DOI: 10.1530/endoabs.49.EP844

low FT4 levels (free thyroxine of 0.61 ng/dl, normal: 0.89-1.76 ng/dl), normal

levels of morning plasma cortisol

(of

19.8 mg/dl, normal:

5-25 mg/dl), and

moderate increase of prolactin (24.4 ng/ml, normal:1.3-20 ng/mL). Thyroxine

substitution therapy was initiated and followed by transsphenoidal adenomect-

omy. Histopathology revealed a mixed pituitary adenoma. Assessement

EP845

performed three month after surgery highlighted persistent hyperprolactinemia

(of 22.9 ng/ml), central hypogonadism (FSH of 10.1 U/l, LH of 2.6 U/l), normal

Cyclic Cushing’s syndrome: a diagnostic challenge

FT4 levels (of 0.95 ng/dl), and persistent pituitary mass (of 36/21/30 mm) on

Elmghari Ghizlane, Elbahi Meryam, Rafii Sana & Elansari Nawal

MRI. The patient will be further followed-up by a multidisciplinary team

Faculty of Medicine and Pharmacy, Marrakech, Morocco.

regarding endocrine and oncologic profile.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

46), basal cortisol: 3.4 mg/dl (n:5-29), growth hormone: 2.25 ng/ml and IGF1:

This case emphasizes that diagnosis of pituitary macroadenoma can be difficult

440 ng/ml (n:70-212). Hypophyseal-thyroid and hypophyseal-gonadal axis were

when occurs in the context of a pre-existing breast cancer. Intensive follow-up is

normal. GH levels measured 30-60-90 and 120 min after oral 75 g glucose

necessary for specific treatment.

tolerance test were

2.16,

1.65,

1.5

and 1.8, respectively. The patient was

DOI: 10.1530/endoabs.49.EP846

diagnosed with acromegaly and intramuscular octreotide 20 mg/month, pre-

dnisolone 5 mg in the morning and 2.5 mg in the evening were initiated before

hypophyseal surgery. Left upper lobectomy of the left lung was performed and

pathologic examination of surgical material revealed squamous cell carcinoma.

VinorelbineCcisplatin chemotherapy was initiated and the patient was scheduled

for hypophyseal surgery.

EP847

DOI: 10.1530/endoabs.49.EP848

Meningoencephalitis as the first clinical sign of a pituitary macro

adenoma: a case report

Ghizlane Elmghari, Ilham Bouizammarne & Nawal Elansari

Department of Endocrinology, Diabetes and Metabolic Diseases CHU

Mohamed VI, Marrakesh, Morocco.

Introduction

The classical revealing manifestations of a pituitary adenoma are represented by

EP849

the combination of a tumor syndrome and endocrine syndrome. The occurrence of

meningoencephalitis as a mode of revelation of a macroadenoma is exceptional.

Case

Abstract withdrawn.

Mr. M.O, 36 years old, with no significant medical history, brutally presented

severe headaches, vomiting, behavioral disorder with fever and bilateral

decreased visual acuity. On examination, the patient was conscious, febrile to

39.8

with nuchal rigidity. At presentation: leukocytosis at

18 000/m3, a

C-reactive protein at 69 mg/l. The head CT scan showed bilateral areas of hypo

density with Intra-and suprasellar invasive lesional process. The magnetic

resonance imaging showed a pituitary macroadenoma 30!32 mm invading the

sphenoid sinus, the right cavernous sinus and elevating the optic chiasm. The

cerebrospinal fluid analysis showed a lymphocytic liquid with elevated protein

and normal glucose level. Culture was negative as well as herpes simplex virus

EP850

PCR. The biological analysis of endocrine hormones balance objectived a pan

Temozolomide alone or in combination with bevacizumab and

hypopanpituitarisme insufficiency. The patient received ceftriaxone, acyclovir,

capecitabine in the treatment of atypical pituitary adenomas - own

replacement therapy and was scheduled for surgery.

experience

Discussion

Maria Kurowska, Joanna Malicka & Jerzy Tarach

Meningoencephalitis is a rare presentation as first manifestation of macro-

Department of Endocrinology, Medical University, Lublin, Poland.

adenoma. In literature, only three cases of Meningoencephalitis were reported as

Introduction

revealing macroadenomas. We illustrate this observation through an unusual and

Atypical pituitary adenomas are tumors refractory to conventional therapy and

serious form of revelation of a macroadenoma.

characterized by a tendency to rapid progression and high recurrence rate. The

DOI: 10.1530/endoabs.49.EP847

aim of the study was to summarize our experience in treatment of atypical

pituitary adenomas with temozolomide (TMZ).

Material

5 patients (3F;2M) aged 44-58 (mean 52.4G5.4) years treated in 2013-2016. We

analyzed the results, tolerance and side effects of TMZ.

Results

EP848

In three patients (1F;2M) atypical corticotroph adenomas were diagnosed (two

A rare case with acromegaly: increased hypophyseal FDG uptake in

Nelson’s syndromes, one Crooke’s cells adenoma), in 1F-prolactinoma resistant

PET/CT performed for lung cancer staging

to dopamine agonists and in 1F-type 3 silent adenoma (GHC, PRLC). The

Veysi Asoglu¹, Ece Celik², Mehmet Celik³, Buket Yilmaz Bulbul³,

disease duration ranged 3-23 years (mean 12.4G7.2). Before TMZ implemen-

Yusuf Durmus¹, Semra Ayturk², Funda Ustun⁴ & Sibel Guldiken³

tation, patients underwent a total of 11 transsphenoidal adenomectomies (1-4),

¹Department of Internal Medicine, Medical Faculty, Trakya University,

four craniotomies, two patients - stereotactic X-ray-therapy, 1 - tomotherapy and

Edirne, Turkey;²Department of Chest Diseases, Edirne Sultan 1. Murat

- bilateral adrenalectomy. All patients started with TMZ monotherapy

State Hospital, Edirne, Turkey;³Department of Endocrinology and

150 mg/m² for five consecutive days with 23-days intervals. The number of

Metabolism, Medical Faculty, Trakya University, Edirne, Turkey;

courses ranged from 2 to 13. The total remission, lasting from 45 months was

⁴Department of Nuclear Medicine, Medical Faculty, Trakya University,

obtained in a patient with Crooke’s adenoma, partial remission in one patient with

Edirne, Turkey.

Nelson’s syndrome, transient stable disease (2-4 months) in two patients (with

Nelson’s syndrome and somatotropinoma). The prolactinoma was refractory to

TMZ. The only side effect was vomiting. In two patients with relapse of Nelson’s

Acromegaly affects 4-6 people in a million and hypophyseal GH releasing

syndrome TMZ was used in combination with bevacizumab (six courses) in 1F

adenoma is the most common cause of the disease. It shows its effects on GH and

and in 1M with capecitabine (CAPTEM - five courses), but in both cases it caused

IGF1. Since they grow rapidly, they are usually diagnosed at the stage of

short-term disease stabilization.

macroadenomas. Heart failure, arthritis, OSAS and DM may develop during

Conclusion

course of the disease. Although the most common accompanying malignancy is

colon cancer, the incidence of malign melanoma, breast, thyroid, gastric and lung

TMZ is the most effective in treatment of atypical corticotroph adenomas as a

single agent and in the first line of treatment, however it is less effective in

cancers is also increased. Increased hypophyseal Fluorine-18 fluorodeoxyglucose

recurrent form of the disease.

uptake is rare on positron emission tomography and computed tomography (FDG-

PET/CT). Since hypophyseal adenomas may give false positive results on

DOI: 10.1530/endoabs.49.EP850

PET/CT, verification should be made by MRI. In this study, we aimed to present a

case with increased FDG uptake in hypophysis and lung on PET/CT. 64-year

male patient was presented with dyspnea and weight loss. Physical examination

revealed prognatia, acral enlargement in hands and feet, dermal thickening and

decreased breath sounds on apikal part of left lung. Chest X-ray and thoracic CT

imagings demonstrated 2 cm sized nodular opacity in the upper lobe of the left

lung. On FDG-PET/CT examination, increased FDG uptake was observed in this

EP851

2 cm sized nodular lesion in the lung and in 3 cm sized hypophyseal region.

Pachydermaperiostosis: a rare syndrome presented with acromegaloid

Hypophyseal MRI was performed and macroadenoma was detected. Ocular

changes

examination revealed hemianopsia. Laboratory examination findings were as

Meliha Melin Uygur¹, Izzet Hakki Arikan², Oguzhan Deyneli¹ &

follows: hemoglobin: 12.3 g/dl (13.7-17.5), sodiuum:140 mmol/l (normal: 135-

Dilek Gogas Yavuz¹

145), potassium: 4.4 mmol/l, creatinin: 0.73 mg/dl, ACTH: 5 pg/ml (normal: 0-

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Marmara University School of Medicine, Endocrinology and Metabolism

EP853

Disease Department, Istanbul, Turkey;²Marmara University School of

Ocult Cushing syndrome: (adicional) difficulties in hypercortisolism

Medicine, Nephrology Department, Istanbul, Turkey.

approach

Ana Filipa Martins¹, João Martin Martins^1,2 & Sónia Do Vale^1,2

Hospital de Santa Maria - Chln, Lisboa, Portugal;²Faculdade de Medicina

Introduction

de Lisboa, Lisboa, Portugal.

Pachydermoperiostosis (PDP) is a rare hereditary syndrome with familial and

idiopathic forms that is characterized by subperiosteal new bone formation with

pain, polyarthritis, cutis vertices grata, seborrhea, hyperhidrosis and digital

Introduction

clubbing. Periostosis and cutaneous thickening along with the absence of any

Cushing syndrome (CS) result from inappropriate exposure to increased non

signs of cardiovascular, pulmonary, hepatic, intestinal and mediastinal diseases

regulated glucocorticoid levels. It remains challenging regarding diagnosis and

causing secondary hypertrophic osteoarthropathy suggest PDP. The incidence of

management. Pituitary ACTH-secreting adenomas account for most of the cases

the disease is unknown. It is manifested mainly by dermatological and

if exogenous and paraneoplasic forms are excluded.

rheumatological symptoms. Rheumatoid arthritis, acromegaly, neurofibromato-

Case report

sis, hypothyroidism must be considered at differential diagnosis.

A 45-year-old women was referred to the endocrine outpatient department

Case report

because of obesity, muscular weakness, high blood pressure (HBP), diabetes

A 21-year-old male presented to the internal medicine department with

mellitus

(DM) and hypercholesterolemia beginning 3 years before. Analytic

polyarthritis and acromegaloid facial features. The patient had clubbing, swelling

evaluation evidenced ACTH- dependent hypercortisolism, with no cortisol

without an inflammation signs at knee joints and wrist; and thickening and folding

suppression after dexametasone 1mg overnight. Low-dose dexametasone (0.5 mg

of the facial skin (cutis verticis gyrata). The patient had hyperhidrosis but didn’t

quid for 48 h) excluded pseudocushing; high dose dexamethasone (2 mg quid for

have enlargement of hand, feet or lingua. Laboratory examination including

48 h) suggested pituitary CS. However no lesion was identified in pituitary RMN

growth hormone assay, thyroid profile, romatoid factor, anti nukleer anticor, anti

and inferior petrous sinus catheterization with simultaneous CRH dynamic testing

CCP, tests for syphilisis, ESR were normal. He did not have family history and

was inconclusive. Treatment with metyrapone 1500 mg/daily normalized 24-h

genetic transmission is ruled out by HPGD gene analysis. There were symmetric

urinary cortisol excretion and morning cortisol levels, but clinical manifestations

subperiostal bone formation at the radiographs of forearms and legs. The

persisted with progressive weight gain, worsened diabetes control, increased

scintigraphy showed a osteoblastic hyperactivation in the distal radius,

blood pressure levels and pathologic rib fractures, despite additional drugs. The

metacarpal bones and tibia. Based on clinical and radiological findings PDP

patient was submitted to bilateral adrenalectomy, which immediately controlled

was diagnosed. We consulted the patient to rheumatology department for arthritis

the disease with no further need for antidiabetic or blood pressure drugs and

and steroid theraphy was started.

significant weight loss.

DOI: 10.1530/endoabs.49.EP851

Discussion

Even when imaging and functional evaluation are diagnostic, CS treatment may

be challenging. Bilateral adrenalectomy is not the first line therapeutic option, but

as in this case correction of hypercortisolism more than apparent normalization of

cortisol levels may require it. Life-long morbidity is expected regarding glico-

and mineralocorticoid reposition, however this is easier to obtain and may be

associated with less co-morbidities than sustained hypercortisolism.

DOI: 10.1530/endoabs.49.EP853

EP852

Temozolomide Treatment in Aggressive Pituitary Adenoma

Pinar Sisman¹, Ahmet Bilgehan Sahin², Ozen Oz Gul³, Soner Cander³,

Erdinc Erturk³ & Canan Ersoy³

¹Harakani State Hospital, Endocrinology and Metabolism Clinic, Kars,

Turkey;²Uludag University Medical School, Department of Internal

Medicine, Bursa, Turkey;³Uludag University Medical School, Department

of Endocrinology and Metabolism, Bursa, Turkey.

Background

EP854

Aggressive pituitary adenomas (APAs) take place phenotypically between benign

A case of cystic prolactinoma responsed to medical treatment

pituitary adenomas and pituitary carcinomas with systemic metastasis. Frequent

Tulay Omma, Nese Ersoz Gulcelik, Anara Karaca & Isilay Taskaldiran

recurrence and resistance to conventional treatments are characteristic features of

Ankara Training and Research Hospital, Ankara, Altındag˘, Turkey.

APAs in their clinical course. Temozolomide is an alkylating agent that has been

used in the treatment of pituitary carcinomas and APAs since 2006. Herein, we

report a patient who received temozolomide treatment due to APA.

Introduction

Case presentation

Cystic prolactinomas are considered resistant to volume depletion by dopamine

A 57-year-old male patient with complaints of headache and visual impairment

agonists (DAs). Because of the effectiveness and tolerability, dopamine agonists

had been admitted to state hospital in 1991. Laboratory and imaging studies had

(DAs) are the first line therapies in prolactinoma and reduce tumor mass as well as

revealed nonfunctioning invasive pituitary macroadenoma, and he had underwent

prolactin levels in most of all patients. Rathke’s cleft cysts, craniopharyngiomas

transcranial operation. The patient had developed pituitary insufficiency after

and arachnoid cysts are differential diagnoses to keep in mind. DAs resistance or

operation; therefore replacement therapy had been started. Thirty radiotherapy

intolerance, psychiatric disorders associated with dopamine agonist use and

(RT) sessions had been performed due to the lack of complete resection of the

patient preference can be indications for surgical intervention. Large,

mass. Then, he was referred to our department. He was reoperated in 2006 and

predominantly cystic prolactinomas are usually treated surgically and are

2009. In magnetic resonance imaging (MRI) after surgeries, a macroadenoma

presumed to be resistant to volume reduction by DAs. Although optimal

(37!35!30 mm in size) was observed and follow-up was planned because of its

management of cystic prolactinomas are not defined yet, several individual case

size to remain stable. In 2012, MRI revealed that the mass grown in size (50!

reports and case series have suggested that DAs may reduce these lesions. Here

40!38 mm). It filled suprasellar cistern and sphenoidal sinus, and infiltrated

we present a patient with cystic prolactinoma responsed to medical treatment.

cavernous sinuses. After six cycles of temozolomide were given with

Case report

conventional RT sessions, minimal reduction in mass size was observed. Six more

A 20-year-old women presented with secondary amenorrhea and spontaneous

cycles of temozolomide was given. After treatment, the mass was measured as

galactorrhea for three months. She has not taken any prolactin-increasing

40!38!28 mm. The patient’s monitoring still continues with stable disease.

medications and was not pregnant. Her biochemical, hematological laboratory

Discussion

tests and hypophysis function tests were normal except prolactin. Her prolactin

In our case, minimal shrinkage and stabilization of the mass size were achieved

level was 133 ng/ml (normal value is 2.7-19.6) and macroprolactin was negative.

after temozolomide treatment. According to the case reports published in the

Pituitary MR scan revealed a 9!7 mm cystic adenoma at the left side of

literature, the effectiveness of temozolomide in APAs is about 55%, although

adenohypophysis. Infundibulum, suprasellar cistern and optic chiasm were intact.

interpretation of efficacy criteria differs in various publications. However, large-

Hence her clinical picture was consistent with prolactinoma, we administered

scale studies are needed to determine the indications, proper doses and duration of

cabergolin 0.25 mg twice a week. After three months of cabergolin therapy her

temozolomide treatment.

prolactin level decreased to

6.5 ng/ml. She had regular menses and no

DOI: 10.1530/endoabs.49.EP852

galactorrhea. After eight months, hypopsis mr scan demonstrated a remarkable

reduction in the tumor size, measured as 6!3.5 mm.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Discussion

Case

In conclusion, it is appropriate to consider dopamine agonist therapy in patients

A 85 years old woman with regulated hypertension admitted with partial loss of

with cystic prolactinomas before considering surgery.

conciousness. She had cachectia and body mass index was 16.7 kg/m². There was

DOI: 10.1530/endoabs.49.EP854

no acute pathology in cranial imaging. Because electroencephalography revealed

findings compatible with nonconvulsive status epilepticus, levatiresatam was

started. In laboratory examination, she had hypokalemia (2.5 mg/dl) resistant to

i.v. replacement. Her serum cortisol was 126 mg /ml (5-20 mg/ml) and ACTH was

331.7 pg/ml (0-60 pg/ml). Hypophysial MRI showed a 6!3 mm lesion in right

hypopysis. She did not any physical signs of Cushing syndrome. In thoracal CT, a

16 mm solid irregular lesion extending to the parencyma and costal pleura in right

EP855

lung was observed. Abdominal CT revealed a 125 mm heterogenous mass and

A case of pituitary apoplexy in a patient with Cushing’s disease due to

satellite lesions in the liver and hypertrophic adrenal glands. A tru-cut biopsy

corticotroph macroadenoma

from the lesion was reported as metastasis of neuroendocrine tumor. The lesion

Elisabeta Sava¹, Bianca Leca¹, Anca Sirbu¹, Olivia Georgescu¹,

was diffusely positive for TTF-1, cytokeratin 7, synaptophysin and chromagranin.

Luminita Cima¹, Suzana Florea² & Simona Fica¹

Ki67 proliferation index was 10-15% and primary tumor was suggested to be

¹Endocrinology Department, Elias University Hospital, Carol Davila

atypical carcinoid tumor of lung according to the immunohistopathological

University of Medicine and Pharmacy, Bucharest, Romania;²Laboratory

findings. The patient died at the 20^th day of intensive care unit due to sepsis.

Department, Elias Hospital, Bucharest, Romania.

Conclusion

Ectopic ACTH syndrome is a rare cause of ACTH dependent Cushing syndrome.

It can be easily included in the differential diagnosis in a patient with classical

Corticotroph macroadenomas are exceptionally found in Cushing’s disease.

signs of Cushing syndrome and without adenoma in hypophysis. However, like

Pituitary apoplexy is a rare endocrine emergency condition caused by either

ours, well-known physical appearance and signs of Cushing syndrome might not

hemorrhage or infarction of the pituitary gland. We report a case of a 56-year-old

be seen in all patients, and the only clinical presentation might be neurocognitive

female diagnosed with type 2 diabetes in 2008. One year after, at the periodical

dysfunctions.

follow up, she presented with uncontrolled diabetes (HbA1cZ12.26%) and

clinical manifestations suggestive for hypercortisolism, therefore insulin therapy

DOI: 10.1530/endoabs.49.EP856

was initiated; hormonal profile revealed baseline cortisolZ26.4 ng/ml, cortisol

level after low-dose dexamethasone suppression testZ21.7 ng/ml, ACTHZ

122 ng/ml, and a 2.4/1.8/2.9 cm pituitary macroadenoma was found. While

waiting for surgery appointment, in January 2010 the patient experienced severe

headache, nausea, vomiting and diplopia. She was admitted to ICU, diagnosed

EP857

with pituitary apoplexy and transferred to neurosurgery department where surgery

Cushing’s disease management through time- a case report

was performed. Clinical improvement of Cushing’s symptoms, diplopia,

Sanja Borozan & Olivera Boskovic

hypertension and diabetes (HbA1cZ6.5% without insulin therapy) was noted.

Clinical centre of Montenegro, Podgorica, Montenegro.

The postoperative pituitary MRI revealed a rest tumor

(7/8 mm); slightly

Cushing’s disease (CD) is a rare disorder caused by an increased secretion of

increased ACTH levels

(70.1 pg/ml) and abnormal

1 mg DXM overnight

adrenocorticotropin hormone (ACTH) from the anterior pituitary gland, usually

suppression test (5.33 ng/ml). She received medical treatment with ketoconazole

as a result of pituitary adenoma. Transsphenoidal tumour resection is the best first

(not tolerated) and cabergoline

(2 mg/week); the clinical manifestation of

line therapy option for these patients but

10-30% of them fail to achieve

hypercotisolism reappeared and diabetes was poorly controlled. Despite

remission and need further treatment modalities to eliminate hypercortisolemia.

medication, ACTH and cortisol secretion remained elevated and pituitary MRI

Long-term outcomes and possible impacts on quality of life in these patients are

scan showed tumor progression. Considering the development of the tumor in

still not well examined. We report a case of a 73-year-old patient who presented in

close proximity of the optic chiasm she was refused for surgery and gamma knife

1982, as 38-year-old women with generalized malaise, facial fullness, increased

radiation therapy, being lost to follow-up for 2 years. In 2016 she was admitted

skin pigmentation, hirsutism, hypertension, hyperglycemia and depression.

with severe hepatic cytolysis (ALTZ766 U/l, ASTZ484 U/l), mild cholestatic

Laboratory evaluation showed elevated serum levels of ACTH and cortisol

syndrome, hypercortisolism and uncontrolled diabetes HbA1cZ9.6%. The

with loss of diurnal variation and no suppression after overnight low-dose

presence of hepatic cytolysis caused postponement of bilateral adrenalectomy.

dexamethasone test. Computerized tomography (CT) scan revealed hypodense

Our patient presented pituitary apoplexy in a corticotroph macroadenoma, with

persistence of Cushing’s disease after surgery and no therapy of hypercortisolism

zone in posterior pituitary and no lesions in adrenal glands. The patient underwent

transsphenoidal surgery which confirmed 5 mm pituitary tumour in posterior lobe

at the moment. Bilateral adrenalectomy is probably the best option, after the

with anterior spreading into normal tissue that inhibited the complete resection.

control of hepatic function.

Histological finding was ACTH

- secreting microadenoma. During the

Keywords: pituitary apoplexy, corticotroph macroadenoma

postoperative course, patient developed diabetes insipidus; depression and high

DOI: 10.1530/endoabs.49.EP855

blood pressure were still present. Serum cortisol level was 832 nmol/l, ACTH

26.3 pmol/l (reference range:1.2-10.2 pmol/l). The patient consented to bilateral

total adrenalectomy in November 1984. which showed adrenal hyperplasia. After

second surgery, the symptoms of CD were diminished and steroid replacement

therapy was started as following treatment. During time, patient developed

hypothyroidism, electrolyte concentrations are kept in balance. ACTH levels

were up to 194 pmol/l (with marked hyperpigmentation localized predominantly

EP856

in face area), cortisolemia up to

579 nmol/l according to which the

Ectopic ACTH syndrome presenting with partial loss of conciousness

Hydrocortisone dose adjustments were made. Recent pituitary magnetic

and nonconvulsive status epilepticus in a patient with no signs of

resonance imaging (MRI) demonstrated no signs for tumour recurrence. After

Cushing syndrome

33 years of therapy, the evaluated quality of life in our patient is not significantly

Eray Onur Mert¹, Samet Yaman¹, Didem Ozdemir², Nagihan Bestepe³,

impaired.

Dursun Ali Saglam⁴, Osman Ersoy⁵, Reyhan Ersoy² & Bekir Cakir²

DOI: 10.1530/endoabs.49.EP857

¹Ankara Yildirim Beyazit University, School of Medicine, Department of

Internal Medicine, Ankara, Turkey;²Ankara Yildirim Beyazit University,

School of Medicine, Department of Endocrinology and Metabolism,

Ankara, Turkey;³Ankara Ataturk Education and Research Hospital,

Department of Endocrinology and Metabolism, Ankara, Turkey;⁴Ankara

Ataturk Education and Research Hospital, Department of Internal Medicine,

EP858

Ankara, Turkey;⁵Ankara Yildirim Beyazit University, School of Medicine,

A case of extrapontine myelinolysis after surgery for a pituitary tumor

Department of Gastroenterology, Ankara, Turkey.

Manuel Cayón-Blanco, M Gloria Baena-Nieto, Rosa Márquez-Pardo,

Rosario López-Valasco, Isabel M Torres-Barea &

Introduction

Lourdes García-García-Doncel

Ectopic adrenocorticotrophic hormone (ACTH) syndrome is associated with

Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.

variable tumor groups most commonly originating from neuroendocrine cells.

Here, we reported a patient considered to have nonconvulsive status epilepticus

Introduction

initially due to neurological symptoms and diagnosed as neuroendocrine tumor

Rapid correction of hyponatremia is known to cause central pontine myelinolysis.

with ectopic ACTH syndrome.

It may concurrently involve other areas of brain as well, referred as extra-pontine

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

myelinolysis (EPM). Isolated EPM however is a very rare occurrence. We present

EP860

a case of EPM where the hyponatremia was secondary to syndrome of

A case of tuberous sclerosis complex associated with non-functioning

inappropriate antidiuretic hormone secretion

(SIADH) after surgery for a

pituitary incidentaloma and moderate hyperprolactinaemia

pituitary macroadenoma.

Zsuzsanna Szanto & Zsuzsa Tanko

Case report

University of Medicine and Pharmacy, Targu Mures, Romania.

A 36-year-old man underwent transsphenoidal surgery for a non-functional 2.4!

2.6!1.8 cm pituitary macroadenoma causing chiasmatic compression. During

the immediate postoperative period, the patient developed polyuria and received

Tuberous sclerosis complex is characterised by non-malignant tumours in the

desmopressin. Six days after surgery, he left the hospital asymptomatic receiving

skin, brain, kidneys, heart, eyes, lung, but sometimes angiomyolipomas may

hydrocortisone. Diuresis volume was normal and desmopressin was not necessary

develop in the adrenals, ovaries, thyroid, and rarely neuroendocrine tumours in

anymore. On the 8th postoperative day, his level of consciousness decreased and

the pancreas, pituitary gland, parathyroids. The case of a 46-years-old female

suffered from seizure requiring intubation. Blood examination revealed severe

patient suffering of tuberous sclerosis and endocrine disturbances is presented.

hyponatremia (serum sodium level of 108 mEq/l) and 1 day later serum sodium

She is known with temporal lobe epilepsy since early childhood, and anxious

increased rapidly to

135 mEq/l. On the 16th postoperative day, orotracheal

depressive disorder with obsessive elements since young adulthood, currently

intubation was discontinued but the patient was unable to communicate. Physical

receiving carbamazepine, sulpiride and fluvoxamine. At 41 years of age she was

examination revealed global hyperreflexia, clonus, dysarthria and gait disturb-

diagnosed with bilateral scleroatrophic kidneys, stage 2 chronic renal disease,

ance. Head MRI on the 18th postoperative day demonstrated intense high-signal

hypocalcemia, and endocrine investigations were recommended. The diagnosis of

bilateral lesions in corpus striatum on FLAIR and DWI, and extrapontine

tuberous sclerosis was based on four major (facial angiofibroma, periungual

myelinolysis was diagnosed. The patient’s symptoms improved gradually after

fibroma, Shagreen patches, cardiac rhabdomyoma) and one minor criteria

rehabilitation and antispasticity treatment. It was suggested that the changes in

(confetti skin lesions). Endocrine investigations and follow-up started from 2012.

serum sodium levels after pituitary surgery were due to SIADH due to

Low serum calcium level (total Ca: 8.32 mmol/l, normal: 9-11, ionic Ca:

degeneration of nerve terminals in the posterior pituitary.

0.92 mmol/l, normal: 1.1-1.6) with high intact parathyroid hormone value (iPTH:

Conclusions

133 pg/ml, normal: 15-67) showed a secondary hypoparathyroidism. Alfacalci-

Incidence of hyponatraemia following pituitary surgery is reported between 3 and

dol and calcium therapy have normalized iPTH (47.8 pg/ml) and calcium levels

25%. The delay in onset of SIADH can lead to practical problems for

(2.34 mmol/l, normal: 2.1-2.56). In 2015, at 44-years of age amenorrhoea-

neurosurgical units where there is very early discharge following pituitary

galactorrhoea syndrome developed due to hyperprolactinaemia (139.9 ng/ml,

surgery. As pituitary surgery may trigger changes in serum sodium leading to

normal:

5-26). Polyethylene glycol treatment showed the presence of

myelinolysis, this possibility should always be borne in mind when treating such

macroprolactin and a moderate genuine hyperprolactinaemia, which was

patients.

explained by the use of antidopaminergic therapy.

5 mg/day bromocriptine

DOI: 10.1530/endoabs.49.EP858

normalized menstrual disturbancies, but psychiatric symptoms worsened,

therefore we reduced the dose to 2.5 mg/day (PRL: 40.75 ng/ml). In 2015 cranial

and abdominal MRI were performed. None of the typical lesions of tuberous

sclerosis were observed, but a 4 mm pituitary microadenoma was detected, which

was interpreted as a non-functioning pituitary incidentaloma. In the literature a

few cases of GH, ACTH- or PRL-secreting pituitary adenomas, and one non-

functioning adenoma were reported.

DOI: 10.1530/endoabs.49.EP860

EP859

Hypopituitarism caused by an intrasellar meningioma: case report

Stavroula Gavriilidou¹, Constantinos Belis¹, Kalliopi Xydiari¹,

EP861

Aikaterini Afentoulidi¹, Vasilios Athanasiou¹, Sofia Malaktari-

Patient with empty sella and clinical features of acromegaly

Skarantavou¹, Symeon Tournis² & Christos Savvidis¹

Dimitra Pappa¹, Pinelopi Thoda¹, Andreas Rizoulis¹, Ioannis Gountios¹,

¹Department of Endocrinology, Hippocratio General Hospital of Athens,

Eftihia Kapsalaki² & Alexandra Bargiota¹

Athens, Greece;²Laboratory for Research of the Musculoskeletal System

¹Department of Endocrinology and Metabolic diseases, University Hospital

“Th. Garofalidis”, Medical School, University of Athens, KAT Hospital,

of Thessaly, Larissa, Greece;²Department of Radiology, University

Athens, Greece.

Hospital of Thessaly, Larissa, Greece.

Meningioma is a common, usually benign, tumor of the brain and the spinal cord

Introduction

that originates from any dura surface. Such lesion accounts for 10 to 15% of

Acromegaly is a systematic disease with charecteristic clinical features, which is

nonadenomatous sellar masses. Purely intrasellar meningiomas are relatively rare

due to GH hypersecretion mainly from pituitary adenomas and in rare cases it can

and can mimic a nonfunctioning adenoma. A 33-year-old man with a history of

be due to ectopic GHRH and GH hypersecretion. Sometimes localizing the source

1.5 year fatigue, anemia and erectile dysfunction referred to our department. The

of hypersecretion is difficult. Here we present a case of a woman with acromegalic

laboratory data revealed low levels of ACTH, Cortisol, FSH, LH and

phenotype and empty sella.

Testosterone, while TSH, FT₄, IGF-1, PRL, K^C and Na^C levels were normal.

Presentation

Pituitary MRI demonstrated the presence of an intrasellar mass measuring 2.4!

A 47 years old woman referred to our department after recent onset of high blood

2.4!1.7 cm in diameter. The suprasellar extension was causing displacement of

pressure, headache and dizziness and a head MRI which revealed an empty sella.

the optic nerves and the chiasm. There were foci of low signal intensity consistent

Clinically she had acromegalic features and acromegaly was confirmed

with areas of calcification or hemorrhage. Formal visual field testing resulted

biochemically (IGF-1 941.1 ng/ml and basic GH 5.41 mg/l and after OGTT

normal. The patient received replacement therapy with hydrocortisone and

3.36 mg/l). A pituitary MRI confirmed the empty sella with no obvious pituitary

testosterone and referred to a Neurosurgeon. Few days before surgery the patient

tissue present. In order to localize the source of the GH hypersecretion further

complained of polyuria and polydipsia and desmopressin was prescribed. The

biochemical and imaging tests were performed

(plasma chromogranin and

mass couldn’t be totally resected through transsphenoidal approach due to its hard

calcitonin, 24 hour urine metanephrines and nonmetanephrines, head and neck

fibrous tissue. The histological report showed Grade I psammomatous

111

CT, abdomen CT,

In-Octreotide scanning) and all were negative.

meningioma. The postoperative MRI revealed residual tumor measuring 1.8!

Determination of IR-GHRH though was indicative of pituitary hypersecretion.

1.8!1.6 cm in diameter. A debulking surgery followed and the postoperative

Octreotide LAR 40 mg failed to result in biochemical control of the disease and

blood tests demonstrated panhypopitutarism with low levels of ACTH, Cortisol,

Pegvisomant (10 mg/day) was added. Eleven months later biochemical control

FSH, LH, Testosterone, TSH, FT₄, PRL and IGF-1. Thyroxine replacement

was achieved (normal for her age IGF-1 and GH ! 1 mg/l), but a pituitary MRI at

therapy was added. Meningiomas of the pituitary fossa represent approximately 5

that time revealed an 9!4.4!6 mm adenoma.

to 10% of intracranial meningiomas. They commonly cause visual dysfunction

Conclusions

and infrequently hormonal insufficiency. In our case the patient presented with

Pegvisomant, a GH antagonist, used as monotherapy or in combination for

hypopituitarism caused by the meningioma, but no visual disturbances. To our

treating acromegaly is very effective in controling the disease, but growth of the

knowledge this is the first case that an intrasellar psammomatous meningioma

pituitary adenomas is being described in rare cases. Although when combined

causes pituitary insufficiency of both the anterior and posterior lobe with normal

with somatostatin analog this risk is lower, in our case revealed the adenoma.

visual fields.

DOI: 10.1530/endoabs.49.EP861

DOI: 10.1530/endoabs.49.EP859

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP862

Conclusions

Lymphocytic hypophysitis is an uncommon cause of hypopituitarism which can

Esthesioneuroblastoma causing ectopic ACTH Syndrome

present symptoms long time after the diagnosis. Due to the inflammatory changes,

Cristina Lorenzo González, Estefanía González Melo, Elena Márquez Mesa,

the patient could present headache and other local symptoms despite the absence

Pilar Olvera Márquez, María Teresa Herrera Arranz, Bruno Francisco

of compression of nearby structures. In this case, if the patient does not respond to

García Bray, Yolanda Zambrano Huerta & Enrique Palacio Abizanda

high doses of steroids, surgery is mandatory.

Hospital Universitario Nuestra Sen˜ ora de la Candelaria, Santa Cruz de

Tenerife, Spain.

DOI: 10.1530/endoabs.49.EP863

Introduction

Esthesioneuroblastoma is an uncommon malignant neoplasm with an average

5-year survival rate of about

45%. Ectopic ACTH syndrome due to

esthesioneuroblastoma is extremely rare and there have been very few cases

reported.

EP864

Case report

Title: IgG4 related hypophysitis

A 54-year-old woman was admitted to our hospital with symptoms of leg edema

Pinelopi Thoda, Dimitra Pappa, Anastasia-Konstantina Sakali,

and general fatigue of one month’s duration. Physical examination showed moon

Eleni Georgiou, Ioannis Gountios & Alexandra Bargiota

facies and edema on her lower extremities bilaterally but no other cushingoid

Department of Endocrinology and Metabolic Diseases, University of

features. Laboratory examination revealed a severe hypokalaemia (1, 99 mmol/l)

Thessaly, Larissa, Greece.

and endocrine tests revealed a marked elevation of plasma ACTH (1123 pg/ml)

and cortisol levels (cortisol in serum 110, 1 mcg/dl and 24-hour urinary cortisol

296, 7 mcg). Dexametasone suppression tests both with 1 and 8 mg were non-

Introduction

suppressible. These physical and endocrine findings were consistent with the

IgG4

Related Hypophysitis

(IgG4-RH) is a newly recognized form of

diagnosis of ACTH-dependent Cushing’s syndrome: ectopic Vs secondary to

hypophysitis. It usually appears as part of IgG4-Related Disease (IgG4-RD),

pituitary macroadenoma. Computed tomography

(CT) scans of the chest,

an immune mediated disease, with manifestations in many organs. Isolated

abdomen and pelvis were normal except for hyperplastic adrenal glands. A

hypophysitis without other IgG4-RD manifestations is rare.

pituitary magnetic resonance image (MRI) showed a normal pituitary; however,

Presentation

there was a large and aggressive mass centred in both nostrils. The mass extended

A 64 years old female referred to our department for further investigation of a

into the frontal sinus and ethmoidal cells. Otolaryngology department was

9 month history of fatigue, muscle weakness, recurrent episodes of right temporal

consulted and a biopsy of the lesion was performed. The pathologic study of the

headaches, anorexia and weight loss and a month’s history of diplopia and right

biopsy confirmed the diagnosis of esthesioneuroblastoma. Therapy with

eyelid ptosis. Past medical history was unremarkable. On clinical examination

ketoconazole 1000 mg daily was initiated preoperatively. Three weeks later the

there was marked proximal muscle weakness, right eyelid ptosis, diplopia, but

patient underwent a combined frontal craniotomy and endoscopic transnasal

visual fields were normal. Laboratory evaluation revealed hypopituitarism of the

approach. Adjuvant postoperative radiation treatment was performed without

anterior pituitary lobe. Magnetic resonance imaging (MRI) showed a thickened

complications. The patient’s symptoms completely resolved and the ACTH and

pituitary stalk and an enlarged heterogenous pituitary gland with expansion to the

cortisol levels returned to normal values.

right cavernous sinus. IgG4 levels were elevated (192 mg/dl, normal values:

Conclusions

8-140 mg/dl). Based on these findings the diagnosis of IgG4-RH was made. The

Cushing’s syndrome due to olfactory neuroblastoma may have satisfactory

patient was commenced on prednisolone 40 mg/day and thyroxine. A remarkable

prognostic and control of symptoms with combined therapy consisting of surgery

clinical improvement was observed within the first forthnight. Three months later

and radiation. We herein present a patient with a 3 year disease free survival after

she had no diplopia, no muscle weakness and repeated MRI of her pituitary gland

successful treatment.

showed great improvement of the previous picture. IgG4 levels were reevaluated

DOI: 10.1530/endoabs.49.EP862

and were found to be reduced.

Conclusion

Isolated IgG4-RH is a rare entity. IgG4 levels should be obtained in cases

suggestive of hypophysitis. Corticosteroid treatment greatly improves the clinical

picture.

DOI: 10.1530/endoabs.49.EP864

EP863

Lymphocytic hypophysitis which underwent surgery despite the

absence of compression of nearby structures. A case report

Javier González¹, Alberto Díez², Alma Prieto² & Marta Fernández²

¹Hospital Virgen de la Luz, Cuenca, Spain;²Hospital Del Bierzo, Leon,

Spain.

EP865

Pituitary apoplexy as the first manifestation of silent somatotropinoma

Introduction

Ewa Obel¹, Marcin Lewicki¹, Magdalena Urbanczuk^1,3, Agata Smolen²,

Lymphocytic hypophysitis is a strange cause of hypopituitarism which can

Beata Matyjaszek-Matuszek¹ & Jerzy Tarach¹

represent a difficult diagnostic and therapeutic challenge.

¹Department of Endocrinology, Medical University, Lublin, Poland;

Objectives and methods

²Department of Epidemiology and Clinical Research Methodology, Medical

Describe the diagnosis, evolution and treatment of a case of lymphocytic

University, Lublin, Poland;³Department of Clinical Pathomorphology,

hypophysitis in a patient who began with hypopituitarism and a year after the

Medical, Lublin, Poland.

diagnosis had local symptoms. We reviewed the medical history of the patient

from the moment the patient contacted with us to the months after the patient went

surgery. It has been collected clinical, laboratory and radiological data during this

Introduction

period.

Pituitary apoplexy is a rare endocrine disorder which can occur due to

Results

haemorrhage into pituitary gland. It is often associated with the presence of

This 51-year-old man presented with low TSH (0,122), low ft₄ values (0.45) and

pituitary adenoma, uncommonly being the first clinical manifestation of an

hypogonadotropic hypogonadism without any other pituitary alterations. His

underlying tumour. It can cause hypopituitarism and diabetes insipidus. Pituitary

visual examination was normal. The MRI demonstrated a 15.5!10!8.5 sellar

adenomas are classified by their secretion properties as functional and clinically

lesion, thickening in the pituitary stalk

(6 mm), loss of differentiation

non-functioning, the latter, however, can exhibit positive immunostaining for

(hyperintensity) of the neurohypophysis and heterogeneous parenchyma of the

pituitary cell types in histologic examination and are thus classified as ‘silent

adenohypophysis. Because of the absence of symptoms in the patient, we

adenomas’.

corrected the deficits and we followed up. At 3 months after diagnosis the patient

Case study

developed adrenal insufficiency so we corrected this new deficit. At 1 year after

A 37-year-old male patient was admitted to the Department of Neurosurgery with

diagnosis the patient presented with severe headache and Tolosa-Hunt syndrome,

complaints of strong persistent headache with accompanying temporal visual

so we began treatment with high dose of dexamethasone. The patient had initial

fields narrowing. Pituitary tumour apoplexy was diagnosed after the imaging

improvement but relapsed after decreasing dexamethasone, so the patient was

revealed a pituitary tumor 25 mm in diameter with features of haemorrhage.

treated with trans-sphenoidal surgery with a total removal of the lesion. The

Preoperative assessment revealed gonadotropin deficiency with low concen-

patient remains asymptomatic on pituitary replacement therapy.

trations of prolactin. After undergoing transsphenoidal resection of pituitary

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

macroadenoma, hormonal evaluation unveiled additional deficiencies in the form

Observation

of secondary adrenal and thyroid insufficiency with accompanying diabetes

A 36-year-old lady (Gravida 3 Parity 2 Live Birth 2), presented to our outpatient

insipidus. At that point, the patient was transferred to the Department of

clinic on May 2007 forsuspicion of acromegaly. Clinical examination revealed

Endocrinology of Medical University of Lublin for further evaluation. The

acromegalic features. Hormonal profile revealed elevated human growth hormone

replacement therapy with hydrocortisone, levothyroxine, testosterone and

(HGH) 47.3 mUI/l and insulin-like growth factor 1 (IGF-1) 576 ng/ml (normal

desmopressin was introduced, stabilizing and improving the patient’s condition.

109-358 ng/ml), her serum prolactin PRL was also mildly elevated 76.7 ng/ml

During the follow-up no restoration of pituitary secretion function in any axis was

Follicle-stimulating hormone

(FSH), luteinizing hormone

(LH), Thyroid

observed. Histologic examination of the tumour sample displayed a larger size

stimulating hormone (TSH) and Free Thyroxine (FT₄) were within normal

than previously assumed (50 mm in the largest diameter), positive immunostain-

range. Cortisol level during hypoglycaemia insulin test was 73 and 107 mg/l.

ing for GH (diffuse) and PRL (sparse) allowing to classify the tumour as silent

Magnetic resonance imaging of the pituitary gland revealed: Left postero-lateral

subtype

3 adenoma. Clinical and laboratory evaluation did not reveal any

intra-pituitary expansive lesion measuring 17!11 mm with extension to the

acromegalic features; decreased prolactin levels persisted.

sphenoid sinus. Final diagnosis was: Pituitary macro-adenoma on GH, with

Conclusions

Hyperprolactinemia and Secondary adrenal insufficiency. She underwent

Pituitary apoplexy and/or hypogonadrotropic hypogonadism can be the first

endoscopic transnasaltranssphenoidal radical excision of the tumor on Mars

symptom of pituitary macroadenoma. Clinically non-functioning adenomas may

2009. Magnetic resonance imaging of the pituitary gland after surgery revealed:

immunostain positively for more than one pituitary hormone determining their

Absence of evidence of adenomatous residue. On June 2010, patient present in 3^rd

classification as silent subtype 3 adenomas.

trimester of the pregnancy. Ophthalmological examination, hormonal profile and

DOI: 10.1530/endoabs.49.EP865

Oral glucose tolerance test (OGTT) of 75 gr glucose were without anomaly. She

then went on to deliver a full-term baby girl by caesarean section in August 2010.

Discussion

Pregnancy in a patient with acromegaly is very unusual, as the enlarging pituitary

adenoma suppresses gonadotropin secretion rendering the patient amenorrheic

and infertile. Up to 30% of HGH-secreting pituitary adenomas also secrete

prolactin and this adds to the problem.Although pregnancy is unusual in

acromegaly, it is by no means rare.

EP866

DOI: 10.1530/endoabs.49.EP867

Unprogrammed pregnancy in women with active Acromegaly: a case

report

Inés Luque-Fernández, Mónica Olivar-Azuara, Ofelia Llamazares-Iglesias

& Almudena Vicente

Endocrinology Division, Virgen de la Salud Hospital, Toledo, Spain.

Introduction

Reports of pregnancy occurring in acromegalic patients are uncommon.

Nevertheless, it appears that women are usually able to carry their pregnancy

to full term

Case

EP868

39 year old woman referred to endocrinology for secondary amenorrhea and

Clinical case report: MEN-1 syndrome with coincident AIP gen

hyperprolactinemia (PRL 55.54 mg/dl). As she mentioned typical symptoms of

mutation and MEN-1 gen deletion

Acromegaly, we extended the study, finding high levels of IGF1 and a pituitary

Inmaculada Gonzalez-Molero¹, Juan Antonio García Arnés², Josep Oriola³,

macroadenoma (25!16 mm) in MRI. Presurgical treatment with Octreotide was

Stella Gonzalez Romero¹, Maria Cruz Almaraz¹, Silvia Maraver⁴,

started

(120 mg/28 days) and complete transsphenoidal surgical resection of

Gabriel Olveira¹ & Francisco Tinahones^1,4

GH/PRL secreting pituitary adenoma was performed. 6 months later, as IGF1

¹Hospital REgional de Málaga, Málaga, Spain;²Medicine Faculty, Malaga

levels and GH during oGTT remained high, and no biochemical remission was

University, Málaga, Spain;³Hospital Clinic, BArcelona, Spain;⁴Hospital

achieved, treatment with octreotide and cabergoline was restarted. 13 months

Virgen de la Victoria, Málaga, Spain.

later, she got unexpectedly pregnant and pharmacological treatment was

withdrawn as soon as pregnancy was diagnosed (7-9 weeks). Patient was

clinically and biochemically evaluated throughout pregnancy with at least one

We present the clinical case of a family with an initial diagnosis of AIP syndrome

visit per trimester. In spite of medical treatment withdrawal, IGF significantly

with AIP mutation and a secondary diagnosis of MEN syndrome associated

decreased compared to preconceptional values. Normal fetal growth and

because of a large MEN-1 gen deletion. A male patient 16 years old was evaluated

development was observed, with no maternal complications (gestational diabetes

because of delayed growth and pubertal development. He had headaches, nausea

or gravid hypertension) and no congenital malformations in the newborn. After

and vomits since seven years old. MRI showed: Large pituitary mass of 47.6!

delivery IGF1 increased to pregestational levels. During the postpartum period,

22!47.2 mm that erode the floor of the sella, extending into the left prepontine

there was no problem for breastfeeding until medical treatment was restarted.

cistern and surrounding the carotid. After some months with high dosis of

Discussion

cabergoline there were not response so surgical treatment was decided. Four

Several reports conclude that GH-supressive treatment can be safely withdrawn

months after surgery MRI showed again a mass of 30!20!30 mm, remained

after conception in most women with acromegaly. In this case, withdrawal of

hipopituitarism and hyperprolactinemia. Family history: The mother consulted

octreotide and cabergoline was safe for obstetrical and fetal outcomes with an

with gynecologist in

2004 because of menstrual disturbances and bilateral

uneventful course of pregnancy and delivery, with a helthy newborn.

galactorrhea. Pituitary macroadenoma without invasion of surrounding structures

was diagnosed. During the follow up the mass had the same volume and Pituitary

DOI: 10.1530/endoabs.49.EP866

axis were normal. Results of the Genetic study of AIP geneheterozygous mutation

in exon 6: 974G O A (p.Arg325Gln.The mother and the brother, had the same

mutation while the rest of the family does not carry it. An MRI and hormonal

analysis were performed in the brother and initially were normal, but last MRI

showed a pituitary microadenoma. Two years ago hypercalcemia appeared in a

routine analysis of the mother. We confirmed hyperparathyroidism and an image

suggestive of adenoma was confirmed in the imaging tests. A parathyroidectomy

was performed. In both sons calcium and iPTH are rising slightly in progressive

analytics. After this, we requested abdominal CT and gastrointestinal and

EP867

pancreatic hormones to rule out a possible association of neuroendocrine tumor.

The results were normal in the two children, but in the mother we discovered a

Acromegaly and pregnancy: case report

pancreatic polypeptide elevation and a 8 cm mass in pancreatic body and tail. The

Maria Khatib

genetic study of MEN gen with MLPA (multiplex ligation dependent probe

Rabta University Hospital, Tunis, Tunisia.

amplification) revealed the following result: heterozygous deletion corresponding

to exon 1- 11(chr11 positions:64571868-64578482).To our knowledge, this is the

Introduction

first case of a family with the two genetics disorders (AIP and MEN-1) matching

Pregnancy in patients with acromegaly is a rare and challenging medical situation.

and resulting in MEN-1 syndrome.

Here in, we report a patient with acromegaly who presented to us in the

DOI: 10.1530/endoabs.49.EP868

3^rdtrimester of pregnancy after endoscopic transnasaltranssphenoidal radical

excision of the tumor.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP869

and natremia of 124 mEq/l. Hyponatraemia was very resistant to treatment

despite hypertonic saline replacements, hence desmopressin was suspended. On

Coexistence of thyrotropinoma and chronic autoimmune thyroiditis, a

next day urine spot analysis showed that natriuresis was 63 mEq/l with serum

diagnostic challenge

sodium 132 mEq/l. This was interpreted as CSW and control was achieved with

Izaskun Olaizola, Nerea Egan˜a, Ismene Bilbao, Maite Perez de Ciriza,

aggressive hypertonic saline replacements and fludrocortisone 0.1 mg/tid. Two

María Luisa Antun˜ano, Estela Elías, Cristina García, Maite Aranburu,

days after, Na levels were normalized and desmopressin was restarted.

Alfredo Yoldi & Miguel María Goena

Hypertonic saline dose was gradually decreased and switched to sodium chloride

Hospital Universitario Donostia, Donostia/San Sebastián, Gipuzkoa, Spain.

tablets. He was discharged on fludrocortisone 0.1 mg/bid, oral sodium chloride

16 g/day, oral desmopressin 0.1 mg/bid, hydrocortisone 20 mg/day, levothyrox-

Introduction

ine 100 mg/id. Two months later he was only on hydrocortisone, desmopressin

TSHomas are rare TSH producing tumors, whereas chronic autoimmune

and levothyroxine.

thyroiditis is a frequent condition. Patients with TSHoma are characterized by

Conclusion

increased circulating levels of peripheral thyroid hormones, but when a chronic

We presented a rare case of a patient with DI and CSWS successfully treated.

autoimmune thyroiditis is associated, they may be normal or low, making the

Hyponatremia in a DI patient may erroneously be interpreted as inadequate DI

diagnosis challenging.

control leading to therapeutic errors. Thus, all clinical and analytical data should

Case report

be evaluated together for an early and proper diagnosis.

A 55 year-old woman, with previous medical history of obesity and impaired

DOI: 10.1530/endoabs.49.EP870

fasting glucose, was diagnosed of primary autoimmune subclinical hypothyroid-

ism, with fT4 1.01 ng/dl (0.85-1.75), TSH 9.45 mUI/l (0.3-4.2) and positive anti-

thyroid peroxidase antibodies. Levothyroxine treatment was started, but despite

increasing doses with fT4 values over the normal range, normalization of TSH

could not be achieved, therefore, she was sent to the Endocrinologist. She was

under levothyroxine 150 mg/day, with fT4 1.87 ng/dl, fT3 4.2 pg/ml (2.0-4.4),

EP871

TSH 54.56 mUI/l. She complained of asthenia and nervousness, with no other

Adipsic diabetes insipidus - a diagnostic and therapeutic challenge

relevant symptoms. On suspicion of resistance to thyroid hormones and the

Daniela Magalhães^1,2, César Esteves^1,2, Maria Manuel Costa^1,2,

asthenia, levothyroxine dose was increased to 175 mg/day, with subsequent blood

Pedro Rodrigues³ & Davide Carvalho^1,2

test: fT4

1.93 ng/dl, fT3

4.3 pg/ml, TSH 40.90 mUI/l, free-a-subunit

370.8

¹Department of Endocrinology, Diabetes and Metabolism of Centro

mUI/mL (!1.3). Pituitary magnetic resonance imaging showed a big infiltrating

Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, Porto,

tumor mass at the pituitary region. The rest of pituitary function was normal. She

Portugal;³Department of Internal Medicine of Centro Hospitalar de São

presented worsening visual impairment. Levothyroxine treatment was withdrawn,

João, Porto, Portugal.

with fT4 0.92 ng/dl, fT3 3 pg/ml and TSH 413 mUI/l. Surgery was performed

with a partial exeresis. Diagnosis of pituitary adenoma was confirmed, visual

Introduction

impairment improved, and TSH and free-a-subunit concentrations fell down to

In diabetes insipidus (DI) the serum sodium is often in the high normal range,

49.2 mUI/l and 220.8 mUI/ml. Treatment with somatostatin analogues has been

required to provide the ongoing stimulation of thirst to replace the urinary losses.

started.

Marked hypernatremia can occur if a central lesion impairs both ADH release and

Conclusions

thirst.

TSHomas can be misdiagnosed if they coexist with chronic autoimmune

Case report

thyroiditis. Normal peripheral thyroid hormones may cause us to not think of

A 57-year-old woman presented with dysuria, polyuria and fever. She was

TSHoma as a cause, therefore, if increasing doses of thyroid hormone therapy do

medicated with ciprofloxacin, however, she maintained symptoms, accompanied

not achieve to normalize TSH, we always have to exclude a thyrotropinoma.

in the next day by nausea, vomiting and notion of decreased urine output.

DOI: 10.1530/endoabs.49.EP869

Analytical study revealed a normal blood count, urea 116 mg/dl and Cr increased

from

0.87

3.85 mg/dl, hypernatremia

155 mEq/l and CRP

41.8 mg/dl.

Urinalysis was normal. Renal ultrasound and abdominal CT did not show

alterations. Her past medical history was significant for diabetes mellitus treated

with metformin 850 mg/bid, arterial hypertension under losartan 25 mg/id and

spironolactone 25 mg/id and dyslipidemia under pravastatinCfenofibrate 40C

160 mg/id. She had a history of hypernatremia known for 1-year that resulted in

EP870

two hospital admissions. We found records of a plasma osmolality (POsm) of

Central diabetes insipidus and cerebral salt wasting syndrome: a

348 mOsm/kg and a urine osmolality

(UOsm) of

947 mOsm/kg. When

challenging coexistence

questioned, she reported polyuria and nocturia, without polydipsia. In the present

Maria Manuel Costa^1,2, Cesar Esteves^1,3, José Luis Castedo¹,

admission, POsm and UOsm were 320 and 118 mOsm/kg, respectively. As there

Josué Pereira^2,4 & Davide Carvalho^1,3

was a record of UOsm incompatible with the diagnosis of DI, the patient

¹Department of Endocrinology, Diabetes and Metabolism of Centro

performed a brief dehydration test, during which UOsm was stable below

Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, University of

350 mOsm/kg and there was no urine output following desmopressin

Porto, Porto, Portugal;³Instituto de Investiga

¸a˜o e Inovação da Saúde da

administration. She performed a therapeutical trial with desmopressin that

Universidade do Porto, Porto, Portugal;⁴Department of Neurosurgery of

resulted in increased UOsmO9% and corresponding reduction of POsm. Basal

Centro Hospitalar de São João, Porto, Portugal.

pituitary function was normal. Pituitary MRI showed a reduced pituitary gland

and thinning of pituitary stalk lower half suggesting the existence of an arachnoid

cyst.

Introduction

Conclusion

Combined central diabetes insipidus (DI) and cerebral salt wasting syndrome

In patients with free access to water, hypernatremia should be exceptional since

(CSW) is a rare clinical finding. However, when this happens, mortality is high

intact thirst mechanism is a powerful defense against hyperosmolality. We report

due to delayed diagnosis and/or inadequate treatment.

a case of severe hypernatremia caused by partial DI with hypodipsia.

Case report

DOI: 10.1530/endoabs.49.EP871

42-year-old man referred to neurosurgery due to a non functional pituitary

macroadenoma with bitemporal hemianopsia. He underwent partial ressection of

the tumour on July 2nd 2015. On the following day of surgery he presented

poliuria with sodium (Na) 149 mEq/l, plasma osmolality (pOsm) 301 mOsm/kg

and urine osmolality

(uOsm) 293 mOsm/kg. He started nasal desmopressin

0.05 mg/day with good response. He was already on dexamethasone 4mg and

EP872

levothyroxine 75 mg due to hypopituitarism. On july 9th he became confused.

Endosalpingiosis - re-thinking risk tumours in acromegaly

Cerebral CT was performed with no significant changes. His natremia dropped to

Daniela Magalhães^1,2, Rita Bettencourt-Silva^1,2, Patrícia Leit

˜o³,

128 mEq/l, with development of poliuria despite maintenance of desmopressin

Paulo Morgado⁴, Conceição Souto-Moura⁵ & Davide Carvalho^1,2

doses. Hemoglobin and hematocrit rose from 9.1 g/l to 11.6 g/l and 27.5-32.5,

¹Department of Endocrinology, Diabetes and Metabolism of Centro

respectively. Thyroid function was normal and the patient was on hydrocortisone

Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicina, Porto,

30 mg/day. At 1200 h he initiated 150 mg/hydrocortisone infusion, but Na did not

Portugal;³Department of Radiology of Centro Hospitalar de São Jo

˜o,

increased. Plasma and urine osmolality were 264 mOsm/kg and 679 mOsm/kg,

Porto, Portugal;⁴Department of Interventional Radiology of Centro

respectively. At

1600 h hydrocortisone was increased and hypertonic saline

Hospitalar de São Joa˜o, Porto, Portugal;5Department of Pathological

replacements started. At 1800 h he was dehydrated with poliuria and vomiting

Anatomy of Centro Hospitalar de São João, Porto, Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction

Endocrine Tumours and Neoplasia

There is circumstantial evidence supporting a role of growth hormone and insulin-

EP874

like growth factor

in the development and progression of tumors.

Insulinoma in MEN type 1 mistaken as temporal lobe epilepsy

Endosalpingiosis is characterized by the presence of non-neoplastic fallopion

Norhaliza Mohd Ali

tube-like epithelium in ectopic anatomical locations.

Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia.

Case report

A 45-year-old woman presented with a constant moderate to intense perianal pain

limiting basic daily life activities. She also complained about pain at right

Multiple endocrine neoplasia type 1 (MEN 1) is a rare autosomal dominant

posterior superior iliac spine area that worsened with body movements. There was

disease characterized by pancreatic, parathyroid, and anterior pituitary tumours.

no history of trauma and inspection of the area and rectal examination were

Hypercalcaemia due to parathyroid tumours is usually the first manifestation.

normal. Her past medical history was significant for acromegaly diagnosed 4-year

Pancreatic islet tumours occur less frequently, among them gastrinomas and

earlier and confirmed by anatomopathological analysis of a pituitary macro-

insulinomas are the most prevalent. Insulinomas can be difficult to diagnose. It

adenoma removed by transsphenoidal surgery. She had history of hyperplastic

was not uncommon for patients to have been misdiagnosed with psychiatric

polyposis of the rectum but further investigation with colonoscopy showed no

illnesses or seizure disorders before insulinoma was recognized. We presented a

apparent mucosal lesions. Pelvic CT revealed a poorly delimitated nodular soft

patient who was diagnosed to have temporal epilepsy, which later turned out to be

tissues densification in the right ischiorectal fossa of indeterminate nature. Pelvic

an insulinoma in MEN-1. A

23-yr-old male presented with an auditory

MRI showed a spiculated soft tissue mass involving the lateral planes of the

hallucination of a voice asking him to kill his mother. He has had seizure for a

levator ani muscle and the internal obturator muscle, conditioning obliteration of

year, and was being treated as temporal lobe epilepsy

(TLE) with two

the fat planes around the sciatic nerve. Given the surgical risks inherent to

antiepileptics. Asymptomatic hypoglycaemia was noted during his follow up

resection of the lesion, CT-guided biopsy was performed and the histological

for TLE; but did not trigger further investigation. He has been having recurrent

examination was compatible with endosalpingiosis. Since the benign nature of the

hypoglycaemia during admission and remains asymptomatic even though his

lesion, medical treatment with an oral contraceptive was chosen.

blood glucose went down as low as 1.8 mmol/l. Fasting C-peptide level taken

Conclusions

during hypoglycaemia was inappropriately normal i.e.

947 pmol/l

(298-

Acromegaly appears to be associated with an increased risk of benign and

1324 pmol/l). MRI pancreas revealed a mass at the head and uncinate of

malignant tumors. This case reports an unusual association between acromegaly

pancreas; measuring

2.86!3.2!2.9 cm. H e was also diagnosed to have

and endosalpingiosis. Surveillance of signs and symptoms in acromegalic patients

hypercalcaemia secondary to primary hyperparathyroidism. Neck US showed the

as well as adequate screening for possible comorbidities is crucial to allow timely

presence of a probable right inferior parathyroid adenoma. He has bilateral renal

diagnosis, clinical differential diagnosis and appropriate treatment of future

calculi; with left proximal ureteric calculus causing moderate hydronephrosis and

lesions.

hydroureter requiring stenting. A final diagnosis of MEN-1 with Insulinoma and

DOI: 10.1530/endoabs.49.EP872

primary hyperparathyroidism was made. He underwent Whipple’s procedure

instead of enucleation of the insulinoma as the tumor is adjacent to the pancreatic

duct and major vessels. A total parathyroidectomy and implantatation of the left

parathyroid was also performed, together with prophylactic thymectomy. He

remains euglycaemic following the surgery. Insulinoma can pose a diagnostic

challenge even to an experience clinician. Misdiagnosis of insulinoma as

psychiatric illness and seizure is common; and might lead to disastrous

consequences. This is unfortunate as insulinoma is curable after surgery. This

case highlights the importance of considering insulinoma in patients presenting

with seizures or psychosis.

DOI: 10.1530/endoabs.49.EP874

Developmental Endocrinology

EP873

Can dehydroepiandrosterone-sulphate be a new diagnostic parameter

in male patients with idiopathic hypogonadotropic hypogonadism?

Kenan Cadirci¹, Ayse Carlioglu¹ & Senay Durmaz²

¹Erzurum Regional and Educational Hospital, Erzurum, Turkey;²Kırıkkale

University, Kırıkkale, Turkey.

DHEA and its sulphate derivative DHEA-sulphate (DHEA-s) are major androgen

EP875

hormones of adrenal origin. The purpose of this study was to investigate DHEA-s

Pregnancy in multiple endocrine neoplasia type 1: a case report

levels in male patients with idiopathic hypogonadotropic hypogonadism (IHH)

Gordana Pemovska¹, Sasha Jovanovska Mishevska¹ & Tatjana Proseva²

and to determine whether DHEA-s levels are a useful marker in the diagnosis of

¹University Clinc of Endocrinology, Diabetes and Metabolic Disorders,

hypogonadotropic hypogonadism. 91 subjects, 31 male patients diagnosed with

Skopje, Macedonia;²Clinical Hospital, Stip, Macedonia.

IHH (mean age 19.7G2.6 years) and 60 healthy males (mean age 20.7G2.6

years) as a control group, were included in the study. The patients in the IHH

group were selected from subjects who had not yet started treatment for

Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited endocrinopathy

hypogonadism and who had no additional disease, while the healthy control group

characterized by tumours of the parathyroid glands, adenohypophyseal and

consisted entirely of individuals presenting to the clinic for routine check-ups.

pancreatic tumours. We present a case of a young, 24 years old female patient

Both groups’ FSH, LH, total and free testosterone, ACTH, cortisol and DHEA-s

with a positive familial background for MEN1 (on the fathers’ side of the family).

levels were investigated. Mean DHEA-s levels were 133.4G56.5 mg/dl in the

She is one of two sisters with determined heterozigocity of the MEN 1 gene (Exon

IHH group and 433.3G160.3 mg/dl in the control group. The difference was

2, codon 111). At the age of 12, insulinoma of the head of the pancreas was

statistically significant (PZ0.000). Total testosterone levels in the patient and

diagnosed in our patient, with dimensions

2!2.5 cm. She underwent two

control groups were 28.0G26.3 nmol/l and 568.1G288.0 nmol/l, respectively

operations in order to remove the insulinoma, with consecutive pancreatojeju-

(PZ0.000), free testosterone levels were 9.7G14.3 pg/ml and 18.0G9.0 pg/ml

nostomia and duodenojejunostomia. In the same period, adenohypophyseal

(PZ0.006). The differences were statistically significant. Low DHEA-s levels in

prolactinoma measuring 8 mm was diagnosed and Cabregoline therapy was

patients with IHH were determined to be independent of age, cortisol and ACTH

initiated. One year before she got pregnant, primary hyperparathyroidism was

at multivariate logistic regression analysis. ROC analysis showed that DHEA-s

diagnosed and hypoparathyroidectomy was counselled, but the patient did not

%38.2 mg/dl supports a diagnosis of IHH with 100% specificity and 100%

decide to do the operation. The possible maternal and foetal complications of

sensitivity. DHEA-s is as useful and predictive marker as total testosterone, which

hyperparathyroidism were pointed out to the patient, but she decided to keep the

is used in the diagnosis of patients with IHH. DHEA-s levels were significantly

pregnancy. The PTH values are above 100 pg/ml (ref. values 15-65 pg/ml) with

lower in patients diagnosed with IHH compared to the control group, and we

increased values of total and iodised calcium (1.5-1.65 mmol/l). The patient is

conclude that DHEA-s may be a predictive marker capable of use in the diagnosis

currently in the seventh lunar month of the pregnancy, with reported normal foetal

of IHH.

development by the gynaecologist, and delivery is planned for the 36th week of

pregnancy.

DOI: 10.1530/endoabs.49.EP873

DOI: 10.1530/endoabs.49.EP875

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP876

considered as first line treatment in patients who failed to surgery or who are not

candidates to surgical treatment. The goal of this initial dosage is to reach GH

The giant who could not stop growing

levels below 1.0 ng/ml and insuline like factor type 1 (IGF1) levels within range

Debra Maxine Gordon

for age and gender. The objective of this study is to determine the percentage of

Wits Donald Gordon Medical Centre, Johannesburg, South Africa.

patients that attain goals for GH and IGF1 after 3-6 doses of Octreoride LAR.

Methods

Introduction

We included patients with acromegaly diagnosis within our centre, between the

The presentation of a patient with Gigantism, gynaecomastia and increasing

years 1995 and 2015 that received a minimum of three applications of Octreotide

height suggests underlying Hypogonadotrophic Hypogonadism. Aetiologies such

LAR before obtaining new levels of GH and IGF1 to determine response to

as a pituitary hamartoma is unlikely.

treatment. We included patients that received surgical treatment before institution

Case study

of Octreotide and those who had contraindications to surgery and had to initiate

A 39 year old male presents with a 20 year history of increasing height, shoe size,

Octreotide as part of initial treatment.

headaches, sweatiness and gynaecomastia for the past 10 years. He was 2.08 m

Results

tall with features in keeping with Acromegaly. He had normal secondary sexual

A total of 34 patients were included, with an average of five applications of

characteristics and Tanner stage 3 gynaecomastia. Acromegaly was confirmed.

Octreotide LAR before evaluation, 67% had surgical treatment, 68% were male,

His bone age was 17 years. He had hypogonadotrophic hypogonadism. Pituitary

with an age average of 47 years, 20% had diabetes, and 38% had systemic

MRI showed an enlarged, partially empty sella turcica and a hypothalamic

hypertension. Initial GH levels were 8.19 ng/ml in average and with an average

hamartoma. He received testosterone cypionate, oestrafem and a somatostatin

tumour diameter of 15 mm. In all patients a decrease in GH and IGF1 levels was

analogue. He improved clinically but his gynaecomastia had worsened. He was

observed (3.65 ng/ml in average), but only 15% attained GH and IGF1 levels

referred for a mastectomy.

goals, 50% continued with active disease and the rest had a discordant pattern.

Discussion

Among patients that received surgical treatment prior to Octreotide LAR only 8%

Acromegaly/Gigantism are uncommon disorders. tumors ususally arise de-novo

attained goals, 52% remained active. Of the patients who did not receive surgery

and secrete GH. Occasionally, there is a family history and an Aryl hydrocarbon

27% attained goals and 46% remained active.

mutation

(FIPA) or Multiple Endocrine Neoplasia should be considered.

Conclusion

Hypothalamic Hamartomas are rare causes of GNRH secretion, but usually

Despite a decrease in GH and IGF1 levels in all patients after Octreotide LAR

present in childhood. This patient’s presentation suggests that the onset of

treatment only 15% attained goals. Patients who did not received surgery had

Acromegaly was in late teenage years, and therefore unlikely to be due to the

better results than patients who received it. This initial mode of treatment is not

Hypothalamic Hamartoma. The enlarged, partially empty sella turcica, suggests

enough to control disease so over 70% of patients will need higher doses of

possible auto-infarction of a prior macroadenoma.

Octreotide LAR and perhaps association with other drugs.

DOI: 10.1530/endoabs.49.EP876

DOI: 10.1530/endoabs.49.EP878

EP877

Intrasellar malignant haemangiopericytoma: a rare case

Tahir Omer, Rahat Tauni, Mark Gurnell & Olympia Kolouri

Cambridge University Hospitals, Cambridge, UK.

EP879

Pasireotide: an effective treatment for resistant acromegaly

We report a case of malignant hemangiopericytoma in sellar region in a 73-year-

Wickrama Kankanamge Maheshi Gihani Amarawardena^1,2,

old lady who initially presented with symptomatic hyponatraemia. She was found

Kamani Dhanushka Liyanarachchi^1,2, John David Charles Newell-Price^1,2,

to have hypocortisolism on short synacthen test. She was treated with

Richard John Martin Ross¹ & Miguel Debono²

hydrocortisone and was found to have secondary hypothyroidism. Her

¹Department of Oncology and Metabolism, University of Sheffield,

gonadotropin levels were commensurate with menopause, prolactin levels were

Sheffield, UK;²Department of Endocrinology, Royal Hallamshire Hospital,

normal and there was no suggestion of diabetes insipidus. Initial pituitary

Sheffield, UK.

magnetic resonance imaging (MRI) was normal. Ten months after the initial

presentation, she developed bi-temporal visual field deficits, and repeat imaging

revealed a large sellar mass compressing the optic chiasm. She underwent

The granulation pattern of somatotroph adenoma is well known to be associated

emergency endoscopic endonasal resection. Histopathology was consistent with

with differing clinical and biochemical characteristics and it has been shown that

malignancy haemangiopericytoma (WHO Grade III). She had residual tumour on

sparsely granulated tumors respond poorly to commonly used somatostatin

repeat imaging and underwent intensity modulation radiotherapy allowing high

analogs. We report a challenging case of acromegaly with a sparsely granulated

precision delivery of radiation to the tumour avoiding nearby structures. Her

tumor, resistant to multiple modalities of treatment given over several years and

repeat MRI seven months after surgery suggests stable appearances, and she is on

ultimately achieving biochemical control with pasireotide. A 26-year-old lady

thyroxine, hydrocortisone and desmopressin replacement. Haemangiopericyto-

presented with classical features of acromegaly. She had no family history of

mas are rare mesenchymal tumours arising from pericytes of the capillaries and

pituitary tumors or hypercalcaemia. An OGTT confirmed acromegaly, IGF-1 was

can happen anywhere in the body. Sellar and parasellar malignant haemangioper-

1710 mg/l and mean growth hormone (GH) was O600 mU/l, indicating high

icytomas are exceedingly rare with only a few cases reported worldwide. They

disease burden. In addition, there was secondary hypogonadism, marginally

can present with mass effects like headache or visual symptoms or symptoms of

elevated prolactin and hypothyroidism. MRI scan showed a

4 cm pituitary

hypopituitarism. They often mimic pituitary adenomas on imaging. There are no

macroadenoma with suprasellar extension and right side cavernous sinus

guidelines available for the optimal management of these tumours as they are

invasion. She underwent trans-sphenoidal pituitary surgery. Histology displayed

rare. They are very aggressive tumours that tend to recur and metastasize, even

moderate amounts of sparsely granular eosinophilic cytoplasm, staining only for

after complete resection, therefore postoperative radiotherapy is essential.

GH. Postoperative investigations showed uncontrolled disease (IGF1-1474 mg/L,

DOI: 10.1530/endoabs.49.EP877

mean GH-228 mU/l) and residual tumor in the cavernous sinus. She received

external beam fractionated radiation. Over the years she received octreotide LAR

(up to 30 mg), lanreotide (up to 120 mg) 2 weekly, cabergoline, pegvisomant and

stereotactic radiosurgery to no avail. Only pegvisomant resulted in some disease

control; however this had to be stopped due to abnormal liver functions. Fifteen

years after the diagnosis, she was started on pasireotide 40 mg monthly. Within a

Growth Hormone IGF Axis - Basic

month, her IGF-1 dropped and has remained within the normal range for age

EP878

(103-310 mg/l). Pasireotide was well tolerated and the patient’s symptoms

improved significantly. Somatostatin receptor subtyping revealed a positivity

Initial response to octreotide LAR in Mexican patients with acromegaly

score of two for both SST5 and SST2a subtypes.

Arturo Pen˜a Velarde & Alma Vergara López

Conclusion

Centro Medico Nacional 20 de Noviembre, México, Mexico.

Tumours that poorly respond to first generation SST, especially sparsely

granulated somatotroph adenomas, can respond to pasireotide and treatment

Introduction

should be considered early in the management of resistant tumours.

In Mexico there is scant literature about medical management and its response in

DOI: 10.1530/endoabs.49.EP879

patients with acromegaly. Octreotide LAR at a dosage of 20 mg weekly is

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP880

Research Centre for Endocrinology, Moscow, RussiaZ0.785). The Duncan post-

hoc test demonstrated significantly lower values of decorin in patients with

The disorder of secretion of somatotropic hormone in women with the

acromegaly compared to patients with Cushing’s disease and healthy controls: (1)

polycystic ovaries syndrome (PCOS) by comparison to patients with the

5015.38 pg/ml (95% CI 4855.71-5175.06), (2) 4469.89 pg/ml (95% CI 4285.85-

non-functional pituitary adenomas (NFPA)

4653.94), (3) 4841.29 pg/ml (95% CI 4633.86-5048.71) (The National Research

Yulduz Urmanova^1,2 & Mushtary Saidnazirkhanova^1,2

Centre for Endocrinology, Moscow, Russia!0.001). This finding was confirmed

¹Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan;²Center of

by performance of Student’s t-test in pairs for groups (1) and (2) (The National

Endocrinology, Tashkent, Uzbekistan.

Research Centre for Endocrinology, Moscow, Russia!0.001) and groups (2) and

(3)

(The National Research Centre for Endocrinology, Moscow, RussiaZ0.008).

Tashkent Pediatric Medical Institute, department of endocrinology, department

Significant negative moderate correlation was demonstrated between decorin and

of dietology, Center of the Scientific and Clinical Study of Endocrinology,

IGF-1 values - rZK0.413 (The National Research Centre for Endocrinology,

department of neuroendocrinoloy, Ministry of Health of the Republic of

Moscow, Russia!0.001). There was also a weak negative correlation of very

Uzbekistan. Republic of Uzbekistan, 100125, Tashkent, Mirzo Ulugbek str. 56.

low significance between decorin and myostatin - rZK0.111 (The National

The aim to study the disorder of secretion of growth hormone for women with

Research Centre for Endocrinology, Moscow, RussiaZ0.425).

PCOS by comparison to patients with NFPA.

Conclusion

Material and methods

The serum decorin levels tend to be reduced in subjects with acromegaly. At the

Under our supervision in the department of neuroendocrinology of the Center of

same time, the levels of myostatin don’t depend significantly on decorin values.

Endocrinology of PH Ministry of RUz ambulatory in a period from September

DOI: 10.1530/endoabs.49.EP881

2015 for December, to 2016, 15 adult patients of fertil age were observed with

PCOS and 15 - with NFPA. Middle age of patients to make 25.5 and 28.9

accordingly. The remoteness of disease hesitated in limits from 7 months to

9 years.

Results

EP882

It was set that in both groups there were neuroendocrine violations peculiar to

each of pathologies. So, in a 1 group of patients with PCOS such violations, as

Could statin modify molecular phenotype of pituitary growth

obesity, met most often, strium, acanthosis, acne, hyperandrogenemiya.

hormone-secreting tumors?

hyperpolymenorheya, and in the second is secondary amenorrheya, hyperpro-

María Rosa Alhambra Expósito^1,2, Paloma Moreno Moreno^1,2, Concepción

lactinemiya, pahhypopituitarism. In both groups there was anovulation, and also

Mun˜ oz Jiménez2, María Ángeles Galvez Moreno1 & Raúl Luque Huertas2

decline of secretion of STH, IGF-1. In addition, in the group of patients with

¹Hospital Universitario Reina Sofía, Córdoba, Spain;²IMIBIC, Córdoba,

NFPA the most for certain mionectic basale levels of trope hormones of

Spain.

hypophysis were educed - STH, LH, FSH on a background hyperprolactinemiya

and normal values of IGF-1, while for patients with PCOS the decline of STH,

Background

LH, FSH, was marked on a background hyperandrogenemiya and declines of

Acromegaly is the consequence of excessive growth hormone (GH) secretion,

IGF-1.Thus, it is set that in the group of patients with PCOS the most reliable

usually produced by a pituitary adenoma. In the last years, statins have been

decline of basale levels of IGF-1 was educed, while the deficit of STH met rarer.

implicated in the response to treatment of patients with acromegaly. Although this

Conclusions

fact is not very clear.

The secretions of STH and IGF- 1 educed in our research of violation confirm

Objective

these literatures that for patients with PCOS the decline of levels of STH and IGF-

To analyze whether pretreatment with statins modifies the adenoma molecular

1 takes place on a background hyperinsulinemiya and hyperandrogenemiya that

phenotype of the acromegalic patients and how this changes could help to

requires further research.

influence the response to treatment.

DOI: 10.1530/endoabs.49.EP880

Material and methods

Observational study including patients with acromegaly, diagnosed at the

Endocrinology and Nutrition Unit of the Hospital Reina Sofía from 2007 to

2012, in which surgery, radiology and molecular phenotyping of the adenoma was

carried out.

Results

22 patients were included (38G15 years old; 65% women). Three patients meet

EP881

cure criteria. These who take statins have lower prolactin levels

(9.33G

2.77 mg/dl) than those who do not (54.30G52.31, P 0.005). There were no

The levels of decorin in patients with Cushing’s disease and acromegaly

differences about molecular phenotype between two groups, it shown in Table 1.

Timur Tsoriev, Zhanna Belaya, Lyudmila Rozhinskaya, Alexandr Ilyin,

Patients meet cure criteria had taken more statins that those who had not (P 0.048).

Larisa Nikankina, Galina Mel’nichenko & Ivan Dedov

Conclusion

The National Research Centre for Endocrinology, Moscow, Russia.

Overall, our results indicate that there is a significant correlation between stantin

pre-surgical treatment and the disease cure. However, there is not correlation

Decorin is myokine expressed and released in response to muscle contractions. It

between use of statin and molecular phenotype.

induces growth and hypertrophy of skeletal muscles in different ways including

myostatin inhibition. It is still not clear whether decorin takes part in development

of muscle atrophy in endocrine pathologies.

Table 1

Objective

To evaluate decorin levels in patients with endogenous hypercortisolism and GH

Statin

oversecretion.

Materials and methods

Yes

Three groups were involved in our study: 1) patients with Cushing’s disease

91.56G72.49

213.90G515.02

O0.05

(nZ29), 2) patients with acromegaly (nZ25) and 3) healthy controls (nZ20).

Prolactine

0.99G1.31

44.18G132.25

O0.05

24-h urine free cortisol (24-hUFC) (immunochemiluminescent assay, Vitros ECi)

Sst1

0.000042G0.000046

0.00279G0.0056

O0.05

and evening salivary cortisol (electrochemiluminescent assay, Cobas e601) were

Sst2

0.0055G0.0067

3.3070G13.1979

O0.05

measured in patients with Cushing’s disease, and IGF-1 (immunochemilumines-

Sst3

0.00067G0.00048

0.0047G0.01146

O0.05

cent assay, Liaison) was evaluated in patients with acromegaly. Serum decorin

Sst5

0.0099G0.00789

0.07180G0.2312

O0.05

levels were measured by enzyme immunoassay Human Decorin ELISA kit

DR1

0.0042G0.0036

0.0296G0.0561

O0.05

SK00641-01, serum myostatin values were also determined (Myostatin ELISA kit

DR2T (2L)

0.0740G0.1185

0.179G0.056

O0.05

Immundiagnostik AG).

(0.018G0.019)

(0.119G0.329)

Results

One-way ANOVA was performed for all patients and controls. There were not

found any differences among the groups in sex (PZ0.959), age (The National

DOI: 10.1530/endoabs.49.EP882

Research Centre for Endocrinology, Moscow, RussiaZ0.180) and BMI (The

National Research Centre for Endocrinology, Moscow, RussiaZ0.270). No

differences were found in myostatin levels among the groups (The National

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP883

have an AE that led to study medication discontinuation and 5.5% to a dose

reduction. The most frequently reported all causality AEs were arthralgia (4.6%),

A surprising and dramatic neuroendocrine-immune phenotype of mice

headache (3.6%), influenza (2.8%) and depression (2.8%), whereas for TRAEs

deficient in Growth Hormone-Releasing Hormone (GHRH)

these were arthralgia (2.6%) and peripheral edema (1.8%). The most frequently

Khalil Farhat¹, Gwennaelle Bodart¹, Chantal Renard¹, Christophe Desmet²,

reported SAE was pituitary tumor recurrence, all causality (nZ320/15 809, 2.0%)

Michel Moutschen³, Frédéric Baron⁴, Yves Beguin⁴, Roberto Salvatori⁵,

and TR (nZ154/15 809, 1%). The reported occurrence of death was highest for

Henri Matens¹ & Vincent Geenen¹

general disorders and neoplasms (benign, malignant and unspecified) in 148 and

¹GIGA-I3-Immunoendocrinology, University of Liege, Liege, Belgium;

146 patients, respectively.

²GIGA-I3-Cellular and Molecular Immunology, University of Liege, Liege,

Conclusion

Belgium;³GIGA-I3-Immunology and Infectious Diseases, University of

The results of this large study of GHRT in adult/adolescent patients with GHD

Liege, Liege, Belgium;⁴GIGA-I3-Hematology, University of Liege, Liege,

complement data from clinical trials and confirm the favorable safety profile of

Belgium;⁵Division of endocrinology Diabetes and metabolis, John hokins

GHRT.

University, Baltimore, Maryland, USA.

DOI: 10.1530/endoabs.49.EP884

In the framework of close interactions between the immune and neuroendocrine

systems, Growth Hormone (GH) has been proposed to exert significant effects on

the immune system, but there is not yet a consensus about GH immunomodu-

latory properties. These studies investigated the immune and anti-infectious

response of dwarf Ghrh^K/K mice presenting a severe deficiency of the

GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell

EP885

responses of Ghrh^K/K mice were not severely affected but a constant B-cell

Effect of GH treatment on coagulation and fibrinolysis parameters in

lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious

prepubertal children with growth hormone deficiency

responses of Ghrh^K/K mice toward Streptococcus pneumonia, a B-dependent

Feneli Karachaliou¹, Helen Pergadou², Anastasia Dettoraki²,

pathogen, Ghrh^K/K mice were unable to trigger production of specific IgM and

Evangelia Boudouvi¹, Maria Kafetzi³, Aspasia Fotinou², Helen Platokouki²

IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with

& Vassiliki Papaevangelou¹

either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These

¹Pediatric Endocrinology Unit, 3rd Department of Pediatrics, University

vaccines both include the serotype 1 (our S. pneumoniae strain) and provide

General Hospital Attikon, Athens, Greece;²Haemophilia Center -

an effective protection in mice. A short GH supplementation to Ghrh^K/K mice

Haemostasis and Thrombosis Unit, Aghia Sophia Children’s Hospital,

(1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to

Athens, Greece;³Biochemistry-Hormonology Department, P and A

Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct

Kyriakou Children’s Hospital, Athens, Greece.

impacts upon spenic areas. Furthermore, after intranasal instillation of a non-

lethal dose (defined by the full clearance by WT C57BL/6 mice after 24 h) of

serotype 1 S. pneumoniae, Ghrh^-/- mice exhibited a dramatic susceptibility. This

Background

was proved by a marked time-dependent increase in pulmonary bacterial, a

Increased fibrinogen levels have been reported in prepubertal children and

septicemia already 24 h after infection and a survival limit of 72 h. We also

adolescents with growth hormone deficiency (GHD), which were reduced after

observed a dramatic decrease in lung B- and T-cell populations and an increase in

rhGH treatment. rhGH treatment has also been shown to exert a beneficial effect

proportion of inflammatory macrophages. By contrast, WT and heterozygote

on the amount of aPAI-1 in children with GHD. Aim of the study was to evaluate

mice completely cleared S. pneumoniae infection after 24 h. In conclusion, our

whether prepubertal GH deficient (GHD) children showed any impairment in

data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays

coagulation- and fibrinolysis-related parameters and the effect of GH therapy on

an important and unsuspected role in defense against S. pneumoniae.

these parameters.

DOI: 10.1530/endoabs.49.EP883

Patients and methods

Fifteen prepubertal children (ten girls and five boys) of a mean (S.D.) age of 9.8

(0.4) yrs with GH deficiency were included in this hospital based prospective

study. Serum levels of PT, APTT, fibrinogen, VII, VIII, AT, PC, D-dimers, Plg,

and PAI-1 were measured before and after 6-12 months of GH treatment.

Results

At baseline all studied parameters were within normal ranges. A significant

EP884

increase in PT values was noted after a mean (S.D.) interval of 9.3 (0.4) months of

treatment: 12.46 (0.2)sec vs 12.1(0.15)sec, PZ0.045. A significant decrease in

Safety of growth hormone replacement therapy (GHRT) in adult

PAI-1 levels (3.04 (0.1) U/ml vs 2.28 (0.3) U/ml, PZ0.018) was noted at the same

patients with GH deficiency: data from kims

time. No significant changes in the rest of parameters were found during the study

Cecilia Camacho-Hubner¹, Peter Jonsson³, Ferah Aydin³, Natasa Rajicic¹,

period.

Jose Cara¹, Roger Abs² & Judith Hey-Hadavi¹

Conclusion

¹Endocrine Care, Pfizer Inc, New York, New York, USA;²Antwerp Centre

GH replacement therapy for 6-12 months led to a significant increase in PT

for Endocrinology, Antwerp, Belgium;³Endocrine Care, Pfizer Health AB,

values, while fibrinogen levels did not change. Moreover, GH treatment reduced

Sollentuna, Sweden.

PAI-1 levels in GHD children, suggesting a beneficial effect of GH treatment on

possible risk of future atherothrombosis. Further evaluation of the clinical

Background

significance of these changes is needed.

The efficacy of recombinant human growth hormone replacement therapy

DOI: 10.1530/endoabs.49.EP885

(GHRT) has been demonstrated, in part, through clinical trials conducted

worldwide. KIMS (Pfizer International Metabolic Database), established in 1994

and active until 2012, includes treatment outcome data and real world safety from

15 809 patients from 31 countries.

Objective

The main objective of this analysis was to evaluate the long-term safety of

patients with hypopituitarism or with Idiopathic GH deficiency receiving GHRT

EP886

in adult life.

Nodular thyroid disease in acromegaly: cohort of 69 patients at a single

Study design

institution

This open label, international, multi-center study enrolled adult and adolescents

Cristina Álvarez-Escolá, Diego Meneses González, Óscar

with hypopituitarism and GH deficiency. Patients were treated according to the

Moreno Domínguez & Lucrecia Herranz de la Morena

standard of care of their physicians. A total of 15 809 patients (94.4% Caucasian,

University Hospital La Paz, Madrid, Spain.

50.5% males, 22.2% childhood-onset) were enrolled, with a mean age (S.D.) of

43.9 yr (15.3) at time of enrollment; the mean duration of follow-up was 5.3 yrs

and 83 128 patient-years. Safety outcomes included all reported causality adverse

Materials and methods

events (AEs), treatment related (TR) and serious AEs (SAEs), including neoplasm

The aims were to evaluate the frequency of nodular thyroid disease (NTD) in

incidence.

acromegalic patients and to correlate clinical and metabolic features with disease

Results

activity and other. We conducted a cross-sectional study including retrospectively

8093

(51.2%) patients were reported to have 27118 AEs, of which 16.6% TR, and

69 acromegalic patients attending to an University Hospital in Madrid, Spain

3998

(25.3%) patients were reported to have 7154 SAEs. 12.2% were reported to

between 1980 and 2016. Mean age was 63 (32-92) years, 63.8% of patients were

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

female. Mean age at diagnosis of acromegaly was 48 (11-78) years, time between

isolated STD (10.3G3.5y). Except from TS, male gender was more frequent at all

initial symptoms and diagnosis was 24 (0-240) months, 50 patients (72.5%) had a

diagnosis. Were associated with oncologic disease nZ182/1968(9.2%):

macroadenoma and 23 (33.8%) were cured after transsphenoidal resection,

nZ97/182(53%) had primary tumours of CNS and nZ66/182(36%) due to

among the other medical treatment or radiotherapy was necessary for attaining

hemato-oncologic disease (leukemia/lymphoma).

disease control. Thyroid function was normal in 42 patients (60.9%), 22 (31.9%)

Conclusions

had hypothyroidism

(15

primary, seven secondary) and

(7.2%) had

Somatotropin supported treatment in our country has evolved along time, with

hyperthyroidism. NTD were observed in 56 patients (81.2%) and 10 (14.5%)

new approved indications after 2010. The most frequent diagnosis remains

had diffuse goitre. Thyroid volume was

16.1

(4.7-272.7) ml. Fine-needle

isolated somatropin deficiency with a high age at submission witch probably

aspiration biopsy (FNAB) was performed in 17 patients. Suspicious or malignant

compromises the final stature. We must have more support for deficient

cytology was detected in 23.5% of the FNABs specimens, all of them (11 patients,

somatropin adult patients.

15.9%) underwent thyroidectomy. Pathology revealed nodular goitre in six and

DOI: 10.1530/endoabs.49.EP887

thyroid carcinoma in five patients (7.2%). Other cancers detected were colorectal,

breast, prostate and gastric in 4 (5.8%), 2 (2.9%), 2 (2.9%) and 1 (1.4%) patients,

respectively. Patients with NTD (nZ56) showed similar age, duration of disease,

thyroid volume, concentrations of GH/IGF-1 at diagnosis and IGF-1 at last

follow-up compared with the group of patients without NTD

(nZ13).

Considering only patients with NTD, thyroid volume was not correlated with

age, estimated acromegaly duration, time between the first symptoms to

diagnosis, fT₄, TSH, GH/IGF-1 at diagnosis or IGF-1 at last follow-up. Thyroid

volume was not different whether acromegaly was active or not (17.5 vs 14.3 mm).

Male Reproduction

Conclusions

EP888

Thyroid structural abnormalities are frequent in patients with acromegaly,

Delayed puberty revealing an uncommon genetic disease: about one

therefore routine physical examination and thyroid ultrasound are recommended

case

in all of them. Thyroid cancer was the most common neoplasia in our study,

El Ansari Nawal & Sara Askaoui

which is similar to other reports.

Service of Endocrinology Diabetes and Metabolic Diseases, Marrakech,

DOI: 10.1530/endoabs.49.EP886

Morocco.

Contexte

Kallmann syndrome is a rare genetic disease which can affect both men and

women. It combines hypogonadotropic hypogonadism which characterised by a

failure to start or to fully complete puberty naturally; olfactory disorders such

hyposmia or anosmia, impaired color vision, deafness, unilateral or bilateral renal

EP887

aplasia and midline anomalies.

Somatropin treatment Supported by NHS: characterization of

Objective

submitted patients - 2006 to 2016

We report a case of this rare syndrome, responsible of delayed puberty view of

Margarida Bastos^1,2, Alice Mirante^1,2, Caldas Afonso^1,3,

infertility.

Carlos Vasconcelos^1,4, Conceição Bacelar^1,3, Conceição Pereira^1,5,

Patient - intervention

Lurdes Lopes^1,6, Marcelo Fonseca^1,7, Joana Serra-Caetano²,

A patient of 23 years, from a non consanguineous marriage, consultant for

Miguel Patrício^1,2, Cesar Marques Esteves^1,11, Florbela Ferreira^1,8,

delayed puberty with a Tanner stage to P2G2, without cryptorchidism or

Graciete Braganc¸a1,9, Luísa Raimundo1,10, Lurdes Matos1,6,

hyposmia.

Lurdes Sampaio^1,8, Manuel Fontoura^1,11 & Teresa Borges^1,3

Intervention

¹Comissa˜o Nacional para a Normalização da Hormona de Crescimento

We realized a hormonal exploration, with a morphological exploration of

(CNNHC), Portugal, Portugal;²Endocrinology and Pediatric Endocrinology

hypothalamic-pituitary region.

Departments of: CH Universitário de Coimbra, Coimbra, Portugal;

Main outcome measure

³CH Porto, Porto, Portugal;⁴CH Lisboa Ocidental, Lisboa, Portugal;

We have suspected this diagnosis through severe hypogonadism (absence of

⁵Oncology Portuguese Institute Francisco Gentil, Lisboa, Portugal;

developpement of secondary sex characteristics). The definitive diagnosis relies

⁶CH Lisboa Central, Lisboa, Portugal;⁷Unidade ULSM, Matosinhos,

on the detection of the genetic anomaly, not available to our level, hormonal

Portugal;⁸CH Lisboa Norte, Lisboa, Portugal;⁹H Fernando Fonseca,

explorations, olfactometry, abnormalities on MRI Kallmann syndrome.

Amadora, Portugal;¹⁰CH Garcia de Horta, Almada, Portugal;

Result

¹¹CH S. João, Porto, Portugal;¹²L. Biostatistics and MI and IBILI, FMC,

Hormonal exploration showed hypogonadotropic hypogonadism. MRI is in favor

U Coimbra, Coimbra, Portugal.

of a predominant Hypoplastic right olfactory tract and the olfactory grooves, with

a normal rod.

Introduction

Conclusion

In our country somatropin treatment is supported by the National Health Service.

Kallmann syndrome is a rare disease, responsible of severe hypogonadism, the

A National Committee (CNNHC) rules and analysis the submission papers of

diagnosis is based on characteristic abnormalities of the olfactory bulbs on MRI.

patients with: isolated/multiple somatotropin deficiency (STD), short stature in:

With the correct diagnosis and treatment, fertility can be achieved in many cases

renal chronic disease (DRC), small for gestational age (SGA), Turner syndrome

and the risk of osteoporosis reduced.

(TS) and Prader Willi syndrome (PWS). In adults only isolated somatropin

DOI: 10.1530/endoabs.49.EP888

deficiency diagnosed in childhood.

Aims

To analyze the characteristics of patients submitted to the CNNHC from 2006 to

2016.

Methods

Retrospective study of cases submitted to CNNHC for somatotropin (2006-2016).

Data collected: demographic, submission date, diagnosis and committee’s

Neuroendocrinology

decision. Statistic analysis by SPSS21 (P!0.05).

EP889

Results

Empagliflozin increases urinary volume output in healthy volunteers

Total submissions nZ1968 corresponding to 1909 children/six adults; Males

with artificial SIADH - a placebo-controlled double blind crossover

(59.5%) and Females

(40.5%). Mainly coming from Pediatric centres

study

(nZ1573/80.3%). Submissions increased along time, with a minimum of 87 in

Julie Refardt¹, Bettina Winzeler¹, Fabian Meienberg¹, Deborah Vogt² &

2007 and a maximum of 252 in 2011. Were approved a total of nZ1412 (72%)

Mirjam Christ-Crain¹

cases: at first submission nZ1243 (63.4%) and after reevaluation nZ169 (8.6%).

¹Department Endocrinology University Hospital Basel, Basel, Switzerland;

Not approved nZ535 (27.2%). Diagnostic prevalence: somatotropin deficiency

²Clinical Trial Unit University Hospital Basel, Basel, Switzerland.

nZ1233 (62.9%): isolated nZ1067(54.4%) and multiple nZ166(8.5%); SGA

nZ324(16.5%), TS nZ177(9%); RCD nZ122(6.2%) and PWS nZ53(2.7%).

Somatotropin deficiency remained the most frequent diagnosis along the years.

Introduction

Age at submission: DRC were submitted earlier (6.4G4.2y), followed by SGA

The Syndrome of inappropriate antidiuresis (SIADH) is the predominant cause of

(7.9G3.0y), TS (8.5G3.6y), PWS (9.4G4.0y), multiple STD (9.7G5.1y) and

hyponatremia and its therapy options are unsatisfying. SGLT2-inhibitors have

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

become a valuable treatment option for type 2 diabetes by increasing glucose

EP891

excretion in the urine with concomitant osmotic diuresis. We therefore

Clinical features and natural history of clinically non-functioning

hypothesized that SGLT2-inhibitors could be a novel treatment option for

pituitary incidentalomas

SIADH.

Pedro Iglesias¹, Karina Arcano¹, Vanessa Trivin˜o2, Paula García-Sancho3,

Material and methods

Juan José Díez¹, Fernando Cordido² & Carles Villabona³

We included 14 healthy volunteers in this prospective placebo controlled

¹Department of Endocrinology, Hospital Universitario Ramón y Cajal,

crossover study. To induce SIADH, participants were concomitantly administered

Madrid, Spain;²Department of Endocrinology, Hospital Universitario A

desmopressin i.v. and hydrated. After the initial oral volume load and

Coru

˜ a, A Corun˜a, Spain;3Department of Endocrinology, Hospital

administration of desmopressin, a single dose of the study drug empagliflozin

Universitario Bellvitge, Barcelona, Spain.

25 mg or placebo was given in random order. The main outcomes were total

urinary volume excretion, glucosuria and the area under the curve (AUC) of the

serum sodium concentration. The outcome measures were obtained 2-8 hours

Objetive

after administration of the study drug.

To assess the clinical features of incidental clinically non-functioning pituitary

Results

adenoma (NFPA) and to analyze its natural history.

Fourteen participants (64% males), BMI 23.1 kg/m² (G2.4), age 28.6 years (G9),

Methods

with similar serum sodium levels on both study days (empagliflozin 140 mmol/l

A multicenter retrospective study in patients with NFPA followed-up from 1992

(G1.5) vs placebo 140 mmol/l (G1.3)) completed the study. Empagliflozin lead

to 2015 was performed.

to significantly increased urinary volume excretion

(579.3 ml G194.8

Results

367.3 ml G158.8; PZ0.001) due to glucosuria

(74.18 mmol G22.3

Fifty-seven patients were studied (29 women (50.9%); age 55.8G16.7 years.

0.12 mmol G0.04; P!0.001). There was no difference in the AUC of the

43.9% were older than 60 years, 40.3% belonged to the age group of 40-60 years

serum sodium concentration under Empagliflozin compared to Placebo

and 15.8% were younger than 40 years. Most patients (nZ55, 96.5%) were

(Difference of AUC 0.2, CI -7.38; 6.98, PZ0.96).

diagnosed by magnetic resonance imaging

(MRI).

71.9%

(nZ41) were

Conclusion

macroadenomas; 2 of them (3.5%) were giant adenomas (S4 cm). Patients

In healthy volunteers with artificially induced SIADH, empagliflozin increased

with macroadenomas were older than those with microadenomas (59.5G16.7 vs

volume excretion due to osmotic diuresis. Most probably due to the short

46.4G18.1 years, PZ0.007). Microadenomas were more common in women

treatment duration serum sodium levels remained unchanged. Additional studies

(41.3

14.3%, PZ0.023). About half of them

(nZ28; 49.1%) showed

in real live setting are needed to further examine the possible role of empagliflozin

suprasellar extension; of these, 19 (33.3%) were accompanied by chiasmatic

as a new treatment option for SIADH.

compression. Invasion of the cavernous sinuses was present in 28.1% (nZ16).

DOI: 10.1530/endoabs.49.EP889

Hypopituitarism was present in

(24.6%) patients. Twenty-four patients

(42.1%) underwent surgery. Twenty-six non-operated patients were evaluated

after a median follow-up of 15.5 months (interquartile range, 5.7-32.7). No

significant changes were found in the maximum tumor diameter at the end of

follow-up (1.2G0.6 vs 1.2G0.7 cm; NS). The majority of NFPAs evaluated

(nZ23, 88.5%) did not show any changes in size. In two cases (7.7%) tumor size

decreased and in one patient (3.8%) increased.

Conclusion

Incidental NFPA is diagnosed by MRI preferably from the 5th decade of life

without sex predilection. Most of them are macroadenomas, more commonly

diagnosed in men and at an older age, compared to microadenomas. The

EP890

suprasellar extension with chiasmatic compression and hypopituitarism are

frequent at diagnosis. Most of the non-operated NFPAs remain with stable tumor

Metformin increases pressure pain threshold in lean PCOS women

size over time, being growth an unusual event.

Marta Kialka¹, Tomasz Milewicz¹, Krystyna Sztefko², Iwona Rogatko²

& Renata Majewska³

DOI: 10.1530/endoabs.49.EP891

¹Department of Gynecological Endocrinology, Medical College, Jagiello-

nian University, Cracow, Poland;²Department of Clinical Biochemistry,

Medical College, Jagiellonian University, Cracow, Poland;³Department of

Epidemiology, Chair of Epidemiology and Preventive Medicine, Medical

College, Jagiellonian University, Cracow, Poland.

EP892

Background

Despite the strong preclinical rationale, there are only very few data considered

Pituitary stalk lesions - experience of single center

Mirjana Doknic^1,2, Sandra Pekic^1,2, Dragana Miljic^1,2, Marko Stojanovic^1,2

the utility of metformin, as a potential pain therapeutic in humans. The aim of this

& Milan Petakov^1,2

study was to determine, the association between metformin therapy and pressure

¹Department Neuroendocrinology, Clinic for Endocrinology, Diabetes

pain threshold (PPT) in lean polycystic ovary syndrome (PCOS) women. We

Mellitus and Metabolic Diseases, Clinical Center Serbia, Belgrade, Serbia;

hypothesized that metformin therapy in lean PCOS women increases pressure

²Schoole of Medicine, University of Belgrade, Belgrade, Serbia.

pain threshold.

Materials and methods

Twenty-seven lean PCOS women with free androgen index (FAI) phenotype O 5

Introduction

and 18 lean healthy controls were enrolled to the study. Fifteen of PCOS women

Lesions of the pituitary stalk (PSL) are a challenging diagnostic problem for

were randomly assigned to be treated with metformin

1500 mg daily for

clinicians. Because of the critical location and role of the pituitary stalk, mass

6 months. PPT and plasma b-endorphins levels were measured in all women at the

lesions in this area are not often biopsied, and the diagnosis may be based on

beginning of the study and after 6 months observation.

clinical evaluation and imaging. Due to biopsy risk, about 40% PSL diagnosis are

Results

‘probable’ or ‘unknown’.The main clinical symptoms of PSL are visual field

We observed increase in pressure pain threshold values measured on deltoid and

defect, DI and hypopituitarism.

trapezius muscle in PCOS with metformin group after 6 months metformin

Aim

administration,

(4.81G0.88 kg/cm², P!0.001 on deltoid muscle and 5.71G

To evaluate etiology, clinical manifestations and MRI in patients (pts) with PSL

1.16 kg/cm² on trapezius muscle). We did not observe any significant changes in

who were seen at our department over 10 years.

PPT values in PCOS without treatment group and controls. We did not observe

Patients

any significant changes in serum b- endorphin levels in any studied groups during

We selected 20 pts (11 females) with abnormal pituitary stalk visualized on MRI.

6 months observation.

The mean age at diagnosis was 38.3 years G10.2 (range, 8-67 years).

Conclusion

Results

We conclude that metformin therapy increases pressure pain threshold in PCOS

Neoplastic lesions were diagnosed in 7 pts (35%): germinoma, pituicytoma,

lean women, without affecting b- endorphin plasma concentration. Our results

craniopharyngeoma, non-Langerhans hystiocytosis, pituitary adenoma, Rathke

may suggest the potential role of metformin in pain therapy. We propose that

cyst and simple cyst one each. Distant metastatic tumors in pituitary stalk were

larger, randomized studies, on metformin impact on pain perception should be

confirmed in 3 pts (15%). Inflammatory lesion were noticed in 4 pts (20%):

performed.

2 lymphocytic infundibuloneurohypophysitis and

2 tuberculosis. Congenital

DOI: 10.1530/endoabs.49.EP890

anomalies were noticed in 2 pts (10%). Four patients (20%) with PSL were of

unclear etiology. Tissue biopsy samples from the pituitary stalk itself were

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

obtained in eight patients. Six pts have suffered from diabetes insipidus. Growth

suppressed after intracerebroventricular (i.c.v.) injection of STM-II and ATM-4

hormone deficiency was the most common hormone deficiency (15 pts, 75%),

upon hyperosmotic shock, suggesting that this heteromer has an essential role in

followed by secondary hypogonadism in 12 pts (60%) and ACTH and TSH

mediating water drinking behaviour on hyperosmotic stress. However, in vivo role

deficiency in 8 pts (40%) each. Complete hypopituitarism was noticed in 8 pts

of SCTR/AT1aR in central osmoregulatory centre is yet to be elucidated.

(40%). Nine pts had visual field defect.

Vasopressin (Vp) is one of the key components to access osmoregulation because

Conclusion

of the physiological link between Vp release and drinking behaviour, meanwhile,

The risks associated with obtaining histological samples from the pituitary stalk,

ANGII and SCT are potent in stimulating Vp release, hence it is a spate of interest

even in the group presented, the diagnosis was frequently based on other clinical

to understand whether SCTR/AT1aR heteromer regulate osmoregulation via Vp

findings and serial MR imaging. For the most challenging pituitary stalk lesions,

release pathway. In this study, we demonstrated that SCTR/AT1aR heteromer is

an individualized approach, guided by clinical expertise, remains the best

involved in the regulation of Vp release and expression, as well as the central

strategy.

neural involvement in PVN. Upon SCT/ANGII-stimulation, plasma Vp release

DOI: 10.1530/endoabs.49.EP892

was largely reduced (47.64% decrease) and Vp expression in PVN is significantly

dropped (64.08% decrease) 15 mins after i.c.v injection of STM-II or ATM-4.

This finding supports the hypothesis of SCTR/AT1aR in mediating water balance,

and also provides concrete basis in demonstrating the in vivo role of a GPCR

heteromer.

DOI: 10.1530/endoabs.49.EP894

EP893

First pediatric case of successfully treated Cushing’s disease in Armenia

Gayane Bayburdyan, Lusine Arakelyan & Yelena Aghajanova

Yerevan State Medical University, Yerevan, Armenia.

EP895

Introduction

The hyponatremia in neurosurgical patients

Cushing’s disease

(CD) is the most common albeit rare in paediatric and

Liudmila Astaf’eva, Maxim Kutin, Yuliya Sidneva & Pavel Kalinin

adolescent population form of ACTH-dependent Cushing’s syndrome, with

Burdenko Neurosurgical Institute, Moscow, Russia.

potentially serious morbidity. Thus, it presents diagnostic and therapeutic

challenges for the clinician. Early diagnosis and treatment of Cushing’s disease is

vital for long-term outcome. Paediatric pituitary-dependent Cushing’s disease,

Background

caused by an ACTH-secreting corticotroph adenoma, accounts for 75-80% of

Hyponatremia is a relatively frequent and serious complication developed in

Cushing’s syndrome and is almost always caused by a pituitary microadenoma.

patients with different neurosurgical pathology. The aim of the study was to

Case report

identify the frequency of occurrence of hyponatremia in neurosurgical patients.

14 yo girl presented to endocrine clinic with severe headaches, increased blood

Materials and methods

pressure

(BP) up to 140/100 mmHg, wide reddish-purple abdominal striae,

A retrospective analysis included 39479 patients operated in the Institute of

amenorrhea and weight gain up to 20 kg during last year. She was unsuccessfully

Neurosurgery from January 2008 to December 2014.

managed by a gynecologist with oral contraceptives for 8 months. In endocrine

Results

clinic patient was examined according to Endocrine Society guidelines with

785 patients (2% of all operated patients): 554 adults and 231 children had

subsequent diagnosis of Cushing’s disease due to ACTH-secreting pituitary

hyponatremia with Na level less than 130 mmol/l. In 63% of cases (497 patients)

microadenoma

(corticotropinoma). Patient underwent surgical removal of

we observed a moderate decrease of Na (125 to 130 mmol/l), in 11% of cases (88

adenoma with gamma knife (GKS) resulting in reversal of symptoms.

patients) the level of Na was less than 120 mmol/l. The mortality rate in patients

Conclusions and follow up

with hyponatremia was 14.3%, what is 10 times faster than that of the rest of

Endocrine parameter normalization after GKS included normal 24-hour urinary

patients without hyponatremia operated during these years. In adults most often

free cortisol (UFC) concentration and normal levels of pituitary and peripheric

hyponatremia developed either after surgical removal of craniopharyngiomas

hormones 4 months. However, posttreatment secondary hypothyroidism was

(11%) or as a result of an acute stroke (22%). In children - after surgery of

diagnosed with TSH of 2.2 IU/ml (0.5-4.0) and FT₄ of 12.1 pmol/l (12.0-22.0).

craniopharyngiomas (10%), astrocytomas (7%), ependymomas (24%) and germ

BP was stable at 110/70 mmHg. Regular menstrual function resumed 6 months

cell tumors (10.5%).

after the surgery, and weight loss of 10 kg was documented 10 months after the

DOI: 10.1530/endoabs.49.EP895

surgery. Adenoma size decreased from 0.6 to 0.2 cm in 7 months by MRI. Current

medications comprised of Levothyroxin 75 mcg only. This is the first case of

successful treatment of paediatric Cushing’s disease in Armenia. Although

transsphenoidal neurosurgery is the gold standard therapy of pituitary Cushing’s

disease, GKS seems to be safe and effective way of treatment, however, long-term

follow-up is necessary.

EP896

DOI: 10.1530/endoabs.49.EP893

Bilateral inferior petrosal sinus sampling and the outcome of

transsphenoidal surgery in patients with Cushing’s disease: experience

of a Tertiary Portuguese Hospital

Ana Coelho Gomes¹, Lia Lucas Neto², Francisco Tortosa³, Maria

Raquel Carvalho¹, Eduardo Barreiros¹, Luís Barreiros¹, José Miguéns⁴ &

Maria Joa˜o Bugalho1

Endocrinology, Diabetes and Metabolism Department, Santa Maria

Hospital, Lisbon, Portugal;²Neuroradiology Department, Santa Maria

EP894

Hospital, Lisbon, Portugal;³Pathology Department, Santa Maria Hospital,

SCTR/AT1aR heteromer related osmoregulation in hypothalamus

Lisbon, Portugal;⁴Neurosurgery Department, Santa Maria Hospital, Lisbon,

Oi Kwan Mak & Billy K.C. Chow

Portugal.

The University of Hong Kong, Hong Kong, Hong Kong.

Introduction

Emerging studies suggest that GPCR oligomerization could confer functional

Bilateral inferior petrosal sinus sampling (BIPSS) is the gold-standard for the

advantages to receptors and even constitute clinical applications. Recent study

differential diagnosis of ACTH-dependent Cushing Syndrome when the pituitary

found that angiotensin II 1a receptors (AT1aR) and secretin receptors (SCTR) can

adenoma on MRI is doubtful or absent. This study aimed to analyze whether

form heteromer and participate in osmoregulation. Studying GPCR dimerization

BIPSS can influence the outcome in patients with Cushing disease (CD).

faces many technical challenges, including selectivity and specificity. Since

Methods

transmembrane (TM) peptides can act as competitors against the interacting

Retrospective, descriptive study. Forty-two patients with CD submitted to

surfaces between two receptors and therefore, it is utilized in this study as a

transsphenoidal surgery (TS) between 2005 and 2016 were divided into two

unique tool to illustrate the specific functions performed by SCTR/AT1aR

groups based on the performance of BIPSS. Different variables were analyzed:

heteromer. STM-II and ATM-4 are discovered as the interacting surfaces of

year of diagnosis, preoperative laboratory tests and pituitary MRI, immediate

SCTR/AT1aR heteromer, in which STM-II can only disrupt heteromer formation,

postoperative laboratory tests, histological findings, postoperative hypopituitar-

while ATM-4 can inhibit both receptor homomer formation. Previous study

ism, presence of permanent diabetes insipidus, follow-up duration and final

shows that hyperosmolality-induced water drinking behaviour in mice is greatly

outcome.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

of the patients, adenomas in 16.8% and CRC in 5%. In total, 27 adenomas and 69

Ten out of forty-two patients with CD were submitted to BIPSS.

HP were detected. The prevalence of CRC, CP and adenoma found in this study

compared to normal population was: 5 vs 1% (PZ0.001); 47.5 vs 32.6%

(PZ0.003) and 16.8 vs 38% (PZ0.001), respectively. Concerning AF, there was

no differences between patients with abnormal and normal colonoscopy.

BIPSS

No BIPSS

p-value

Conclusions

The prevalence of CRC and CP was significantly higher in patients with

Diagnosis Year (%):

0/70/30

9/47/44

0.355

acromegaly. On the contrary, adenoma was significantly less prevalent. No

1995-2000 / 2001-2010 /

association between any of the factors studied and the phenotype CRC/CP was

O2010

observed. To our knowledge, this is one of the largest Portuguese series,

Preoperative sellar MRI

20/0/30/50

66/16/0/6

!0.01

nevertheless results have yet to be validated.

(%): Microadenoma /

DOI: 10.1530/endoabs.49.EP897

Macroadenoma / Indeter-

minate Lesion / No Image

Preoperative Laboratory

100/0

59/13

0.159

Tests (%): Classical /

Non-Classical

Immediate Postoperative

40/40

41/41

Laboratory Tests (%):

Criteria for Cure /

EP898

No Criteria for Cure

Acromegaly and malignant neoplasms

Histology (%): Adenoma /

60/10/30

78/3/9

0.462

Vânia Gomes, Eduardo Barreiros, Luís Barreiros, Florbela Ferreira,

Corticotroph Hyperplasia /

Ana Gomes, Ana Filipa Martins, Ana Sofia Osório, Ana Wessling,

Normal tissue

Catarina Silvestre, Dinis Reis, Ema Nobre, Maria Raquel Carvalho,

Postoperative anterior

20/20/20

28/25/44

0.713

Mário Mascarenhas, Sónia do Vale, José Miguéns & Maria João Bugalho

pituitary deficiency (%):

Santa Maria Hospital, Lisbon, Portugal.

Isolated / Multiple / None

Permanent Diabetes

0/100

6/94

0.418

Introduction

Insipidus (%): Yes / No

Acromegaly is a rare disease resulting from pathological oversecretion of growth

Mean Follow-Up (years)

5.7G3.8

6.8G5.1

0.544

hormone (GH) and insulin-like growth factor-1 (IGF-1). The clinical spectrum

(0-11)

(1-21)

includes cardiovascular and respiratory diseases but also increased risk of benign

Final Outcome (%):

70/30

47/50

0.386

Remission / Active Disease

and malignant neoplasms.

Objectives

Evaluate the prevalence of cancer and seek for associated factors in acromegaly.

Note: In some parameters the sum of the partial percentages is not 100%

Methods

because some patients didn’t have that information.

Retrospective study of 94 patients with acromegaly treated in a single tertiary

center from 1985 to 2016. The group with malignant neoplasms was compared

Discussion

with the group without malignancy. Statistical analysis was performed with SPSS

Groups were different in terms of the preoperative imaging. For the other

software, version 20. Statistical significance: P ! 0.05.

variables, no differences were observed. The final outcome, despite the higher

Results

number of macroadenomas in the group without BIPSS was not statistically

63.8% of the patients were female and the mean age at diagnosis was 48.7G12.9

different. Results await further confirmation.

years. Median GH and mean IGF-1 at diagnosis was 9.8 ng/ml (range: 0.61-228)

and 857.4G412.7 ng/ml, respectively. Median diagnostic delay of acromegaly

DOI: 10.1530/endoabs.49.EP896

was 7 years (range: 1-36). Cancer was present in 13 (13.8%) of the 94 patients.

Colon cancer was diagnosed in five patients (5.3%), breast cancer and renal cell

carcinoma each in 3 (3.2%), follicular thyroid cancer, melanoma and endometrial

carcinoma each in 1 (1.1%). In three cases, cancer was found before acromegaly

(breast cancer in 2 and colon cancer in 1). One patient had two malignancies

(thyroid and renal cell carcinoma). The diagnostic delay of acromegaly was

higher in the group with malignant neoplasm

(PZ0.004). There was no

EP897

statistically significant difference between the two groups relative to GH, IGF-1,

The prevalence of colorectal cancer and colon polyps in acromegaly:

age and body mass index at diagnosis and gender.

thirty years’ experience of a tertiary referral center

Conclusions

Vânia Gomes, Luís Barreiros, Eduardo Barreiros, Florbela Ferreira,

Colon cancer was the most prevalent, followed by breast and renal carcinoma.

Ana Gomes, Ana Filipa Martins, Ana Sofia Osório, Ana Wessling,

In the group with malignant neoplasms, diagnostic delay was significantly higher,

Catarina Silvestre, Dinis Reis, Ema Nobre, Maria Raquel Carvalho,

suggesting that prolonged exposure to high GH and IGF-1 levels can be related to

Mário Mascarenhas, Sónia do Vale, José Miguéns & Maria João Bugalho

cancer development. Search for cancer should be a major task in the follow-up of

Santa Maria Hospital, Lisbon, Portugal.

these patients.

DOI: 10.1530/endoabs.49.EP898

Introduction

Several studies suggest a higher risk of colorectal cancer (CRC) and colon polyps

(CP) in acromegaly, however there is still controversy regarding associated

factors (AF) able to contribute for its development. Data on the prevalence of

CRC and CP in Portuguese patients with acromegaly are limited.

Objectives

To assess the prevalence of CRC and CP in acromegalic patients and compare to

EP899

the normal Portuguese population. To determine the relevance of a number of AF

Endogenous Cushing’s syndrome ( clinical and biochemical features in

(growth hormone, insulin-like growth factor-1, body mass index and age at

a large cohort of patients

diagnosis, gender, diagnostic delay and disease duration) for its development.

Lucio Vilar¹, Clarice Vilar², José Luciano Albuquerque², Erik Trovão¹,

Methods

Ana Carolina Thé¹, Patricia Gadelha¹, Maíra Melo¹, Barbara Gomes¹,

Retrospective study of 101 acromegalic patients assisted in a tertiary center from

Thaíse Borges¹, Izabela Cardoso¹ & Ruy Lyra¹

1985 to 2016, who underwent at least one colonoscopy. Comparative analysis

¹Division of Endocrinology, Hospital das Clinicas, Federal University of

with data from screening studies conducted in the normal Portuguese population.

Pernambuco, Recife (Pernambuco), Brazil;²Endocrine Research Center of

Statistical analysis was performed with SPSS software, version 20. Statistical

Pernambuco, Recife (Pernambuco), Brazil.

significance: P! 0.05.

Results

Of the 101 patients (female: 62.4%; mean age at diagnosis: 49.5G12.8 years),

Patients and methods

47.5% presented abnormal colonoscopy with CP, which were more frequent in

We retrospectively analysed the clinical and biochemical characteristics of a

the left colon. Histological analysis identified hyperplastic polyps (HP) in 29.7%

cohort of 150 patients with endogenous Cushing’s syndrome (CS). Cushing’s

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

disease (CD) accounted for 61.3% of cases (nZ92), ectopic ACTH secretion

Conclusion

(EAS) 7.3% (nZ11), and adrenal diseases 31.3% (nZ47). Among CD cases,

Mild hyponatremia can predate the diagnosis of a malignancy. However, in our

there were 19 macroadenomas (20.6%), a female predominance (60.5%) and a

series of 11/52 patients, in only one was hyponatremia studied. The lack of

median age of 33 years old (range 14-55). Bronchial carcinoid was the most

importance given to the finding of frank hyponatremia, albeit mild, could delay

frequent cause of EAS (nZ7). When biochemical and clinical features were

tumor diagnosis.

compared in cases of CD and EAS, the only significant difference was the higher

DOI: 10.1530/endoabs.49.EP900

frequency of hypocalemia in EAS

(80% vs. 15%; P!0.001). Concerning

screening tests, the sensitivities of overnight

1 mg-DST (cut-off, 1.8 mg/dl

(50 mmol/l)), UFC and late night salivary cortisol (LNSC) were 94%, 90% and

96%, respectively. The combination of two of these tests yielded a sensitivity of

98% ACTH levels were normal (42%) or elevated (58%) among patients with

CD; they were above the normal range in all EAS cases and !10 pg/ml in all

patients with adrenal disorders. Regarding dynamic tests, HDDST had a mean

sensitivity and specificity of

79/55

and

70/100%, respectively, using the

supression cut-offs of O50% and O80%, respectively. The diagnostic accuracy

of CRH test and desmopressin test did not significantly differ (PZ0.28) in the

EP901

distinction between CD and EAS. The combination of HDDST and CRH or

Hyperprolactinemia as a manifestation of hormonally inactive pituitary

desmopressin tests was more accurate than each test alone. The overall diagnostic

adenoma

accuracy of BIPPS was 94%. Pituitary MRI depicted all macroadenomas and 64%

Zamira Khalimova & Mijgona Safarova

of microadenomas. CT scan and/or MRI detected 90% of bronchial carcinoid, as

Center for the Scientific and Clinical Study of Endocrinology, Uzbekistan,

well as all thymic carcinoid.

Tashkent, Uzbekistan.

Conclusion

CD and EAS cannot be accurately be distinguished based only on clinical and

biochemical features. LNSC was the most sensitive screening test for CS.

Aim

The work was initiated to study prolactin levels in hormonally inactive pituitary

DOI: 10.1530/endoabs.49.EP899

adenoma by the size of the tumor.

Material and methods

We examined 85 patients with hormonally inactive pituitary adenomas, 45

women and 40 men among them aged from 18 to 50 years (mean age 44.5G3.85

years). The disease duration from the onset to diagnosis based on the medical

history and MRI ranged from 1 to 15 years.

Results and discussion

Guided by the aim of study we divided the patients into three groups. 26 patients

with the tumor size up to 10 mm were included into the first group. Thirty-three

patients with the tumor size up to 20 mm comprised the second group. Twenty-six

patients with the tumor size 30 and more mm were included into the third group.

EP900

Analysis of hormonal parameters demonstrated correlation between prolactin

Hyponatremia predating the diagnosis of malignancy in oncological/

level and the tumor size. Hyperprolactinemia was registered in 2, 45 and 100% of

hematological patients with SIADH

patients in the first group, second and third groups, respectively. In patients with

Irene Crespo-Hernández¹, Martin Cuesta-Hernández¹, Alejandro Santiago-

macroadenomas hyperprolactinemia was clinically presented in combination with

Perez¹, Emilia Gomez-Hoyos², Ana Ortola-Buigues², Paz de Miguel-

hypopituitarism. Among patients of the third group, chiasmal and cephalgic

Novoa¹, Joan Chafer-Vilaplana¹, Alfonso Calle-Pascual¹ &

syndromes, the latter with the oculomotor nerve damage, were the main

Isabelle Runkle¹

symptoms; lactorrhea-amenorrhea syndrome came the third.

¹Hospital Clínico San Carlos, Madrid, Spain;²Hospital Clínico de

Conclusions

Valladolid, Valladolid, Spain.

Quite frequent sign of hormonally inactive adenoma, hyperprolactinemia upon

formations in chiasmal-sellar area not always can be an outcome of prolactin-

Introduction

secreting adenomas; the fact is to be taken into account in choosing the treatment

Euvolemic hyponatremia

(HN) caused by the Syndrome of Inappropriate

tactics.

Antidiuretic Hormone Secretion (SIADH) can predate a diagnosis of malignancy.

DOI: 10.1530/endoabs.49.EP901

It is thus essential to accurately diagnose the etiology of HN/SIADH when

detected.

Methods

Retrospective, descriptive study of all 52 oncological/hematological malignancy

patients diagnosed with SIADH in our Department between January 2011 and

EP902

December 2016. HN was detected via computerized Primary-care/hospital case

histories, and the computerized laboratory data base. Hyponatremia was

considered to predate detection of malignancy/initiation of diagnostic study

when a serum sodium (SNa) !135 mmol/l was detected 6 months before

Abstract withdrawn.

definitive oncological/hematological diagnosis (PTD). A patient was considered

probably euvolemic (PE) when SNa descent was accompanied by a predominant

pattern of lowering serum urea, creatinine and Uric acid levels, probably

hypovolemic (PH) if urea, creatinine and Uric acid levels rose while not

hypervolemic. SNa in mmol/l.

Results

Males: 32/52(61.5%), mean age:63.4 (S.D.:11)years. Etiology of SIADH: lung

cancer: 18/52(34.6%), gastrointestinal: 6/52 (23.1%), genitourinary: 11/52 (21%),

hematological: 5/52 (9.6%). 11/52 (21%) patients presented HNO 6 months

PTD: median 40 (24-60), median age: 67 (63-76) years, initial SNa: 133 (130-

134). Three patients were PH. Eight were PE, one receiving enalapril, another

EP903

carbamazepine, another thiazide. In 5/8 (62%) PE patients, case histories revealed

no initial cause for HN. HN was present a median of 25 (19-40.5) months PTD,

range: 14-41. Initial SNa: 133 (129.5-133). None presented a low Urine Density.

Abstract withdrawn.

Hyponatremia was persistent, present in 42/50 (84%) tests, with a continuum up

to ectopic-SIADH diagnosis, suggesting that SIADH induced their sustained

hyponatremia. Etiology: lung (epidermoid), endometrial, breast, gastric, prostate.

In only 1/11 (9%) patients was hyponatremia studied PTD, with SIADH workup

responsible for prostate tumor diagnosis.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP904

hyperintensive T2

(22/55,

40%; 12/55,

21.8%;

9/55,

16.4%, respectively).

HypoT1/hypoT2 tumors had the smallest volume.

Study of CHD7 gene in KAL 1-negative patients previously diagnosed

Conclusion

with congenital hypogonadotropic hypogonadism that develop new

In all type of pituitary tumors hypointensive MR-signal (either T1 or T2) was

pituitary deficiencies

associated with infrasellar tumor expansion and smaller tumor volume. In

Beatriz Lecumberri^1,2, Francisco Javier Rodríguez², Óscar Moreno¹,

contrast, hyperintesive T2 was associated with suprasellar tumor expansion and

Manuel de Santiago¹, Manuel Nistal^2,4, Elena Vallespin^2,3, Angel Campos^2,3

bigger tumor volume. IsoT1/isoT2 tumors were found only in NFA group;

& Karen Heath^2,3

hypoT1/hypoT2 tumors were observed only in somatotropinomas so further

¹Endocrinology Department, La Paz University Hospital, Madrid, Spain;

investigations should be carried on to prove the diagnostic value of these results.

²IdiPAZ, Madrid, Spain;³INGEMM; La Paz University Hospital, Madrid,

Accurate determination of T1/T2 signal intensity can be used as additional

Spain;⁴Pathology Department, La Paz University Hospital, Madrid, Spain.

predictors of hormonal and proliferative activity of pituitary tumors.

DOI: 10.1530/endoabs.49.EP905

Introduction

Recent studies suggest that some patients initially diagnosed with congenital

hypogonadotropic hypogonadism

(CHH), may evolve towards a combined

pituitary hormonal deficiency (CPHD). Heterozygous pathogenic CHD7 variants

impair neural cell crest guidance causing CHARGE syndrome and have been

associated with abnormal pituitary development/function/structure and isolated

CHARGE features, including HH. We aimed to genotype CHD7 and phenotype

EP906

thoroughly those adult patients previously diagnosed with CHH that developed

Cholinergic modulation of the hypothalamic-pituitary-adrenal activity

new pituitary deficiencies during the follow-up.

and somatotroph function in smokers and non-smokers

Patients

Jesús Pérez-Luis^1,2, Judith López-Fernández^1,2, Isabel Mascaren˜o1,2 &

From 20 unrelated KAL 1-negative patients with a past CHH diagnosis followed

Javier Salvador³

in our adult endocrinology clinic during an average of 21.2 years (13-37), we

¹Hospital Universitario de Canarias, Tenerife, Spain,²Universidad de La

selected those with new pituitary deficiencies

- 7/20, all males, mean age

Laguna, Tenerife, Spain,³Hospital Universidad de Navarra, Pamplona,

37.2

years

(29-53)

- and studied CHD7

using a targeted NGS panel

Spain.

(HYPOPIT.V1). Markedly low IGF-1 levels were detected in 6/7 (85%) and of

TSH in 4/7 (57.4%).

Results

Introduction and objectives

2/7 patients (28.6%) harboured heterozygous CHD7 rare variants. The variant of

The inhalation of tobacco smoke leads to an acute increase in cortisol, ACTH and

unknown significance NM_017780:exon31:c.G6255T:p.L2085F that suggests

GH concentration, both in chronic smokers as in non-smokers. However, most

pathogenicity but lacks functional sudy, was found in a 53-year-old male, that has

studies have failed to demonstrate differences between both groups in basal levels

a left temporal arachnoid cyst, a pars intermedia cyst, low IGF-1 levels, a

of these hormones in plasma or urine. Additionally, cholinergic pathways have

pigmentary glaucoma treated with iridotomy, aortic elongation and a “Sertoli-

been shown to play an inhibitory role in ACTH secretion in non-smokers. UFC

cell-only syndrome” diagnosis based on testicular biopsy performed at 38 years.

and circulating levels of cortisol, ACTH and GH were evaluated basally and after

Another

37-year-old-male, that was hormonally and surgically treated for

pyridostigmine in smokers and non-smokers.

bilateral cryptorchidism during childhood, and currently shows a partial empty

Subjects and methods

sella, absence of neurohypophysis and low TSH and IGF-1 levels, had the rare

We studied UFC (urinary free cortisol) on 24 h urine samples and the effects of

pathogenic heterozygous variant NM_017780.3:c.8416COG:p.Leu2806Val,

administration of placebo and pyridostigmine on ACTH, cortisol and GH

involved in CHARGE, isolated HH, and in a few CPHD cases with atypical

secretion in 10 young males: five smokers and five non-smokers. In each test,

CHARGE features. Curiously both fathers of these two patients died before 65

placebo or pyridostigmine (120 mg) were given orally in random order on

years of age due to lung diseases (the first being cancer).

different days at 0830. Blood samples were drawn at 0830, 0900 and then every

Conclusions

15 min until 1130. Area under the curve was calculated. Data are expressed as

Our results suggest that CHD7 should be included in the genetic study of CHH

mean G SEM.

patients, especially in those that develop new pituitary deficiencies over time.

Results

DOI: 10.1530/endoabs.49.EP904

Basal levels of UFC, plasma ACTH, and serum GH were not different between

smokers and non-smokers. In contrast, basal serum cortisol was higher in smokers

at 1015 (15.42G1.38 vs 10.29G1.40 mcg/dl) and 1045 (12.96G1.14 vs 8.89G

1.19 mcg/dl). PD raised GH secretion within each group, while it decreased

cortisol at 1015 (15.42G1.38 vs 13.20G1.50 mcg/dl) in smokers and ACTH at

1115

(16.87G1.54 vs 12.49G1.65 pg/ml) in non-smokers.

Conclusions

EP905

Chronic smoking is associated with increased basal serum cortisol and normal

MR-characteristics as predictors of pituitary adenomas hormonal and

UFC, while it is related to a decrease in serum cortisol after pyridostigmine.

proliferal activity

Besides, an inhibitory effect of cholinergic stimulation on ACTH is confirmed in

Yulya Krivosheeva, Alexander Dreval, Evgenia Panteleeva, Galina Stashuk

non-smokers.

& Irena Ilovayskaya

DOI: 10.1530/endoabs.49.EP906

Moscow Regional Research and Clinical Institute, Moscow, Russia.

Introduction

Previous studies demonstrated a relationship between T1- and T2-weighted signal

intensity and tumor growth pattern in pituitary somatotropinomas. The goal of

this retrospective study was to analyze the MRI characteristics of pituitary

macroadenomas with different hormonal activity in newly diagnosed patients.

EP907

Material and methods

Diagnosis, treatment and follow-up of non-functioning pituitary

Pre-treatment T1- and T2-weighted MR-images (Intera Achieva, PHILIPS, 3.0T)

adenomas

of patients with 42 non-functional adenomas (NFA), 18 macroprolactinomas, 55

Ana Barrera-Martín¹, Paloma Moreno-Moreno¹, María-Rosa Alhambra-

somatotropinomas were analyzed, taking into account the intensity of the signals

Expósito¹, Aura-Dulcinea Herrera-Martínez¹, Ángel Rebollo-Román¹,

produced by the tumors, as well as their dimensions and growth direction. The

Pedro-Blas García-Jurado² & María-Ángeles Galvez-Moreno¹

results were expressed as M? (25%; 75%).

¹Endocrinology Service. Hospital Universitario Reina Sofia, Córdoba,

Results

Spain;²Radiology Service. Hospital Universitario Reina Sofia, Córdoba,

In NFA group, majority of patients (30/42, 71%) had isointensive T1-signal in the

Spain.

most common combinations with hyperintensive or isointensive T2 (18/42, 42.9

and 9/42, 21.4%, accordingly). NFA’s volumes did not differ between these

subgroups. In prolactinoma group 15/18 (83.3%) patients showed hyperintense

Introduction

T2 in the most common combination with isointensive T1 (7/18, 38.9%) and

Non-functioning pituitary adenomas

(NFPAs) represent the most common

hypointensive T1

(6/18,

33.3%). IsoT1/hyperT2

prolactinomas had bigger

pituitary tumour. They usually appear in the middle age of life, without

volume compared to hypoT1/hyperT2 ones. In somatotropinoma group 43/55

differences between genders. Mass growth produces the first symptoms so the

(78.2%) patients had hypointensive T1 in combinations with hypo-, iso- or

diagnosis is usually late. Surgery is the first-line treatment with variable success

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

(19-83%). The objective of this study is to evaluate the symptoms, diagnosis,

EP909

treatment and final state of patients with NFPAs.

Cholinergic modulation of the hypothalamic-pituitary-adrenal activity

Methods

and somatotroph function in DM-1

Observational retrospective study of patients with NFPAs evaluated between

Jesús Pérez-Luis^1,2, Judith López-Fernández^1,2, Isabel Mascaren˜o1,2 &

January 2002 and December 2015 at “Hospital Universitario Reina Sofía” in

Javier Salvador³

Córdoba. Results were analysed with SPSS 18.0.

¹Hospital Universitario de Canarias, Tenerife, Spain;²Universidad de La

Results

Laguna, Tenerife, Spain;³Hospital Universidad de Navarra, Pamplona,

34 patients, 50% women. Mean age: 56.2G11.9 years old. Mean follow-up: 5.2G

Spain.

3.9 years (range: 1-14 years). Symptomatology: 38.2% campimetric alterations,

35.3% headache and 11.8% symptoms derived from hormonal deficits. 29.4%

incidental diagnosis in magnetic resonance imaging. Mean diameter of tumour:

Introductions

30.2G11.4 mm. 64.7% extrasellar growth, 55.9% chiasmal compression, 23.5%

Alterations of the somatotrophic and hypothalamic-pituitary-adrenal (HPA) axes

grade I of Knosp classification. Initial treatment: 91.2% transsphenoidal surgery

occur frequently in patients with poorly controlled DM-1. These disorders could

(8.8% cabergoline).

64.7% post-surgery complications. Anatomopathological

be related to abnormalities in the cholinergic tone regulating both hormonal axes.

diagnosis: pituitary adenoma, except

1 patient with tissue necrosis;

11.8%

Subjects and Methods

patients had p53 positive; mean Ki-67: 2G2.4%. Only 5 patients were cured after

UFC (urinary free cortisol) on 24 h urine samples and the effects of placebo and

the first surgery (2 patients had recurrence) and 29 had radiological persistence of

pyridostigmine on ACTH, cortisol, GH and glucose circulating levels were

disease. Adjuvant treatment: cabergoline (10 patients), radiotherapy (11 patients),

studied in

16 young males: 10 normal controls and 6 patients with poorly

radiosurgery

patients), second surgery

(10

patients) and third surgery

controlled DM-1 (HbA1c 9.2%) without retinopathy or nephropathy. Placebo or

(2 patients). Finally, 26.5% of patients are cured and 73.5% have persistent

pyridostigmine (120 mg) were given orally on different days at 0830. Blood

disease. Hormonal deficits:

44.1% pre-surgery and

79.4% post-surgery.

samples were drawn at 0830, 0900 and then every 15 min until 1130. Area under

Campimetry improved in all patients.

the curve (AUC) was calculated for the full sampling period and for 1 hour

Conclusions

intervals. Data are expressed as meanGSEM.

i) There are not differences in the prevalence of NFPAs by gender in our series.

Results

ii) The diagnosis was motivated by the symptomatology (predominantly visual);

UFC (47.21G7.29 vs 33.70G2.63 mcg/24 h, P!0.05), and GH and glucose

less frequent incidental diagnosis. iii) Most patients underwent transsphenoidal

levels were higher in diabetics than in controls, whereas ACTH and cortisol levels

surgery, being the success of this first surgery in our series less than the published

were not different. Pyridostigmine did not alter ACTH nor cortisol levels, while it

rates.

raised GH secretion within each group, with the greatest increase in diabetics

DOI: 10.1530/endoabs.49.EP907

(AUC 0-60 min: 149.46G82.34 vs 23.68G12.01 ng/ml/60 min, P!0.05). UFC

was negatively correlated with HbA1c. Basally, GH did not correlate with ACTH

nor cortisol levels.

Conclusions

The higher UFC figures in diabetics suggest some degree of hypercortisolism in

poorly controlled DM-1. Cholinergic activation in diabetics elicits GH

hyperresponse, but does not modify cortisol nor ACTH levels, either in diabetics

or controls. This fact speaks against an altered common mechanism in the

cholinergic system regulating somatotrophic and HPA axes in DM-1, suggesting

EP908

that cholinergic tone is not involved in the raised UFC excretion seen in these

patients.

Decreased prolactin levels in plasma and cerebrospinal fluid in naïve to

treatment patients with multiple sclerosis

DOI: 10.1530/endoabs.49.EP909

Agnieszka Baranowska-Bik¹, Dorota Uchman², Lidia Martynska³,

Malgorzata Kalisz³, Anna Litwiniuk³, Wojciech Bik³,

Boguslawa Baranowska² & Jan Kochanowski²

¹Department of Endocrinology, Centre of Postgraduate Medical Education,

Warsaw, Poland;²Department of Neurology, Medical University of

Warsaw, Warsaw, Poland;³Department of Neuroendocrinology, Centre of

EP910

Postgraduate Medical Education, Warsaw, Portugal.

Increased GH response to GHRH plus pyridostigmine unrelated to

augmented glomerular filtration rate in DM-1

Background

Jesús Pérez-Luis^1,2, Judith López-Fernández^1,2, Isabel Mascaren˜o1,2 &

Data from the literature has documented a remarkable immune-modulating role of

Javier Salvador³

prolactin. Previous evaluations of prolactin levels in patients with multiple

¹Hospital Universitario de Canarias, Tenerife, Spain;²Universidad de La

sclerosis (MS), disease of autoimmune origin, showed conflicting results. Thus, to

Laguna, Tenerife, Spain;³Hospital Universidad de Navarra, Pamplona,

clarify the impact of prolactin on MS pathology we decided to assess prolactin

Spain.

levels in plasma and cerebrospinal fluid in naïve to treatment subjects with newly

diagnosed MS.

Material and methods

Introduction and Objectives

A total number of 83 individuals were included: 41 patients with MS (30

In patients with poorly controlled DM-1, the frequently observed alterations of

females/11 males) and 42 age-matched controls (36 females/6 males). All MS

somatotrophic axis seem to be related to abnormalities in the hypothalamic

subjects were newly diagnosed and they were without any treatment at the time of

cholinergic tone regulating this axis. The effects of cholinergic stimulation on GH

taking the samples of blood and cerebrospinal fluid. Prolactin was determined

responses to GHRH were evaluated in patients with poorly controlled DM-1 and

both in plasma and cerebrospinal fluid, and cytokines (TNF-alpha, IL-6, IL-10)

the relationship of these responses to metabolic control and kidney function tests.

were evaluated in plasma in all subjects.

Subjects and Methods

Results

Microalbuminuria and creatinine clearance (GFR) on 24 h urine samples, and the

Prolactin levels in plasma were found to be markedly lower in MS patient when

effects of GHRH plus placebo and plus pyridostigmine on GH and glucose

compared to those of the controls (7.64G5.99 ng/ml vs 10.12G6.76 ng/ml;

circulating levels were studied in

16 young males: 10 normal controls and

P!0.05). These results correspond with concentration of prolactin measured in

6 patients with poorly controlled DM-1 (HbA1c 9.2%) without retinopathy or

cerebrospinal fluid as in MS individuals prolactin was significantly decreased

nephropathy. On different days, placebo or pyridostigmine (120 mg) were given

(2.84G0.35 ng/ml vs 3.42G0.89 ng/ml; P!0.05). The comparison of cytokines

orally at 0830 and GHRH 50 mcg IV at 0930. Blood samples were drawn at 0830,

levels revealed no differences between the examined groups. A positive

0900 and then every 15 min until 1130. Response parameters were calculated.

correlation between prolactin concentration in plasma and TNF-alpha levels

Data are expressed as meanGSEM.

was found in MS subjects.

Results

Conclusion

GHRH raised GH levels within each group. However, while GH responses were

Decreased levels of prolactin may reflect disturbed pituitary activity as well as

not different between diabetics and controls after GHRH plus placebo, they were

disrupt immunological system regulation at the early stage of multiple sclerosis.

actually higher after GHRH plus pyridostigmine in diabetics (AUC of response of

Acknowledgment

GH: 4085.83G1227.86 vs 1914.46G385.06 ng/ml/120 min, P!0.05). GFR was

The study was supported with CMKP grant no.501-1-31-22-2015.

greater in diabetics, although not significant

(134.85G20.62

110.12G

8.13 ml/min). GH was not correlated with glucose in any of the tests.

DOI: 10.1530/endoabs.49.EP908

Furthermore, HbA1c, microalbuminuria and GFR showed no correlation with

GH in diabetics.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

primary objective of the study is to assess the safety and efficacy of Omnitrope^w

In this study, the higher GH responses to GHRH plus pyridostigmine in diabetics

in adults treated in routine clinical practice, with particular emphasis placed on

suggest that there is an augmented cholinergic tone in poorly controlled DM-1

the risk of glucose intolerance or diabetes and normalisation of IGF-I levels.

patients. Furthermore, these findings are not related with the higher GFR observed

Results

in diabetics.

As of December 2016, 1121 patients had been enrolled on the study, of whom 586

DOI: 10.1530/endoabs.49.EP910

(52.3%) were pre-treated with another rhGH. Mean (standard deviation [SD])

. In total

patient age is 49.7 (15.3) years, and mean (SD) BMI is 29.4 (6.3) kg/m²

2455 adverse events (AEs) in 665 (59.3%) patients have been reported, with 444

(in 247 [22%] patients) of these regarded as serious. One hundred and thirty-nine

AEs in 80 (7.1%) patients were suspected to be drug-related; these included

general disorders/administration site conditions in 19 patients, nervous system

disorders in 23 patients and musculoskeletal/connective tissue disorders in 24

patients. A total of 26 serious AEs in 17 (1.5%) patients were suspected to be

EP911

related to Omnitrope^w treatment, including one incidence of diabetes. Of the 188

Increased morbidity associated with the treatment of

patients who discontinued treatment, 47 (25%) did so due to an AE.

craniopharyngioma

Conclusions

Cristina Capatina^1,2, Anda Dumitrascu², Andra Caragheorgheopol² &

Based on this interim analysis, Omnitrope^w treatment in adults with GHD is well

Catalina Poiana^1,2

tolerated in a real-life clinical practice setting, both in previously treated and

¹Carol Davila University of Medicine and Pharmacy, Department of

rhGH-naïve patients. The ongoing PATRO Adults study will provide further data

Endocrinology, Bucharest, Romania;²C.I.Parhon National Institute of

on the diabetogenic potential and overall safety of long-term GH treatment in this

Endocrinology, Bucharest, Romania.

population.

DOI: 10.1530/endoabs.49.EP912

Background

Craniopharyngioma is a rare epithelial tumor of the central nervous system,

affecting both children and adults and associated with significant morbidity.

Objective

To study the posttreatment evolution of craniopharyngioma in children and adults

EP913

in a large mixed cohort.

Clinical case description of family with hereditary pituitary adenoma

Material and Methods

Tatiana Tarasova, Ekaterina Pigarova, Larisa Dzeranova, Anatoly Tulpakov

We performed a retrospective review of craniopharyngioma patients evaluated in

& Ivan Dedov

the National Institute of Endocrinology in Bucharest between 1990 and 2016.

Endocrinology Research Centre, Moscow, Russia.

Results

A total of 82 patients (59 adults, 39.27G15.5 years old; 23 children, 12.96G4.2

years old) with a mean follow-up of 6.85 years were included. All underwent

Introduction

surgery

(57

cases,

69.5% transcranial,

cases,

30.48% transsphenoidal

In recent years, more attention is driven to the cause of hereditary forms of

approach,), 34 being operated on more than once. 13 patients (15.85%) were

pituitary adenomas. Although for most cases causal genes are not discovered yet,

irradiated (1 before surgery, the others after). The surgical excision was complete

AIP mutations are the most prevalent.

in 26 cases (31.7%). Surgery led to anosmia (in 7 cases), CSF leak (3 cases),

Materials and Methods

subdural hematoma (2 cases). After surgery 21 cases (25.6%) had cognitive

Case descriptions, high-parallel sequencing using a gene panel (MEN1, CDKN1B,

impairment, 5 (6.09%) had hypothalamic syndrome (diurnal sleepiness, appetite

PRKAR1A, GNAS, AIP, SDHA, SDHB, SDHS, SDHD, PRKCA, CDKN2C,

and memory dysfunction). The endocrine dysfunction was aggravated after

CDKN2A, POU1F1, PTTG2).

treatment in 64 cases (78%), improved in 5 (6%) and stable in 14 cases (17%).

Case description

The evolution of the tumor revealed stable remnant in

29 cases

(35.3%),

Index case - a 59-year-old man with clinical features of acromegaly (the size of

progressively increasing remnant in 23 (28%), recurrence in 2 (3.4%) and cure in

adenomas at baseline 3.9!3.2!3.9 cm, growth 165 cm), secondary diabetes

28 cases (34.14%) during follow-up. There was no significant difference in the

mellitus, multinodular goiter, obesity I grade, arterial hypertension. First clinical

complications rate between children and adults.

symptoms were noted since the age of 30 years. At the age of 51 he underwent

Conclusions

transcranial adenomectomy, then at the age of

years

- transnasal

Craniopharyngioma is a tumor frequently necessitating repeated treatments,

adenomectomy. Because of persistent disease activity he was initiated medical

associated with very significant morbidity. The results and complications of

therapy with sandostatin analogs (40 mg of octreotide depo) without hormonal

treatment are similar in adults and children.

control of acromegaly - IGF 497.5 ng/ml (15-250) and GH 80 ng/ml (0-1.2).

DOI: 10.1530/endoabs.49.EP911

MRI after surgery pituitary adenoma with supra-, infra- and parasellar extension.

The patient’s

28-year-old son also has acromegaly

(intrasellar pituitary

macroadenoma at MRI (the size of adenomas 0.7!1.2!0.6 cm), first clinical

symptoms were noted since the age of 27 years, growth 167 cm, without

complication); he was operated transnasally at the age of 28 years without

postoperative remission: GH at OGTT

2.67-2.52-1.95-2.05-2.37 ng/ml, IGF

567.2 ng/ml (60-280). Genetic investigation revealed a mutation in exon 6 of the

EP912

AIP gene pR271W (not previously described, possible pathological).

Conclusion

The PATRO adults study of Omnitrope for the treatment of adult

AIP mutation in our family with hereditary pituitary adenoma is associated with

patients with growth hormone deficiency: latest results

high aggressiveness and resistance to medical therapy with somatostatin analogs.

Paolo Beck-Peccoz¹, Charlotte Hoybye², Robert Murray³, Suat Simsek⁴,

Markus Zabransky⁵ & Gunter Stalla⁶

DOI: 10.1530/endoabs.49.EP913

¹Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda

Ospedale Maggiore Policlinico, Milan, Italy;²Karolinska University

Hospital, Stockholm, Sweden;³St James’s University Hospital, Leeds, UK;

⁴Medisch Centrum Alkmaar, Alkmaar, The Netherlands;⁵Sandoz Inter-

national GmbH, Holzkirchen, Germany;⁶Max Planck Institute of

Psychiatry, Munich, Germany.

EP914

Molecular and genetic basis of the disease in families with pituitary

adenomas

Introduction

Tatiana Tarasova, Ekaterina Pigarova, Larisa Dzeranova, Anatoly Tulpakov

The ongoing, international, open, longitudinal, non-interventional study, PATRO

& Ivan Dedov

Adults, aims to determine the long-term safety and efficacy of Omnitrope^w

Endocrinology Research Centre, Moscow, Russia.

(Sandoz), a recombinant human growth hormone (rhGH). Safety data from an

interim analysis are presented here.

Methods

Introduction

Eligible patients are male or female adults who are receiving treatment with

Most of the work on the analysis of molecular genetic defects in pituitary

Omnitrope^w and who have provided informed consent. Patients treated with

adenomas devoted to the study of 1-2 candidate genes. The high-performance

another rhGH before starting Omnitrope^w therapy are eligible for inclusion. The

parallel sequencing is more promising.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Materials and Methods

pathways are known for the regulation of apoptosis. Additionally, these two

There were a total of 26 families (58 patients, 36 (62.1%) men and 22 (37.9%)

pathways could activate cAMP-response-element-binding protein (CREB), which

women) with pituitary adenomas secretion of various types. The number of

has been shown to promote cell survival. Therefore, their phosphorylation levels

families with homogenous type was 17 (somatotropinomas 13, prolactinomas 2,

in the cerebellum were compared between Sct-/- and WT mice. The basal levels

corticotropinomas 1, inactive pituitary adenomas 1), with a heterogeneous type -

of phosphor-ERK1/2

(pERK1/2) and phosphor-CREB

(pCREB) showed a

of theses families had somatotropinomas/inactive pituitary adenomas,

significant decrease in Sct-/- mice, but not phosphor-AKT

(pAKT). The

2 families had prolactinomas/inactive pituitary adenomas. The number of family

cerebellar slices obtained from Sct-/- displayed a dose-dependent increase of

members with hypertension ranged from 2 to 7.The high-performance parallel

pERK1/2 and pCREB, but not pAKT, in response to graded concentrations of

sequencing was implemented with the gene panel (MEN1, CDKN1B, PRKAR1A,

secretin peptide and the impaired phosphorylation of ERK1/2 and CREB in Sct-/-

GNAS, AIP, SDHA, SDHB, SDHC, SDHD, PRKCA, CDKN2C, CDKN2A,

cerebellar slices was able to be recovered by the treatment of secretin compared

POU1F1, PTTG2).

with WT, suggesting the involvement of ERK1/2 and CREB. Specific inhibitors

Genetic investigation

were applied for further confirmation. Secretin failed to reduce the level of

According to a study in four patients with somatotropinomasidentified mutations

activated Caspase-3 when either ERK1/2 or CREB was inhibited, revealing that

were AIP p.R271W and p.A411GfsX47, one patient was identified with

ERK1/2 and CREB was required for secretin’s neuroprotective function. Our

polymorphisms with unproven value in pathological gene SDHA p.V589V, and

results clearly provide evidence that ERK1/2 and CREB play a role in mediating

one patient with the phenotype of McCune-Albright syndrome had heterozygous

the anti-apoptotic function of secretin.

p.S163P replacement in SDHB gene.

DOI: 10.1530/endoabs.49.EP916

Conclusion

The genetic changes using a multi-gene panel were identified in only 20% of

tested families. New gene candidates are highly needed for familial pituitary

adenomas.

DOI: 10.1530/endoabs.49.EP914

EP917

Predictors of remission after transsphenoidal adenomectomy in patients

with Cushing’s disease

Eugenia Marova, Galina Kolesnicova, Svetlana Arapova, Andrey Grigoriev

& Anasteysa Lapshina

EP915

Endogrinology Research Centre, Moscow, Russia.

Pituitary adenoma with gigantism and TSH-induced hyperthyroidism:

a case report

Abstract

M Gloria Baena-Nieto, Rosa Márquez-Pardo, Manuel Cayón-Blanco,

Cushing’s disease (CD) is the heavy disease of the hypothalamic-pituitary-

Lourdes García-García-Doncel, Rosario López-Velasco & Isabel M Torres-

adrenal axis. The cause of the disease is pituitary adenoma (corticotropinoma).

Barea

Hypersecretion of ACTH by a pituitary adenoma leads to increased secretion of

Hospital de Jerez, Jerez, Cádiz, Spain.

cortisol by the adrenal cortex and the development of total endogenous

hypercortisolism. The gold standard treatment for this disease is surgical removal

Abstract

of corticotropinoma. However, adenomectomy is not effective in all cases and

A 14-yr-old male patient with acromegaly and TSH-induced hyperthyroidism is

approximately 20% of cases after the radical treatment fails to achieve remission

reported. He was referred for hormonal study due to clinical suspicion of

of the disease and then comes the relapse. The aim of our work was to evaluate the

acromegaly. Physical examination showed acromegalic/gigantism features (high

factors influencing the result of adenomectomy in patients with the Cushing’s

stature:

194.5 cm (PO90), such as: abnormal growth of the hands and feet,

disease and identification of recurrence predictors. Materials and methods:

furrowed forehead and pronounced brow ridge). No goiter was found. GH levels

retrospective assessment of clinical and hormonal factors in 84 patients with CD,

were high and were not suppressed after oral glucose (GH: 12.50 ng/ml, GH after

influencing early and long-term results of adenomectomy.

glucose: 6.19 ng/ml; IGF-1: 1391 ng/ml); Serum thyroid hormones levels were

DOI: 10.1530/endoabs.49.EP917

high, although TSH levels were not suppressed (TSH: 0.96 mU/ml, T4: 3.57 ng/dl

T3:

11.06 pg/ml). Antithyroglobin, antimicrosomal autoantibody, and TSH

receptor antibody were negative. Gonadotropines, prolactine and ACTH leves

were normal

(Prolactina:

12.79 ng/dl, LH:

9.37, FSH:

4.56, Testosterona:

760.9 ng/dl, Cortisol:

5.9 mcgr/dl, ACTH: 15.1 pg/ml). A pituitary magnetic

resonance imaging of the pituitary revealed a 7-mm adenoma. He was diagnosed

of acromegaly and hyperthyroidism. Pre-operative treatmen with octreotide was

iniciated and transsphenoidal surgery was performed to remove the pituitary

adenoma. Post-operative serum thyroid hormone and GH levels returned to

EP918

normal, and IGF-1 levels were still elevated (786 ng/ml). Immunohistochemical

Copeptin after arginine infusion for the differential diagnosis of the

staining of the operative specimen showed positive reactions to both TSH and

polyuria-polydipsia syndrome “The CARGO-Study”

GH. Pituitary gigantism is a rare condition caused by growth hormone secreting

Bettina Winzeler, Nicole Nigro, Julie Refardt & Mirjam Christ-Crain

pituitary tumor. Choromophobe adenoma producing either acromegaly and

University Hospital Basel, Basel, Switzerland.

hyperthyroidism have been described in a limited number of cases none of them

on an infant.

Background

DOI: 10.1530/endoabs.49.EP915

The spectrum of polyuria-polydipsia syndrome (PPS) includes diabetes insipidus

(central or nephrogenic) and primary polydipsia. In clinical practice the

differential diagnosis particularly of central diabetes insipidus (cDI) and primary

polydipsia

(PP) is often difficult. The current gold standard

- the water

deprivation test (WDT) with or without vasopressin (AVP) measurements - lacks

reliable diagnostic accuracy. Arginine infusion is known to stimulate various

hormones secreted by the anterior pituitary gland such as growth hormone and

EP916

prolactin. Based on own preliminary data we hypothesized that arginine also

Secretin protects from apoptosis by activation of ERK1/2 and CREB

stimulates AVP mirrored by copeptin, the C-terminal part of the precursor

Lei Wang & Billy Chow

peptide. The aim of this study was to evaluate the diagnostic utility of copeptin

The University of Hong Kong, Hong Kong, Hong Kong.

measurements after arginine infusion in patients with PPS.

Methods

Between 2013 and 2017 patients with polyuria-polydipsia syndrome were

Abstract

included in this prospective study. Patients underwent first a standard water

There are a growing number of studies identifying secretin as a neuroprotective

deprivation test for diagnosis of PP or cDI and second an arginine infusion

factor. Consistently, our previous data showed that neuronal apoptosis

(L-Arginine Hydrochloride 0.5 g/kg body weight i.v. over 30 min). Blood was

considerably increased in the developing cerebellum from secretin knockout

withdrawn at different time points (e.g. 30, 45, 60 min) after arginine infusion for

(Sct-/-) mice. However, the underlying mechanisms remained poorly understood.

copeptin measurements. Additionally, 20 healthy controls underwent arginine

Extracellular signal-regulated protein kinase

(ERK) and AKT signalling

infusion without prior WDT.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

have been reported as immune-related adverse effects. However, nivolumab-

A total of 51 patients (63% female) were enrolled. 28 (55%) patients were

induced hypophysitis has a lower incidence than ipililumab.

diagnosed with PP, 11 (22%) with complete DI and 12 (23%) with partial DI. The

Case report

study was terminated in January 2017. Final results of copeptin levels will be

A 69-years old man with metastatic melanoma started to receive nivolumab. Ten

measured in batch analysis in February 2017 and compared between patients with

weeks after the first cycle of nivolumab he presented hyperthyroidism in blood

complete cDI, partial cDI and PP as well as 20 healthy volunteers. We would be

test. As it was suspected Hashimoto’s thyroiditis none antithyroid drug was

delighted to present the final results of this study at the 19th European Congress of

started. The thyroid scintigraphy and the presence of anti-thyroid peroxidase

Endocrinology.

antibodies confirmed the diagnosis and the thyroid function was monitoring.

Significance

Forty days later, the laboratory findings showed hypothyroidism and levothyr-

If our hypothesis is true, copeptin measurements after arginine infusion are a

oxine was provided. Nivolumab treatment continued to be administered. Three

promising new tool in the differential diagnosis of polyuria-polydipsia syndrome

months later, the patient was admitted because of general weakness and mild

with the advantage of short and safe test protocol.

confusional state. Blood test showed severe hyponatremia (110 mEq/l) with a

DOI: 10.1530/endoabs.49.EP918

decreased plasma osmolarity

(250 mOsm/kg). Adrenal insufficiency was

suspected so a new blood sample was taken in order to determine cortisol

(2.68 mg/dl) and ACTH (! 5 pg/ml) and hydrocortisone treatment was beginning

promptly. The assessment of hypothalamic-pituitary-gonadal axis showed a slight

decrease in testosterone (1.24 ng/ml) with LH and FSH normal levels. Insulinlike

growth factor-1 (IGF-1) was normal, as well as prolactin. Thyroid function was

abnormal because of discontinuation of treatment with levothyroxine: TSH

25.47 mUI/ml, FT4 0.39 ng/dl. Magnetic resonance imaging scan was performed

EP919

and it was reported as mild enlargement of the pituitary gland and the stalk.

Diabetes mellitus in Cushing’ syndrome: a systematic review

Hydrocortisone treatment was continued after the patient was discharged from

Thizá Londero^1,2, Ana Marina Moreira^1,2, Cristiane Leita˜o1,2,

hospital. Two weeks later, normal sodium levels were showed in biochemical test.

Ticiana Rodrigues^1,2 & Mauro Czepielewski^1,2

Discussion

¹Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil;²Universidade

Monoclonal antibodies used in malignant melanoma as ipililumab or nivolumab

Federal do Rio Grande do Sul, Porto Alegre, Brazil.

could cause several endocrine auntoimmune disorders. Despite hypothyroidism is

a common adverse effect, hypophysitis is a rare finding associated to nivolumab in

Introduction

contrast to ipililumab. Clinicians should suspect this pathology in order to achieve

Diabetes mellitus (DM) is an expected condition in Cushing syndrome (CS) but

a promptly diagnosis.

there are few data about prevalence and factors associated to occurrence of DM in

DOI: 10.1530/endoabs.49.EP920

these patients.

Objective

To determine the main aspects of DM in CS through a systematic review (SR) of

the literature.

Methods

MEDLINE and LILACS were searched for studies published until March, 2016.

Search strategy comprised the terms “Diabetes Mellitus”, “Glucose Intolerance”,

“Hyperglycemia”,

“Cushing Syndrome”,

“Pituitary ACTH hypersecretion”,

“diabete melito”,

“Cushing”. Observational/interventional studies in patients

with endogenous CS with characterization of DM were included. We excluded

case reports, animal models, and studies about exogenous hypercortisolism or

EP921

subclinical CS.

Kallmann syndrome: about eleven clinical cases

Results

Liliana Fonseca, Claúdia Amaral, Jorge Dores, Isabel Palma, Rui Carvalho,

The initial search yielded 726 titles, 58 were full-text reviewed. Of these, 12 were

Helena Cardoso, Joana Vilaverde & Fátima Borges

included in RS. Seven studies (all cross-sectional) accessed DM prevalence. Most

Centro Hospitalar e Universitário do Porto, Porto, Portugal.

patients were women (93.5%) aged 40-50 years, with disease duration between

29 and 180 months. Pituitary, adrenal and ectopic-ACTH were origin of CS in 325

(70.65%), 134 (29%) and 2 (0.5%) patients, respectively. DM prevalence ranged

from 17 to 47%. Four studies evaluated the role of body mass index (BMI) on DM

Idiopathic congenital hypogonadotropic hypogonadism (CHH) is a rare

occurrence, but none of them found a statistically significant difference. Two

reproductive disorder that is primarily caused by a gonadotrophin-realising

studies demonstrated a higher risk of DM in older ages at CS diagnosis. The

hormone (GnRH) deficiency. When CHH is associated with hyposmia or

correlation of DM and severity of hypercortisolism was analysed in four articles

anosmia is designated by Kallmann Syndrome (KS). This syndrome is a

and two of them presented a positive result. The effect of CS remission on DM

genetic disorder with significant genetic heterogeneity that may present as a

cure was accessed by two studies, with discordant results. DM was associated

sporadic or familial case, following autosomal dominant, autosomal

with higher mortality. Three studies (open-label trials) analysed effect of CS drug

recessive, or X - linked recessive modes of inheritance. This work aim is

therapy on glycaemic control. Mifepristone demonstrated a diabetes improvement

to review all KS cases followed in the Endocrinology service. A total of 11

after 6 months, as rosiglitazone after 30-120 days.

cases were evaluated, 10 men and 1 woman. Patients were mainly diagnosed

Conclusion

in late adolescence, between 17 and 18 years old, when sought a doctor for

DM is a frequent CS comorbidity and its occurrence seems to depend on age at

delayed puberty. All cases presented hypogonadotropic hypogonadism and

diagnosis and disease duration. If CS remission leads to DM remission is still

hyposmia or anosmia with MRI olfactory bulb atrophy criteria. No other

uncertain.

changes in the neuroendocrine axis were found. The patients were followed

DOI: 10.1530/endoabs.49.EP919

between 2 and 33 years (mean time 12 years). All had gonadal steroid

hormones treatment (testosterone or estrogens) and had a good secondary

development of the sexual characteristics, Tanner stage IV/V. Three patients

had fertility therapy with gonadotropin and until now only the girl had

clinical improvements. Four cases made a genetic study: two mutations in

KAL1 gene, one in FGFR1, and one in PROK2 were found. The two patients

with KAL1 mutation presented cryptorchidism and one the two also had

unilateral renal agenesis. The patient with FGFR1 mutation also had an

EP920

history of cryptorchidism. The one with recessive mutation for PROK2 only

Thyroiditis and hypophysitis caused by nivolumab

presented anosmia and hypogonadotropic hypogonadism.

Leticia Perez Fernandez, Isabel Azcona Monreal, María Martinez Garcia,

Conclusion

Maria Elena Lopez Alaminos, Pablo Trincado Aznar, Diana Boj Carceller,

The presence of a delayed pubertal development is suspicious of CHH/KS

Diego Alvarez Ballano & Patricia de Diego García

occurrence. In our study, patients with KS presented good clinical results with the

H.U. Miguel Servet, Zaragoza, Spain.

use of gonadal steroid hormones attaining stages IV/V of Tanner. Women appear

to have better fertility responses to therapy than men, although this findings

Introduction

demand further investigation.

Nivolumab is an anti-programmed cell death-1 monoclonal antibody approved for

DOI: 10.1530/endoabs.49.EP921

the treatment of metastatic malignant melanoma. Several endocrine disorders

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Paediatric endocrinology

Methods

Retrospective observational study with analysis of clinical records of children and

EP922

adolescents with GHD under treatment with GH in the period from 2012 to 2016.

Endocrine manifestations of multisystem Langerhans cell histiocytosis

Statistical analyses were performed using SPSS 24.0 for Windows.

Diana Oliveira¹, Flavia Napoli², Enrica Bertelli², Alessandra Maggioni²,

Results

Sandra Paiva¹, Francisco Carrilho¹ & Natascia Di Iorgi²

The final sample consisted in 49 patients, 61.2% were male. Mean age at the

¹Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital

beginning of therapy was 9.7G4 years (0.13-16.92). Mean height z-score at time

and University Center, Coimbra, Portugal;²Pediatric Clinic, Endocrinology

of diagnosis was K3.16G0.94, corresponding the mean z-score of the target

and Diabetes Unit, IRCCS G Gaslini, University of Genova,

height to K1.24G0.77. The mean delay in bone age was 2.22G1.50 years (0-6.5

Genova, Italy.

years). Two growth hormone stimulation tests (clonidine and L-Dopa) were

performed in 69.4% of the cases. Brain MRI showed changes in 42.9% of the

cases. Of the

49 patients,

55.1% had an idiopathic GHD, 30.6% isolated

Introduction

deficiency and 14.3% had multiple deficiencies. Mean age at the time of diagnosis

Multisystem Langerhans cell histiocytosis

(LCH) is a rare heterogeneous

was 11.16, 8.84 and 6.57 years in the three groups respectively. Mean treatment

disorder caused by accumulation in multiple organs of dendritic cells

duration was 3.92 years (in 14.2% less than 1 year). The z-score variation in the

phenotypically similar to cutaneous Langerhans cells. Pituitary involvement

group of idiopathic GHD was 0.99, 1.50 and 2.53 in the group of isolated and

is present in about 25% of cases, and central diabetes insipidus is the most

multiple deficiencies respectively.

common deficit in that setting. Panhypopituitarism is rare, but hypothalamic-

Discussion

pituitary dysfunction is amongst the most frequent long-term complications of

As previously described, GHD is more prevalent in males. Comparing the three

the disease.

groups, patients with multiple deficiency are diagnosed earlier and have better

Case report

results with the treatment (higher z-score variation).

We describe the case of a child with normal health status until the age of 7. He

developed polyuria and polydipsia, was hospitalised and submitted to a water

DOI: 10.1530/endoabs.49.EP923

deprivation test, considered indicative of psychogenic polydipsia. At 14-years-

old, elevated liver enzymes were attributed to EBV infection. Liver ultrasound

showed hepatomegaly and heterogeneous echotexture. At

16-years-old, he

presented with hypernatremia, delayed puberty and short stature, as well as slowly

progressive dyspnea. Investigation revealed multiple pituitary deficits (hypogo-

nadotrophic hypogonadism, secondary hypothyroidism, secondary adrenal

insufficiency, growth hormone deficit) and central diabetes insipidus. Brain

magnetic resonance imaging showed a hypothalamic mass (17 mm). He was

started on hormonal replacement therapy

(urofollitropin, human chorionic

gonadotropin, levothyroxine, cortisone, desmopressin). LCH was suspected,

Pituitary - Basic

and chest computed tomography revealed multiple cystic pulmonary lesions

suggestive of the diagnosis, later confirmed by pulmonary biopsy. He started

EP924

standard treatment with vinblastine and prednisone, with intermediate response

SSTR2 inhibits GH-secreting pituitary tumoral cells migration and

after 6 weeks. He developed glucocorticoid-induced diabetes and needed multiple

invasion by increasing cofilin phosphorylation

daily injections of insulin.

Erika Peverelli¹, Elena Giardino¹, Donatella Treppiedi¹, Marco Locatelli²,

Conclusions

Andrea G Lania³, Maura Arosio¹, Anna Spada¹ & Giovanna Mantovani¹

This case report illustrates the importance of investigating multiple signs and

¹Endocrine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore

symptoms that arise in a multisystem and complex disorder. In this case, the

Policlinico; Department of Clinical Sciences and Community Health,

endocrine consequences of LCH assume a central role. As was the case here,

University of Milan, Milan, Italy;²Neurosurgery Unit, Fondazione IRCCS

central diabetes insipidus can be the first manifestation of the disease, but its

Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;³Endocrine Unit,

diagnosis is not always straightforward. Early diagnosis can prevent or delay

IRCCS Humanitas Clinical Institute, Humanitas University, Rozzano, Italy.

permanent complications associated with multisystem disease; pituitary deficits,

once established, are mostly permanent.

DOI: 10.1530/endoabs.49.EP922

Although generally benign, pituitary tumors frequently present local

invasiveness that strongly reduces neurosurgery success. We recently

demonstrated a role for the actin binding protein cofilin in promoting non

functioning pituitary tumors invasiveness and an inhibitory effect of

dopamine receptor type 2. Somatostatin (SS) receptor type 2 (SSTR2) is

the main target of pharmacological therapy of GH-secreting pituitary

tumors, reducing both GH secretion and cell proliferation, but its effects on

cell invasion have never been investigated. Aims of this study were: i) to

evaluate the effects of SSTR2 agonist on migration and invasion of rat

somatomammotroph GH3 cells and human GH-secreting pituitary tumoral

cells, and ii) to investigate the molecular mechanisms focusing on the role of

cofilin and the cytoskeleton protein FLNA, that directly interacts with

EP923

SSTR2. Our data demonstrated that SSTR2 agonist BIM23120 incubation

Growth hormone deficiency - the experience of one pediatric

significantly reduced migration (31.3%G12.2%, P!0.01) and invasion on

endocrinology unit of a Portuguese hospital in the last 5 years

collagen IV (22%G3.6%, P!0.001) of GH3, these data being replicated in

Jorge Abreu Ferreira, Fábio Barroso, Cristiana Martins, Joana Freitas,

human GH-secreting tumoral cells (14G2.9% and 41.7G11.3% reduction

Helena Cardoso, Maria João Oliveira & Teresa Borges

of cell migration and invasion, respectively, P!0.05). Moreover,

Paediatric Endocrinology Unit - Centro Materno Infantil do Norte - Centro

BIM23120 induced a marked increase of phosphorylated (inactive) cofilin

Hospitalar e Universitário do Porto, Porto, Portugal.

in both GH3 and primary tumoral pituitary cells (about 2.7 and 2.1-fold over

basal, respectively). This effect was completely abolished by specific ROCK

inhibitor Y27632 but not by pertussis toxin, suggesting an involvement of

Introduction

Rho/ROCK/LIMK pathway and excluding a role for inhibitory hetero-

Hypopituitarism is a clinical syndrome of deficiency in growth hormone (GHD)

trimeric G proteins. Co-immunoprecipitation experiments revealed an

production, which can occur isolated or associated with others pituitary defects.

association of SSTR2 with FLNA, cofilin and LIMK1, suggesting a role

GHD has an incidence of 1:4000 to 1:10 000. It may be idiopathic, congenital or

for FLNA as scaffold protein mediating SS effects on cofilin pathway. In

acquired.

conclusion, our data revealed an inhibitory effect of SSTR2 on GH-secreting

Purpose

pituitary tumor cells migration and invasion involving ROCK-dependent

Characterize the paediatric population with GHD followed at the Paediatric

phosphorylation of cofilin.

Endocrinology Unit of our centre and compare the clinical presentation and

DOI: 10.1530/endoabs.49.EP924

treatment response of the patients with an idiopathic form with the ones with

isolated and multiple hormonal deficiencies.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP925

EP927

Anti-proliferative effect of sodium metaarsenite (KML001) on

Ketoconazole induces inhibition of cell viability and apoptosis in an

ACTH-secreting pituitary adenoma cells

ACTH-secreting tumour cell line model

Dong Sun Kim¹, Jung Hwan Park¹ & Yeon-Ah Sung²

Roberta Patalano¹, Claudia Pivonello¹, Domenico Solari²,

¹Department of Internal Medicine, Hanyang University College of

Francesca Vitulli², Davide Iacuaniello¹, Monica De Leo¹,

Medicine, Seoul, Republic of Korea;²Department of Internal Medicine,

Mariarosaria Negri¹, Donatella Paola Provvisiero¹, Luigi Maria Cavallo²,

Ewha Womans University School of Medicine, Seoul, Republic of Korea.

Paolo Cappabianca², Annamaria Colpo¹ & Rosario Pivonello¹

¹Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia,

Università Federico II di Napoli, Naples, Italy;²Dipartimento di

Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Sezione di

KML001 is an orally bioavailable and water soluble trivalent arsenic

Neurochirurgia, Università Federico II di Napoli, Naples, Italy.

compound having anti-cancer activity via controlling the numerous

signaling pathways including phosphoinositide 3-kinase (PI3K)/Akt and

extracellular signal-regulated kinase (ERK) signaling pathways. PI3K/Akt

and ERK signaling pathways are overactivated in adrenocorticotropic

Chronic cortisol excess as a consequence of ACTH overproduction from a

hormone (ACTH)-secreting pituitary adenoma. In this study, we evaluated

pituitary tumour is responsible for the development of Cushing’s disease

the effects of KML001 on cell viability, cell cycle, apoptosis, and ACTH

(CD). The first-line treatment for CD is pituitary surgery, but medical

secretion in mouse ACTH-secreting pituitary adenoma cells, AtT-20 cells.

treatment is an alternative second-line approach to control cortisol excess.

KML001 inhibited the cell viability in time-dependent and concentration-

Among pharmacological agents, the adrenal-blocking drug ketoconazole

dependent manners and significantly decreased the ACTH secretion in a

(KT), is able to control cortisol excess in the majority of patients with CD.

concentration-dependent manner. As the treatment time or treatment

During KT treatment, the adrenal block of cortisol production is expected to

concentration increased, KML001 significantly increased the percentage

induce increase in ACTH levels, but conflicting data demonstrated ACTH to

of AtT-20

cells in apoptosis. As the treatment time or treatment

be increased, unchanged or decreased, suggesting a possible direct KT effect

concentration increased, KML001 significantly increased the percentage

on the pituitary tumour. The aim of the current study was to evaluate the

of AtT-20

cells in the G0/G1

phase and significantly decreased the

effects of KT on cell viability and apoptosis in mouse corticotroph tumour

percentage of AtT-20 cells in the S and G2/M phases. The effect of KML001

cell line (AtT20-D16). MTT assay was assessed to evaluate cell viability and

on numerous signaling pathways was determined by western blots. The

to evaluate the induction of cell apoptosis the study of mitochondrial

phosphorylated form of Akt and mammalian target of rapamycin (mTOR)

membrane potential by JC-1 assay and of PARP cleavage by western blot

proteins were decreased in KML001-treated AtT-20 cells. The phosphory-

were performed. KT induced a dose- (from 10-12 M to 6!10-5 M,

lated form of ERK protein was also decreased in KML001-treated AtT-20

concentrations covering KT therapeutic range of 200-1200 mg/daily) and

cells. However, the phosphorylated form of p38 and JNK protein were

time - (from 24 h to 144 h) dependent inhibition of cell viability (82.4%,

increased in KML001-treated AtT-20

cells. Consequently, KML001

P!0.0001 at

6!10-5M, 84.4% P!0.0001 at 4!10-5 M, 81.1%

inhibited cell proliferation in ACTH-secreting pituitary adenoma cells via

P!0.0001 at 2!10-5 M and 34% P!0.01 at 10-5 M after 144 h). KT

inhibition of cell cycle by inhibition of PI3K/Akt and ERK signaling

treatment at 24 and 48 h induced depolarization of mitochondrial membrane

pathways and induction of apoptosis by activation of p38-MAPK and JNK

potential

(108%, P!0.027 at IC50 2.5!10-5 M) followed by PARP

pathways and might reduce ACTH secretion. These results suggest that

cleavage, confirming the activation of apoptosis. In conclusion, these

KML001 could be a candidate for the treatment of persistent or recurrent

preliminary data suggest that KT has a direct effect on pituitary tumour

Cushing’s disease.

significantly reducing cell viability and inducing apoptosis on a corticotroph

DOI: 10.1530/endoabs.49.EP925

tumour cell model, shedding new light on the possible mechanisms by which

KT may control cortisol excess in CD.

DOI: 10.1530/endoabs.49.EP927

EP926

Angiogenesis-related proteins in pituitary adenomas

Ninelia Minaskan Karabid¹, Michael Atkinson² & Natalia Pellegata¹

EP928

¹Institute of Diabetes and Cancer (HMGU), Munchen, Germany;²Institute

GPR101 orphan receptor: a novel cause of growth hormone

of Radiation Biology (HMGU), Munchen, Germany.

deregulation

Dayana Abboud¹, Adrian Daly², Nadine Dupuis¹, Céline Laschet¹,

Bernard Pirotte³, Albert Beckers² & Julien Hanson^1,3

Laboratory of Molecular Pharmacology, GIGA-Molecular Biology of

Pituitary adenomas are frequent intracranial tumors that often associate with

disease, University of Liege, Liege, Belgium;²Department of Endo-

the hypersecretion of pituitary hormones or may be non-secreting

crinology, CHU of Liege, Domaine Universitaire du Sart-Tilman, Liege,

(nonfunctioning pituitary adenomas, NFPA). Tumors resembling human

Belgium;³Laboratory of Medicinal Chemistry, Centre for Interdisciplinary

NFPAs develop with complete penetrance in rats affected by the multiple

Research on Medicines (CIRM), University of Liege, Liege, Belgium.

endocrine neoplasia syndrome, MENX. This syndrome is caused by a

germline loss of function mutation in p27^Kip1. Gene expression array

analysis performed in our group identified a considerable number of genes

deregulated in rat pituitary tumors compared to normal pituitary tissues.

GPR101 is an orphan G-protein coupled receptor with unknown ligand. In

Some of the deregulated transcripts are associated with angiogenesis,

2014, an international study clearly pointed to a strong association between

including vascular endothelial growth factor (Vegf), angiopoietin-1 (Ang-1)

this receptor and the X-linked acrogigantism (X-LAG) syndrome, which

and -2 (Ang-2). VEGF and ANG-2 were found to promote angiogenesis in

begins in childhood and causes the “tallest giants”. The children (carriers of

several tumor types, while ANG-1 inhibits this process and stabilizes mature

the GPR101 duplication on the X chromosome) grow abnormally even

vessels. We analyzed mRNA and protein expression changes of these 3

before they are one year old, secrete phenomenal quantities of growth

genes in the pituitary adenomas of MENX-affected rats and compared the

hormone, and develop pituitary adenomas that do not respond to current

results with similar analyses conducted on the corresponding human tumors.

therapies. The mechanism by which GPR101 contributes to increased

We could show that Ang-1 was down regulated in rat and human NFPAs

growth hormone secretion is currently not known. Nevertheless, the lack of

whereas Ang-2 mRNA was highly expressed in almost all of the rat pituitary

mechanistic insight into the function of GPR101 precludes its validation as a

adenomas and was enhanced in less than the half of the human NFPAs. Vegf

drug target. This lack of knowledge on GPR101 is the consequence of the

mRNA was up-regulated in MENX-rats but not in NFPAs. At the protein

paucity of specific pharmacological/research tools currently available.

level, we have so far set up the immunohistochemical staining for Ang1 and

Therefore, we propose to study GPR101 functions and its role in growth

-2 on both rat and human tumors. We could show that rat pituitary adenomas

hormone regulation. First, we determined the receptor precise cellular

and human NFPAs show reduced cytoplasmic Ang-1 staining compared to

localization and trafficking. We also deciphered its constitutive signalling

adjacent non tumor cells while Ang-2 was more strongly expressed in tumor

pathways by detecting high cAMP levels as well as arrestin recruitment to

areas.

GPR101. We completed our study with an examination of receptor coupling

DOI: 10.1530/endoabs.49.EP926

to other pathways and G proteins. In parallel, we screened small molecule

libraries in order to identify GPR101 specific ligands, to establish the link

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

between GPR101 and X-LAG with a pharmacological approach. Further-

EP931

more, we applied targeted mutagenesis to modulate the receptor constitutive

Whole exome sequencing of two non-secreting pituitary adenoma

activity in order to understand the receptor function at a molecular level.

tumors from the same patient

These GPR101 mutants will help us to understand the role of this receptor in

Vita Rovite¹, Raitis Peculis¹, Inga Balcere⁴, Janis Stukens², Ilze Konrade⁴,

GH regulation and/or to treat people suffering from pituitary dysfunction.

Andra Valtere⁴, Jurijs Nazarovs², Olivija Caune⁴, Valdis Pirags^2,3 &

This information is an absolute prerequisite to link molecular pharmacology

Janis Klovins¹

of GPR101 with physiological functions.

¹Latvian Biomedical Research and Study Centre, Riga, Latvia;²Pauls

DOI: 10.1530/endoabs.49.EP928

Stradins Clinical University Hospital, Riga, Latvia;³Faculty of Medicine,

University of Latvia, Riga, Latvia;⁴Riga Eastern Clinical University

Hospital, Riga, Latvia.

Pituitary adenomas (PA) are benign tumors that develop in pituitary gland.

Hormone secreting PA can cause overproduction of pituitary hormones leading to

different systemic endocrine disorders

(acromegaly, Cushing’s disease and

others). Non-secreting PA can promote headaches (stretching of the dural sheath)

and visual field defects (chiasma compression). We managed to obtain resected

EP929

tumor samples from the patient having non-secreting PA, first tumor was resected

Potential role of biguanides and statins in the treatment of pituitary

in 2010, after operation patient had rapid regrowth and second resection was

adenomas

performed in 2012. Patient had two AIP gene variants rs641081 and rs4930199 in

Mari C. Vázquez-Borrego¹, Antonio C Fuentes-Fayos¹, Alejandro

genomic DNA. Whole exome sequencing of both tumors and genomic DNA from

Ibán˜ez-Costa1, Cristobal Blanco-Acevedo2, Eva Venegas-Moreno3,

white blood cells was carried out using single end sequencing in 3 batches on

María A Gálvez-Moreno⁴, Alfonso Soto-Moreno³, Justo P. Casta

˜o¹ &

IonProton semiconductor sequencing system with average coverage 10x. Data

Raúl M. Luque¹

analysis was performed using Galaxy main server

(http://usegalaxy.org/).

¹Maimonides Institute of Biomedical Research of Cordoba (IMIBIC); Reina

Variants were annotated using Annovar tool and obtained variants filtered.

Sofia University Hospital (HURS); Department of Cell Biology, Physiology

SNVs were filtered according to following parameters: sequencing depth O10,

and Immunology, University of Cordoba; CIBER Physiopatho, Cordoba,

base Q at SNV position O13, non-synonymous SNV or stop-gain or stop-loss

Spain;²Neurology Service, HURS/IMIBIC, Cordoba, Spain;³Metabolism

SNV, variation represented on both strands. Remaining SNV were manually

and Nutrition Unit, Virgen del Rocío Hospital; Biomedical Institute of

inspected for irregularities using IGV. 9 non-synonymous SNVs were found in

Seville (IBIS), Seville, Spain;⁴Service of Endocrinology and Nutrition,

both tumors and not in genomic DNA, further 24 additional nonsynonymous

HURS/IMIBIC, Cordoba, Spain.

SNVs were found in the second tumor that were not present in the first. The

detected alterations include ALKBH8, ASB12, CST1, CLMN, PRSS41, ENPP1,

E2F6 and SNVs in other genes, that are described to influence various cell

Pituitary adenomas (PA) comprise a commonly underestimated pathology in

functions, like regulation, signalling and cell cycle. All SNVs still to be validated

terms of incidence and associated morbimortality. To date, somatostatin and

by Sanger sequencing. Our findings indicate that second tumor had increased

dopamine analogs represent the main medical treatment, but an appreciable

number of variations compared to first tumor, that could be caused by regrowth of

subset of patients are resistant or poorly responsive to these drugs. Therefore, the

second tumor from specific cell subpopulation from initial PA. Exome sequencing

search for new approaches to control tumor growth and/or hormone secretion is

helps to discover genetic spectrum of known PA gene alterations and reveals new

crucial. Biguanides such as metformin (MF; commonly used to treat type-2

potential PA causative factors.

diabetes), phenformin

(PF) and buformin

(BF) have been shown to exert

DOI: 10.1530/endoabs.49.EP931

antitumor actions in different tumor types. Likewise, statins (such as atorvastatin

or simvastatin) treatment have been also related to antineoplastic effects in several

tumor types. Accordingly, the aim of this study was to elucidate the direct effect

of biguanides and statins, alone or in combination, on key functional parameters

(i.e. cell viability, hormone secretion, etc.) in human PA cell-cultures [non-

functioning pituitary adenomas (NFPAs; nZ8), corticotropinomas (ACTHomas;

nZ7) and somatotropinomas (GHomas; nZ4)] and/or rodent pituitary cell-lines

(AtT-20 and GH3). The results showed that biguanides and statins clearly

inhibited cell viability in pituitary cell-lines (being PF and simvastatin the most

EP932

effective compounds, respectively), and a similar effect was also observed with

Ubiquitin specific peptidase 8 (USP8) in human corticotroph pituitary

biguanides in all PA-subtypes. Additionally, the co-administration of biguanides

tumors- possible targets and mode of action

and statins did not alter the initial inhibitory actions of these compounds

Isabel Weigand¹, Lisanne Knobloch¹, Jens T. Vanselow², Jorg Flitsch³,

separately in cell lines, which might suggest that biguanides and statins exert their

Carmelia M Monoranu⁴, Wolfgang Saeger⁵, Christian Hagel⁵,

effects through common signaling pathways. In addition, biguanides were able to

Sabine Herterich⁶, Cristina Ronchi¹, Andreas Schlosser²,

significantly reduce GH and ACTH secretion in GH3 and AtT-20 cell lines,

Martin Fassnacht^1,6, Timo Deutschbein¹ & Silviu Sbiera¹

respectively. Taken together, our results reveal a clear inhibitory effect of

¹Division of Endocrinology and Diabetes, University Hospital Wuerzburg,

biguanides and statins on PA cell viability and, given their demonstrated clinical

Wuerzburg, Germany;²Rudolf Virchow Center for Experimental Biome-

safety, suggest a potential therapeutic role of these compounds for the treatment

dicine, University of Wuerzburg, Wuerzburg, Germany;³Neurosurgery,

of patients with PA.

University Hospital of Hamburg-Eppendorf, Hamburg, Germany;⁴Institute

Funding

of Pathology, University of Wuerzburg, Wuerzburg, Germany;⁵Institute of

Junta de Andalucia (CTS-1406, BIO-0139), MINECO (BFU2013-43282-R),

Neuropathology, University Hospital Hamburg-Eppendorf, Hamburg,

CIBERobn and Merck Serono. CIBER is an initiative of Instituto de Salud Carlos

Germany;⁶Central Laboratory, University Hospital, University of

III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain.

Wuerzburg, Wuerzburg, Germany.

DOI: 10.1530/endoabs.49.EP929

Recently, somatic, heterozygous mutations in the gene encoding the deubiqui-

tinase USP8 have been identified in 30-60% of corticotroph tumors. These

mutations were found to hinder binding of

14-3-3

proteins, increasing its

deubiquitinating activity. One substrate is Epidermal Growth Factor Receptor

(EGFR), USP8 triggering EGFR recycling and increased EGFR signaling.

However, tumors harboring mutations in USP8 are smaller than WT tumors,

EP930

raising the debate if EGFR, as a potent growth factor, is the only substrate of

USP8 in these tumors. We aimed to identify other putative USP8 targets that

might explain the tumorigenesis and increased ACTH secretion of these cells. A

Abstract withdrawn.

literature search revealed several proteins with deregulated expression associated

with corticotroph tumors that might be the result of increased USP8

deubiquitination (such as the transcription factors TR4 and CREB). Candidates

were analyzed by IHC for their expression levels on FFPE tissue (corticotrophs

(nZ54), functionally inactive

(nZ19), somatotrophs (nZ12) adenoma and

normal pituitary glands (nZ5)). We further metabolically labeled, transiently

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

transfected the murine corticotroph cell line AtT-20 with USP8 WT or mutant

prolactinoma patients according to our previous genechip study. In this study, we

plasmids and performed Tandem-Ubiquitin-Binding-Entity

(TUBE)-assays,

demonstrated that PP4C was crucial for D2R expression and PRL secretion in rat

followed by nanoLC-MS/MS analysis to identify changes in poly-ubiquitinated

pituitary MMQ cells.

protein abundance. Of the 10 analyzed proteins by IHC, 4 had an altered

Methods

expression pattern between USP8 WT and mutated tumors, namely p27/^kip1

In this study, we used rat pituitary MMQ cells which could secrete abundant

(mean expression: 1G0.8 vs 0.4G0.6 (PZ0.01), HSP90 (mean expression: 1.8G

prolactin and express functional dopamine receptors. RNA interference on PP4C

0.8

0.7G0.8 (PZ0.03), CRHR (mean expression: 0.4G0.5 vs 0.6G0.7

gene was carried out in rat pituitary MMQ cells. The pCDH vector was used as a

(PZ0.2) and PRKACA (mean expression: 0.6G0.8 vs 1.1G0.6 (PZ0.1). TUBE

PP4C overexpression system to assess the functional consequences of PP4C

assays revealed an increased de-ubiquitination of Small Ubiquitin-Like Modifier

overexpression. Total RNA and proteins were extracted from rat pituitary MMQ

(SUMO3) in USP8^mut transfected cells, suggesting co-occurrence of another

cells after PP4C silencing or overexpression. Q-PCR method was used to detect

post-translational protein modification. In conclusion, these results suggest a

the changes in D2R mRNA levels. And western blotting was used to detect the

much more complicated mechanism of action of the identified mutations in USP8,

changes in D2R protein levels. Enzyme-linked immunosorbent assay (ELISA)

with sumoylation adding another dimension to the regulation of a USP8 mediated

was carried using ELISA kit for rat PRL.

equilibrium between degradation and recycling.

Results

DOI: 10.1530/endoabs.49.EP932

PP4C silencing increased D2R expression and decreased PRL secretion in rat

pituitary MMQ cells. PP4C overexpression reduced D2R expression and

enhanced PRL secretion in rat pituitary MMQ cells.

Conclusion

Our study indicates that PP4C restrains D2R expression and increases PRL

secretion in rat MMQ cells. These findings suggest the potential role of PP4C in

the pathogenesis of prolactinoma.

EP933

DOI: 10.1530/endoabs.49.EP934

Acquired temozolomide resistance in ACTH-secreting pituitary tumour

cells

Ticiana Silva, Peter Van Koetsveld, Fadime Dogan, Richard Feelders &

Leo Hofland

Erasmus MC, Rotterdam, The Netherlands.

Introduction

Temozolomide (TMZ) treatment has been used for aggressive pituitary tumours

with positive results, but has proven ineffective in controlling tumour regrowth in

cases of disease recurrence. TMZ resistance has been linked to the expression of

EP935

O6-methyl-guanine-DNA-methyltransferase

(MGMT) protein and mismatch

HER2, EGFR and PDGF family members as potential prognostic

repair components (MMR). In the present study, we describe the development

markers and their therapeutic implications

of an in vitro model of acquired resistance to TMZ and the mechanisms involved

Ana Silvia Corlan¹, Anca Cimpean¹, Marius Raica¹, Eugen Melnic² &

in such resistance.

Raluca Amalia Ceausu¹

Methods

¹Department of Microscopic Morphology/Histology, Angiogenesis

Mouse AtT20 corticotroph pituitary adenoma cells were used. The TMZ

Research Center, University of Medicine and Pharmacy Timisoara,

resistance protocol consisted of three challenges of TMZ using a previously

Timisoara, Russia;²Department of Pathology, Nicolae Testemitanu

determined EC₅₀ (50% of the maximal effect) dose. AtT20 cells treated with

University of Medicine and Pharmacy, Chisinau, Moldova, Chisinau,

challenges of the vehicle dimethyl sulfoxide were used as control.

Republic of Moldova.

Results

The first TMZ challenge already induced a significant increase in EC₅₀ (decreased

sensitivity) in TMZ-challenged cells (17 mM vs control 3 mM, P!0.001). After

Background

9 weeks following the third TMZ challenge, TMZ-challenged cells remained

The role of EGFR, HER2, PDGF-A and the axis PDGF-B/ PDGFR-b in the

resistant (18 mM vs control 2 mM, P!0.001). In control cells, TMZ treatment

pathogenesis of pituitary adenomas and their correlation with the tumoral

caused an accumulation of cells in G2/M phase (P!0.001), while in TMZ-

immunoprofile are poorly understood.

challenged cells no accumulation was observed (PZ0.91). In control cells,

Materials and methods

50 mM of TMZ induced maximum 11-fold stimulation of apoptosis (1132G241%

The study included 92 cases. We used morphological stains, immunohistochem-

vs 100G5%, PZ0.0008), whereas in TMZ-challenged cells a significantly lower

istry and molecular methods to characterize the tumors.

(2.4-fold) increase in apoptosis was observed

(244G55% vs 100G26%,

Results

PZ0.003). The mRNA expression of MGMT was higher and of MMR

33.33% of adenomas showed a positive immunohistochemical reaction for

components (MSH6, MSH2 and PMS2) was lower in TMZ-challenged cells

HER2- with a membranous and cytoplasmatic pattern- the first one prevailing.

compared to control cells (P!0.001).

The restriction of HER-2

expression to the membrane was noticed in the

Conclusion

basophilic cells of basophilic or mixed adenomas. For the acidophilic cells: the

The present study describes an acquired temozolomide resistant cell corticotroph

expression of HER2 was mostly cytoplasmatic with a granular pattern. In pure

pituitary adenoma model. The TMZ resistance is demonstrated by a sustained

adenomas, the only significant correlation with the expression of HER-2 was

increase in TMZ EC₅₀, a lack of cell cycle changes and lower TMZ-induced

shown for prolactinomas. For bihormonal adenomas we obtained a significant

increase in apoptosis. Acquired TMZ resistance is associated with strongly

correlation of HER-2 with the coexpression of GH-PRL, PRL-LH, TSH-FSH,

increased MGMT expression and lowered expression of components of the MMR

TSH-LH. The gene amplification pattern confirmed the expression of HER-2 in

system.

33,3% of adenomas positive for HER-2. For adenomas positive for EGFR, we

obtained a significant correlation with the coexpression of GH-PRL, PRL-TSH

DOI: 10.1530/endoabs.49.EP933

(partial correlation), PRL-ACTH (total correlation). We analyzed the effects of

PDGF-A and PDGF-B on adenoma cells, depending on their immunoprofile. For

each of these 2 factors, 60-80% of tumor cells were immunohistochemically

positive. We obtained data contradictory to the published one: a positive

correlation between PDGF-A and prolactin expression. We confirmed the known

association between PDGF-B and somatotropinomas.

Discussions and conclusions

EP934

We identified a positive correlation between PDGF-B and PDGFR-b expression,

PP4C restrains dopamine D2 receptor expression in rat pituitary

implying a role for this axis in the pathogenesis of pituitary adenomas. The FSH-

MMQ cells

LH association induces the overexpression of HER-2 in pituitary adenomas,

Na Yi & Bin Lu

specifying a unique subtype of adenomas. We noticed the expression of EGFR in

Huashan Hospital, Fudan University, Shanghai, China.

peritumoral macrophages and folliculo-stellate cells, leaving new opportunities

for studying the role of folliculo-stelate cells and the pathogenic role of EGFR in

these tumors.

Objective

Decline in the number of D2 receptor (D2R) is considered as the reason of

DOI: 10.1530/endoabs.49.EP935

resistance to dopamine agonists (DA). PP4R2 gene was observed up-regulated in

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP936

pituitary magnetic resonance imaging (MRI) analyses, 92 (74.2%) patients with

SS had completely empty sella, 29 (23.3%) had partially empty sella, and 1

Carbohydrate metabolism disturbances at different types of acromegaly

patient had microadenoma, and 2 had normal pituitary MRI results.

treatment

Conclusions

Alexandr Dreval’ & Anna Vinogradova

Improved obstetric care and effective interventions for postpartum hemorrhage

Moscow Regional Scientific Research Clinical Institute named after

have limited the prevalence of SS in developed countries. However, in developing

M.F.Vladimirskiy, Moscow, Russia.

countries like Turkey, SS due to postpartum bleeding remains common. Thus,

physician’s awareness of the symptoms of SS is urgently required to avoid the

Purpose

associated morbidity and mortality.

To investigate the carbohydrate metabolism in depend on acromegaly treatment.

Keywords: Hypothalamic amenorrhea, osteoporosis, pituitary gland

Material and methods

DOI: 10.1530/endoabs.49.EP937

23 patients with newly diagnosed acromegaly (NA) were observed. Carbohydrate

metabolism were investigated after somatostatine analogues treatment (SSA) (14

patients) or after surgery (TSA) (9 patients). Groups were comparable on age,

BMI, acromegaly duration. Were researched HbA1c, fasting plasma glucose level

(FPG), indexes of insulin resistance (the HOMA-IR, a Matsuda-index), areas

under the curve of insulin within the first 30 minutes (AUCins30) and from 30 to

120 minute (AUC ins30-120) of the oral glucose tolerance test initially and after

the treatment.

Results

EP938

At NA patients FPG, HbA1c authentically (P!0.05) worsened within 3-6

Prevalence of discordant acromegaly after surgical treatment and its

months of SSA treatment and considerably (P!0.08) improved after TSA. In

clinical implications in a third LEVEL hospital in Latinamerica

3 months of SSA therapy extent of depression of an AUCins30 considerably

Mireya Pérez, Arturo Pen˜a, Carlos Rojas & Alma Vergara

exceeded extent of depression of an AUCins30-120

(in

11 and 2.3 times

Centro Médico 20 de Noviembre, Mexico, Mexico.

respectively (P!0.05)). Whereas in 3 months after TSA extent of depression of

an AUCins30 was comparable to extent of depression of an AUCins30-120 (2.4

times and 3.2 times respectively).

Background

Conclusions

Acromegaly results from excess growth hormone (GH) secretion by a pituitary

The decreasing of hepatic IR and peripheric insulin sensitivity in condition of

adenoma in 95% of the cases. Discordant acromegaly is defined by the elevation

higher level of insulin in compare with patients receiving SSA at most of these

of GH with normal levels of insulin-like growth factor type 1 (IGF-1) or normal

patients leads to normalization of carbohydrate metabolism. The greatest changes

levels of GH associated with an elevation of IGF-1. Its an important situation in

of parameters of carbohydrate metabolism

(Matsuda-index augmentation,

the follow-up period of patients with acromegaly because there is little

depression of the NOMA-IR index, insulin secretion depression) are noted in 3

information about patient treatment, comorbidities and follow-up. The objective

months of SSA therapy, and further remain at the previous level or change

of this study was to describe the prevalence of discordant acromegaly after

slightly. It is recommended to carry out control of a condition of carbohydrate

pituitary surgery, follow changes in GH and IGF-1 patterns over time and explore

metabolism at patients with an acromegaly, first of all, in 3 months both after the

possible correlations with blood pressure and HbA1C.

carried-out surgical treatment, and after the beginning of SSA therapy.

Methods

Keywords: acromegaly; insulin resistance; secretion; insulin; somatostatine

We retrospectively analyzed the prevalence and characteristics of patients who

analogues; carbohydrate metabolism

had an elevated IGF-1 but normal GH or an elevation of GH with normal IGF-1,

DOI: 10.1530/endoabs.49.EP936

in consecutive post-surgical acromegaly cases from the year 2000 to 2015 at our

institution. To define discordant acromegaly in our study hormonal evaluation

was obtained at the 3 months post surgically (GH, and IGF-1). Discordant patients

were categorized into two groups according to the postoperative GH and IGF-1:

high IGF-1 group (normal GH and high IGF-1), high GH group (high GH and

normal IGF-1). We followed discordant patients at 6 and 12 months with GH,

IGF-1, magnetic resonance (only at 6 months), blood pressure and HbA1c.

Pituitary - Clinical

Results

The prevalence of discordant acromegaly was 11.7% (9/77). Of this patient

EP937

population 77.7% (7/9) changed their biochemical pattern after 12 months of

Four decades without diagnosis: Sheehan‘s syndrome, a retrospective

follow-up. Of these, 11.3% (1/9) in the high GH group became inactive, 66.6%

analysis

(6/9) became active (high IGF-1 group), and 22.2% (2/9) remained discordant

Deniz Gokalp¹, Gulistan Alpagat², Alpaslan Kemal Tuzcu¹,

(both in the high GH group) and had normal suppression of GH to glucose.

Mithat Bahc¸eci3, Sadiye Tuzcu4, Fatime Yakut5 & Azat Yildirim6

Positive correlations were found between the level of IGF-1 at 6 months with

¹Department of Endocrinology, Acibadem Medical University, Istanbul,

systolic blood pressure

(RZ0. 89, PZ0. 001) and diastolic blood pressure

Turkey;²Department of Endocrinology, Dicle University School of

(RZ0.891; PZ0.002). No correlation was found between GH, IGF-1 and HbA1c

Medicine, Diyarbakir, Turkey;³Izmir Ataturk Education and Research

or tumor size.

Hospital, Izmir, Turkey;⁴Department of Nuclear Medicine, Gazi Yasargil

Conclusions

Education and Research Hospital, Diyarbakir, Turkey;⁵Department of

Discordant acromegaly in the postsurgical state is a rare entity, with variation in

Radiology, Diyarbakir Memorial Hospital, Diyarbakir, Turkey;⁶Azad

hormonal patterns at 12-month follow up and a positive correlation with blood

Yildirim Department of Orthopedics, Gazi Yasargil Education and Research

pressure levels. We suggest that this patients need to be carefully followed due to

Hospital, Diyarbakir, Turkey.

the high likelihood of recurrence, particularly if the elevation is of IGF-1 and with

the presence of residual tumor.

Aim

DOI: 10.1530/endoabs.49.EP938

Sheehan‘s syndrome

(SS) remains a frequent cause of hypopituitarism in

undeveloped and developing countries, but due to improvements in obstetric care,

it is rare in developed countries. We aimed to share the results of a retrospective

study analyzing the demographic, clinical, imaging, and hormonal characteristics

of a large group of patients with SS, and also increase awareness of this syndrome

especially in developed countries.

Methods

The medical records of 124 patients with SS patients who were followed up in the

EP939

Endocrinology Department of Dicle University between 1995 and 2015 were

A case of IgG4-related hypophysitis with long-term cyclic evolution

assessed retrospectively.

Iconaru Laura, Baleanu Felicia, Muteganya Raoul & Karmali Rafik

Results

CHU Brugmann, Bruxelles, Belgium.

The mean period of diagnostic delay was 20.37G8.34 years on average. 5.7% of

patients with SS were literate; 62% of patients delivered at home. Anemia was

identified in 64.5% of SS patients. Mean blood sodium levels were 129.8G11.3

Introduction

mEq/L. The mean urine densities were 1013G6.5. Osteoporosis and osteopenia

IgG4-related disease is a newly recognized entity associated with autoimmune

were found in 44 (35.4%) and 71 (57.2%) patients, respectively, According to

conditions involving almost every organ system, characterized by elevated serum

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

IgG4 as well as mass like tissue infiltration by IgG4-positive plasma cells.

EP941

Pituitary gland can be involved and can presented as hypophysitis.

Presurgical medical treatment in Cushing’s disease

Case description

Paloma Moreno-Moreno¹, Ana Barrera-Martín¹, Alejandro Iban˜ ez-Costa2,

We report a case of a 56-year-old man, who has been suffering for the nine last

María Rosa Alhambra-Expósito¹, Concepción Mun˜oz-Jiménez1,

years of episodes of fatigue and headaches with spontaneous remission was

María Ángeles Gálvez-Moreno¹, Justo P Castan˜ o-Fuentes2 &

admitted to our hospital for headaches, fatigue, myalgia, diplopia and visual

Raúl M Luque-Huertas²

disturbances. The endocrine assessment revealed a complete ante-hypopituitar-

¹Management Unit of Clinical Endocrinology and Nutrition, University

ism. Dynamic LHRH and CRH tests revealed a delayed but robust response of

Hospital Reina Sofía, Córdoba, Andalucia, Spain;²Department of Cell

gonadotrophins and corticotrophin. MRI scan showed nodular thickening of the

Biology, Physiology and Immunology, Instituto Maimónides de Investiga-

pituitary and pituitary stalk with minimal compression of the optic chiasm. Other

ción Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía,

pathology than sarcoidosis was suspected and further investigation showed high

CIBER Fisiopatolo, University of Córdoba, Córdoba, Andalucia, Spain.

levels of blood IgG4. All these findings were highly suggestive for a diagnosis of

IgG4-related hypophysitis. Steroids were administered and within 24 hours, the

patient became completely asymptomatic. A month later, thyroid and gonadal

Introduction

function normalized. Cranial MRI scan showed a net decrease in the size of the

The duration of hypercortisolism in Cushing’s disease

(CD) appears to be

pituitary gland compared to the previous examination.

inversely related to the reversibility of complications, which in turn increase

Conclusions

mortality. This makes it necessary to identify medical therapies capable of

We report a case of IgG4-related hypophysitis who responded completely and

normalizing cortisol overproduction before transsphenoidal surgery. The aim of

rapidly to steroids. Intriguingly, according to his pas medical history, he might

this study was to determine if the clinical data of patients with CD before surgery

have presented a cyclical evolution of his disease with periods of spontaneous

allow predicting the presence and/or abundance of somatostatin

(ssts) and

remission. It’s a rare condition but increasingly recognized and should be sought

dopamine (DRs) receptors at the corticotrophic adenoma, in order to start a more

in face of an acute swelling of the pituitary gland and/or its stalk, since its

effective and personalized presurgical medical treatment.

favorable response to steroid therapy should help to avoid unnecessary surgery.

Patients and methods

Keywords: Hypophysitis, IgG4-disease, panhypopituitarism

Retrospective study performed through review of clinical histories and molecular

DOI: 10.1530/endoabs.49.EP939

profile analysis of corticotrophic tumors. We included all patients diagnosed with

CD (2005-2014) treated with transsphenoidal surgery, and whose tumor sample

was analyzed in the Department of Cell Biology, Physiology and Immunology of

the University From Córdoba. The correlation study was performed using

Spearman’s r.

Results

Nine women with CD and molecular profile analysis of corticotrophic tumor. Age

47.33G12 years. A positive correlation was observed between tumor size at

diagnosis and levels of receptor expression sst2 [rZ0.731 (PZ0.04)], sst3 [rZ

0.735

(PZ0.038)], DR2 [rZ0.821 (PZ0.023)], DR4 [rZ0.946 (PZ0.000)]

y DR5 [rZ0.900 (PZ0,037)]. In addition, there was a marked inverse

correlation between ACTH levels at diagnosis and the sst5

receptor

[rZ

K0.767 (PZ0.016)].

Conclusions

EP940

Tumor size at the diagnosis of CD seems to show a direct correlation with the

Duhok/IRAQ acromegaly; one year of experience

levels of expression of sst2 and DR2 receptors, suggesting that in patients with

Bayar Qasim

CD with macroadenoma in the initial study, preoperative treatment with

Unviersity of Duhok/College of Medicine, Duhok, Iraq.

somatostatin analogs and/or dopamine may be helpful. In addition, the inverse

correlation between ACTH levels at diagnosis and sst5 expression questions

whether the specific analogues of this receptor would be useful in the preoperative

Background

treatment of CD.

Acromegaly is a rare hormonal disorder; the prevalence is w60 cases/million

DOI: 10.1530/endoabs.49.EP941

population1, Incidence: 3.3 new cases/million/year1 Mortality rate 2-4 times that

of general population2. It is usually the result of a somatotrope adenoma in more

than 95% of cases.

Aim

By June 2016, we were celebrating one year of experience in acromegaly. It was

first time to open acromegaly service in Duhok city/Kurdistan region/IRAQ. This

review will include all registered patients during this year. Aim of this revision to

give a brief about our patients’ characteristics and how we can plan for future?

Methods

EP942

This is retrospective study involving ten patients, all patients diagnosed by high

Characteristics and 1-year follow-up of patients with profound

IGF1 level followed by GH suppression test and MRI of pituitary gland. Those

hyponatremia due to primary polydipsia - a multicentre prospective

patients underwent transphenoidal resection, diagnosis confirmed by histopathol-

observational study

ogy too.

Clara Sailer^1,3, Bettina Winzeler^1,3, Nicole Nigro¹, Isabelle Suter-Widmer¹,

Results

Birsen Arici¹, Martina Bally², Philipp Schuetz^2,3, Beat Mueller^2,3 &

Our patients characteristics are shown. The median age of presentation was 44.9.

Mirjam Christ-Crain^1,3

Headache and acral enlargement was the most common presentation.

¹Endocrinology, Diabetology and Metabolism, University Basel, Basel,

Discussion

Switzerland;²Division of Endocrinology, Diabetology and Metabolism,

Most patients with acromegaly are diagnosed with a macroadenoma. This review

Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland;

include ten patients, eight of them were from Duhok including Zaxo and Akre,

³Department of Clinical Research, University Hospital Basel, Basel,

two of them they moved to live in this city, one from the capital Baghdad and

Switzerland.

another patient from syrian refugee. The prevalence of acromegaly in Duhok city

was 8.2 persons/million/year 4, while the incidence was of new cases was

5.3/million/year. This high number of patients reflects the new input for patients

Introduction

to this service as this was not present before June 2015. Eight patients were

Hyponatremia due to excessive fluid intake (i.e. primary polydipsia (PP)) is

operable they prepared by somatostatin analogue followed by surgery.

common. It may culminate in profound hyponatremia - carrying considerable risk

Conclusion and recommendations

of morbidity. However, data on patients with PP leading to hyponatremia is

The two dilemmas we are facing here in Duhok/IRAQ are: First; delayed

largely lacking. Herein, we describe the characteristics of polydipsic patients

diagnosis as reflected by the fact all of our patients are macroadenoma at

hospitalised with profound hyponatremia, and assess one-year outcomes.

presentation, that is why we need to increase awareness about this disease.

Method

Secondly; low compliance for medical treatment: to improve this we need to

In this prospective observational study, we included 23 patients with an episode of

provide free measurement of both GH and IGF1 levels for all patients receiving

profound hyponatremia (%125 mmol/l) due to PP. Patients were classified into

somatostatin analogue treatment.

subgroups: psychogenic polydipsia (PsyP), dipsogenic polydipsia (DiP), and beer

DOI: 10.1530/endoabs.49.EP940

potomania (BP). Symptoms, laboratory findings, and factors contributing to

hyponatremia (co-morbidities, medication, and liquid intake) were assessed. A

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

1-year follow-up was performed to evaluate recurrence of hyponatremia,

in these patients. We hypothesized that non-classical cardiovascular risk factors

re-admission rate, and mortality.

such as epicardial fat

(EF), interventricular septum thickness

(IST), carotid

Results

intima-media thickness (CIMT), may be increased in ACRO and contribute to this

Of the 23 patients (median age 56 years [IQR 50-65], 74% female) 7 had PsyP, 8

higher cardiovascular morbidity.

DiP, and 8 BP. Median serum sodium of all patients was 121 mmol/l (IQR 114-

Objective

123), median urine osmolality 167 mmol/l (IQR 105-184), and median copeptin

To evaluate EF, IST, and CIMT in patients with ACRO compared to controls and

3.6 mmol/l

(IQR

1.9-5.5). Psychiatric diagnosis, particularly dependency

identify possible predictors in this non-classical cardiovascular risk factors.

disorder (43%) and depression (35%), were highly prevalent. Factors provoking

Material and methods

hyponatremia were found in all patients (e.g. acute water load, medication, stress).

We studied CIMT, IST, EF in 30 patients with ACRO (16 males, 5 with active

During the follow-up period, 67% of patients were readmitted, 52% of these with

disease) and 30 matched controls (by age, sex and body mass index (BMI)).

re-hyponatremia, and three patients (38%) with BP died.

Results

Conclusion

Both cohorts were identical regarding the presence of cardiovascular risk factors

Patients with PP have a high prevalence of addictive and affective disorders.

(CVRF. The ACRO cohort presented higher EF and IST compared to the control

Given the high recurrence, re-hospitalisation, and mortality rate, careful

group (0.65G0.16 vs 0.43G0.14 cm, PZ0.001 and 11.31G1.17 vs 10.64G

monitoring and long-term follow-up including controls of serum sodium,

1.47 mm, PZ0.035, respectively). The presence of ACRO (ß 0.545, P!0.001;

education and behavioural therapy is needed.

R2 297) was the unique positive predictor of EF, while BMI and hypertension

DOI: 10.1530/endoabs.49.EP942

were positive predictors of IST (ß 0.379, PZ0.006 and ß 0.344, PZ0.013,

respectively, R2 0.298) in a multiple linear regression model.

Conclusions

Patients with ACRO have higher EF and higher IST (influenced by hypertension

and BMI), compared with matched controls despite a similar prevalence of

CVRF. Increased EF and IST could partially contribute to this increased

cardiovascular morbidity and mortality observed in acromegaly.

DOI: 10.1530/endoabs.49.EP944

EP943

Success rates of pituitary surgery in acromegaly - a tertiary centre

experience in Romania

Minodora Betivoiu¹, Iulia Soare¹, Sorina Martin^1,2, Anca Sirbu^1,2,

Alice Albu^1,2, Carmen Barbu^1,2 & Simona Fica^1,2

¹Endocrinology Department, Elias Hospital, Bucharest, Romania;

²Endocrinology Department, Carol Davila University of Medicine and

EP945

Pharmacy, Bucharest, Romania.

Pituitary insufficiency - etiopathogeny and diagnostic aspects

Corina Crista¹ & Georgiana Hotaran²

Clinic of Endocrinology, University of Medicine and Pharmacy ‘Victor

Background

Babes’, Timisoara, Romania;²University of Medicine and Pharmacy

Pituitary surgery is the first treatment option for acromegaly. The reported success

‘Victor Babes’, Timisoara, Romania.

of pituitary surgery varies between 75 and 95% for microadenomas and 45 and

68% for macroadenomas. The aim of this study was to report our experience

regarding the remission rate after pituitary surgery in acromegaly patients.

The study group was represented by 155 cases of pituitary insufficiency (age:

Methods

37.21G16.05; F/MZ116/39) hospitalized in the Clinic of Endocrinology

This retrospective study included 70 patients diagnosed with acromegaly in our

Timi¸oara during the period

2006-2014. The cases were classified into

clinic between 2009 and 2016. The criteria used to define remission were random

ethiopatogenic groups, as follows: iatrogenic pituitary insufficiency (23.87%),

GH !1 ng/ml and normalization of IGF1 levels for gender and age.

tumor compression (21.29%), ischemia (14.84%), idiopathic hypogonadotropic

Results

hypogonadism (3.87%), congenital pituitary insufficiency (6.45%), empty sella

11 patients were lost of follow-up after the first diagnostic visit. We analysed 59

(6.45%), functional pituitary insufficiency (23.23%). In majority, the studied

acromegaly patients (33 women and 26 men) with a mean age at diagnosis of

cases presented hypogonadism (95.48%), while hypothyroidism was found in

44.93G13.57 years. Microadenoms were found in 15 (25.4%) and macro-

65.16% patients and

50.32% of the cases presented adrenal insufficiency.

adenomas in 44 (74.6%) patients. 6 (10.2%) patients associated both GH and

Neurological signs caused by the tumoral mass were found in 42.58% cases. The

prolactin hypersecretion. Pituitary surgery was performed in 41 patients of which

ischemic and congenital forms of the pituitary insufficiency associated mostly

(21.4%) were cured. Aditional 7 (21.2%) patients were cured after second

panhypopituitarism (100%, respectively 50%), while the iatrogenic form and

surgery and radiotherapy. Radiotherapy was the first treatment in 11 patients of

those caused by tumor compression presented in high percentages partial pituitary

which 3 (27.2%) were cured. Persistent disease after sugery and/or radiotherapy

insufficiency. The comparison of the hormonal parameters

(ethiopatogenic

was treated with somatostatin analogs (26), dopamin agonists (18) and GH

groups) revealed: significant inferior serum levels of testosterone in the

receptor bloacker (6) in mono or combination therapy.

congenital form and empty sella vs tumor compression (P ! 0.05); significant

Conclusions

inferior levels of the serum estradiol (P ! 0.01) in congenital panhypopituitarism

The rate of surgical success in our patients was found to be low (40% for

vs functional secondary hypogonadism; significant inferior levels of the serum

microadenomas, 6.8% for macroadenomas). This could be explained by the fact

TSH (P ! 0.05) in patients with pituitary insufficiency caused ischemia vs tumor

that most patients presented late at the macroadenoma stage.

compression; significant inferior levels of FT4 (P ! 0.05) in empty sella and

DOI: 10.1530/endoabs.49.EP943

ischemic form vs iatrogenic pituitary insufficiency. The applied therapy targeted

the cause of the hypopituitarism and the hormonal substitution.

DOI: 10.1530/endoabs.49.EP945

EP944

Acromegaly and cardiovascular risk

Betina Biagetti¹, Anna Aulinas², Natividad Lopez¹, Esther

EP946

García-Fernandez¹, Maria José Arnau-Vives¹, Andrea Ciudin¹,

Gabriel Obiols¹, Belen Dalama¹ & Jordi Mesa¹

¹Vall d’Hebron Hospital, Barcelona, Spain;²Hospital Universitari de Vic,

Abstract unavailable.

Barcelona, Spain.

Background

Acromegaly (ACRO) is associated with increased cardiovascular morbidity and

mortality, however, there is no evidence of an increase in ischemic heart disease

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP947

morphological response without biochemical response is uncommon, whereas

MR without BR is relatively frequent, even more than the coexistence of both.

Long-term outcomes of medical therapy in patients with acromegaly:

a retrospective analysis

DOI: 10.1530/endoabs.49.EP948

Iulia Simona Soare¹, Minodora Andreea Betivoiu¹, Sorina

Carmen Martin^1,2, Anca Elena Sirbu^1,2, Carmen Gabriela Barbu^1,2,

Alice Ioana Albu^1,2 & Simona Fica^1,2

¹Department of Endocrinology, Diabetes and Metabolic Diseases, Elias

Emergency University Hospital, Bucharest, Romania;²University of

EP949

Medicine and Pharmacy ‘Carol Davila’, Bucharest, Romania.

Ocular findings in adult subjects with congenital, lifetime, isolated,

untreated growth hormone deficiency

Background

Augusto C N Faro¹, Virginia M Pereira-Gurgel¹, Roberto Salvatori²,

Acromegaly is a rare severe disease which, untreated, leads to increased

Viviane C Campos¹, Gustavo B Melo³, Francielle T Oliveira¹, Alecia

cardiovascular and respiratory morbidity and mortality. Pituitary surgery is the

A Oliveira-Santos¹, Carla R P Oliveira¹, Francisco A Pereira¹,

first-line therapy, and medical treatment (somatostatin receptor ligands SRLs,

Ann Hellstrom⁴, Luís A Oliveira-Neto¹ & Manuel H Aguiar-Oliveira¹

dopamine agonists DA, and GH receptor antagonists GHRAs) is indicated for

¹Federal University of Sergipe, Aracaju/Sergipe, Brazil;²The Johns

persistent disease. While selected patients are treated with DA and GHRAs, SRLs

Hopkins University School of Medicine, Baltimore, MD, USA;³Hospital de

remain the mainstay of acromegaly therapy.

Olhos de Sergipe, Aracaju/Sergipe, Brazil;⁴Sahlgrenska Academy,

Objective

The Queen Silvia Children’s Hospital, Goteborg, Sweden.

The aim of this study is to report our results regarding medical therapy in patients

with persistent acromegaly after surgery and/ or radiotherapy.

Ocular function is fundamental for environmental adaptation and survival

Patients and methods

capacity. Growth factors are thought to be necessary to reach a mature eyeball and

We retrospectively reviewed 59 patients (33 women and 26 men), diagnosed with

consequent adequate vision. However, the consequences of the deficiency of

acromegaly, mean age at diagnosis 44.93G13.57 years, managed between 2009

circulating growth hormone (GH) and its effector insulin-like growth factor I

and 2016 in our department. Controlled disease was defined as normal IGF-1 for

(IGF-I) on the physical aspects of the human eye are still debated. A model of

age and sex and random GH!1 ng/ml.

untreated isolated GH deficiency (IGHD) may clarify this issue. The aim of this

Results

study was to assess the physical aspects of the eyeball of adult IGHD individuals

19 patients, cured after surgery or radiotherapy were excluded.

31 patients

who have never received GH therapy. A cross sectional study was carried out at

received medical therapy and 9 were lost during follow up. 26 were treated with

the University Hospital, Federal University of Sergipe, Brazil, including 25 adult

SRLs alone or in combination therapy, 3 received DA alone, one DA and GHRAs

IGHD subjects homozygous for a null mutation (c.57C1GOA) in the GHRH

and one GHRAs alone. SRLs were used as monotherapy in 13 (50%), tritherapy in

receptor gene, and

matched controls. All underwent endocrine and

(11.5%), in combination with DA in 9 patients (34.6%) and with GHRAs in one

ophthalmological assessment. The main outcome measures were visual acuity,

(3.8%). IGF-1 normalization was achieved in 10 patients (32%), 7 receiving SRLs

intraocular pressure, refractive error, ocular axial length (AL), anterior chamber

(five in monotherapy, one with DA and one in tritherapy), two DA alone and 1

depth, and central corneal thickness (CCT). Despite unmeasurable serum IGF-I,

with GHRAs alone. Random GH!1 ng/ml was achieved in six patients (19.3%)

there was no difference between the groups in visual acuity, intraocular pressure,

(three in monotherapy SRLs, two in association with DA and one on DA alone).

and refractive error. IGHD subjects exhibited lower absolute values of AL

Controlled disease was found in five patients

(16.1%)

(three receiving

(22.5G0.6 vs 23.5G1.0 mm, P! 0.0001), anterior chamber depth (2.98G0.3 vs

monotherapy with SRLs, one with tritherapy and one with GHRAs).

3.26G0.3 mm, PZ0.001) and CCT (539G28 vs 546G28 mm, PZ0.04) than

Conclusion

controls. All values were within their normal ranges. While mean stature in IGHD

In long-term follow-up, almost 40% patients got full control of acromegaly, but

group was

78% of the controls, mean IGHD axial AL was 96%. These

only 20% of them on medical treatment. Medical approach in acromegaly should

observations suggest no relevant consequences of congenital lack of pituitary GH

be individualized, combination therapy could provide additional biochemical

and of circulating IGF-I on physical ocular findings. Autocrine or paracrine

control, but new therapies should be implemented.

growth factors may be more relevant to ocular growth.

DOI: 10.1530/endoabs.49.EP947

DOI: 10.1530/endoabs.49.EP949

EP948

Resistant prolactinomas: Retrospective study of ten cases

EP950

Marta Araujo Castro, Nuria Palacios García, Javier Aller Pardo,

Evaluation of estrogen effects on the anterior pituitary hormones by

Ainhoa Abad López, Virginia Oses Zarate, Laura Mateos Moreno &

using combined pituitary stimulation test (CPFT) in the Korean

Javier Estrada García

postmenopausal women

Puerta de Hierro’s Hospital, Madrid, Spain.

Sung-Woon Kim & Seungjoon Oh

School of Medicine, Kyung Hee University, Seoul, Republic of Korea.

About 10-15% of prolactinomas (P) are resistant to Dopamine agonists (DA). We

analyzed retrospectively ten resistant prolactinomas (RP) treated at our center

Pituitary hormonal status was important for the evaluation of various diseased

between 1995 and 2014, to identify useful variables to predict DA resistance and

state of hypothalamo-pituitary target organ axis as well as tumorous condition.

its different patterns

(biochemical resistance

(BR), morphological resistance

Measurement of growth hormone (GH), adrenocorticotrophic hormone (ACTH)

(MR) or both). BR is defined as the failure to normalize prolactin (PRL) levels

and cortisol during insulin-induced hypoglycaemia were commonly used to

with R 2 mg/week of cabergoline (C) for at least 3 months. MR is considered

assess pituitary condition on hypoglycaemia stress. Sexual axis was evaluated

when at that dose the tumor size is not reduced by at least 50%. The median age

with target organ hormones, i.e. estradiol or testosterone and LHRH stimulated

was

30.6

years and

subjects were male. All patients had secondary

luteinizing hormone

(LH) and follicle stimulating hormone

(FSH). TRH

hypogonadism and 1 had TSH and GH deficiency. The median PRL levels

stimulated prolactin

(PRL) and thyroid stimulating hormone(TSH), and

were 548 (127-1000) ng/ml. There were eight macroprolactinomas (MP) and two

simultaneously evaluated with thyroid hormones (free T4 and T3). All these

microprolactinomas (mP), with an average size of 1.78 (0.4-3.5) cm. Seven had

separated axes were evaluated once with combined pituitary stimulation test

suprasellar extension and three invasion of cavernous sinuses. The median dose of

(CPST) by combined use of regular insulin (0.1 unit/kg body weight), 100 to

C used was 3.4 (2-7) mg/week. The median follow-up was 93.2 (26-348) months.

500 mg of TRH (TSH releasing hormone) and 100 mg of LHRH respectively. We

Five patients had MR, 1 BR and 4 patients both. Seven patients (2 mP and 5 MP)

checked out pituitary hormonal status with CPST in normal Korean

underwent transsphenoidal surgery. The indication was BR and MR in 4, BR in 1

postmenopausal women for physiological situation of pituitary function after

and MR in the other 2 patients. The surgical remission was achieved in 3 patients.

naturally shut down of oestrogen. We enrolled total 230 women, who were 30

The remaining 4 patients were treated with DA and one of them also received

adult GHD (growth hormone deficiency), 116 postmenopausal (PMS), 17 PMS on

radiotherapy. All of them achieved remission. In the 3 non-operated patients an

ERT (oestrogen replacement therapy) and

regularly menstrual women

adequate hormonal control was achieved, but with tumor persistence. In

(normal). We did find GH response to hypoglycaemia (indirect) was much

conclusion, prevalence of male sex, a size larger than 1 cm and suprasellar

higher than that of GHRH (direct) stimulation. These findings were meant that

extension were higher in our resistant patients than that reported in non-resistant

GHRH-GH axis was more responded to life threatening stress, then mobilized

prolactinomas; thus, these features could predict DA resistence. The

glucose and stabilized human energy system. Peak GH levels after

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

excision led to disease remission. Currently, 15 months postoperatively, the

patient has no complaints, is normokalemic (without potassium supplements) and

normoglycemic on metformin monotherapy.

Conclusion

The case is noteworthy for the atypical clinical presentation, severity of the

hypokalemia and excellent treatment outcome. The authors emphasize the

importance of high clinical suspicion for secondary causes of DM when

investigating patients with new onset diabetes, as diagnosing and treating the

underlying cause may render the diabetes and its complications potentially

curable and preventable respectively.

DOI: 10.1530/endoabs.49.EP951

EP952

Uncomplicated pregnancy in a patient with McCune Albright syndrome

(MAS) and active acromegaly

Terroba Larumbe¹, Crespo Soto¹, Anacabe Goyogana¹, De Luis Roman²,

Urbon Lopez De Linares¹, Cuellar Olmedo¹, Ventosa Vi

˜a¹,

Calleja Baranda¹ & Cabezas Garcia¹

H.U. Rio Hortega, Valladolid, Spain;²H. Clinico Universitario, Valladolid,

Spain.

Introduction

The association of acromegaly and polyostotic fibrous dysplasia is a rare entity

that presents more difficulties in achieving an effective treatment than classical

acromegaly. Pregnancy is infrequent and carries a high risk when acromegaly is

active.

Clínical case

A 27 year old woman surgically treated for facial asymmetry, without café-au-lait

spots or precocious puberty, was evaluated in 1992 after a normal pregnancy. In

the biochemical tests the following was observed: PRL 95 ng/ml (1.2-40), GH

20.9 ng/ml not suppressed during oral glucose overload, IGF-I 943 ng/ml (101-

333), T4 and T3 elevated with suppressed TSH. The rest of the data including

basal hormones did not show significant alterations. Imaging tests showed diffuse

hypoglycaemia stimulation were mild suppressed with ERT than that of PMS

hyperplasia/adenomatosis of the pituitary gland (14 x 20 x 6 mm) with increased

without oestrogen replacement. We will investigate all pituitary hormonal status

left lining and cavernous sinus invasion and findings compatible with fibrous

with future full data processing in Korean postmenopausal women by CFST.

dysplasia affecting numerous bones of the base of the skull and the cranial vault.

In the thyroid scan, a multinodular goiter with calcifications was found. Therapy

DOI: 10.1530/endoabs.49.EP950

with bromocriptine

(BC)

2,5 mg/day and methimazole was initiated, but

acromegaly remained active because the patient refused treatment with

subcutaneous octreotide. In 1996 she had an uncomplicated second pregnancy

and in January 2000 intramuscular Sandostatin LAR 30 mg/month could be

included in the treatment. Magnetic resonance performed after pregnancy showed

a small 5-mm focal image compatible with a microadenoma and a pituitary gland

close to normal. In 2007 Sandostatin was replaced by GH receptor antagonist

Pegvisomant, 20 mg/day subcutaneous because the control objective for IGF-I

EP951

was not achieved. With this therapy the patient, who also received cabergoline

Acute presentation of cushing disease: severe hyperglycemia and

0.5 mg/wk and metimazol 5 mg/d, was asymptomatic and IGF-I, PRL, thyroid

refractory hypokalemia

function, cardiac tests, fundus and campimetry were normal.

Carlos Tavares Bello^1,2, Francisco Sousa Santos², Catia Ferrinhos²,

Discussion

Filipa Alves Serra^2,1, Joao Sequeira Duarte² & Carlos Vasconcelos²

This patient with MAS presented primary hyperthyroidism, hyperprolactinemia

¹Hospital de Egas Moniz, Lisbon, Portugal, Portugal;²Hospital das Forcas

and acromegaly with partial response to Sandostatin LAR but complete response

Armadas, Lisbon, Portugal, Portugal.

to pegvisomant. This drug can be especially useful in the management of MAS-

acromegaly for the risks involved in surgery and radiotherapy. Although

uncontrolled acromegaly can complicate pregnancy, especially by increasing

Introduction

the risk of gestational diabetes and hypertension, in this case, pregnancy evolved

Cushing’s syndrome (CS) is a rare disease resulting from prolonged exposure to

without incident.

supraphysiological levels of glucocorticoids. Cushing’s Disease is the most

frequent cause of endogenous CS. This disease has a broad spectrum of clinical

DOI: 10.1530/endoabs.49.EP952

manifestations and is associated with an increased morbi-mortality. Diabetes

Mellitus (DM) and hypokalemic alkalosis affects up to 50 and 10% of CS patients

respectively. Disease onset and severity reflects the magnitude of cortisol excess,

being ectopic ACTH production is the most frequent cause of acute, severe CS.

Cushing disease tends to have a slower onset with gradual appearance of the

EP953

typical phenotype and associated metabolic consequences.

Impact of etiology, age and gender on onset and severity of

Case report

hyponatremia in patients with hypopituitarism

A 62 year old male with a known medical history of obesity and hypertension was

Dragana Miljic^1,2, Sandra Pekic^1,2, Mirjana Doknic^1,2, Marina

admitted to the emergency department with altered mental status, hyperglycemia

Nikolic-Djurovic^1,2, Marko Stojanovic^1,2, Vera Popovic² & Milan Petakov^1,2

and hypokalemia. Physical examination was remarkable for obesity, moon face,

¹Department of Neuroendocrinology, Clinic for Endocrinology, Diabetes

facial plethora and proximal muscle weakness. At admission: plasma glucose was

and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia;

452 mg/dl serum potassium 2.7 mmol/l and arterial pH 7.6. Excessive iv fluids led

²Belgrade University School of Medicine, Belgrade, Serbia.

to congestive heart failure that was treated with standard doses of furosemide.

Diuretics were soon stopped due to severe refractory hypokalemia (1.7 mmol/l)

that after correction required maintenance iv potassium chloride doses of

Hyponatremia can unmask hypopituitarism and secondary adrenal insufficiency

120 mEq/day. Further laboratory (dexamethasone suppression tests 1 and 8 mg

due to potent non-osmotic stimulation of vasopressin release under stressful

and inferior petrosal sinus sampling) and imaging (pituitary macroadenoma)

conditions. Patients and methods: In a retrospective study 25 patients (13f/12m,

investigations confirmed Cushing’s Disease. Endoscopic transphenoidal tumor

age 58.9G18.6 years) with hyponatremia (119.7G10.5 mmol/l) were identified

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

among 260 in-patients treated for hypopituitarism in our department over a

¹Endocrinology Service. Hospital La Mancha Centro, Alcázar de San Juan,

decade. Results: Hyponatremia was recorded in 9.6% of our patients. In 84% it

Spain;²Neurology Service. Hospital La Mancha Centro, Alcázar de San

was the key to diagnosis of hypopituitarism. Patients with hyponatremia and non-

Juan, Spain.

functioning pituitary macro adenomas (group 1. NFPA nZ15) were significantly

older (71.47G4.8 years), compared to patients with hyponatremia from other rare

causes of hypopituitarism (group 2. nZ10; age 40.2G15.3 years, P!0.01):

Introduction

congenital (nZ2), Sheehan’s syndrome (nZ2), intracranial aneurysm (nZ2),

A link between Dopamine agonists and development of impulse control disorders

lymphocytic hypophysitis (nZ1), traumatic brain injury (nZ1), surgery and

is well recognized in the field of neurology. A similar finding in endocrine

radiotherapy for astrocytoma

(nZ1), pituitary metastasis from bronchial

patients is emerging.

carcinoma

(nZ1). Male preponderance in patients with NFPA

(10/15

i.e.

Case report

We report the case of a 38-year-old man with pathological addiction to gambling

66.7%) was in contrast to female predominance in patients with other causes of

associated with low dose cabergoline treatment for a mixed growth hormone (GH)

hypopituitarism (8/10 i.e. 80%). Hyponatremia was more severe in group 2

and prolactin (PRL)-secreting pituitary adenoma. At the age of 29 he was

compared to group 1 (113.5G10.9 mmol/l vs. 124.3G8.1 mmol/l, P!0.01).

diagnosed with mixed (GH and PRL) functioning invasive pituitary adenoma.

Conclusion: Hyponatremia is not uncommon in patients with hypopituitarism,

After surgery and radiotherapy he was given medical therapy with somatostatin

especially at presentation. In older patients, NFPA is the most common

analogues and cabergoline. During follow-up somatostatin analogues were

pathology, usually leading to gradual onset of hypopituitarisim and non-specific

withdrawn but he continued cabergoline treatment to control hypersecretion and

symptoms, while acute hyponatremia can occur with pituitary apoplexy. In

the residual tumour. During follow-up the patient reported pathological gambling

younger patients severe acute hyponatremia is more common leading to diagnosis

habits. He had spent a large sum of money and, although he had tried to stop

of unrecognized secondary adrenal insufficiency and hypopituitarism from

gambling many times he was unable to quit. He did not stop his gambling

various causes.

behaviour despite a marital crisis and divorce. He had even been to a centre for

DOI: 10.1530/endoabs.49.EP953

addictive disorders without success. We decided to withdraw cabergoline. His

impulse-control disorder

(ICD) resolved within months after cabergoline

discontinuation. After 6 months, somatomedin C level was in normal range,

PRL level was mildly high with no sexual dysfunction and the tumour had not

grown.

Conclusions

EP954

The gambling episodes diminished after the discontinuation of cabergoline,

providing evidence for a causal relationship. Cabergoline-induced pathological

Changes in pituitary tumour biology and behaviour in FIPA patient

gambling and another ICDs are probably underreported, and physicians should

with GH secreting aggressive pituitary macro adenoma

consider screening for these in patients treated with dopamine agonists. Screening

Dragana Miljic^1,2, Sandra Pekic^1,2, Mirjana Doknic^1,2, Marina

for ICDs should be undertaken in all patients with DA-treated prolactinomas.

Nikolic-Djurovic^1,2, Marko Stojanovic^1,2, Emilija Manojlovic-Gacic^3,2,

Marta Korbonits⁴, Jaqueline Trouillas⁵, Alexandre Vasiljevic⁵,

DOI: 10.1530/endoabs.49.EP955

Vera Popovic² & Milan Petakov^1,2

¹Department of Neuroendocrinology, Clinic for Endocrinology, Diabetes

and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia;

²Belgrade University School of Medicine, Belgrade, Serbia;³Institute of

Pathology, Belgrade, Serbia;⁴Barts and the London School of Medicine,

London, UK;⁵Institute de pathologie multu-site des HCL, Lyon, France.

EP956

Rare causes of hypopituitarism in adults in a tertiary care institution

40-year-old female patient presented with acromegaly in 2008 (GH 61 (g/L, IGF-

Sandra Pekic Djurdjevic^1,2, Mirjana Doknic^1,2, Dragana Miljic^1,2,

1 774 ng/ml PRL 1500 mU/L). Macro-adenoma invading the right cavernous

Marko Stojanovic^1,2, Marina Nikolic Djurovic^1,2, Zvezdana Jemuovic¹,

sinus was found on MRI and she underwent two pituitary surgeries revealing

Milica Medic Stojanoska³, Vera Popovic² & Milan Petakov^1,2

sparsely granulated GH adenoma with scattered PRL cells, low Ki 67 and

¹Clinic for Endocrinology, Diabetes and Diseases of Metabolism, University

negative p53

immuno-staining. Her second cousin was treated for macro

Clinical Center, Belgrade, Serbia;²School of Medicine, University of

prolactinoma. Both patients tested negative for germline mutations in the AIP and

Belgrade, Belgrade, Serbia;³Clinic for Endocrinology, University Novi

menin genes. Treatment with somatostatin analogue and dopamine agonist was

Sad, Novi Sad, Serbia.

initiated. She was well controlled (GH 1.1 (g/L and IGF-1 291 ng/ml) until 2011

(IGF-1 576...608 ng/ml, GH 4.1 (g/L) when she received 20 Gy gamma knife

radio surgery, to the right para-sellar rest and clivus with good response (2012

Objective

IGF-1 235-306 ng/ml). In 2014 she became symptomatic with headache, VI

Hypopituitarism is a rare disease,a pituitary adenoma and is treatment being the

cranial nerve palsy and biochemical deterioration

(GH 5.3 (g/L and IGF 1

most common cause of it. In recent years there is increased reporting of rare

549 ng/ml). In November 2015 she developed VII & VIII cranial nerve palsy and

causes of hypopituitarism acquired in adulthood, such as other sellar and

biochemically deteriorated (GH 13 (g/L and IGF-1 857 ng/ml). MRI disclosed

parasellar masses, brain damage caused by radiation and traumatic brain injury

tumour progression from the right para-sellar to the infra-sellar region infiltrating

(TBI), vascular lesions, infiltrative/immunological/inflammatory diseases and

clivus, sphenoid and temporal bone and posterior cranial fossa with progressive

infectious diseases. Aim of our study was to increase the awareness to these rare

rise in GH 16(g/L and IGF-1 909 ng/ml levels despite treatment with somatostatin

causes of hypopituitarism.

analogue and dopamine agonist. Avid tracer uptake was noted in the pituitary

Patiens and methods

tumour and neck lymph node on the left side on FDG PET CT and SST2

We performed a cross-sectional database study in our population investigating the

scintigraphy. Third surgery using the posterior cranial fossa approach was

etiology of hypopituitarism in 558 patients in a tertiary care institution recorded

performed. Tumour biology revealed sparsely granulated GH adenoma with high

for the last 11 years. We excluded the patients with pituitary adenomas and

proliferative activity Ki

67 17.2%, positive p53 and 2/10 mitoses. Revised

congenital hypopituitarism. Sixty-eight patients

(32

male,

36 female) were

immunohistochemistry revealed recurrent sparsely granulated GH adenoma

included in the study (mean age 37.3G2.0 years, range 16-72 years).

expressing SSTR2 and Pit1 with low proliferation (Ki 67: 0, mitoses: 0) positive

Results

p53 (1%) grade 2a. This case illustrates our AIP negative FIPA patient with

According to the causes of hypopituitarism the patients were divided in several

sparsely granulated GH adenoma and aggressive behaviour refractory to

groups: nonpituitary sellar and parasellar masses in 10 patients (pituicytoma

multimodality treatment during long term follow up.

nZ1, chordoma nZ2, metastasis nZ3, intravascular lymphoma nZ1,

DOI: 10.1530/endoabs.49.EP954

Langerhans cell histiocytosis nZ3), brain damage in 27 patients (TBI in 9

patients and cranial irradiation in 18 patients), vascular causes in 17 patients

(aneurysm nZ1, apoplexy nZ3, Sheehan’s syndrome nZ6, subarachnoid

hemorrhage nZ6, glomangioma nZ1), immunological/infiltrative/inflammatory

disease in 7 patients (primary hypophysitis nZ6, secondary hypophysitis nZ1)

and pituitary infections in 7 patients (viral hypophysitis-hemorrhagic fever with

EP955

renal syndrome, tuberculosis). Growth hormone and ACTH deficiencies were the

Gambling and cabergoline

most common hormonal deficits (57/68, 84%), followed by FSH/LH deficiency

Julia Silva-Fernández¹, Francisco Javier Gómez-Alfonso¹, Florentino Del

(52/68, 76%), TSH deficiency (49/68, 72%) and ADH deficiency (8/68, 12%).

Val-Zaballos¹, Belvís Torres-Arroyo¹, Paloma González-Lázaro¹, Álvaro

Ten patients (14.7%) had isolated pituitary hormone deficiency, 13 patients

García-Manzanares Vázquez de Agredos¹, María López-Iglesias¹,

(19.2%) had

2-3

pituitary hormone deficiencies and

pituitary hormone

Rafael García-Ruiz² & Inés Gómez-García¹

deficiencies were present in 45 patients (66.1%).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

effects from autoimmunity and disruption of self-tolerance. They include

A high index of suspicion is required for diagnosing rare causes of

colitis/diarrhea, dermatitis, hepatitis, and endocrinopathies

(hypophysitis

hypopituitarism. The symptoms and signs of hypopituitarism are usually

(0-17%), thyroid dysfunction (0-4%) and primary adrenal insufficiency (0.3-

nonspecific and the recognition of these patients remains the challenge.

1.5%). Ipilimumab-associated hypophysitis is a new form of autoimmune

DOI: 10.1530/endoabs.49.EP956

pituitary disease with an average time of

11 weeks after starting therapy,

suggesting a cumulative effect. Patients may present with weakness, headache,

nausea, anorexia, confusion, memory loss, behavior change, hallucinations, visual

impairment, loss of libido, temperature dysregulation, fever, and chills. Hormone

levels show varying degrees of hypopituitarism, and MRI may be normal or

reveal pituitary gland enlargement and thickening of the stalk. Symptoms resolve

EP957

after withdrawal of the drug and starting hormone replacement; however,

Recombinant Human Growth Hormone Treatment in liver transplant

pituitary function may be impaired for considerably longer or even lifelong.

patient. Case report

Conclusion

Corina Galesanu

The increasing use of immune checkpoint inhibitors such as ipilimumab is an

University of Medicine and Pharmacy ‘Grigore T.Popa’, Iasi, Romania.

emerging cause of hypophysitis that generalists, ER physicians, oncologists, and

endocrinologists need to be aware of.

Background

DOI: 10.1530/endoabs.49.EP958

Linear growth is often impaired after successful liver transplantation. Factors that

negatively impacted growth are age, graft function and corticosteroid

immunosuppression. Short-statured prepubertal liver transplant recipients who

do not show sufficient compensatory growth after transplantation benefit from

treatment with recombinant human growth hormone (rhGH).

EP959

Cas report

A case of hypopituitarism caused by hemorrhagic fever with renal

We communicate the results after the first year of rhGH treatment in a child of 12

syndrome

years old, identified with growth failure after a liver transplantation. Liver

Seung Hee Yu & Kiyoung Lee

transplant (live donor- the mother) to 9 years for secondary cirrhosis (biliary

Gachon University Gil Medical Center, Incheon, Republic of Korea.

atresia), malabsorption syndrome, secondary osteoporosis with multiple femoral

fractures on pathological bone. Height Z108 cm (K 5, 92 SDS), and the weight

was Z20 kg (K2, 5 SDS). Bone age Z7 years. Bone mineral density (BMD-

Hemorrhagic fever with renal syndrome (HFRS) is a severe systemic infection

DXA)-whole bodyZ0.718 g/cm² (low bone mass acquisition). Blood samples for

caused by hantaviruses that included Hantaan, Seoul, Dobrava, Saaremaa, and

baseline growth hormone (GH) secretion, serum insulin-like growth factor (IGF-

Puumala. In Korea, the most common virus is Hantaan. The classical symptoms

I) concentrations serum alkaline phosphatase, alanine aminotransferase,

of HFRS are fever, hemorrhage, hypotension, and renal failure, but the clinical

y-glutamyl transferase, and total bilirubin concentration, serum free T, and

course can be very diverse. Among them, endocrinologic complications, such as

TSH levels were determined every 6 months. He was treated with subcutaneous

hypopituitarism were developed rarely by HFRS. A 49 years-old man admitted

injections of rhGH at 0.35 mg/kg/ wk. for one year. Treatment was begun after 3

our hospital with fever, myalgia and thrombocytopenia. He was diagnosed as

years of x liver transplantation. He was treated for that with tacrolimus and

HFRS caused by Hantaan and clinical manifestations. In oliguric phase of renal

prednisolone. After the first year, rhGH treatment was continued.

failure, abnormalities of thyroid function, fT4

0.35 ng/dl

(0.89-1.78), T3

Results

24.43 ng/dl (60-180) and TSH 0.358 uIU/ml (0.55-4.78), were found and other

After 12 months of treatment, median serum levels IGF-I increased from 86 to

hormone tests were performed for differential diagnosis. The level of basal

231 ng/ml. Height velocity increased from 2 cm/yr. to 10,2 cm/yr. and BMD-

hormones were prolactin 13.77 ng/ml (2.1-17.7), GH 2.10 ng/ml (0-1), IGF1

DXA whole body from 0.718 g/cm² to 0.997 g/cm² (C38%); leanCBMC from

112.87 mg/l

(124-310), ACTH

27.8 pg/ml

(10.0-60.0), cortisol

13.82 mg/dl

15735.6 g to 19510.5 g (C24%); fat decreased from 4378 g to 2990.7 (K32%);

(5.27-22.45), LH

3.94 mIU/ml (1.5-9.3), FSH

2.75 mIU/ml (1.4-18.1) and

and total weight increased with 12%. There were no rejection episodes.

testosterone 104.99 ng/dl (241-827). These results indicated secondary hypogo-

Conclusion

nadism and hypothyroidism and no evidence/was seen hypothalamic or other

In our case rhGH treatment was effective in short, non-GH deficient, liver-

pituitary disease by sella MRI. According to this result, partial hypopituitarism by

transplanted child receiving long term glucocorticoid treatment.

HFRS was suspected in the patient. After conservative treatment, manifestations

and laboratory investigation were improved. He was discharged and tested the

DOI: 10.1530/endoabs.49.EP957

basal hormones again at the outpatient clinic. The results were fT4 1.16 ng/dL, T3

110.43 ng/dl, TSH 1.490 uIU/ml, prolactin 8.27 ng/ml, GH 0.41 ng/ml, IGF1

254.24 mg/l, ACTH 30.9 pg/ml, cortisol 10.36 mg/dl, LH 2.83 mIU/ml, FSH

6.54 mIU/ml and testosterone 214.05 ng/dl. The thyroid function was recovered

to normal level spontaneously and the gonadal hormones were still low level.

EP958

Compared with initial hormone level, the pituitary function is recovering

Immune checkpoint inhibitors: an emerging cause of hypophysitis

sequentially. Our experience suggests the important to investigate the

Ali Rizvi & Brooke McAdams

endocrinologic complications of HFRS and to determine whether treatment of

University of South Carolina School of Medicine, Columbia, South

hormone replacement is needed.

Carolina, USA.

DOI: 10.1530/endoabs.49.EP959

Aim

To describe 2 cases of immune-mediated hypophysitis due to the therapeutic use

of Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA4)-blocking antibody.

Case 1

EP960

A 62 year-old male with history of metastatic melanoma was started on

Prevalence and Incidence of pituitary tumors: a nation-wide Popu-

Ipilimumab. After finishing the 4th at 2 months he complained of weakness,

lation-based study using Korean National Health Insurance claims data

fatigue, and fever, prescribed ciprofloxacin and prednisone 20 mg daily, and felt

Kyeonghye Park^1,2, Junggyu Choi¹, Se Hee Park², Joo Young Nam¹,

better. 2 days later he was hospitalized with weakness, BP 86/65 mmHg and

Sun Ok Song¹, Young Duk Song¹ & Eun Jig Lee²

temperature 101.7F. TSH was 0.050 uIU/ml, free T4 0.48 ng/dl, and free T3

¹National Health Insurance Service Ilsan Hospital, Goyang, Republic of

1.20 pg/ml FSH 1.2 mIU/ml, LH 0.8 mIU/ml, and prolactin 0.3 n/ml (all low). A

Korea;²Yonsei University College of Medicine, Seoul, Republic of Korea.

Cosyntropin Stimulation Test showed the following cortisol levels (in ug/dl):

baseline

2.60,

30 min post-injection

6.30, and

60 min post-injection

7.90.

Pituitary MRI was normal. The clinical picture was consistent with severe,

Purpose

recent-onset panhypopituitarism. The patient was treated with IV fluids, stress-

We conducted this study to determine the prevalence and incidence of pituitary

dose dexamethasone, and levothyroxine, and discharged on hormonal replace-

tumors in South Korea.

ment. He continues to do well on multi-hormonal endocrine replacement therapy.

Methods

Discussion

This is a nationwide population- based retrospective study. We analysed two

Ipilimumab (Yervoy*) is a monoclonal CTLA4 antibody and immune checkpoint

national databases, the Korean National Health Insurance (NHI) claims database

protein-modulator approved for treatment of melanoma, and being studied in

and Rare Intractable Disease

(RID) registration database, which include

lung, prostate, and bladder cancer. Mechanisms of overcoming tumor-induced

information on every patients with pituitary tumor diagnosed through uniform

immune tolerance trigger ‘Immune-related adverse events’ (IRAEs) as side

criteria from 2009 to 2013. Pituitary tumor was defined into three types based on

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

the ICD-code; i) D35.2

(benign pituitary neoplasm), ii) D35.2CE

22.0

Case presentation

(acromegaly) CE24.0 (Cushing disease), or iii) D35.2CE22.0CE24.0CE22.1

A 41-year-old man admitted to our hospital with gluteal and scapular mass. He

(Hyperprolactinemia) &co-entered D35.2.

had a clinical history of acromegaly which had been diagnosed two years ago, and

Results

was treated with trans-sphenoidal surgery. After surgery, although remission was

The prevalence and incidence of pituitary tumors were described based on the

not achieved, he had no doctor visit and control. On physical examination he had

three definitions. By definition i),

25 135 patients had pituitary tumors and

typical acromegalic features and there was palpable mass on right gluteal and

included in the prevalence estimates. The prevalence was 40.8, 31.4 and 50.1 per

scapular region, which was noticed by the patient within the last two months.

10⁵ populations in total, men and women, respectively. During 2011-2013, total

Laboratory examination revealed high levels of GH

(10.8 ng/ml), IGF1

8 234 incident cases were identified and the incidence was 17.3, 13.7 and 21.0 per

(1072 ng/ml). Abdominopelvic CT revealed an

93!68 mm mass on right

10⁵ in total, men and women, respectively. By definition ii), total 25 135 patients

kidney, 100!65 mm on the right gluteal region and 200!80 mm on the right

had pituitary tumors and prevalence was 52.4, 37.5 and 67.1 per 10⁵ populations

scapular region. Thorax CT revealed metastatic noduler lesions on the right lung.

in total, men and women, respectively. For the incidence estimate, 10 359 patients

The diagnosis of metastatic renal clear cell cancer (RCC) was verified with gluteal

were identified and the incidence was 21.6, 15.8 and 27.3 per 10⁵ in total, men and

and scapular biopsies. Pituitary MRI revealed residual makroadenoma (2 cm).

women, respectively. By definition iii), total 30 175 patients had pituitary tumors

Therapy for acromegaly with octreotide LAR was initiated. The patient

and prevalence was 62.9, 38.7 and 86.8 per 10⁵ populations in total, men and

underwent radiation therapy for the tumors of right scapular, gluteal region. At

women, respectively. For the incidence estimate, total 12 544 patients were

the same time patient recieved interferon-alfa therapy for metastatic RCC. After

identified and the incidence was 26.1, 16.3 and 35.9 per 10⁵ in total, men and

three months of treatment, scapular, gluteal mass regressed but renal mass and

women, respectively.

lung metastasis progressed with diffuse plevral effusion on the right side.

Conclusions

Sunitinib treatment was started for the follow up.

This study provides reliable information of the epidemiology of pituitary tumors

Discussion

in Asian population, and may help to manage this disease accordingly within our

Therefore we report a very rare case of acromegaly with RCC. In adition to the

healthcare system.

increased circulating GH/IGF-1 levels, local expression of GHR and IGF-1/IGF-IR

DOI: 10.1530/endoabs.49.EP960

in the tumor tisues may partly contribute to the growth of multiple tumors. Type

1/IGF1R has an influence on renal cells malignant transformation by induction of

cell proliferation, dediferantiation and antiapoptotic effect. The risk of RCC

progression would have been very high had the acromegaly been left untreated.

control of acromegaly is mandatory in acromegalic patients with cancer.

DOI: 10.1530/endoabs.49.EP962

EP961

Prevalence of acromegaly in eight counties of North-East Romania

Laura Feraru¹, Carmen Vulpoi^1,2, Voichita Mogos¹, Corina Galesanu^1,2,

Dumitru Branisteanu^1,2, Maria-Christina Ungureanu^1,2, Letitia Leustean^1,2,

Cristina Cristea¹, Simona Mogos^1,2, Catalin Buzduga^1,2, Raluca Balaceanu¹

& Cristina Preda^1,2

¹University Hospital ‘St Spiridon’, Iasi, Romania;²University of Medicine

and Pharmacy ‘Gr. T. Popa’, Iasi, Romania.

EP963

Introduction

The prevalence of acromegaly is estimated to be 6-28/100000 but several studies

Infundibular lesion presenting with central diabetes insipidus and

suggest that acromegaly is underdiagnosed and its prevalence is underestimated.

hypogonadism

Aim

Gulay Simsek Bagir, Filiz Eksi Haydardedeoglu, Okan Bakiner,

To measure the prevalence of clinically relevant acromegaly in a well-defined

Emre Bozkirli & M Eda Ertorer

population using data from 01.04.2004 to 01.11.2016.

Baskent University Faculty of Medicine, Adana, Turkey.

Method

Cross-sectional study performed in 8 counties from the North-East Romania. Data

Introduction

of patients with acromegaly were collected using the INFOWORLD programme

Pituitary stalk lesions fall into three categories: congenital and developmental

and acromegaly diagnosis code E22.0. The number of inhabitants for each county

(rathke cleft cyst, ectopic neurohypophysis), inflammatory and infectious

was in accord with 2011 Census and 2007 Statistical Directory. We identified all

(hypophysitis, sarcoidosis, tuberculosis), and neoplastic

(Langerhans cell

acromegalic patients who were born and resided for each of the eight counties

histiocytosis, germinoma, metastatic tumors). Herein, we report a case with

diagnosed in the Department of Endocrinology from the University Hospital

infundibular lesion presenting with central diabetes insipidus and hypogonadism.

‘St Spiridon’ Iasi, Romania.

Case report

Results

A 27-years old woman was admitted to our clinic with the story of amenorrhea

238

(164 females and 74 males) patients with acromegaly were identified in a

and polydipsia lasting for three years. She was on desmopressin for two years. Her

total population of 4.2 million inhabitants. The prevalence for Iasi County was

physical examination was unremarkable. Hormonal profile was: TSH:

9,94/100000, Suceava County 5.49/100000, Bacau County 4,13, Galati County

0.79 uIU/ml (0.4-4.67), freeT4: 15.49 pmol/l (11.5-22.7), FSH: 2.03 mIU/ml

1,50, Neamt County 3,94, Botosani County 7,17, Vaslui County 7,37/100000 and

(1.2-15.4), LH:

1.02 mIU/ml

(1.24-7.8), Estradiol:

28.7 pg/ml

(30-119),

Vrancea County 3,53/100000.

Prolactin: 35.3 ng/ml (2.8-29.2), early morning cortisol: 15.2 mg/dl (4.3-22.4)

Conclusions

and IGF1:

152 ng/ml

(117-329). Pituitary MRI demonstrated a

7!5 mm

The highest prevalence was identified in 3 counties (Iasi, Vaslui and Botosani).

infundibular mass with suprasellar extension. Diagnostic work-up for infundib-

The explanation of this results may be the more frequent use of diagnostic

ular lesions was performed, including; chest X-ray, computed tomography (CT)

procedures like CT or IRM, the concern of local endocrinologists to identify this

of thorax, purified protein derivated

(PPD) test and measurement of serum

type of pathology. The sex distribution of the selected population was in favour of

angiotensin converting enzyme (ACE) for ruling out granulomatous diseases.

female patients (2F:1M) and was not consistent with 1:1 sex distribution of

Neck ultrasound, bone scintigraphy, skeletal survey, brain CT and measurement

previous studies.

of beta-HCG were performed for ruling out infiudibular neoplastic lesions, Serum

DOI: 10.1530/endoabs.49.EP961

anti-thyroid peroxidase, anti-thyroglobulin antibody were measured. All were

negative. She exhibited no autoimmune background. Serum IgG4 was normal, as

well. In addition to existing desmopression, estrogen-progesteron therapy was

introduced and menses recovered in a few months. Due to rapid radiological

progression at follow-up, methyl prednisolon 1 mg/kg per day was begun for a

possible infundibulohypophysitis. Significant radiological regression was

EP962

observed at the second month of glucocorticoid therapy.

A male patient with acromegaly and metastatic renal cell carcinoma:

Conclusions

lung, gluteal and scapular metastasis

Pituitary stalk lesions have diverse causes and hypophysitis is one of them. In our

Ziynet Alphan Uc¹ & Ozgur Demir²

case, histopathological diagnosis was not possible due to critical location of the

¹Endocrinology Department, Usak University School of Medicine, Usak,

infundibular lesion. After detailed work-up, a diagnosis of possible infundibu-

Turkey;²Endocrinology Department, Ankara University School of

lohypophysitis was made and ampiric glucocorticoid therapy was introduced and

Medicine, Ankara, Turkey.

resulted in radiological regression.

DOI: 10.1530/endoabs.49.EP963

Acromegaly is a chronic condition associated with an increased risk of cancer.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP964

panhypopituitarism met - at 10 from 18 patients (55,5%%), while in the 1

group of panhypopituitarism not observed. A bytemporal hemianopsia also with

Pregnancy in Cushing’s disease after treatment with surgery and

greater frequency was observed for patients 2 groups - 11 supervisions (61,1%%).

cyber-knife radiosurgery

In addition, secondary amenorrhea met a bowl also for patients 2 groups - 6

G Gonca Oruk¹, Ali Olmezoglu², Melda Apaydin³ & Gonul Guven

¸⁴

(33,3%%). Such violations, as secondary ?steopeniya, endocrine encephalopathy,

¹Department of Endocrinology and Metabolism, Ataturk Training and

delay of physical and sexual development were educed only in 2 groups of

Research Hospital, Katip Celebi University, Izmir, Turkey;²Department of

patients. Thus, the most expressed neuroendocrine and ophthalmology violations

Radiation Oncology, Celal Bayar University, Manisa, Turkey;³Department

met for patients 2 groups. For patients with the giant adenomas of hypophysis the

of Radiology, Ataturk Training and Research Hospital, Katip Celebi

decline of level of STH, FSH is first of all marked, LH (45%%).

University, Izmir, Turkey;⁴Department of Neurosurgery, Ataturk Training

Conclusions

and Research Hospital, Katip Celebi University, Izmir, Turkey.

From preliminary data of comparative description of sizes of tumour of sellar area

and level of STH a tendency took place to that as far as growth size of tumour of

Women affected by Cushing’s disease (CD) are often infertile due to abnormal

the Turkish saddle the basale level of STH of plasma was below. For a receipt the

follicular development or anovulation. In these patients, first line treatment is

further protracted supervision of data of patients is required of reliable results

pituitary surgery, which is effective in more than

83% of cases with

with an estimation in a dynamics MRI and STH of plasma with realization of

microadenomas, but only in about 35% of those with macroadenomas. When

loading tests, research of IGF1 and estimation of quality of life for questionnaire

surgery do not normalize circulating ACTH and cortisol concentrations, such

of adult growth hormone deficiency (AGDQoL).

drugs, e.g. ketoconazole or metirapone, and radiotherapy are used as adjuvant

DOI: 10.1530/endoabs.49.EP965

treatment. Concerning radiotherapy, more precise and focused approaches of

delivering larger amounts of radiation have been introduced recently in the

management of pituitary tumors. Cyber-knife radiosurgery (CKR) is considered

as a possible treatment for patients affected by unsuccessfully surgically treated

pituitary adenoma or not suitable for surgery. The disadvantages of this technique

seem to be the length of time to the onset of remission, which is known to be at

least of

6 months, and the possible adverse effects. In patients treated with

radiotherapy, however, mild hypercortisolism can persist for a long time and

fertility could not be restored, even when menses have been normalized. We

report here a case of a 37-yr-old female patient with Cushing’s disease (CD) due

to ACTH-secreting 5 mm adenoma on the left side of the pituitary. Because

EP966

complete clinical remission was not obtained by a transsphenoidal surgery in

Gender differences in real-life GH dosing patterns in adults with GH

2010, CKR was performed for to achieve remission in January 2011. Thereafter,

deficiency (AGHD): experience from a Registry in France

treatment with ketoconazole, at the dose of 400 mg daily, normalized serum

Françoise Borson-Chazot¹, Evguenia Hacques², Véronique Pascal-

cortisol and UFC levels, allowing the recovery of regular menses. Because of low

Vigneron³, Sylvie Salenave⁴ & Béatrice Villette²

FT4 and low TSH and undetectable AbTPO values, L-T4 replacement was

¹Hôpital Louis Pradel, Bron, France;²Novo Nordisk, La Défense, France;

started. 5 years after CKR, morning ACTH, cortisol concentrations, 24-h urinary

³Centre Hospitalo-Universitaire Régional, Nancy, France;⁴Hôpital Bicêtre,

free cortisol (UFC) and cortisol levels after 1-mg dexamethasone (1-mg dex)

Kremlin Bicêtre, France.

administration were normalized. MRI also showed partial shrinkage of the

pituitary tumor. The patient, who had regular menses, became pregnant 60

months after CKR. During pregnancy, plasma ACTH, serum cortisol and UFC

Introduction

levels increased. Fasting glucose levels (FGL), HbA1c and blood pressure were

Usually GHD women require higher GH doses than males, especially those with

normal all throughout pregnancy. Overall, patient’s body weight increase was

exogenous oestrogens (guidelines). This fact was assessed in real-life practice in

13.6 kg. At the 38th week of an uneventful pregnancy, the patient delivered

France.

vaginally a healthy female newborn (length 48 cm, weight 2600 g). The baby and

Methods

the mother did not show any biochemical signs or clinical symptoms of hypo- or

Data were from a Registry in 84 sites treating AGHD (Norditropinw) up to 5

hypercortisolism. In conclusion, pregnancy should be considered at risk in

years. Naïve patients did not receive GH 6 months before inclusion. Statistics

patients with CD, even the patient has normalized cortisol levels. Moreover,

were descriptive.

periodic evaluation of pituitary function is mandatory during gestation, due to the

Results

high risk of hypopituitarism.

328 patients (129 naïve) were included; mean age 49.2 years (G 14.3 S.D.). 180

DOI: 10.1530/endoabs.49.EP964

were females (55%) with 72 (40%) naïve; data missing for 6. 147 (81.7%) women

had a gonadotropic deficiency: 83 (79%) non-naive and 54 (75%) naive treated

with oestrogen therapy. At inclusion the median IGF-1 SDS (Q1;Q3) in naive

population was K2,20 (K3.20;K1.30) and in non-naïve was 0.00 (K1.30;

C1.10). The median starting dose was similar for naive women and men:

0.20 mg/d. After the first year until the end of the follow up (FU) the median dose

for naïve women was higher than for men. The median dose was higher for non-

naive females (Table 1). At the end of the FU, the median IGF1 SDS (Q1; Q3) in

naive population was C0.30 (K0.50;C0.80) and in non-naïve was C0.50

(K0.40;C1.20).

EP965

Table 1 Median GH dose (Q1;Q3) (mg/day)

The clinic-hormonal description of patients with giant pituitary

adenomas

Year

\ naive

_ naive

\ non-naive

_ non-naive

Yulduz Urmanova & Kamola Alimova

Inclusion

0.20

(0.20;0.30)

0.20

(0.20;0.30)

0.40

(0.20;0.60)

0.30

(0.20;0.40)

¹Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan;

0.40

(0.30;0.50)

0.30

(0.20;0.40)

0.40

(0.30;0.70)

0.35

(0.20;0.50)

²Center of Endocrinology, Taskent, Uzbekistan.

0.50

(0.30;0.60)

0.30

(0.20;0.40)

0.40

(0.30;0.60)

0.40

(0.20;0.50)

0.50

(0.30;0.70)

0.39

(0.20;0.50)

0.40

(0.30;0.60)

0.30

(0.20;0.50)

0.50

(0.40;0.70)

0.37

(0.20;0.50)

0.40

(0.30;0.65)

0.40

(0.20;0.52)

The aim

0.60

(0.45;0.80)

0.40

(0.30;0.50)

0.40

(0.30;0.70)

0.30

(0.20;0.52)

To study the results of researches 35 patients with different pituitary tumours of

sellar area, from them men - 17 (48,6%%), women - 18 (51,4%%).

Materials and methods

Conclusion

Depending on sizes there are the adenomas of hypophysis, educed on CT/?RI,

In real life, physicians consider the recommendation of higher GH dose for

patients were up-diffused on two groups: the first group of patients is

AGHD women at steady state, while the starting dose remains similar in both

macroadenomas (from 20 to 30 mm) - 17 (48,6%%), and second group of

genders. Data from this Registry is consistent with the published data from other

patients - giant - (more than 30 mm) - 18 (51,4%%).

observational studies.

Results

It was educed, that in

groups of patients most often there was

DOI: 10.1530/endoabs.49.EP966

panhypopituitarism

- at

from

patients

(44,4%%), post-operating

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP967

EP969

Is there a role of immunohistochemical expression of pituitary

A case with headache and pitosis: pituitary macroadenoma or

hormones and proliferative marker ki-67 on long-term outcome in our

ophtalmoplegic migraine?

acromegalic patients?

Filiz Eksi Haydardedeoglu, Gulay Simsek Bagir, Okan Bakiner,

Mustafa Sahin, Caglar Keskin, Saba Kiremitci, Esra Erden, Asena Canpolat,

Emre Bozkirli & Melek Eda Ertorer

Murat Cinel, Sule Canlar, Ozgur Demir, Sevim Gullu, Rifat Emral,

Baskent University Adana Teaching and Research Center, Adana, Turkey.

Murat Faik Erdogan, Vedia Gedik, Nilgun Baskal & Demet Corapcioglu

Ankara University School of Medicine endocrinology and Metabolic

Case

Diseases Department, Ankara, Turkey.

A 28-year old man was admitted to our hospital with complaints of three days of

severe headache, diplopia and ptosis of the right eye. He had pituitary

Expression of hormones other than GH may affect the prognosis in acromegalic

macroadenoma and had been on cabergolin 0.25 mg/week for the last six

patients. Generally, Ki-67 is a well-known proliferative index used to predict

months. At physical examination, he demonstrated ptosis and inability to move

remission in pituitary adenomas. We aimed to evaluate the relationship of

the right eye medially. Magnetic resonance imaging showed a 13!12 mm

immunohistochemical expression pituitary hormones, ki-67 and remission. Also

pituitary mass with suprasellar extension and hemorrhage. Visual field analysis

we evaluated the role of pre, post-operative clinical and laboratory values,

was abnormal except the lateral movement of the right eye. Laboratory hormonal

pathological characteristics on long-term remission. We included 64 acromegaly

analysis showed mild cortisol deficiency only. According to clinical, radiological

patients that were treated surgically and followed up in our Endocrinology and

and laboratory results, he was diagnosed as non-functional pituitary adenoma

Metabolic Diseases Department. Demographic, clinical, laboratory and imaging

with apoplexy and III.cranial nerve palsy due to increased intrapituitary pressure.

data were collected. We also re-evaluated the immunohistochemistry of all

Intravenous methyl-prednisolone was started and symptoms resolved. One month

pituitary hormones and ki-67 marker from paraffin blocks. We followed 64

after discharge, although he was using methyl prednisolone 4 mg, he was again

patients (38 women, 26 Male; mean age 46.7G11.8) for 61.8 (6-192) months. We

admitted with complaints of nausea, vomiting, hypotension and ptosis. He was

did not found any relationship between remission and multihormonal expression

immediately taken to pituitary surgery via transnasal-transsphenoidal approach.

in our patients. We also did not found a significant relationship between ki-67

His complaints dissolved following the procedure and he was well at discharge.

expression or sex with remission. Early diagnosis age

(PZ0.045), greater

Histopathological analysis of the operation specimen exhibited a pituitary

adenoma diameter

(PZ0.002), low preoperative LH

(PZ0.036) and high

adenoma with necrosis and hemorrhage. On the fifth postoperative day, he was

postoperative IGF1 (P!0.0001) only factors that are significantly related with

re-admitted with diplopia, photophobia, phonophobia, nausea and vomiting.

low rate remission. Preoperative cortisol levels are related to ki-67 index level

Recurrent headache attacks lasting for about one week within the last 6 months

(PZ0.004). Low preoperative LH and high postoperative IGF1 levels and tumor

reminded accompanying ophtalmoplegic migraine. Eighty mg eltriptan and

diameter may be predictive for remission and low cortisol levels may be

parenteral pulse steroid (1000 mg methyl prednisolone/5 days) were started. The

predictive for the high ki-67 index.

patient had no longer experienced an attack.

DOI: 10.1530/endoabs.49.EP967

Conclusion

Pituitary apoplexy and ophtalmoplegic migraine are rare clinical entities.

Ophthalmoplegic migraine has been recognized as a cranial neuralgia and

characterized by repetitive III, IV and / or VI. cranial nerve palsies. If there is

persistent headache and cranial nerve palsies following surgical decompression of

an adenoma with pituitary apoplexy, accompanying ophtalmoplegic migraine

should be kept in mind.

EP968

DOI: 10.1530/endoabs.49.EP969

Investigation of the pituitary functions long-term after the acute CNS

infections

Gamze Cetinkaya¹, Aysegul Ulu Kilic², Zuleyha Karaca¹,

Mehmet Doganay², Z T Yuce², Kursad Unluhizarci¹, Fahrettin Kelestimur¹

& Fatih Tanriverdi¹

¹Erciyes University Medical School Department of Endocrinology, Kayseri,

Turkey;²Erciyes University Medical School Department of Infectious

EP970

Diseases, Kayseri, Turkey.

Somatostatin analogues-induced diabetes mellitus in acromegalic

patients reverts after drug withdrawal: a long-term study

Daniele Cappellani¹, Claudio Urbani¹, Chiara Sardella¹,

Objectives

Giulia Marconcini¹, Claudio Marcocci¹, Giuseppe Rossi² &

Acute bacterial or viral CNS infections have been shown to result in

Fausto Bogazzi¹

hypopituitarism during the acute phase, and 6-24 months after the event in a

¹Department of Clinical and Experimental Medicine - Section of

few studies. However, there are no data in the literature regarding the long term

Endocrinology, University of Pisa, Pisa, Italy;²Epidemiology and

pituitary functions after acute CNS infections. This cross-sectional study was

Biostatistics Unit - Institute of Clinical Physiology, National Research

designed to evaluate the pituitary functions long-term after the acute bacterial or

Council (C.N.R.), Pisa, Italy.

viral CNS infections.

Methods

19 patients with ages 18-65 (mean: 39.53G17.089 years; 11 male patients, eight

Context

patients female) were included in the study. There were seven patients with acute

Therapy with somatostatin analogues (SSAs) may have deleterious effects on

bacterial meningitis, nine patients with acute viral encephalitis, and three cases of

glucose metabolism in patients with acromegaly, often leading to development of

acute meningoencephalitis. Basal pituitary hormone levels were measured and

diabetes mellitus (DM).

glucagon stimulation test was performed 17-92 months (mean 48.47G25.19

Aim of the study

months) after the acute CNS infections. MRI was performed to evaluate the

To evaluate whether DM, which developed during therapy with SSAs, may revert

pituitary gland volume and to rule out any co-incidental pituitary mass.

after drug withdrawal and cure of acromegaly with pituitary adenomectomy.

Results

Design

There were a total of 5 patients out of 19 (26.3%) with hypopituitarism; 3 (15.7%)

Retrospective cohort study, in a tertiary referral center.

with isolated GH deficiency, 1 (5.2%) with isolated FSH-LH deficiency and 1

Patients

(5.2%) with combined FSH-LH and GH deficiency in the study group. Mean

Eighteen acromegalic patients without DM at the diagnosis of acromegaly treated

pituitary volume was substantially lower in patients with hypopituitarism when

with SSAs as a primary therapy, and then cured by pituitary adenomectomy.

compared to the patients without hypopituitarism. But the difference was not

Methods

statistically significant.

Endocrine status and glucose homeostasis were evaluated at diagnosis of

Conclusion

acromegaly and at least every six months during SSAs therapy. At each control

This study clearly demonstrated that high frequency hypopituitarism, GH

patients were classified in one of the following classes: normal glucose tolerance,

deficiency in particular, was still present long term after the acute bacterial or

prediabes, overt diabetes.

viral CNS infections. Therefore, the patients with acute meningitis, meningoen-

Results

cephalitis and/or encephalitis need to be screened at least 4-5 years after the acute

Median follow-up after starting SSAs therapy was 60 months (IQR 53.2-96.2).

event.

During SSAs therapy, all patients had controlled acromegaly defined by normal

DOI: 10.1530/endoabs.49.EP968

serum IGF-1 concentrations for the age. Among the 13 euglycaemic patients at

diagnosis three developed prediabetes and three diabetes, whereas, among the five

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

prediabetic patients at diagnosis two worsened to overt diabetes; three remained

Table 1 Results of basal endocrine and biochemical investigations of

in the prediabetic range (PZ0.04). After cure of acromegaly with pituitary

patient

adenomectomy and subsequent SSAs withdrawal, prediabetes reverted in five out

of six patients, and diabetes in all five patients (in three reverted to euglycaemia,

Parameter (unit)

Value

while in two reverted to prediabetes) (PZ0.01).

Conclusions

Glucose (mg/dl)

In acromegalic patients with controlled disease changes of glycaemic status

Na (mmol/l)

137

induced by SSAs are not permanent.

K (mmol/l)

4.5

DOI: 10.1530/endoabs.49.EP970

FT₄ (ng/dl)

2.69

TSH (mIU/ml)

4.70

Cortisol (mg/dl)

8.7

Vanillylmandelic acid (mg/24 s)

1.56

Metanephrine (mg/24 s)

168

Normetanephrine (mg/24s)

298

EP971

Table 2 Results during insulin tolerance test

Pituitary metastases of lung cancer presenting with hypopituatrism

Guzin Fidan Yaylalı¹, Senay Topsakal¹, Serkan De

˘ irmenciog˘ lu2 &

Parameter

Value

Semin Melahat Fenkçi¹

¹Pamukkale University Medical Faculty Endocrinology Metabolism

Glucose (mg/dl)

Depatment, Denizli, Turkey;²Pamukkale University Oncology Department,

Cortisol (ug/dl)

Denzili, Turkey.

GH (ng/ml)

0.45

ACTH (pg/ml)

!0.5

Pituitary tumors are the most frequent intracranial neoplasm, affecting 11 000 of

the world wide population. However metastases in this location are rare and

uncommon presentation of systemic malignancy. Although diabetes insipidus

Table 3 Results during ACTH stimulation test

secondary to cancer metastasis to the pituitary gland is a common manifestation,

anterior pituitary failure is rare. We present a K57-year-old man with

Parameter

hypopituitarism secondary to pituatry metastasis from lung cancer.

Case report

Minute

A 57-year-old patient active smoker presented with headache of 1 month. Cranial

Cortisol (mg/dl)

18.6

MRI revealed multiple subcortical lesions and hypophyseal noduler lesion 13.6

mm in diameter. The computary tomography scan of the Chest, Abdomen and

Pelvis revealed a 23!22 mm rregularly margined mass in mass in the upper left

lobe with mediastinal lymph nodes, liver and right adrenal metastases.

multinodular goiter. On clinical examination; height 153 cm, weight: 67 kg,

Assessment of pituitary function revealed panhypopituitarism; Cortisol:

BMI:29 BP: 120/70 mm/Hg. The other physical examination findings were

3.17 mg/dl, ACTH:11.5 pg/ml free T₄

0.64 ng/dl

(normal range

0-97-1.65),

normal. Radiologic findings included: Abdominal MRI: in the right adrenal gland,

thyroid stimulating hormone level of 0.005 mUI/ml (normal range 0.5-4 IU/ml),

20!12 mm and 33!13 mm in left adrenal gland adenomas was detected. The

total testosterone level of

0.025 ng/ml (normal range 2.5-10 ng/ml), follicle

laboratory findings were shown in Table 1. Basal Cortisol levels were detected as

stimulating hormone level of 0.5 IU/ml (normal range 1-8.4 IU/ml), luteinizing

6.6 mg/dl and insulin tolerans test and ACTH stimulation test were performed.

hormon level of 0.1I U/l (normal range 1-10.5 IU/l) and normal urine osmolarity.

(Table 2, Table 3).

Complete blood count showed the following: hemoglobin 13.6 g/dl, white cell

Conclusion

count 12.64 K/ul, and platelet count 322 K/ul Evaluation of serum chemistry

Acth deficiency is rare in elderly patients is a complex disease and many diseases

revealed lactate dehydrogenase

245 IU/l, sodium

129 mmol/l potassium

that mimic. Sometimes patients are diagnosed by chance. When this case was

4.3 mmol/l. A hormone replacement therapy was indicated urgently. Fiberoptic

examined for adrenal adenoma, ACTH deficiency was unexpectedly detected and

bronchoscopy did not show any endobronchial lesion. Histopathologic exami-

replacement therapy was started. The clinic has the patient improved rapidly with

nation of brochoalveolar lavage revealed metastasis of lung adenocarcinoma.

replacement therapy.

Conclusion

Despite the fact that pituitary metastasis are rare, they must be evaluated in the

DOI: 10.1530/endoabs.49.EP972

presence of pituitary involvement. It may be difficult to differentiate symptoms

due to panhypopituitarism from the constitutional symptoms caused by cancer

progression. Considering that the life expectancy is limited for advanced lung

cancer patients, detection and appropriate treatment of hormonal insufficiency are

important to improve their quality of life.

DOI: 10.1530/endoabs.49.EP971

EP973

Clinical, histological, molecular features and outcomes of

craniopharyngiomas: Single centre experience in Toledo, Spain

Almudena Vicente¹, Beatriz Moreno², Mónica Olivar¹, Ana Martínez¹,

Manuela Mollejo², Julia Sastre¹ & José López¹

Department of Endocrinology, Complejo Hospitalario de Toledo, Toledo,

EP972

Spain;²Department of Pathology Complejo Hospitalario de Toledo, Toledo,

ACTH deficiency in patient with bilateral adrenal adenomas

Spain.

Semin Melahat Fenkçi, Senay Topsakal & Guzin Fidan Yaylalı

Pamukkale University Endocrinology Department, Denizli, Turkey.

Background

Craniopharyngiomas (CPs) are epithelial tumors that typically arise in the

Introduction

suprasellar region. They are associated with high levels of morbidity related to

ACTH deficiency is a rare disease with non-specific symptoms such as anorexia,

tumour location and/or treatment-related injuries. Recent discoveries have also

fatigue and weight loss. Due to these silent symptoms the disease is easily

led to a better understanding of CP development and potential treatments.

overlooked and may escape detection for a long time, especially in elderly patient.

Objetive

Case

To analyse the clinical, pathological, molecular features and outcomes of patients

67-year-old female patient applied with complaints of fatigue. Bilateral adrenal

with CP.

adenoma was detected during ultrasonographic evaluation and and patient was

Design

consulted to endocrinology clinic Her personal history included osteoporosis and

Retrospective observational study.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

EP975

Clinical records review and re-evaluation of histologic samples from patients who

The use of increasing doses of cabergoline in the management of

underwent surgery of CP in our institution between 1999 and 2016.

cabergoline-resistant prolactinomas

Results

Lucio Vilar^1,2, Clarice Vilar², José Luciano Albuquerque¹,

There were 26 patients (53.8% male), mean age at diagnosis 37 years (range 2-

Patricia Gadelha¹, Ana Carolina Thé¹, Erik Trova˜o1, Thaíse Borges1,

73). Mean follow-up was 86 months (range 3-288). The commonest presenting

Izabela Cardoso¹ & Ruy Lyra¹

symptoms were: visual alterations 84% (nZ21), headaches 53.8% (nZ14), and

¹Division of Endocrinology, Hospital das Clinicas, Federal University of

behaviour disorders 11.4% (nZ3). 92.3% (24/25) of tumours had suprasellar

Pernambuco, Recife (Pernambuco), Brazil;²Endocrine Research Center of

involvement, with cystic component in 80.8% (16/26). Median tumour size was

Pernambuo, Recife (Pernambuco), Brazil.

30.4 mm (12-50). Initial surgical approach was transcranial in 96.2% (nZ25).

Available histological and molecular results were: 72% (nZ18) adamantinoma-

tous CP and 28% (nZ7) papillary CP (PCP). Three PCP harboured BRAF V600E

Introduction

mutation. In these cases, the average number of surgical interventions were higher

Dopamine agonists

(DA) are the ideal treatment for prolactinomas and

(4 vs1.3) and time to recurrence was shorter (34 vs 99 months). Three patients

cabergoline (CAB) is the drug of choice, for being much more effective and

(11.4%) undergone radiation therapy. Last neuroimaging assessment showed

better tolerated than bromocriptine. However,

10-15% of patients with

residual tumour in 50% of patients. At the end of follow-up, panhypopituitarism

prolactinomas are considered to be resistant to CAB, as they dot not achieve

and diabetes insipidus were detected in

72% (18/25) and

75% (18/24)

prolactin (PRL) normalization, while in use of conventional doses of this drug.

respectively. Symptoms related to hypothalamic dysfunction were found in

Objective

76% (19/25). The mortality was 11.5% (nZ3). Causes of death were: initial

To evaluate the effiaccy of increasing doses of CAB in prolactinomas refractory to

surgery related complications (1), multiple recurrent PCP harboured mutation

CAB 3 mg/wk by in order to achieve prolactin (PRL) normalization.

BRAF v600E (1) and cardiovascular disease (1).

Patients and methods

Conclusions

We prospectively evaluated the management of consecutive patients with

In our study, treatment of craniopharyngiomas were associated with high rates of

prolactinomas refractory to CAB 3 mg/wk who were submitted to progressive

tumor persistence and substantial morbidity. Tumours harboured BRAF V600E

increases in CAB dose, as needed and tolerated every 3 months, up to 9 mg/week.

mutation seemed to be associated with poor prognosis.

The patients were recruited over a 12-month period. Exclusion criteria were

DOI: 10.1530/endoabs.49.EP973

previous pituitary surgery or radiotherapy. Echocardiogram evaluation was

performed in each patient every 6 months.

Results

Twenty five patients were included in this study, 20 with macroprolactinomas.

Overall, normalization of PRL levels was achieved in 18 patients (72%): in 3

(12%) with a dose up to 4 mg/wk, in 9 (36%) with 5 mg/wk and in 6 (24%) with

6-7 mg/wk. No patients benefited from doses O7 mg/wk. No significant

echocardio-graphic valve abnormalities were detected.

Conclusion

CAB doses up to 7 mg/wk were well tolerated and enabled PRL normalization in

EP974

(72%) patients with prolactinomas resistant to CAB 3 mg/wk. No patients

Cushing’s disease: is there a Continuum from corticotroph hyperplasia

benefited from doses O7 mg/wk.

to adenoma?

DOI: 10.1530/endoabs.49.EP975

Ana Coelho Gomes¹, Lia Lucas Neto², Francisco Tortosa³,

Maria Raquel Carvalho¹, Eduardo Barreiros¹, Luís Barreiros¹,

José Miguéns⁴ & Maria Joa˜o Bugalho1

¹Endocrinology, Diabetes and Metabolism Department, Santa Maria

Hospital, Lisbon, Portugal;²Neuroradiology Department, Santa Maria

Hospital, Lisbon, Portugal;³Pathology Department, Santa Maria Hospital,

EP976

Lisbon, Portugal;⁴Neurosurgery Department, Santa Maria Hospital, Lisbon,

Long-term efficacy of octreotide LAR in acromegaly patients,

Portugal.

a prospective single centre study with 7 years follow up

¹, Azra Burekovic^1,2 & Amela Dizdarevic-Bostandzic^1,2

Zelija Velija-Asimi

Introduction

¹Medical Faculty University of Sarajevo, Sarajevo, Bosnia and

Successful long-term management of patients with Cushing’s disease

(CD)

Herzegovina;²Clinical Centre University of Sarajevo, Sarajevo, Bosnia

remains a challenge. Few studies have analyzed the long-term recurrence rates of

and Herzegovina.

CD after transsphenoidal surgery (TS).

Objectives

Objective

1) to compare the outcome of patients with and without postoperative criteria for

The aim of this single centre prospective open trial was to evaluate the long-term

cure; 2) to compare the outcome of patients with and without a histological

efficacy of octreotide LAR in acromegaly patients.

diagnosis of adenoma.

Methods

In total of 19 patients with acromegaly diagnosed at Endocrinology Department

Retrospective, descriptive study. Forty-two patients with CD submitted to TS

of Clinical Centre of University in Sarajevo, somatostatin sensitive (ten females

between 2005 and 2016 were included. Variables analyzed: postoperative criteria

and eight males, age range 40-68 years, six patients with microadenoma and 12

for cure, CD remission and recurrence rates, histological findings.

patients with macroadenoma) were treated with octreotide. Follow-up period was

Results

7 years (2009-2016). The concentration of human Growth Hormone (hGH) and

Surgical remission was achieved in thirty-eight patients. The mean follow-up was

insulin-like growth factor-1

(IGF-1) were evaluated every 6 months, while

6.8 years. Sixteen patients recurred. The mean time to recurrence was 4.6 years.

magnetic resonance imaging was taken every year during follow-up period.

Immediate postoperative evaluation was performed in 34 cases; criteria for cure

Results

were observed in seventeen. Patients with clinical recurrence who presented

During the first year of treatment ten patients were included. In the second year, a

postoperative criteria for cure had a mean disease free-time of 7.1 years, opposed

further seven patients were involved. During the last 4 years, five patients were

to 2.2 years in those without biochemical criteria for cure (P-value 0.032). Six

included. During the seventh year of follow-up, the treatment was successful

patients without biochemical criteria for cure after surgery are in remission.

discontinued at four patients, two patients was passed away due to co-morbidities

Histology documented an adenoma in thirty patients; from these, eleven recurred.

and at two another patients’ treatment was cancelled due to cancer; so currently we

Discussion

followed total of

11 patients. One of patient was treated by Gamma Knife

In this study, 42.1% of the patients who achieved remission, after TS, recurred.

radiosurgery and after that developed pituitary deficiency, but he is needed to

This finding emphasizes the need for continued biochemical and clinical follow-

continue with octreotide treatment because of high hGH and IGF-1 level. During

up. On the other hand, some patients without postoperative criteria for cure were

octreotide treatment, significantly reduced GH (50.87G10.56 vs 3,4G0.76 ng/ml,

in remission, at last observation. Thus, suggesting that biochemical criteria for

P!0,005), IGF-1 (777.66G118.40 vs 349G97.54 ng/ml, P!0.005) and adenoma

cure may be achieved at different timings from patient to patient. Evidence for

size (from 9.6 to 8 mm; P!0.05). GH decrease to less than 1 ng/ml was achieved in

recurrence in eleven patients with adenoma suggests that CD may be a continuum,

66% of cases; tumour size decrease was achieved in 49%, while normalization of

in which there is a basal corticotroph hyperplasia likely to evolve to adenoma.

IGF-1 was achieved in 88% of the patients, respectively. At 1-4 years of follow-up,

DOI: 10.1530/endoabs.49.EP974

20% of acromegaly patients had withdrawn treatment, without recurrence. Two

patients on octreotide treatment have uncontrolled acromegaly.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

tolerance test

(OGTT) have been suggested as early predictor of surgical

Octreotide LAR treatment is effective in decrease of GH, IGF-1 and tumour size

remission (Kim 2012). However, the value of this approach remains to be defined.

in well-selected acromegalic patients.

Aim

DOI: 10.1530/endoabs.49.EP976

The purpose of our study is to evaluate the utility of measurement of GH level

during a 2-week postoperative OGTT as a predictor for surgical outcome in

patients with acromegaly.

Materials and methods

Ten patients (five women and five men) with an average age of 47.4G14.8 years

(range 27-71 years) who had underwent total transsphenoidal adenomectomy

performed by one neurosurgeon were included in this study. All patients harbored

macroadenomas, with average size of

18.9G5.2 mm (range

13-29 mm).

Measurement of GH level during OGTT was performed 14 days after surgery.

EP977

The outcome of TSS was evaluated 6 months after surgery by OGTT and

Is there a gender difference in clinically nonfunctional pituitary

measurement of insulin-like growth factor 1 (IGF-1). The biochemical remission

adenomas?

of acromegaly according to the 2010 remission criteria were defined as nadir GH

Iffet Da

˘ delen Duran¹, Ne¸e Ersoz Gulc¸elik2, Dilek Berker1 &

level on an OGTT !0.4 mg/l along with age and gender normalized values of

Serdar Guler¹

IGF-1.

¹Ankara Numune Education and Research Hospital, Department of

Results

Endocrinology and Metabolic Diseases, Ankara, Turkey;²Ankara

Initial basal GH level was 23.7G24.9 mg/l, initial IGF-1 patient /IGF-1ULN ratio

Education and Research Hospital, Department of Endocrinology and

was 2.7G0.6. Six months after surgery the remission of acromegaly was achieved

Metabolic Diseases, Ankara, Turkey.

in five patients (50%) - mean IGF-1 patient/IGF-1ULN - 0.7G0.2, mean nadir

GH level on an OGTT - 0.30C0.09 mg/l. Nadir GH level on an 2-week

postoperative OGTT was less than 1.0 mg/l in all patients with remission of

Introduction

acromegaly. Whereas, all patients with persistence of the disease had nadir GH

Clinically nonfunctioning pituitary adenomas (NFPA) are the most common

levels O1.0 mg/l on an early postoperative OGTT.

pituitary tumor type. They are usually recognized after they cause symptoms

Conclusion

especially when tumor size increases and eventually invades adjacent structures.

Our initial data suggest that nadir growth hormone level on an

2-week

Nevertheless the discovery would also be accidental. In the literature some kind of

postoperative OGTT less than 1.0 mg/l associated with remission of acromegaly

gender difference is reported in NFA’s behavioral results such as pituitary axis

6 months after surgery. Further researches are required to specify long-term

deficits or consequences of surgery however they resulted with controversial

outcomes.

reports. In our study we investigated if there is male/female preponderance in

terms of NFA’s some number of features.

DOI: 10.1530/endoabs.49.EP978

Materials and methods

We retrospectively examined 101 patients diagnosed as NFA biochemically and

radiologically. All patients were questioned for each possible symptom of

pituitary adenoma at diagnosis. Every patient was examined by laboratory

pituitary hormonal tests. Pituitary adenomas were radiographically evaluated by

MRI (dimensions(mm): d1!d2!d3). Microsurgical resection of adenoma was

performed in patients with symptomatic or large and invasive tumors.

Results

101 patients (57 female (56.4%) and 44 male (43.6%)) were assessed in the study.

The age at diagnosis was younger for women than men (40.0 yr vs 51.4 yr,

P:0.000). Tumor size were larger for men (d1: 21.9G2.6 mm vs 9.4G1.4 mm,

EP979

P:0.000). Among the rate of symptoms headache was the most frequent. Blurred

Giant macroprolactinoma in women still exist

vision was more common in men (45.5% vs 26.8%, P:0.06). The frequency of

Laura Dragomir¹, Stefan Florian^1,2, Ana Valea^1,2 & Cristina Ghervan^1,2

pituitary hormone deficiency was more common in men (37.0% vs 12.1%). 43

¹Emergency County Hospital, Cluj-Napoca, Romania;²University of

(42%) patients have been performed pituitary surgery. Postsurgical hypopituitar-

Medicine and Pharmacy ‘Iuliu Hatieganu’, Cluj-Napoca, Romania.

ism was more commonly seen in female, whereas permanent DI was more

abundant in male, with nonsignificance in both issues (38.5% in female vs. 27.5%

in male, P:0.34; 7.7% in female vs. 13.3% in male, P:0.60; respectively).

Background

Conclusion

Prolactinomas are the most common hormone-secreting pituitary tumors and are a

Sex would be a prognostic parameter in NPA patients in terms of hypopituitarism,

common cause of anovulation and infertility. Giant prolactinomas (0.5-4.4% of

postoperative hypopituitarism and tumor mass. In our study, women were shown

all pituitary tumors) are rare tumors characterized by their large size (O4 cm),

to be diagnosed earlier and men were defined to have larger tumors. Greatly

compressive symptoms and extremely high prolactin secretion (O1000 ng/ml).

would be explained with the mass effect, we determined hypopituitarism was

Men are most commonly affected, with a reported male to female ratio of 9:1.

more common in men. Selectively postsurgical hypopituitarism, however

Case report

nonsignificant, was found more common in female group in our study.

We present the rare case of 53-years-old female, with a history of amenorrhea

DOI: 10.1530/endoabs.49.EP977

from age 35, who was never investigated or treated. In December 2015 she was

admitted in the neurosurgery department for severe headaches and visual

impairment. On clinical examination, left eye mydriasis and left lateral nystagmus

were noted. A head CT showed a pituitary tumor of 55 mm diameter, invading the

sphenoid sinus, both cavernous sinuses, the left orbit and compressing the third

ventricle, with mass effect. The blood tests revealed a very high serum prolactin

of 32625 ng/ml (4-23) and low sexual and gonadotrophic hormones. Given the

clinical and CT aspects, decompressive transcranial surgery was performed,

resulting in rapid improvement of the neurological signs and lowering of the PRL

EP978

levels to 1980 ng/ml. Nasal fistula and transient diabetes insipidus occurred after

The value of early postoperative OGTT as a predictor of surgical

surgery and were cured by sphenoid sinus filling and treatment with

outcome in patients with acromegaly after total transsphenoidal

desmopressin. For the residual prolactin secretion, Cabergoline treatment was

adenomectomy

started (1.5-2 mg/week) which resulted in prolactin suppression and diminuation

Alexandr Tsiberkin, Vladislav Cherebillo, Uliana Tsoy, Anna Dalmatova,

of the tumoral remaint. The restoration of the gonadotrophic secretion resulted in

Lidiya Belousova & Elena Grineva

numerous painful ovarian cysts that were cured by bilateral oophorectomy.

Federal Almazov North-West Medical Research Centre, Saint Petersburg,

Conclusions

Russia.

We present this rare case in order to highlight the importance of the etiological

investigation of secondary amenorrhea in women. The patient almost died

Introduction

because of the mass effect of a benign tumor, easily manageable by medical

Transsphenoidal surgery (TSS) is the treatment of choice for patients with

treatment and suffered multiple complications due to the neglect of her secondary

acromegaly. However, even after radical surgery persistence of acromegaly may

amenorrhea.

remain up to thirty percent by resent studies (Starnoni, 2016). Nadir growth

DOI: 10.1530/endoabs.49.EP979

hormone (GH) level less than 1.0 mg/l on an early postoperative oral glucose

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP980

for nodules bigger than 1 cm or nodules with malignancy criteria. Thyroid fine

needle aspiration biopsy demonstrated undetermined atypia in 27.3%, suspicious

Associated neoplasia in Romanian acromegalic patients

follicular neoplasia in

36.4%, follicular neoplasia in

9.1% and suspicious

Simona Silea¹, Simona Galoiu^1,2, Anda Dumitrascu¹, Dan Niculescu^1,2,

malignancy in 27.32% of the subjects. All patients underwent total thyroid-

Ionela Baciu^1,2 & Catalina Poiana^1,2

ectomy. Pathological examination of thyroid tissue revealed follicular variant

¹C.I. Parhon National Institute of Endocrinology, Bucharest, Romania;

papillary thyroid cancer in 5, classic and follicular variant papillary thyroid cancer

²C. Davila University of Medicine and Pharmacy, Bucharest, Romania.

in 3, diffuse sclerosing variant papillary thyroid cancer in 1, solid variant papillary

thyroid cancer in 1 and follicular, classic and clear cell papillary thyroid cancer in

Introduction

one patient. 72.7% of the patients had multifocal disease and 63.7% of the

Acromegaly has various complications that significantly alter patients’ lives, one

subjects had unilateral disease. Lymphovascular invasion and extrathyroidal

of which is developing neoplasia, a subject of high interest in the scientific

extension were present in 9.1 and 18.2% of the subjects, respectively. No distant

community during the last years but without any firm conclusions.

or local metastasis was detected during mean follow-up period of 28.72G16.18

Aim

months.

The main objective of this paper was to verify if Romanian acromegalic patients

Conclusion

are susceptible to developing neoplasia and what types of tumors are associated

Patients with acromegaly should be considered for the presence of thyroid cancer.

with acromegaly. Another purpose of the paper was to identify the risk factors

DOI: 10.1530/endoabs.49.EP981

involved in tumor predisposition.

Methods

This observational, retrospective study considered 336 acromegalic patients (217

of them females, 64.6%) followed from 2001 until 2015 in report to the evolution

of acromegaly and the development of associated diseases, mainly neoplasia.

Results

Acromegalic patients had a higher risk of developing associated neoplasia (40%

EP982

benign and 10% malignant). Activity of the disease was not an important factor

The triglyceride (TG)/HDL Cholesterol (TG/HDL-C) ratio as marker of

(except for the thyroid - 54.84% of the patients had active acromegaly), whereas

adipose tissue dysfunction at patients with acromegaly

initial values of IGF-1 seemed to influence the developing of prostate neoplasia

Oksana Khyzhnyak, Miroslava Mykytyk & Iurii Karachentsev

(mean corrected value 4.58, PZ0.025). Sex has proved to be a factor too: women

Institute of Endocrine Pathology Problems, Kharkiv, Ukraine.

were more prone to developing neoplasia than men (57.14 vs 34.29%), and

especially multiple types of tumors. The most frequently associated types of

neoplasia in our patients were developed in: thyroid (47% women, 20.95% men),

Background and aims

breast (11.93%) and uterus (5.99%)-for women, and colon (9.52%) and prostate

The ratio of TG/ HDL-C can identify cardiometabolic risk and cardiovascular

(6.67%)-for men. The longer the duration of active acromegaly the higher was the

disease. The visceral adiposity index (VAI) is a sex-specific index, in which

risk of developing colonic neoplasia.

measurements of body mass index and waist circumference are combined with

Conclusions

TG and HDL-C concentrations. T? study association between VAI and TG/HDL-

The results suggest that we need to perform a more meticulously screening of

C and the value of TG/HDL-C ratio as a marker of disfunction of visceral

associated tumours in acromegalic patients, not only using ultrasound and

adiposity tissue at patients with acromegaly.

colonoscopy for the thyroid gland and colon, but also mammography as well as

Subjects and methods

PSA level determination. These evaluations should be taken into consideration

Eighty-eight patients (30 men and 58 women; aged 17-75 years) with acromegaly

periodically in all our acromegalic patients, regardless of the evolution of their

were under investigation. Disease activity was evaluated according to the

main disease.

Consensus Conference criteria (2000). Blood samples for GH, IGF-1, TG, HDL-C

DOI: 10.1530/endoabs.49.EP980

and total cholesterol were taken in fasting state. VAI score and normal values

used by M. C. Amato et al., 2011. It was considered the normal VAI in an age-

dependent group to 30 years !2.52, from 31 to 42 years - !2.23, from 43 to 52

years - !1.92, from 53 to 66 years - !1.93 and more than 67 years - !2.00

Taking into account a value VAI, all patients were divided on two groups: with

normal VAI (55.7%) (group 1) and high VAI (44.3%) (group 2). The 10-years-old

general cardiovasculary risk (CVD) was determined by a calculator «General

EP981

CVD Risk Prediction».

Results

Clinical and histopathologic characteristics of thyroid cancer in the

At nonlinear correlation, TG/HDL-C ratio was highly correlated with VAI in both

patients with acromegaly

men (r_sZ0.96, PZ0.00001) and women (r_sZ0.97, PZ0.00001), that TG/HDL-C

Buket Yilmaz Bulbul¹, Mehmet Celik¹, Nuray Can², Semra Ayturk¹,

can serve as more adequate criterion of estimation of disfunction of visceral

Ebru Tastekin², Atakan Sezer³, Funda Ustun⁴ & Sibel Guldiken¹

adiposity tissue at patients with acromegaly. This supposition confirms exposed

¹Department of Endocrinology and Metabolism, Medical Faculty, Trakya

by us for patients in a general group positive correlation TG/HDL-C with the level

University, Edirne, Turkey;²Department of Pathology, Medical Faculty,

of GH (r_sZ0.38, PZ0.0001). Before TG/HDL-C it was suggested to use for

Trakya University, Edirne, Turkey;³Department of Surgery, Medical

identification of cardiometabolic risk in general population (M. R. Salazar et al.,

Faculty, Trakya University, Edirne, Turkey;⁴Department of Nuclear

2014). In a group with high VAI 10-years-old CVD risk and MS risk in 1.6 and 1.4

Medicine, Medical Faculty, Trakya University, Edirne, Turkey.

times, according higher, than in a group with normal VAI (OR 1.56, OR 1.42).

Conclusion

Aim

By the equivalent of VAI for the estimation of expressed of disfunction of visceral

There are some studies suggesting that the risk of developing cancers,especially

adiposity tissue at patients with acromegaly can serve also TG/HDL-C ratio.

thyroid cancer, is increased in the patients with acromegaly. The prevalence of

DOI: 10.1530/endoabs.49.EP982

thyroid cancer is 1.2-10.6% among the patients with acromegaly. In this study, we

aimed to evaluate clinical and histopathologic characteristics of thyroid cancer

among the patients with acromegaly.

Method

We retrospectively evaluated the patients with acromegaly who had been

followed-up by our department between the years 2005 and 2016 and diagnosed

EP983

with thyroid cancer.

Anti-proliferative effects of high doses cabergoline in patients with

Results

prolactinoma

(81.8%) of 11 subjects were female and 2 (18.2%) patients were male. The mean

Oksana Khyzhnyak, Teona Gogitidze, Miroslava Mykytyk,

age of the patients at the time of acromegaly diagnosis was 41G11years. Among

Iurii Karachentsev, Nadiya Barabash & Katerina Manskaya

subjects who had been followed for 11.45G9.37 years, all except one patient

Institute of Endocrine Pathology Problems, Kharkiv, Ukraine.

were not in remission and were receiving medical treatment. All subjects were

diagnosed with thyroid cancer after the diagnosis of acromegaly and the mean

time until the diagnosis of thyroid cancer was.27G9.23 years. In terms of thyroid

The aim of the study

hormone status, nine subjects were euthyroid and two patients were found to have

To investigate the anti-proliferative effect of cabergoline (CAB) which was used

central hypothyroidism. Thyroid ultrasonographic examination revealed multi-

in different regimes of suppressive therapy during 12 months in patients with

nodular goiter in all patients. Thyroid fine needle aspiration biopsy was performed

prolactinoma (PROL).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Subjects and methods

EP985

It was examined and underwent a 12 month course of treatment by selective

Venous glucose levels, peak GH and peak cortisol during Insulin

dopamine agonist CAB 61 patients with PROL: microadenoma 42, macro&giant

Tolerance Test using 0.15 UNITS/Kg and 0.1 UNITS/Kg body weight

PROL - 19. (52 women/9 men) aged 16-66 years. The total duration of the disease

Phillip Yeoh¹, Ashley Grossman^2,1, Shern L Chew¹, Pierre Bouloux^3,1,

ranged from 1 to 60 months, average (12.3G10.1) months. PROL was verified

Bernad Khoo^3,1, Paul Carroll^4,1, Simon Aylwin^5,1 & Stephanie Baldweg^6,1

using MRI 1.5T. Pituitary volume was calculated by the Di Chiro-Nelson. Were

¹The London Clinic, London, UK;²John Radcliffe Oxford, Oxford, UK;

estimated total and partial secretory activity (PSA) in PROL. PRL blood levels

³Royal Free Medical School, London, UK;⁴Guys & St Thomas Hospital,

(ng/ml) were determined. Applied two modes of therapy: 1 - the mode of gradual

London, UK;⁵Kings College Hospital, London, UK;⁶UCLH Hospitals,

increase of a CAB dose, since 0.5 mg/week with the subsequent control of the

London, UK.

PRL blood level in each 4 weeks and titration CAB dose if necessary (increase in

a week dose by 0.25-0.5 mg); 2 - the mode of high starting doses from

calculation: the quantity of tablets CAB (0.5 mg) corresponded to frequency rate

Insulin Tolerance Test

(ITT) is a procedure commonly done by Endocrine

of increase of the PRL blood level in relation to the upper limit of age norm, but

Specialist Nurse in endocrine department. We look at over 120 ITT results done in

no more than 4 mg (8 tablets) a week. The statistical data analysis was carried out

2 endocrine centres using Insulin Actrapid 0.15 UNITS/kg and 0.10 UNITS/kg

with SPSS version 9.0.

dose plotting the glucose levels at 30, 45 and 60 min. We also look at peak GH

Results

and peak cortisol on each of these groups.

At purpose of high starting doses of CAB after 1 mth of treatment PRL level in

Aims

58.1% of patients decreased to the reference values, including in patients with

We wanted to know how many percentage of patients achieving hypoglycaemia

macroPROL after 1 month at 26.3% of patients had achieved target levels, after 3

below 0.5 mmol/l, 0.5-1.0 mmol/l, 1.1-1.5 mmol/l, 1.6-2.0 mmol/l and above

months - at 84.2%, and by 6 months of treatment - at 100% patients. In all patients

2.0 mmol/l. We also look at percentage of peak GH response achieving over

it was a statistically significant decreasing the pituitary volume after 12 months of

9 microgram/l, between 8-9 microgram/l and below 8 microgram/l. In the peak

treatment (P !0,001), but only in patients who were treated high starting high

cortisol response, we looked at results over 550 nmol/l; 500-550 nmol/l; 450-

dose CAB recorded decrease in the size of adenoma by 50% or more of the basal

500 nmol/l; 400-450 nmol/l and below 400 nmol/l. Within these data, we also

volume: at 9 microPROL and 4 macroPROL.

look at a small groups of results for patients’ using 0.15 UNITS/kg as repeat dose

Conclusions

and repeat ITT using the lower dose to compare if these are difference in these

The most expressed anti-proliferative effect is noted at application of high starting

markers.

doses of CAB. Optimum therapeutic average and cumulative doses of CAB for

Summary

achievement of maximum therapeutic effect at patients with microPROL are

We are unable to draw summary at the moment as well still got 30 data to go

doses of

0.8 mg/week and

33.8 mg/year, respectively; for patients with

through.

macro&giant PROL - 1.3 mg/week and 67.6 mg/year, respectively. At patients

DOI: 10.1530/endoabs.49.EP985

with microPROL the positive therapeutic effect is reached on a smaller

cumulative CAB dose which is associated with a lower risk of complications in

the long term period.

DOI: 10.1530/endoabs.49.EP983

EP986

EP984

Long-term impact of primary medical and surgical therapy on bone

density in men versus women with prolactinomas

Invasive macroprolactinomas and its response to treatment in male

Lukas Andereggen¹, Janine Frey², Robert Andres¹, Marwan El-Koussy³,

patients

Jurgen Beck¹, Luigi Mariani⁴ & Emanuel Christ^2,4

Alin Abreu, José Hernández, Margarita Velasco, Pablo Triana &

¹Neurosurgery, Bern, Switzerland;²Endocrinology, Bern, Switzerland;

Orlando Casta

˜o

³Neuroradiology, Bern, Switzerland;⁴Neurosurgery, Basel, Switzerland;

¹Centro Medico Imbanaco, Cali, Colombia;²Instituto Nacional de

⁵Endocrinology, Basel, Switzerland.

Endocrinología, La habana, Cuba;³Universidad Libre Seccional, Cali,

Colombia.

Purpose

The prevalence of pathological bone densities in men and women with

Introduction

prolactinomas treated either primary surgically or medically are infrequently

Prolactin-producing pituitary adenomas are the most common pituitary tumors in

reported across large cohorts. In the present study, we aimed at comparing the

clinical practice. In men they are more aggressive and their response to

impact of either therapeutic approach on the bone density in men vs women with

pharmacological treatment is unknown.

prolactinomas.

Objective

Methods

Describe the clinical characteristics and response according to the treatment of a

Retrospective case-note study including all consecutive patients with prolacti-

group of male patients with invasive macroprolactinomas.

nomas in whom osteodensitometry data was available at study entry and long-

Materials and methods

term follow-up (S 12 months). Bone mineral density (BMD) was assessed by

A retrospective descriptive study, a series of cases, in 30 patients, attending two

dual-energy X-ray absorptiometry. Clinical and biochemical characteristics,

pituitary clinics (National Endocrinology Institute in Havana, Cuba and Imbanaco

tumor size, and remission rates were recorded.

Cali Colombia Medical Center) between 2002 and 2012. Results Between the two

Results

types of treatment were compared and measures of central tendency and test of

Hundred patients (40 men, 60 women) met inclusion criteria. At baseline, men

Student or Kruskal Wallis were used.

had a significantly higher prevalence of pathological BMD than women (28 vs

Results

2%, P!0.001). Primary medical therapy was considered in 47, first-line surgery

The mean age was 44G13.8 years; the disease duration was 5.2G4.1 years; 96%

in 53 patients. Median follow-up time was 79 months (range 12-408 months).

of the patients presented headache, followed by hypopituitarism (80%). The

Long-term PRL values significantly decreased in both cohorts, regardless of the

median prolactin value at admission was 487 ng/ml. 53% required surgery plus

primary treatment. There was a persisted need for dopamine (DA)-agonists in

dopaminergic agonists; in this group there was a decrease in prolactin levels of

75% men compared to 42% women (PZ0.001). The prevalence of pathological

86% at 6 months and 96% at 12 months; in the dopaminergic agonist group, there

BMD in men remained significantly higher than in women (37 vs 7%, P!0.001),

was a 71% decrease at 6 months and 95% at 12 months. Surgical patients had the

independent of the primary treatment strategy.

mayor Tumor size reduction 11.4 mm compared with 8.3 mm, however a year

Conclusions

there were no difference between the groups.

The prevalence of pathological BMD in men remains significantly higher than in

Conclusion

women, independent of the primary treatment strategy. While osteoporosis

Surgical treatment plus dopaminergic agonist showed no differences with medical

prevention and treatment is mainly focusing on women, awareness of the bone

treatment in reducing prolactin values during the first year of treatment regardless

loss in men with prolactinomas should not be underestimated.

of tumor size.

DOI: 10.1530/endoabs.49.EP986

DOI: 10.1530/endoabs.49.EP984

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP987

EP989

Stenosis of the external auditory canal in an acromegalic patient: a

Preoperative HDDST in the prognosis of CD remission after

novel complication

transshenoidal endoscopic surgery

Hee Kyung Kim, Jee Hee Yoon, Yun Ah Jeong & Ho-Cheol Kang

Gussaova Natalya, Tsoy Ulyana, Cherebillo Vladislav, Dalmatova Anna,

Department of internal Medicine, Chonnam National University Medical

Belousova Lidiya, Mitrofanova Lyubov & Grineva Elena

School, Gwangju, Republic of Korea.

Federal Almazov North-West Medical Research Centre, Saint-Petersburg,

Russia.

Acromegaly is associated with a range of comorbidities, including cardiovascular

disease, diabetes, hypertension and sleep apnea. Bony overgrowth and soft tissue

Purpose

thickening not only cause typical external features of acromegaly, but also

Transsphenoidal endoscopic surgery

(TSS) is the first-line treatment for

debilitating musculoskeletal aches. Recently, a few papers reported auditory

Cushing’s disease (CD). Persistence and recurrence of hypercortisolism after

complications of acromegaly, but there has been no report on narrowing of the

TSS considered important problem. In this case search for CD remission

external auditory canal as a complication of acromegaly. A

58-year-old

predictors is actual.

acromegalic patient complained of fullness of both ears. He had transsphenoidal

Aim

surgery for GH-secreting pituitary adenoma 17 years ago. Somatostatin analogue

To study the role of preoperative oral high-dose dexamethasone suppression test

therapy was discontinued 2 years earlier, because nadir GH after oral glucose

(HDDST) in the prognosis of CD remission after TSS.

loading and IGF-1 level were normal. On laboratory exam, random GH was

Materials and methods

0.82 ng/ml, and IGF-1 264.74 ng/ml (reference range, 71-263). On otolaryngo-

60 patients with Cushing’s disease (nine men, 51 women, mean age 41 years

logic examination, both auricles were very hard and immobile, and orifices of

(15-73) who had underwent TSS were included. HDDST was performed in all

external auditory canals (EAC) showed slit-like openings. In left ear, eardrum

cases before the TSS. Postoperative examination was done one and two years

examination was impossible due to severe stenosis of EAC. On temporal bone

after surgery. Remission criteria were: secondary adrenal insufficiency (the need

CT, both ears showed thickening of tympanic membranes and evidence of chronic

for glucocorticoid replacement) or combination of normal midnight serum

otitis media with severe soft tissue thickening of left EAC. Pure tone audiometry

cortisol level, normal 24 h urine free cortisol (UFC) excretion and serum cortisol

documented mild hearing loss in left ear. The patient declined any further

suppression less than

50 nmol/l in

1-mg dexamethasone test. The optimal

evaluation and therapeutic intervention. Ear complications of acromegaly has not

threshold value of serum cortisol suppression in the HDDST for prediction of

received much attention so far. We report a case of ECA stenosis developed in an

CD remission after TSS was calculated by ROC-analysis.

acromegalic patient, as a novel complication of acromegaly.

Results

DOI: 10.1530/endoabs.49.EP987

One year after surgery CD remission was confirmed in 39 patients, whereas in

21 patients hypercortisolism persisted, after two years - in 36 and 24 patients,

respectively. The optimal threshold value of serum cortisol suppression in the

HDDST for prediction of CD remission in one year after TSS was 72%. Test’s

sensitivity and specificity were 82% and 84%, respectively. The probability of

wrong prediction was 17% (PZ0.0001).Two years after TS optimal threshold

value of serum cortisol suppression remained 72%, with sensitivity and specificity

86% and 80%,the probability of wrong prediction was 16% (PZ0.001).

Conclusion

According to our data serum cortisol suppression more than 72% in HDDST may

be used as a prognostic criterion for CD remission after TSS.

DOI: 10.1530/endoabs.49.EP989

EP988

Is Pegvisomant correct choice for acromegaly patient with dilated

cardiyomypathy?

Murat Cinel, Caglar Keskin, Rifat Emral & Demet Corapcioglu

Endocrinology and Metabolism Department, Ankara University Faculty of

Medicine, Ankara, Turkey.

Objectives

Acromegaly may arise with several clinical presentations and cardiac

involvement is the most important factor affecting the course of the disease.

Case

EP990

A 32-years old man admitted to hospital complaining with shortness of breath.

Somatostatin analogs in the treatment of acromegaly: single centre

After initial evaluation he was diagnosed as ‘cardiac failure’. Cardiac evaluation

experience

revealed that he had ‘dilated cardiomyopathy’ with ejection fraction (EF) of 20%,

Agne Abraitiene^1,2, Aiste Aleknaite^1,2 & Gintare Zelnyte²

global hypokinesia without valvular disease and coronary angiography was

¹Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania;

detected as normal. After immediate cardiac treatment he was consultated to

²Vilnius University Medical Faculty, Vilnius, Lithuania.

endocrinology because of hyperglycemia. When the patient evaluated for

hyperglycemia, physical examination findings consistant with acromegaly. He

Introduction

was diagnosed as acromegaly with high IGF-1 and GH level and 19 mm

The purpose of this study was to evaluate effectiveness of somatostatin analog

macroadenoma in pituitary MRI. Because of heart failure, surgery was delayed

(SSA) treatment in patients with acromegaly.

and medical therapy was initiated. After 6 months of therapy with high dose

Methods

somatostatin analogue treatment, his cardiac status did not show any

The study involved retrospective data collection from charts of 29 patients with

improvement and we decided transnasal transsphenoidal adenomectomy. After

acromegaly who received medical therapy at Vilnius University Hospital

surgery he was not in remission and somatostatin analogues were initiated again.

Santariskiu klinikos in 2016.

At the 6 months of additional therapy, IGF-1 and GH level were not in normal

Results

range. We decided to add pegvisomant to therapy. At the

2nd week of

Patient population consisted of 10 males (34.5%) and 19 females (65.5%), mean

combination therapy, he developed severe cardiac failure with EF 10% and

age 58G26 years. Primary SSA therapy was administered in 13 (44.8%) patients

therapy was discontinued. After cessation of pegvisomant, his symptoms revealed

who refused or had contraindications to surgical treatment. Secondary medical

minimally.

therapy was applied in 16 (55.2%) of patients with recurrent disease after

Conclusion

transsphenoidal surgery.

28 patients received SSA treatment

of them in

As we know cardiac problems are the first leading cause of death in acromegaly.

combination with a dopamine agonist (DA)), 18 patients recieved high-dose SSA

Cardiac involvement may appear any of the followings; hypertension, valvular

treatment

(Sandostatin LAR 40 mg or Somatuline Autogel 120 mg every 4

heart diseases, arrhythmias, hypertrophic cardiomyopathy and dilated cardiomyo-

weeks). Based on GH and IGF-1 results, control and partial control was achieved

pathy. Most of the patients treated with pegvisomant show decreased cardiac

in 16 (57.1%) and 8 (28.6%) patients receiving SSA treatment (GDA). 4 (14.3%)

muscle mass in hypertrophic cardiomyopathic patients. There is no data about

medically treated patients remained uncontrolled. High-dose SSA treatment

pegvisomant use in acromegalic patients with dilated cardiomyopathy. Should we

failed to achieve disease control in 4 (22.2%) of patients. Disease control and

use it cautially in dilated cardiomyopathic patients?

partial control was attained in 5 (38.5%) and 5 (38.5%) of patients with primary

DOI: 10.1530/endoabs.49.EP988

SSA treatment and in 12 (75%) and 3 (18.8%) of patients with SSA treatment

after transsphenoidal surgery. We found higher mean IGF-1 level in primary SSA

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

treatment group as compared to secondary SSA treatment patients (455G56 mg/l

EP993

vs 307G40 mg/l, PZ0.04)

Conclusions

SSA treatment (GDA) results in disease control in 57.1% of patients with

Abstract withdrawn.

acromegaly. High-dose SSA treatment failed to achieve disease control in 22.2%

of patients. SSAs are more effective when applied after transsphenoidal surgery as

disease control is achieved in greater percentage of patients and mean IGF-1 level

is lower when compared to patients who refused or had contraindications to

surgical treatment.

DOI: 10.1530/endoabs.49.EP990

EP994

A eight successful pregnancies in six Algerian women with acromegaly:

EP991

a monocenter study of Pierre and Marie Curie center.

Biochemical normalization in acromegaly after 79 months’ treatment

Safia Mimouni

with Pasireotide: case report

Pierre and Marie Curie Center, Algiers, Algeria.

Chiara Bima¹, Sabrina Chiloiro¹, Donato Iacovazzo²,

Tommaso Tartaglione³, Maria Elena Bracaccia¹, Antonella Giampietro¹,

Introduction

Antonio Bianchi¹ & Laura De Marinis¹

Acromegaly usually results from GH hypersecretion elaborated by somatotrop

¹Pituitary Unit, Catholic University of the Sacred Heart, Rome, Italy;

adenoma. The occurrence of a pregnancy in an acromegaly is an infrequent event,

²Centre for Endocrinology, Barts and The London School of Medicine,

but better described in recent years. It could be aggravate GH secretion and tumor

Queen Mary University of London, London, UK;³Department of

volume.

Radiology, Catholic University of the Sacred Heart, Rome, Italy.

Objective

Describe eight pregnancies including twin pregnancy in six acromegalics patients

Pasireotide, a multireceptor-targeted somatostatin analogue, was approved for the

hospitalized in the endocrinology department of the Pierre and Marie Curie center

treatment of acromegaly, after being studied in two large, randomised, multi-

in Algiers.

center clinical trials. We reported the history of a 76 years old man affected by

Materials and method

acromegaly, treated with Pasireotide long acting release (LAR) as first line

Materials: Eight pregnancies; their mean Age was 35.5 years.meanwhile of

therapy. Acromegaly was diagnosed in 2009, as the result of endocrinological

diagnosis: MRI revealed: macro adenoma (nZ7) and microadenoma (nZ1); The

investigation suggested by altered facial appearance and macroglossia. Hormonal

Visual Field was normal, Hypopituitarism was observed in 1 case and thyrotoxic

assays demonstrated high levels of IGF1 (584 ng/ml) and GH (8.7 ng/ml), without

insufficiency in er 1 case. No diabetes mellitus or hypertension were noted.

any suppression of GH at oral glucose tolerance test. Patient consequently

Patients underwent surgery

(nZ5), surgery and radiotherapy

(nZ1). The

underwent brain magnetic resonance (MRI), with the finding of a 7 mm expansive

pregnancies were spontaneous in all cases.

formation of the right half adenohypophysis, suggestive for pituitary micro-

Method: Diagnosis of acromegaly: HGPO/GH; GH/IGF1,magnetic RM imagin-

adenoma. Patient, in November 2009, was enrolled in CSOM230C2305 study and

ing pituitary and Visual Field were performed before conception and at T1, T2,

was treated with Pasireotide LAR at blided dosage, with biochemical control of

T3 of the pregnancy and in the postpartum. We have searched Diabetes Mellitus,

disease and progressive reduction of the pituitary adenoma volume. In May 2016,

gravid hypertension, the Childbirth Incidents, and we examinated Newborns.

following the onset of dyspnea, dysphagia and dysphonia, patient was diagnosed

Results

with anti-MuSK-positive myasthenia gravis, treated with apheresis and steroid

Eight pregnancies resulted in nine healthy babies. Gestational diabetes occurred

therapy, currently in good control. In this period, in according to the detection of

in Three cases and regresses in the postpartum in two cases; No Gravid

very low level of IGF1

and in consideration of concomitant diagnosis of

hypertension. The IGF1 and GH concentrations did not change significantly

myasthenia gravis, therapy with Pasireotide LAR was discontinued and patient

during pregnancy and in the postpartum. Growth adenoma was noticed in two

continued follow-up. The last brain MRI, performed in May 2016, documented

cases but without defect in any visual field. Fetal malformations were not

the stability in size and morphology of the known pituitary microadenoma. Eight

observed, birth weight was normal.

months later, in January 2017, patient is actually in remission, with IGF1 in the

Conclusion

normal reference range for age and gender (196 ng/ml) and GH !2.5 ng/ml

Acromegaly remains a rare cause of infertility. Pregnancy in women with active

(0.5 ng/ml). This clinical case shows the efficacy of Pasireotide in gaining

acromegaly or uncontrolled acromegaly may be associated with an increases risk

biochemical control of acromegaly, factor that is primarily implicated in the

of gestational and gravid hypertension. Pregnancy is occasionally associated with

reduction of disease morbidity and mortality.

an enlargement of adenoma.All these data must be confirmed by prospective

DOI: 10.1530/endoabs.49.EP991

studies.

DOI: 10.1530/endoabs.49.EP994

EP995

EP992

Abstract withdrawn.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP996

19.9 pg/ml; C10 min: IPS: 123.9 pg/ml and OIPS: 10.9 pg/ml; C15 min: IPS:

16.2 pg/ml and OIPS: 12.2 pg/ml).

Sheehan syndrome presenting 21 years later as severe heart failure

Conclusion

Ana Gonçalves Ferreira, Sofia Alegria, Maria Carlos Cordeiro &

The localization of the catheters into the inferior petrosal sinus allow to achieve a

Jorge Portugal

higher diagnostic central/peripheral ACTH gradient as compared to other catheter

Hospital Garcia de Orta, Almada, Portugal.

localization.

DOI: 10.1530/endoabs.49.EP997

Introduction

Sheehan syndrome (SS) is caused by postpartum necrosis of the pituitary gland,

associated with significant haemorrhage during or after delivery. It is rare in

developed countries, but still frequent in underdeveloped ones. We present a rare

presentation of this syndrome.

Clinical case

A 48 years old black woman presented at the emergency department for long term

fatigue and dyspnea that worsened a few days before. Her physical examination

revealed muffled heart sounds, decreased breath sounds inferiorly and bilaterally,

a puffy face and dry skin. Also, she had a slurred speech and hoarseness. No other

EP998

significant findings. No relevant past medical history, except for a complication in

Ipilimumab-induced hypophysitis

her second pregnancy (at 17 years), with a significant internal haemorrhage at

Silvia María Maraver Selfa¹, María Molina Vega¹,

term and an emergency caesarean section (stillborn). No subsequent lactation.

Inmaculada González Molero², Isabel Mancha Doblas¹ &

Amenorrhea since then. Blood tests: Hb 9.3 g/dl

(microcytic, hypochromic

Francisco Tinahones Madue

˜o^1,2

anaemia); LDH 1778UI/; CK 6793UI/L; AST 401UI/L; ALT 168UI/L; AF

¹Universitary Hospital Virgen de la Victoriatoria, Malaga, Spain;²Malaga

366UI/L; total cholesterol 366 mg/dl; LDL 293 mg/dl; triglycerides 218 mg/dl.

Regional Universitary Hospital, Malaga, Spain.

Arterial blood gas analysis: hypoxemia and slight hypercapnia. Chest x-ray:

bilateral pleural effusion and cardiomegaly. Abdominal ultrasound: cholelithiasis.

EKG: low QRS voltage. Echocardiogram: severe bilateral ventricular systolic

Hypophysitis are a heterogeneous group of inflammatory lesions affecting the

dysfunction raised filling pressures on the left, enlarged atriums and pericardial

hypophysis. Have been described hypophysitis secondary to administration of

effusion. Heart coronarography: no evidence of coronary artery obstruction. Her

immunomodulatory drugs such as interferon and anti-cytotoxic T lymphocyte

thyroid function tests were suggestive of central hypothyroidism

(TSH

antigen-4

antibodies

(CTLA-4). Ipilimumab is an anti-CTLA-4

human

0.70 mU/L; FT4 !0.24). Pituitary functions test reaveled panhypopituitarism

monoclonal antibody that blocks the union between CTLA-4 and B7 receptor

(FSH 4.1 UI/L; LH 2.6 UI/L; Estrogen!10 pg/ml; Testosterone !10 ng/dl;

on antigen-presenting cells causing an antitumoral effect and increasing the

prolactin 0.8 ng/ml, IGF1). ACTH was not reliable because the patient had been

production of autoantibodies. Hypophysitis has been described in 17% of patients

started on corticosteroids before L-thyroxine. Sellar MRI showed an empty sella.

treated with this drug and usually appears before the fourth dose. Clinical

Given her medical history in this clinical setting we believe a SS, left undiagnosed

presentation is similar to other causes of hypophysitis.

for 21 years, caused the panhypopituitarism.

Case report

Conclusion

44 years old man. Medical history: ocular melanoma with hepatic metastases 12

This case is illustrative of a rare presentation of SS, with severe heart failure and

years after surgery. After the 3rd cycle of treatment with intravenous Ipilimumab

low prolactin levels (unusually found).

(3 mg/kg per 3 weeks), the patient began with intense headache. Cranial MRI

showed an increased hypophysis so a morphofunctional study of hypophysis was

DOI: 10.1530/endoabs.49.EP996

performed. Laboratory evaluation: fasting blood glucose 76 mg/dl, creatinine

0.77 mg/dl, sodium 135 mg/dl, aspartate transaminase (AST) 80 UI/l, alanine

transaminase (ALT) 311 UI/l, gamma-glutamyltransferase (GGT) 776 UI/l, TSH

0,04 mUI/ml, free T4

0.65 ng/dl, serum cortisol

(0800 h)

14 mg/dl, ACTH

19 pg/dl, prolactin 8.83 ng/ml, FSH 11.97 mUI/ml, LH 3.23 mUI/ml, testosterone

1.2 ng/ml, GH 0.77 ng/ml, IGF-1 83.4 ng/ml (94-252). Pituitary MRI with

contrast: glandular thickening with extension to cavernous sinus and irregular

contrast enhancement. After the diagnosis of Ipilimumab-induced hypophysitis

with gonadal and thyroid axis deficiency associated, Ipilimumab was stopped.

EP997

The patient began levothyroxine replacement therapy and treatment with

prednisone 60 mg/day, with a progressive dose decrease during a month until

Localization of the catheters during Bilateral sampling of the inferior

get the correct replacement dose.

petrosal sinuses can impact diagnostic power?

Conclusion

Sabrina Chiloiro¹, Alessandro Pedicelli², Iacopo Valente²,

The use of new immunomodulatory drugs makes necessary to identify and define

Tommaso Tartaglione², Antonio Bianchi¹, Antonella Giampietro¹,

this hypophysitis cause and set out protocols with the oncologists to avoid undue

Chiara Bima¹, Liverana Lauretti³, Carmelo Anile³, Alfredo Pontecorvi¹

delay in its diagnosis and treatment.

& Laura De Marinis¹

¹Pituitary Unit, Catholic University of the Sacred Heart, Rome, Italy;

DOI: 10.1530/endoabs.49.EP998

²Department of Radiology, Catholic University of the Sacred Heart, Rome,

Italy;³Department of Neurosurgery, Catholic University of the Sacred

Heart, Rome, Italy.

Introduction

Bilateral sampling of the inferior petrosal sinuses (IPSS) is considerate actually

the best diagnostic test for Cushing.

Patients and methods

We retrospectively reviewed our series of patients undergone IPSS for Cushing

disease and we compared the difference between central and peripheral ACTH

EP999

gradient in basal condition and after CRH stimulation in cases of localization of

Somatostatin Analogue Treatment of a Persistant TSH-Secreting

the tip of the catheters inside the inferior petrosal sinus or at the confluence of the

Adenoma: a report of case

inferior petrosal sinus into the internal jugular vein. All the pituitary contrasted

İlknur Ozturk Unsal, Erman Cakal, Mahmut Apaydın, Melia Karakose,

Magnetic Resonance was blinded reviewed by two dedicated neuro-radiologist.

Bekir Ucan & Mustafa Ozbek

Results

Saglik Bilimleri Universty Diskapi Yildirim Beyazit Traning and Research

A total of 10 patients achieved an IPSS with CRH stimulation suggestive for

Hospital, Ankara, Turkey.

Cushing syndrome. Four patients had a MR visible pituitary adenomas. In any

cases, infiltration of the para-sellar region was detected. At each time point of the

CRH-test during IPSS (basal, C3, C5, C10, C15 min), central/peripheral

Introduction

ACTH gradient was higher in cases of localization of catheters inside the inferior

Thyrotropinomas are usually considered when the TSH level is inappropriately

petrol sinus (IPS) as compared to cases of localization of catheters outside (OIPS)

elevated or normal in a hyperthyroid patient with increased serum T₄ levels,

the inferior petrosal sinus (respectively basal IPS: 9.3 pg/ml and OIPS: 3.8 pg/ml;

regardless of the presence of visible tumor on imaging. The prevalence of these

C3 min: IPS: 68.9 pg/ml and OIPS: 27.8 pg/ml; C5 min: 35.5 pg/ml and OIPS:

adenomas, which account for 0.5-3% of all pituitary tumors has been estimated to

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

be around one case per million. Most thyrotroph adenomas are large and invasive

EP1001

at diagnosis, and present with signs and symptoms of an expanding mass,

A case of pituitary apoplexy. a acute medical emergency and restitutio

including temporal visual field defects. Here, we report a patient treated with

ad integrum

somatostatin analogue with pituitary macroadenoma and hyperthyroidism.

Pilar Rodriguez, Maria Lainez, Maria Jose Lopez, Eloisa Roldan &

Case reports

Isabel Rebollo

A 64-year-old female patient, who had undergone surgical procedure in 2014 for

Complejo Hospitalario Huelva, Huelva, Spain.

solitary fibrous tumor in the left parietal region, applied to be checked because of

enlarged hypophysis gland documented via cranial MRI performed during

follow-up visits. Laboratory findings revealed high levels of fT₃ (8.56 pg/ml) and

A 50-year-old woman with no history of interest who was admitted in hospital for

fT₄ (2.1 ng/ml) with TSH (6.32 UI/ml) higher than its normal limit. On the MRI

progressive headache 2 weeks of evolution refractory to treatment that was

of the hypophysis, a 22!18!14 mm lesion consistent with macroadenoma,

accompanied by emetic syndrome and paresthesias in face and arms. A CT scan

which was heterogeneously contrasted after IV Gad injection, was detected in the

of the skull (urgency) was performed which was normal. Neurology improves

mid-left half of the pituitary gland. The lesion exceeds the lateral inter-carotid line

with analgesia and steroids, presenting mild drowsiness and mild hyponatremia

in the left aspect and surrounds the left ICA higher than 240 degree. Other

(121 mEq/l). A cerebral MRI was performed, showing a right subacute

hormones of the anterior hypophysis were within the normal range. SHBG was

hemorrhagic adenoma of 1 cm that protrudes into the suprasellar cisterna without

153.9

(30-100 nmol/l) and alpha subunit was 3.9 (0-1.6 IU/l), which were high.

compressing the optic chiasm and extending slightly to the right cavernous sinus.

There was no response to TRH stimulation test. Methimazole was commenced at

Subsequently it begins with severe headache and vomiting, aiming hemiparesis of

a dose of 20 mg and transnasal transsphenoidal pituitary adenomectomy was

predominance crural initially improving with hydrocortisone until it presents

performed. Somatostatin analogue (Octreotid LAR 10 mg/28 day) therapy was

convulsive crisis with prolonged decrease of consciousness and loss of control of

started for the patient, who had residual adenoma (20!15 mm) and in whom

sphincters, with difficult handling of ions. Urinary skull CT scan is performed

euthyroidism could not be achieved. Methimazole was interrupted in the 9th

with images compatible with mild diffuse cerebral edema, so that it enters the ICU

month of somatostatin analogue treatment and determining that the size of

with low level of consciousness and agitation with anisocoria and analytically it is

adenoma is 10!9!8 mm.

objectively a plasma sodium of 108 mEq/l, remaining in this service five days.

Conclusion

Campimetry was performed by the Ophthalmology Service that was normal and

Most thyrotrophs express variable number of somatostatin receptors (SSTR),

consulted the Neurosurgery Service together with Endocrinology was decided

particularly SSTR2 and SSTR5. Somatostatin analogues could be considered in

conservative management, ruling out endonasal transsphenoidal decompression.

the treatment of persistent disease following the surgical procedure performed for

No precipitating factors have been identified. Once stabilized, the patient was

TSH-secreting adenomas.

switched to hydrocortisone 100 mg/8 h, Hypothesis Polyuria clinic and suspicion

DOI: 10.1530/endoabs.49.EP999

of partial DI progressing favorably after being discharged after 44 days of

treatment with hydrocortisone and replacement desmopressin. Since then and

after more than three years of the onset of the picture is followed by the

Endocrinology Service, discarding other hormonal deficits. At present, five years

later, there is no neuro-endocrine symptomatology, with adrenal axis recovery

without substitute treatment and in treatment with desmopressin 100 mg with

withdrawal approach, in joint follow-up with skull MRI study and hypophysis

without alterations, normal. To conclude the interest of this case based on the

literature and the entity we describe as a potentially serious acute pituitary stroke

with vital risk and that is resolved satisfactorily with conservative treatment

EP1000

minimizing sequelae and restitution ad integrum, with autoimmune and

Spindle cell oncocytoma of adenohypophysis: report of a rare pituitary

differencial diagnois without evidence of underlying causes and satisfactory

tumor

evolution with conservative management.

Carlos Marques Pontinha, Manuela Mafra, Luís Cerqueira,

DOI: 10.1530/endoabs.49.EP1001

Amets Sagarribay, Fernando Fonseca & Ana Agapito

Centro Hospitalar Lisboa Central, Lisbon, Portugal.

Introduction

Pituitary adenomas represent 95% of all sellar masses. Spindle cell oncocytoma

(SCO), a rare histopathological entity (0.4% of all sellar tumours), clinically

presents as a non-functional pituitary adenoma. According to WHO

2016

Classification of Tumours of the CNS it is a Grade l tumour, but prognosis

remains uncertain since recurrence is frequently seen among the few cases

reported.

EP1002

Clinical case

Resistant microprolactinoma with partial empty sella

A 59 year-old man presented with progressive fatigue, loss of libido and visual

Sevgul Faki, Sefika Burcak Polat, Cevdet Aydin, Reyhan Ersoy

blurring for 5-years. He had pale and hairless skin and on visual field assessment a

& Bekir Cakir

bitemporal hemianopsia was diagnosed. Hormonal evaluation confirmed low

Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit

testosterone and gonadotrophins as well as central hypothyroidism and

University, School of Medicine, Ankara, Turkey.

hypocortisolism. PRL and IGF1 levels were normal. MRI scan revealed a T1

and T2 isointense 29!17!17 mm sellar mass with suprasselar extension causing

optic chiasm compression. Transsphenoidal surgery removed a grossly bleeding

Introduction

tumour. Histopathological examination revealed a neoplasm composed of

Prolactinomas are the most common hormonally active pituitary tumors that

interlacing fascicles of spindle cells with eosinophilic and oncocytic cytoplasm.

account for 40-60% of all pituitary adenomas and are usually successfully treated

Tumour cells had moderate nuclear atypia and 2 mitotic figures per 10 HPF

with dopamine agonists. Surgery or radiotherapy is reserved for drug

(Ki67/MIB-1 Proliferation Index 2-5%) were identified. The immunohistochem-

intolerance/resistance or in neuro-ophthalmological emergencies. We present a

istry profile was Vimentin/S100/GFAP/EMA/Synaptophysin positive. The final

patient with refractory microprolactinoma with empty sella treated by

diagnosis was SCO. Visual acuity and Goldmann perimetry improved

transsphenoidal surgery.

significantly, but hypopituitarism persisted. MRI scan, 3 months after surgery,

Case

showed a contrast enhanced 9!6!11 mm solid intrassellar mass - normal

42-year-old female patient admitted with a 14 years history of prolactinoma being

pituitary tissue or residual tumour? Reassessment is scheduled in the next

treated with dopamine agonists for ten years. At the end of the tenth year, the

3 months.

tumor was resistant to high dose cabergoline (4 mg/week). Magnetic resonance

Commentary

imaging

(MRI) revealed a partial empty sella with

6.5!3.5 mm pituitary

An apparent total resection of a SCO was obtained. However, prognosis is

adenoma. She underwent transsphenoidal surgery. Histopathologically, a

difficult to predict due to the short time of follow-up. Presence of cytological

pituitary adenoma with rare mitotic figures, Ki-67 index of 2%, no expression

atypia and mitosis in this case and knowledge of frequent recurrence rates obeys

of p53 and no other features of atypia was identified. Immunohistochemistry

to a stringent follow-up. The histogenesis of SCO remains unsolved. According to

showed expression of prolactin by majority of the cells. Postoperative MRI

the latest genetic data, SCO and granular cell tumour of the sellar region

demonstrated empty sella (height of the gland was 2 mm) and no residual mass.

(GCTSR) may be variants of another rare tumour, the pituicytoma.

After operation, cabergoline was restarted because of high prolactin levels and

DOI: 10.1530/endoabs.49.EP1000

amenorrhea. Despite a substantial increase in dosage there was no clinical

improvement in amenorrhea and galactorrhea and there was not any biochemical

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

response. Her other anterior pituitary hormones were normal while serum

unremarkable. Initial investigations were consistent with SIADH

(sodium:

prolactin was 255 ng/ml (4.79-25.3 ng/ml) in her last visit.

109 mmol/l, serum osmolality: 243 mOsm/kg, urine Na: 59 mmol/l and urine

Conclusion

osmolality: 191 mOsm/kg). Urea, creatinine and random glucose were normal.

A minority of patients, ranging from 10-20% in different series does not achieve

CT Head showed pituitary enlargement with sellar expansion. Pituitary profile

normoprolactinemia and/or tumor shrinkage despite treatment with high doses of

showed high prolactin: 8305 mIU/ml, low IGF-1: 78.1 mg/l and low testosterone:

dopamine agonists. Those tumors are usually macroadenomas with cavernous

3.83 nmol/l with normal LH and FSH. Thyroid function was normal with intact

sinus invasion and rarely microadenomas. Resistance can be documented by

pituitary-adrenal axis

(normal Glucagon and ACTH stimulation tests). MRI

demonstrating the absence or poor expression of D2 receptors on the membrane

pituitary confirmed macroadenoma with heterogeneous solid-cystic mass (2.0!

surface of tumor cells, or abnormalities at a postreceptor level. However,

1.9!1.5 cm) with deviation of pituitary stalk. He was treated with Cabergoline

molecular biology studies cannot be routinely performed in our center. Exchange

0.5 mg per week and few days of fluid restriction with improvement of sodium

of cabergoline with bromocriptine was successful in few cases in the literature.

level to 137 mmol/l and prolactin to 61 mIU/l after 2 weeks. Over 5 months

DOI: 10.1530/endoabs.49.EP1002

follow up; he remained asymptomatic with normal sodium and prolactin on

Cabergoline. Hypogonadisim has resolved and IGF-1 has normalized. Repeat

MRI 4 months after discharge showed significant reduction in macroadenoma size

to 1.4!1.3!0.7 cm with pituitary stalk being in midline.

Discussion

Hyponataemia complicating pituitary macroadenomas is usually related to

secondary hypoadrenalism. However, the presence of SIADH with intact

pituitary-adrenal axis in such cases is very rare with only seven cases reported

in literature (six non-functioning macroadenomas and one macroprolactinoma).

The mechanism of AVP release in these cases is not fully understood, but is

EP1003

thought to be related to local mechanical stress on the AVP neurons axonal

Acromegaly: clinical experience and determinants of remission

terminal and dislocation of pituitary stalk and neurohypophysis by pituitary

Ayten Eraydin¹, Ersin Akarsu¹, Zeynel A Sayiner¹, Mesut Ozkaya¹,

tumor.

Ibrahim Erkutlu², Suzan Tabur¹ & Mustafa Araz¹

Conclusion

¹Department of Endocrinology and Metabolism, Faculty of Medicine,

We hereby report the second case of SIADH secondary to macroprolactinoma

University of Gaziantep, Gaziantep, Turkey;²Department of Neurosurgery,

with normal pituitary-adrenal axis. Pituitary macroadenomas should be

Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.

considered in differential diagnosis of SIADH even in context of preserved

Introduction

pituitary-adrenal axis.

Acromegaly is a chronical and rare disease which is accompanied by excessive

DOI: 10.1530/endoabs.49.EP1004

growth hormone (GH) secreting hypohysis tumor. In this study we presented

acromegaly patients’ datas who admitted to our center between the years 1998-

2016. We discussed patients’ charecteristics and we aimed to investigate the

determinants which is effecting the remission rate of the patients’.

Method

70 acromegaly patients datas were analyzed retrospectively in our center. We

evaluated patients’ clinical, laboratory, imaging and treatment modalities

informations. The parameters accepted as remission criteria are as follows:

1) Basal GH!2.5 mg/l,

2) Having GH!1 mg/l level after glucose-growth

hormone supression test, 3) Having normal IGF-1 (insulin-like growth factor-1)

level in accordance with age and gender.

EP1005

Results

Clinical characterization and comparison of patients with hipophysary

57.1% of the patients were female. Mean age was 44G12. Mean age was 38G12

tumors and primary empty sella

when the diagnosis established. 97.1% of the patients had typical acromegaly

Alin Abreu, María Eugenia Casanova & Orlando Casta

˜o

symptoms. Other findings are: headache (77.1%), sweating (58.6%), vision defect

Universidad Libre Seccional, Cali, Colombia.

(15.7%), galactorrhea (10%), impotence (10%). Preop GH and IGF-1 levels were

18.3G15.8 mg/l,

954G349 mg/l respectively.

87.1% of the patients had

macroadenoma and % 61.4 of the patients had cavernous sinus invasion. Eight

Introduction

of the patients had drug therapy, 62 of them had surgery as first line therapy. 29%

Non-functioning pituitary tumors and primary empty sella are a common

of the patients’ pathology reports revealed that GH-Prolactin positive staining.

pathology within the differential diagnosis of pituitary masses. The mani-

Somatostatine analogues were administered to 64.5% of the patients after surgery.

festations will depend on the size of the tumor and the compression of adjacent

On the 3th month follow up remission rate was 53.5%, on the 12th month

structures being the most frequent neurological symptoms. Clinically the two

remisson rate was 65%, on the late period of the follow up remisson rate was

entities are very similar and no clinical tools are known to be able to help the

77.1%. There was statistically significant difference between preop GH levels,

differential diagnosis.

adenoma size, cavernous sinus invasion, ki67 proliferation index and remission

Objective

rate (P!0.05).

Perform a clinical and comparative characterization between patients with non-

Conclusion

functioning pituitary tumors and primary empty sella.

We concluded that high preop GH levels, adenoma size, cavernous sinus invasion,

Materials and methods

high ki67 proliferation index were the determinants of the poor outcome. Besides

A retrospective cohort study conducted in a highly complex center of the city of

surgeon experience should take into consideration for better outcome.

Cali, Colombia between January 2002 and December 2014.

DOI: 10.1530/endoabs.49.EP1003

Results

A total of

141 cases were found, 32% had a microadenoma, 30% had a

macroadenoma and 38% had a primary empty sella. 61% of the patients with non-

functioning pituitary tumors were women, as well as 51% of the cases of primary

empty sella. The largest number of patients with pituitary tumors were between 20

and 40 years old while in primary empty sella was between 40 and 59 years.

Headache was reported in 88% of cases, followed by visual disturbances in 59%

and galactorrhea in

41% of cases. As expected, the non-functioning

macroadenomas were those with the highest prolactin value with mean of

50 ng/ml. 97% of nonfunctioning microadenomas reported headache being more

frequent than in cases of macroadenomas and primary empty sella, this suggests

EP1004

the presence of an additional tension component.

A rare case of macroprolactinoma presenting with SIADH

Conclusion

Khaled Dukhan & Khaled Ashawesh

Nonfunctioning pituitary tumors and the primary empty sella are frequent entities

Hamad Medical Corporation, Doha, Qatar.

within the pituitary masses. The clinical distinction of these entities is quite

difficult and requires the accomplishment of an adequate clinical history,

adequate interpretation of hormonal and imaging studies.

Case

DOI: 10.1530/endoabs.49.EP1005

A 52-year-old gentleman was admitted with dizziness and collapse. Past medical

history revealed dyslipidemia treated with statin. Physical examination was

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1006

Results

During follow-up (median 7.5 years - 2135.94 person years), 47 patients died,

Prolactinomas in men: retrospective analysis

versus 33 expected from general population, corresponding to a SMR of 1.39

Teresa Rego, Carolina Neves, Ana Margarida Palha, Luisa Cortez,

(95% CI 1.02-1.84). Females had a doubled mortality ratio: SMR 2.13 (95%CI

Fernando Fonseca & Ana Agapito

1.30-3.29. 254 patients (69.8%) were operated and 87 patients (23.9%) were

Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,

irradiated. After pituitary surgery and/or radiotherapy, pituitary tumour remnant

Portugal.

diameter decreased with 35.62G37.35% (range 0-100%). Only 24 (6.6%) of

patients were cured after radical therapy (no remnant). Cox-regression analysis

Introdution

demonstrated that age at diagnosis and pituitary tumour diameter at last

Prolactinomas in men are rare and the majority are macroadenomas. Some studies

evaluation remained independent predictor factors correlated to mortality (hazard

suggest that these tumors in men have higher proliferative activity and

ratio HR 1.07 (95%CI 1.046-1.101, P!0.001 and respectively HR 1.02 (95% CI

aggressiveness indicating gender-specific differences in biological behavior.

1.046-1.101, PZ0.018)), whereas pituitary surgery or radiotherapy, pituitary

Dopamine agonists (DA) are considered first-line therapy.

failure had no impact.

Material/methods

Conclusions

Retrospective analysis of male patients diagnosed with prolactinoma between

In our patients with pituitary NFA mortality is still increased, especially in

2005 and 2016. Age at presentation, clinical, hormonal and image data were

women, influenced independently by the age at diagnosis and residual pituitary

collected. Mode and responses to therapy were analysed.

tumour diameter. A greater extent of tumour removal may increase survival.

Results

DOI: 10.1530/endoabs.49.EP1007

Twenty two patients with median age at diagnosis of 50.8 years were observed.

Sexual dysfunction was the main complaint (59.1%), followed by headaches

(50%) and visual disturbances (36.4%). Imagiology revealed macroadenoma in

95% of the cases (19% giant). At the time of diagnosis mean value of prolactin

(PRL) was 3.662 ng/ml (min 177 ng/ml, max 23.200 ng/ml). Hypogonadism was

present in 54.5%. Fourteen patients (63.6%) were treated with DA as the only

therapy and eight patients (36.4%) with DA and neurosurgery. From the latter

three presented pituitary apoplexy, four were misdiagnosed as non-functioning

adenoma and onepresented cerebrospinal fluid rhinorrhea. None of these patients

were cured after surgery and all received medical therapy. At the last visit

EP1008

normalization of PRL level were observed in 59.1% of the patients (71.4% treated

Autoimmune hypophysitis with isolated corticotroph cell destruction

with AD as only therapy) and 77.8% of the remaining presented a PRL level less

due to Pembrolizumab treatment in a female patient with metastatic

than 2X upper limit of normal. Reversal of hypogonadism occurred in 66.7%.

melanoma

Previous and after therapy MRI findings were available in

12 patients. A

Emmanouil Vasileiou¹, Charalampos Tsentidis², Andreas Bampilis²,

reduction R50% in tumor maximum diameter was achieved in 8 patients. The

Vasiliki Ntova², Grigoria Betsi² & Georgia Kassi²

mean follow-up was 5.4 years.

¹Private Practitioner, Samos Island, Greece;²Department of Endocrinology,

Commments

Metabolism and Diabetes, Nikaia General Hospital ‘Ag. Panteleimon’,

Our data confirms that prolactinomas in men are usually symptomatic

Athens, Greece.

macroadenomas. Although DA were efficient in reducing tumor size and

normalizing PRL, surgery was performed as first-line therapy in four patients due

to misdiagnosis and possibly late referral to our department. The correct diagnosis

Introduction

is crucial for successful treatment and avoidance of unnecessary surgery.

Pembrolizumab is a programmed death receptor-1(PD-1)-blocking antibody, used

in a variety of advanced malignant tumors with promising results, although

DOI: 10.1530/endoabs.49.EP1006

adverse events are not rare.

Case report

We present the case of an adult female, with negative personal and family history

of autoimmune diseases, who developed malignant superficial melanoma of right

wrist 6 years ago. She was initially treated with surgical resection (lesion and

ipsilateral axillary lymphadenectomy) and high dose interferon treatment and

re-operated due to multiple regional right in transit and left axillary lymph node

metastases. Melanoma was positive for B-Raf mutation and the patient received

Vemurafenib for 3.5 years and then Ipilimumab for four months (lung metastasis).

During that period she developed subclinical hypothyroidism, treated with

thyroxin. She finally received treatment with Pembrolizumab

(multiple

mediastinal and right axillary lymph node metastases) with gradual tumor

EP1007

recession within 4 months. She developed acute pancreatitis, without diabetes

Residual tumour diameter may influence reduced survival in females

mellitus, treated conservatively. Two months after full melanoma recession she

with nonfunctioning pituitary macroadenomas

developed fatigue, anorexia and diplopia for a few days without significant

Simona Galoiu^1,2, Iulia Burcea¹, Simona Silea¹, Oana Voicu¹,

findings in brain MRI. A 5-month period followed with exacerbations and

Ionela Baciu^1,2, Anda Dumitrascu², Andra Caragheorgheopol² &

remissions of somnolence, cognitive dysfunction, anorexia, and weight loss and

Catalina Poiana^1,2

finally developed hypotension and hypoglycemia. After a low morning cortisol

¹Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;

(4 mg/dl) measurement, she received full hydrocortisone replacement therapy

²C.I. Parhon National Institute of Endocrinology, Bucharest, Romania.

with complete symptoms remission. Thyroxin dose was increased and vitiligo

was developed during that period. There were no significant findings in

hypophysis MRI and melanoma restaging showed complete disease remission.

Objective

Hormonal profile (2nd menstrual cycle day) showed: PRL 12 ng/ml (1.9-25), LH

Patients with pituitary macroadenomas and concomitant hypopituitarism have a

1.2 mIU/ml (1.1-11.6), FSH 2.6 mIU/ml (0.7-11.1), E2 461 pg/ml (13-166),

reduced life expectancy due to various comorbidities.

SHBG 103 nmol/l (18-114), GH 0.93 ng/ml (0.06-5), IGF-1 195 ng/ml (94-252),

Aim

ACTH 1 pg/ml (7-50) while SST for cortisol was 1, 3 and 3 mg/dl at 0, 30, 60 min

To investigate mortality in patients with non-functioning pituitary adenomas

respectively.

(NFAs) and independent prognostic factors influencing survival.

Conclusion

Design

Pembrolizumab completely controlled metastatic melanoma in our patient

Retrospective cohort study in a tertiary neuroendocrine university department.

through immune stimulation. Hypophysitis with isolated corticotroph cell

Methods

destruction was developed as an adverse event. If confirmed in other cases

A total of 364 patients (177F/187M) evaluated for a macroNFA between 2001 and

Pembrolizumab could be used in treatment of refractory Cushing’s disease.

2016 were studied. PAMCOMP computation program was used to calculate

standardized mortality ratio (SMR). Cox regression analysis revealed indepen-

DOI: 10.1530/endoabs.49.EP1008

dent factors associated with mortality.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1009

(72.2%), dyslipidemia (10.2%), sleep apnoea (71.8%), and 17.7% had history of

CVD. In the HTN group, the mean age at diagnosis of acromegaly was 48 years

Aggressive pituitary tumors: a tertiary center experience

(S.D. 12.7) and the mean age at the start of PEGV (Baseline) was 56 years (S.D.

Adriana Lages¹, Isabel Paiva¹, Leonor Gomes^1,2, Patrícia Oliveira¹,

12.1) vs 36.3 years (S.D.11.7) and 43 years (S.D. 12.7) for non-HTN group. Time

Francisco Belo¹, Diana Oliveira¹, Diana Martins¹, Mara Ventura¹,

from diagnosis to PEGV treatment was 8.4 years (S.D. 8.5) vs 6.5(S.D. 7.2) in HTN

Nelson Cunha¹ & Francisco Carrilho¹

and non-HTN group respectively. At baseline systolic BP(SBP) was 138.3 and

¹Coimbra Hospital and University Center, Coimbra, Portugal;²Faculty of

diastolic BP(DBP) 85 mmHg. Follow up at year 5 showed SBP 134.5 and DBP

Medicine University of Coimbra, Coimbra, Portugal.

82.5 mmHg. Average IGF-1 level at baseline was 488.9 and 218 ng/ml at year 5.

Conclusions

Background

HTN is a common comorbidity in acromegaly. Patients with HTN tend to be older

Pituitary adenomas

(PA) are common intracranial tumors that are mainly

at diagnosis and start of PEGV and have multiple CV risk factors. With PEGV

considered benign. A small group of patients exhibit clinically aggressive

treatment, blood pressure levels remain stable over time.

behavior sometimes unrelated to the histopathological or radiological features.

DOI: 10.1530/endoabs.49.EP1010

Methods

Twelve patients were selected harboring a PA with clinical features of

aggressiveness. All the patients underwent pre and postoperative endocrinolo-

gic/neuroradiologic evaluation.

Results

10/12 patients were male, mean age at diagnosis 38.1 years (range 12-58) and

mean follow-up 14.3 years (range 5-28; died 3/12). In 9/12 cases, the first

manifestation was visual impairment (visual field loss, reduction in visual acuity

and/or cranial nerve palsies). All the patients had invasive pituitary macro-

EP1011

adenomas with expansion into surrounding anatomical structures (11 cavernous

Assessment of macroprolactin through post-PEG monomeric prolactin

sinus; 7 sphenoid sinus; 7 bone invasion). The 12 patients underwent a total of 52

measurement and comparison with gel fitration chromatography in

surgical procedures

(median

4; range

3-6). Apparently total removal was

hyperprolactinemic samples

achieved in 8/12 patients at the first surgical procedure. Regarding histological

Antonio Ribeiro-Oliveira Jr & Maria do Carmo D Gontijo

subtype: 5 gonadotrophinomas; 2 null-cell adenomas; 2 corticotrophinomas; 1

Federal University of Minas Gerais, Belo Horizonte, Brazil.

thyrotrophinoma; 1 prolactinoma and 1 plurihormonal adenoma (GH/ACTH).

Proliferation markers as ki67 O3% was identified in 4; O2mitoses/10 HPF in 3

and p53 IHC expression in 4/12 cases. Six patients underwent radiation therapy

Macroprolactin interference is a common problem in the interpretation of

(RT) postoperatively (5 conventional external RT; 1 stereotactic radiosurgery).

immunoassays for prolactin. Identifying macroprolactinemia can prevent

Medical therapy was tried in 4/12 patients: 3 with dopamine agonists; 1 with

errors in diagnosis and subsequent delivery of treatment to patients. The

somatostatin analog (pasireotide); 2 with steroidogenesis inhibitors (ketoconazole

search for macroprolactin through polyethylene glycol (PEG) precipitation

and metyrapone). Possible metastatic pulmonary disease was identified only in

followed by percentage recovery is the most common used method in

one case; the patient died of tumor progression 10-years after the diagnosis.

clinical laboratories. This study aimed to evaluate the implementation of

Conclusion

macroprolactin assessment in hyperprolactinemic samples, with the

Aggressive pituitary tumors constitute a challenging but not completely defined

interpretation of the results based on validated post-PEG monomeric

entity. We found an elevated number of surgical procedures by patient and

prolactin reference range. It also aimed to verify whether post-PEG

smaller proportion of RT/medical treated patients compared with literature,

monomeric prolactin measurements could match the results obtained

however, with similar outcomes. Adverse results in treatment are possibly related

through Gel filtration chromatography (GFC). Samples from 40 healthy

to difficulty in early detection of this patients’ subgroup that must be treated with a

subjects were utilized for the validation of the post-PEG monomeric

multimodal approach.

prolactin reference range, according to predetermined data quality. The

DOI: 10.1530/endoabs.49.EP1009

macroprolactin assessment by PEG precipitation was then performed on 112

hyperprolactinemic samples

(96

women), and results obtained by

percentage of post-PEG prolactin recovery were compared with post-PEG

monomeric prolactin concentrations. Twenty-five out of the 112 hyperpro-

lactinemic samples were randomly selected for evaluation through GFC for

further comparisons. Assessment of post-PEG monomeric prolactin

concentration with an appropriate validated reference range showed greater

specificity than the conventional criterion of percentage of post-PEG

prolactin recovery, as it identified samples with both excess macroprolactin

EP1010

and monomeric bioactive prolactin, and also reduced the rate of

Hypertension, acromegaly and pegvisomant treatment: Experience

indeterminate results. Furthermore, most of the results obtained in samples

from ACROSTUDY

analyzed by GFC were in agreement with results obtained by post-PEG

Greisa Vila¹, Arrt Jan vanderLely², Sebastian Neggers², Anton Luger¹,

monomeric prolactin measurement. The assessment of macroprolactin

Susan Webb³, Beverly Biller⁴, Peter Jonsson⁵ & Judith Hey-Hadavi⁶

through a validated post-PEG monomeric prolactin reference range should

¹Medical University of Vienna, Vienna, Austria;²Erasmus University

be adopted as it outperformed the current utilized criterion.

Medical Centre, Rotterdam, The Netherlands;³Universitat Autonoma de

DOI: 10.1530/endoabs.49.EP1011

Barcelona, Barcelona, Spain;⁴Massachusetts General Hospital, Boston,

Massachusetts, USA;⁵Pfizer ACROSTUDY Endocrine Care, Sollentuna,

Sweden;⁶Pfizer Endocrine Care, New York, USA.

Introduction

Hypertension (HTN) is a major cardiovascular (CV) risk factor and independent

predictor of the increased mortality in patients with acromegaly. Surgical cure of

acromegaly is associated with improvement in blood pressure

(BP) levels,

however little is known on the effect of pegvisomant (PEGV) treatment on HTN.

EP1012

Methods/design

Sheehan syndrome: Sequential hormone failure and late diagnosis

ACROSTUDY is an open-label, international, prospective, non-interventional

Cristiana Costa¹, Ana Filipa Martins¹, Alexandra Araujo¹ &

study monitoring the long-term safety of PEGV. After informed consent, study

Sonia do Vale^1,2

patients were enrolled on an ongoing basis. Data were analysed to identify the

¹Endocrinology Department, Santa Maria Hospital, North Lisbon Hospital

clinical characteristics and evolution of HTN in patients with acromegaly treated

Center, Lisbon, Portugal;²Endocrinology Department, Lisbon Medical

with PEGV.

School, Lisbon, Portugal.

Results

As of May 31, 2016, data from 2090 patients (15 countries) were available. At

ACROSTUDY start, 1038 patients (49.7%, 51% male) had diagnosed HTN

Introduction

(96.4% were on anti-HTN medications). Most HTN patients were Caucasian

Postpartum infarction of the anterior pituitary, known as Sheehan’s syndrome, is a

(95%) and 75.8% was treated with PEGV before ACROSTUDY start. Modifiable

rare cause of hypopituitarism. In many cases, the hormones deficiency is

CV risk factors that were reported besides HTN were BMI O25 (87.2%), diabetes

sequential which implies late diagnoses.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Case Report 1

EP1014

A 51-year-old woman was observed because her mother had medullary thyroid

Renal prognosis of diabetic patients with and without central diabetes

carcinoma. She had no evidence of endocrine neoplasia. Nevertheless, she was

insipidus

experiencing fatigue, hair loss and dry skin for several months. Her history

Junichi Yatabe¹, Midori Yatabe¹, Tetsuya Babazono², Yasuko Uchigata² &

included a postpartum haemorrhage at 22 with blood transfusion requirement. She

Atsuhiro Ichihara¹

was unable to breastfeed and mentioned oligomenorrheic cycles after that and

¹Tokyo Women’s Medical University, Endocrinology and Hypertension,

took two years to get pregnant again. Menopause was at 43. Physical examination

Tokyo, Japan;²Tokyo Women’s Medical University, Diabetes Center,

was unrevealing. Baseline endocrine evaluation revealed low gonadotrophines,

Tokyo, Japan.

IGF-1 and fT4 with inappropriate normal tyrotrophin, PRL of 2.5 ng/ml and

morning cortisol of 8.7 mcg/dl with ACTH of 15.3 pg/ml. A multiple pituitary

stimulation test confirmed the deficiency of all anterior pituitary hormones except

Background

the pituitary-adrenal axis. Levothyroxine reposition was prescribed.

It has been suggested that higher arginine vasopressin (AVP) concentration may

Case report 2

be associated with greater eGFR decline in diabetic patients not using inhibitors

A 78-years-old woman was referred to the endocrinology outpatient department

of the renin-angiotensin system (Diabetologia 2013). If excessive AVP action is

after hospital admission due to hypotension, hyponatremia (113 mmol/l) and

detrimental to renal prognosis, then diabetic patients with central diabetes

rhabdomyolysis that improved with corticotherapy. She reported asthenia,

insipidus (CDI) may have relatively preserved renal function. Therefore, we

weakness, myalgias and anorexia that worsened progressively 2 years before

aimed to compare long-term renal prognosis of diabetic patients with and without

admission. Her third pregnancy occurred at the age of 28, with severe blood loss

CDI.

at delivery, inability to breastfeed, oligomenorrheic cycles after that and

Methods

menopause at 36. Endocrine evaluation confirmed a panhypopituitarism and the

We retrospectively identified 39 diabetic patients with CDI followed up at our

CT scan showed an empty sella turcica. She became asymptomatic with

university hospital for more than 4 years. Propensity matching for baseline age,

hydrocortisone and levothyroxine reposition.

sex, BMI, HbA1c, eGFR, SBP, DBP, urinary protein, and length of observation

Conclusion

was performed to select 39 control diabetic patients without CDI in the same

These cases represent two very late diagnosis of Sheehan’s syndrome.

hospital.

Appropriate obstetric/gynaecologic history and clinical suspicion are required

Results

to avoid late manifestations of the disease, namely an adrenal crisis, because the

Baseline demographics of the CDI group were as follows: age 45.6 years, 41%

pituitary-adrenal axis is usually the last one failing. Timely treatment may

female, BMI 27.2, HbA1c 7.0%, eGFR 90.4 ml/min/1.73 m², blood pressure

dramatically improve quality of life of these patients, who may experience

122/79 mmHg and observation of 1862 days (mean values). There was no

hypopituitarism for long years before diagnosis.

significant difference in eGFR at the end of observation period (Control: 86.3G

DOI: 10.1530/endoabs.49.EP1012

28.1 vs CDI: 85.8G33.7 ml/min/1.73 m²) or the slope of eGFR (Control: K0.9G

/year) between groups. On the other

3.6 vs CDI: K1.1G10.7 ml/min/1.73 m²

hand, eGFR variability (standard deviation) was significantly greater in the CDI

group

(Control:

7.9G5.1

vs CDI:

18.3G13.3 ml/min/1.73 m², P!10^K5).

Considering that excessive fluctuations in eGFR are damaging to the kidney in

general, CDI patients may exhibit milder decline in eGFR when eGFR variability

and other factors, such as the use of renin-angiotensin system inhibitors, are

matched between groups.

Conclusion

A simple analysis of long-term eGFR revealed no significant difference between

EP1013

diabetic patients with and without CDI. Nevertheless, confounding factors, such

Multimodal treatment in pituitary carcinoma arising from a

as greater eGFR variability in CDI patients, may have weakened the relationship

ACTH-expressing pituitary macroadenoma with an unexpected

between AVP action and decline in renal function.

long-term survival

DOI: 10.1530/endoabs.49.EP1014

Cesar Boguszewski, Felipe Schwambach, Karina Manosso &

Sthefanie Pallone

SEMPR (Endocrine Division), Department of Internal Medicine,

Federal University of Parana, Curitiba, Brazil.

Pituitary carcinoma (PC) is defined by the presence of pituitary tumor that is

either not contiguous with the primary sellar tumor and/or has metastasized

to distant sites. It is very rare and associated with poor prognosis, with

a median survival of 12 months when systemic metastases are present, and

EP1015

30 months when metastases are confined to the central nervous system.

Osilodrostat maintains normalized urinary free cortisol levels in a

A 20 years-old man was first diagnosed with a nonfunctioning pituitary

majority of patients with Cushing’s disease: Long-term results from an

macroadenoma in 1981 and submitted to transsphenoidal surgery (TSS).

extension to the LINC-2 study

Histology showed ACTH positive tumor, p53 negative and Ki-67 1%. Three

Jacques Young¹, Betul Hatipogulu², Mark E Molitch³, Xavier Bertagna⁴,

years later a recurrence was detected and a new TSS followed by

Nathalie Barbier⁵, Nicholas Sauter⁶, Beverly M K Biller⁷ &

conventional radiotherapy

(Rxt) was performed. Hormone replacement

Rosario Pivonello⁸

therapy (HRT) was initiated for TSH, ACTH and FSH/LH deficiencies. In

¹Department of Endocrinology, Hôpital Bicêtre, Université Paris-Sud,

2000, at age 39, he complained of prolonged nasal obstruction. Imaging

Assistance Publique Hôpitaux de Paris, Paris, France;²Endocrinology and

showed a giant invasive sellar tumor with extension to suprasellar region,

Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA;³Division of

cavernous sinus, and nasopharynx; multiple extra-axial lesions in the

Endocrinology, Metabolism, and Molecular Medicine, Northwestern

posterior fossa suggesting meningeal secondary implants and a large mass in

University, Chicago, IL, USA;⁴Department of Endocrinology, Centre de

the cervical-thoraco-lumbar spine. Histology of the resected giant adenoma

Référence des Maladies Rares de la Surrénale, Hôpital Cochin, Faculté de

and the spinal lesion confirmed an ACTH-expressing PC with a high

Médecine Paris Descartes, Université Paris 5, Paris, France;⁵Novartis

proliferative index. Fractionated stereotactic Rxt was performed. Cabergo-

Pharma AG, Basel, Switzerland;⁶Novartis Pharmaceuticals Corporation,

line and pasireotide were prescribed, but discontinued after some months

East Hanover, NJ, USA;⁷Neuroendocrine Clinical Center, Massachusetts

due to side effects. Tumor regrowth occurred in 2009 when surgery was

General Hospital, Boston, MA, USA;⁸Dipartimento di Medicina Clinica e

repeated for removal of the main tumor followed by Rxt directed to

Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli,

cerebellar lesions, and again in

2015, when a microsurgery guided by

Naples, Italy.

localization systems and electrophysiological monitoring was carried out.

Temozolomide was prescribed but patient refused the use. Currently, at age

55, he is doing well, working, and maintaining a stable clinical condition

Background

under HRT. Latency time from the diagnosis of pituitary adenoma to PC was

In the

22-week LINC-2

study, osilodrostat

(LCI699), a potent oral

11b-

19 years, and his survival of 16 years after diagnosis of PC has no parallel in

hydroxylase inhibitor, normalized urinary free cortisol (UFC) levels in 15 of 19

the literature to date.

patients with Cushing’s disease (CD). The most common AEs were nausea,

diarrhea, asthenia, and adrenal insufficiency (nZ6 each). Here, we report the

DOI: 10.1530/endoabs.49.EP1013

31-month efficacy and safety results from LINC-2 extension.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Methods

EP1017

Patients receiving clinical benefit at week

22 could enter two consecutive

Evaluation of upper gastrointestinal system in acromegaly

extensions and continue on the same dose of osilodrostat; dose adjustments were

Pinar Sisman¹, Murat Pekgoz², Mete Sisman³, Soner Cander⁴,

allowed. Response rate: proportion of patients with UFC%ULN (controlled) or

Ozen Oz Gul⁴, Erdinc Erturk⁴ & Canan Ersoy⁴

UFCOULN but R50% decrease from baseline (partially controlled). The

¹Harakani State Hospital, Endocrinology and Metabolism Clinic, Kars,

maximum safety follow-up from core baseline was 40.3 months.

Turkey;²Sirnak State Hospital, Gastroenterology Clinic, Sirnak, Turkey;

Results

³Muradiye State Hospital, Surgery Clinic, Bursa, Turkey;⁴Uludag

Sixteen patients entered the extension, 12 remained on treatment at month 31.

University Medical School, Department of Endocrinology and Metabolism,

Three patients discontinued during extensions (AEs, nZ2; consent withdrawal,

Bursa, Turkey.

nZ1). One patient decided not to continue on to extension-2. The response rate at

month 31 was 100% (controlled, 14 (87.5%); partially controlled, 2 (12.5%))

when missing values were imputed using the last available measurements and

Background

56.3% without imputation ((controlled, 8 (50.0%); partially controlled, 1 (6.3%)).

Because of prolong exposure to elevated endogenous growth hormone (GH) and

No patient had escape from response (UFCOULN at R2 consecutive visits on

insulin-like growth factor (IGF-1) levels in acromegaly, it is resulted in multipl

maximum tolerated dose after initial UFC normalization) during the extension.

comorbidities such as somatic growth, hypertension, diabetes and sleep apnea.

Mean (S.D.) changes in clinical signs of CD from baseline to month 31 (nZ11)

Systemic complications caused by acromegaly include gastrointestinal (GIS)

were: SBP (mmHg), K3.4 (18.5); DBP (mmHg), K5.4 (9.9); weight (kg), K4.5

involvement. In our study it was planned to evaluate the upper GIS findings by

(5.7); and BMI (kg/m²), K1.8 (2.3). The most common clinical AEs were

using endoscopic and ultrasonographic methods in acromegaly patients.

diarrhea, hypocortisolism-related AEs

(nZ6 each), headache, asthenia, and

Subjects and methods

nausea (nZ5 each). Mean (S.D.) plasma ACTH (pmol/l; normal, 1.8-9.2) at

Thirty-nine acromegaly patients who had attended to our center for the last

baseline (nZ15), week 22 (nZ15) and month 31 (nZ10) were 20.0 (10.4), 80.5

6 months were recruited to the study. Upper GIS endoscopies and abdominal

(145.5), and 54.0 (35.1), respectively.

ultrasonography were performed to all patients.

Conclusion

Results

In the majority of patients with CD, osilodrostat maintained normal UFC levels

Of the patient included in the study, 23 were male and 16 were female. The mean

for O2.5 years with a long-term safety profile similar to that after 22 weeks; no

age of the patients was 51.4G11.0 years. The mean duration of acromegaly was

new safety signals emerged. Two phase 3 studies are ongoing to further evaluate

104.3G88.6 months. Upper GIS endoscopy was performed in 39 patients and

osilodrostat in patients with CD.

hiatal hernia, esophagitis and gastritis, duodenitis or gastric ulser were found in

DOI: 10.1530/endoabs.49.EP1015

(%7.6), 2 (%1.7) and 31 (%79.4) patients, respectively. In the pathologic

evaluation of gastric antrum biopies, intestinal metaplasia was detected in

(%30.7) patients and helicobacter pylori was positive in 13 (%33.3) patients.

Abdominal ultrasonographic evaluation revealed cholelithiasis findings in

(%38.6) patients.

Discussion

As a result of our study, there was no statistically significant difference between

age also sex and hiatal hernia, esophagitis, gastroduodenitis, ulcer development in

acromegaly patients. Preoperative GH elevation did not affect the development of

hiatal hernia, whereas preoperative IGF-1 elevation significantly increased hiatal

EP1016

hernia development. The incidence of developing cholelithiasis was statistically

Acromegaly: assessing the clinical outcome through a 10-year

significantly higher in patients with advanced age, long disease duration and no

experience at a tertiary care hospital in Pakistan

postoperative biochemical control. Limitations of our study are the lack of a

Shehla Tabassum & Najmul Islam

control group and the low number of patients. There is a need for controlled

Aga Khan University, Karachi, Pakistan.

studies involving more patients in acromegaly patients.

DOI: 10.1530/endoabs.49.EP1017

Background

Acromegaly is due to excess Growth hormone (GH) production, usually as result

of pituitary adenoma. The diagnosis is often preceded by around 5 years of active

but unrecognized disease. Clinical expression of the disease in each patient

depend on the levels of GH and Insulin-like Growth Factor-1 (IGF-1), age, tumor

size, and the delay in diagnosis. Successful remission after Trans-sphenoidal

surgery (TSS) is reported to be found in 52.5% of cases in the developed

countries.

EP1018

Objectives

Disposition index in active acromegaly: A pilot study

This study was designed primarily for the evaluation of diagnostic characteristics

Dan Alexandru Niculescu^1,2, Roxana Dusceac^1,2,

of acromegaly and establishment of its management outcomes over a span of

Andra Caragheorgheopol², Nicoleta Popescu² & Catalina Poiana^1,2

10 years at a tertiary care hospital in Pakistan.

¹Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;

Methods

²C. I. Parhon Institute of Endocrinology, Bucharest, Romania.

It was a Descriptive cohort study. Total

53 patients with biochemical and

radiological diagnosis of Acromegaly were included in study between October,

2005 to September, 2015. Patients’ medical record files were reviewed and data

Background

recorded.

Active acromegaly is characterized by decreased insulin sensitivity

(ISen).

Results

However, insulin secretion (ISec) may not increase satisfactorily to compensate

Of the 53 subjects, with mean age of 39.68G14.35 years, 33 (62.3%) were male

for the low ISen.

while 20 (37.7%) were female.The patients presented at a mean duration of

Aim

5.90G4.12 years after onset of symptoms. The most frequent complaint was

To assess ISen and ISec and to calculate disposition index

(DI) using an

somatic growth features in the form of enlarged hands and feet noted by 51

intravenous glucose tolerance test (IVGTT) in patients with active acromegaly.

(96.2%) pts. Overall, 50 (94.3%) patients underwent TSS for removal of pituitary

Methods

adenoma while 3 (5.7%) patients refused to opt surgical option. Only 3 (6%)

Twelve patients (7 men, 5 women) with active acromegaly and 2 normal subjects

patients achieved biochemical and radiological remission after 6 months of

(2 men) underwent a standard IVGTT with a glucose dose of 0.3 g/kg of body

surgery. Among 47 patients with persistent disease after TSS, 26 (55.3%) were

weight. Eight patients had normal glucose tolerance (NGT) and 4 had impaired

treated with radiosurgery/radiotherapy, 12 (25.5%) underwent repeat TSS and

glucose tolerance (IGT). None were on medication for acromegaly of glucose

(19.1%) opted for medical treatment, mostly with Cabergoline.

intolerance. ISen was calculated as the slope of the glucose curve between 10 and

Conclusion

75 min (the rate of glucose disappearance) divided by the area under the insulin

TSS is followed by the documentation of a high rate (94%) of failure to achieve

curve between 0 and 75 min. ISec was calculated as the acute insulin response, the

remission and majority of patients have to opt radiotherapy/repeat TSS for the

delta area under the insulin curve between 2 and 10 min after glucose infusion.

persistent disease. With the continuously improving surgical skills, we expect that

DI was calculated as ISen times ISec.

the figures attaining remission after primary TSS will rise in the decades to come.

Results

Keywords: Acromegaly, Characteristics, Management Outcome

Subjects with NGT (8 patients with acromegaly and 2 normal subjects) had a

DOI: 10.1530/endoabs.49.EP1016

significantly higher DI than patients with IGT (801 (632, 1762) vs. 172 (98, 247);

P!0.001). Inside the IGT group there were both patients with extremely low ISen

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

(0.02

L!100 000/pmol!min) and unsatisfactorily increase in ISec

(3862

study (CSOM230CIC05) will provide real-world evidence on the efficacy and

pmol!min/l) and patients with nearly normal ISen (1.09 L!100 000/pmol!

safety of the multi-targeted SSA long-acting pasireotide in uncontrolled

min) but very low ISec (244 pmol!min/l).

acromegaly patients.

Conclusion

Methods

Both insulin sensitivity and insulin secretion contribute to glucose intolerance in

This non-interventional study will analyze efficacy and safety data in acromegaly

acromegaly. DI clearly differentiate glucose intolerant patients from glucose

patients (R18 years) already treated (for R6 months) with monthly pasireotide

tolerant ones.

(retrospective dataset) or about to be treated (prospective dataset). About 200

DOI: 10.1530/endoabs.49.EP1018

prospective patients (2-year follow-up) and 50 retrospective patients are expected

to be enrolled. Outcome measures will include biomarkers (GH and IGF-1),

pituitary imaging, symptom- and quality of life (QoL) scores. The primary

objective is to document treatment efficacy within the prospective data subset; the

endpoint will be the proportion of patients who achieve IGF-1 !1 upper limit of

normal (ULN) and GH !1 mg/l after 6 months. Secondary endpoints will include

the proportion of patients at

months

(retrospective) or within

years

(prospective) who achieve IGF-1 !1 or !1.3 ULN and GH !1 or 2.5 mg/l,

EP1019

change in tumor size, signs and symptoms, QoL and incidence of hyperglycemia.

In well-controlled patients with acromegaly, glucose homeostasis

Safety assessments will include adverse events, hematology, clinical chemistry

correlates with the level of disease control rather than with the type of

and physical examinations. Interim analyses will be performed once at least 50

treatment

retrospective patients have been exposed to 6 months of treatment and 100

Charlotte Verroken, Bruno Lapauw & Guy T’Sjoen

prospective patients have been treated for at least

6 months, respectively.

Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.

Descriptive statistics, as well as, absolute and relative frequencies will be

reported.

Objective

Conclusion

Acromegaly is often accompanied by abnormalities in glucose and lipid

ACRONIS will provide European real-world data to increase our understanding

metabolism, which tend to ameliorate upon treatment. However, few studies

of the long-term efficacy and safety of pasireotide in uncontrolled acromegaly.

have investigated whether glucose homeostasis and lipid profiles are differently

DOI: 10.1530/endoabs.49.EP1020

affected by different treatment regimens. This study aimed to compare glucose

homeostasis and lipid profiles in patients with acromegaly who are well-

controlled after surgery or under stable treatment with long-acting somatostatin

analogs (SSA) either in monotherapy or in combination with pegvisomant.

Methods

Cross-sectional study in 21 patients with a diagnosis of acromegaly (aged 59.1G

EP1021

10.9 years, 10 males), who were controlled (i.e. serum IGF-1 levels under sex-

Thyrotropin secreting microadenoma - case report of a patient with

and age-specific thresholds) after surgery (SUR; nZ5) or under treatment with

goiter

SSA (SSA; nZ10) or SSA C pegvisomant (COMBI; nZ6). Glucose, insulin,

Sónia do Vale^1,2, Ana Filipa Martins¹, Dolores López-Presa³,

total cholesterol, HDL-C and LDL-C were measured from fasting serum samples.

Cristiana Costa¹ & José Miguéns⁴

Triglycerides were measured during a mixed-meal tolerance test

(MMTT).

¹Endocrinology Department, Santa Maria Hospital, North Lisbon Hospital

Insulin resistance was evaluated using the homeostasis model assessment of

Center, Lisbon, Portugal;²Endocrinology Department, Lisbon Medical

insulin resistance (HOMA-IR); insulin sensitivity was evaluated by hyperinsu-

School, Lisbon, Portugal;³Pathology Department, Santa Maria Hospital,

linemic-euglycemic clamp.

North Lisbon Hospital Center, Lisbon, Portugal;⁴Neurosurgery

Results

Department, Santa Maria Hospital, North Lisbon Hospital Center, Lisbon,

IGF-1 levels tended to be lower in SUR (138.4G54.4 ng/ml) as compared to SSA

Portugal.

(194.5G16.3 ng/ml) or COMBI (173.3G52.3 ng/ml) (PZ0.056). After adjust-

ment for age and BMI, between-group differences were observed for HbA1c

(PZ0.048), fasting glucose (PZ0.022), and HDL-C (PZ0.015), with lower

Introduction

levels in SUR as compared to SSA or COMBI. No differences were observed in

The prevalence of pituitary thyrotropin secreting tumors (TSH-omas) is 1-2 cases

fasting insulin, cholesterol, LDL-C, HOMA-IR, glucose disposal rate during

per million inhabitants, most of them being macroadenomas. The differential

clamp, or triglyceride levels during MMTT. Independently of the treatment

diagnosis may be challenging, especially for microadenomas.

regimen, IGF-1 levels correlated positively with fasting glucose and insulin levels

Case Report

(ßZ0.52 and ßZ0.57, both PZ0.010), with HOMA-IR (ßZ0.66, PZ0.003), and

A 50-year-old male was observed at the endocrinology department with

inversely with glucose disposal rate (ßZK0.60, PZ0.006).

multinodular goiter. He noticed progressive neck enlargement over the previous

Conclusion

months but denied other complaints. There was no family history of thyroid

In patients with acromegaly who are controlled after surgery or under stable

pathology. He presented hot sudorific hands and a large nodular goiter.

medical therapy, indices of glucose homeostasis correlate with circulating IGF-1

Laboratory evaluation revealed a predominantly high T3 with non-suppressed

levels, independently of the treatment regimen.

TSH (TSH 1.73 mU/ml (Reference range - RR: 0.55-4.78), T3-2.08 ng/ml (RR:

DOI: 10.1530/endoabs.49.EP1019

0.60-1.81), T4-11.7 mg/dl (RR:4.5-10.9), FT3-7.74 pg/ml (RR: 2.3-4.2), FT4-

1.93 ng/dl (RR: 0.8-1.76)). The sonography showed an enlarged thyroid gland

with bilateral nodules of 37, 50 and 70 mm. Additional evaluation revealed

negative anti-thyroid antibodies, high total testosterone and SHBG, chromogranin

A, alpha-subunit of glycoproteic hormones

(aGS) and aGS/TSH ratio, but

otherwise normal pituitary function and no evidence of other endocrine neoplasia.

There was no TSH or aGS response to TRH administration and the MRI revealed

EP1020

a 6 mm pituitary lesion. Thyroid nodules cytology was benign. A TSH-oma was

admitted and long-acting octreotide administered, with normalization of thyroid

European observational study of long-acting pasireotide for

function and subsequent trans-sphenoidal tumor resection. Pathological analysis

uncontrolled acromegaly: ACRONIS study design and rationale

revealed an adenoma with positive TSH immunohistochemistry. Over the next

Andrea Giustina¹, Gesine Enderle², Daniela Mesenka³, Debolina Mondal⁴

months, there was TSH suppression and secondary hypothyroidism, during which

& Christof Schofl⁵

levothyroxine was administered, and subsequent recovery of normal thyroid

¹Cattedra di Endocrinologia, Universita’ Vita e Salute San Raffaele, Milan,

function. Slight reduction of the goiter was observed.

Italy;²Novartis Farma S.p.A, Origgio, Italy;³Novartis s.r.o., Prague, Czech

Discussion

Republic;⁴Novartis Healthcare Pvt. Ltd., Hyderabad, India;⁵Centre of

Distinguishing pituitary TSH-omas from thyroid hormone resistances may be

Endocrinology and Metabolism, Obstmarkt 1, 96047 Bamberg, Germany.

challenging, but it is important for correct therapeutic options and avoid

endocrine and neurological complications. Baseline thyroid function and

Introduction

sonography do not adequately distinguish both entities, but the absent family

Acromegaly is a rare, serious disease caused by the presence of a pituitary

history, high SHBG, aGS and aGS/TSH ratio, blunt TSH and aGS response to

adenoma secreting an excessive amount of growth hormone (GH), which leads to

TRH, and FT3/FT4 normalization with long-acting octreotide, together with a

a consequent increase in circulating insulin-like growth factor-1 (IGF-1) levels,

small but existent pituitary adenoma, prompted a microthyrotropinoma diagnosis.

and excessive skeletal growth and soft tissue enlargement. It is usually managed

DOI: 10.1530/endoabs.49.EP1021

by surgery and/or treatment with somatostatin analogs (SSA). The ACRONIS

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1022

technique (TFS vs TSS P!0.05), but not in age, pituitary function or number

of interventions.

Non-functioning pituitary adenoma; improved endocrine outcomes

Conclusion

with increasing surgical experience: The Manchester Cohort

It is important to identify those patients in risk of developing permanent DI, which

Sumithra Giritharan¹, Tara Kearney¹ & Kanna Gnanalingham²

in our case were those with bigger tumors that required TFS.

¹Department of Endocrinology, Salford Royal NHS Foundation Trust,

Salford, UK;²Department of Neurosurgery, Salford Royal NHS Foundation

DOI: 10.1530/endoabs.49.EP1023

Trust, Salford, UK.

Case notes of 150 consecutive patients (58% male) who underwent pituitary

surgery by a single surgeon for non-functioning pituitary adenoma and

endocrine follow up at our centre between July 2005 and February 2015

were reviewed. All patients underwent endoscopic transsphenoidal surgery

as the first approach. Post-operative pituitary function was assessed by

measurement of baseline pituitary hormonal profile and a glucagon

EP1024

stimulation test to assess ACTH and GH axis. Mean age at surgery was

Etiology and some clinical characteristics of hypopituitarism over the

61 years (range

23-87 years). Pre-operatively,

63.3% of patients had

years of follow up

evidence of hypopituitarism and vision was affected in 58% of patients.

Milica Medic Stojanoska^1,2, Bojan Vukovic^1,2, Ivana Bajkin^1,2,

Post-operatively, hypopituitarism was detected in 70% of patients. New

Tijana Icin^1,2, Andrijana Milankov^1,2, Jovanka Novakovic Paro^1,2,

hormone deficiency developed in 25.3% of patients. Post-operative vision

Jovana Prodanovic^1,2 & Nikola Curic^1,3

improved 46.6% of the total cohort and remained static in 47.3% of patients.

¹Clinical center of Vojvodina, Clinic for Endocrinology, Diabetes and

During this time period, 10% of patients underwent further surgery and 28%

Metabolic Dieseases, Novi Sad, Serbia;²Medical Faculty University of

of patients were referred for radiotherapy. To assess if increasing surgical

Novi Sad, Novi Sad, Serbia;³Clinical Center of Vojvodina, Center for

experience affected patient outcomes, data was assessed in two time periods;

Laboratory Medicine, Novi Sad, Serbia.

patients undergoing surgery in the early years between 2005 and 2010

(nZ67) and patients undergoing surgery in the latter years between 2011

and 2015 (nZ83). There was no significant difference between pre-op

hypopituitarism between these groups however, there was a statistically

The data of etiology and clinical characteristics of hypopituitarism in

significant difference in terms of post-operatively hypopituitarism, with a

different countries differes. The aim of the study is to investigate etiology

lower number of patients in the latter group experiencing post-operative

and some clinical characteristics of patients with hypopituitarism that were

hormone deficiency (79.1% vs 62.7%, PZ0.033). Furthermore, there was a

treated in the Clinical center of Vojvodina. The study was conducted as a

statistically significant difference in terms of pre-operative visual status,

retrospective study. There were 32 males and 28 female patients. Mean age

with more patients in the latter group without any visual compromise (28.4%

was 52.2G17.5 years. Data was analized before and after substitution of

vs 51.8%, PZ0.008). There was no significant difference in terms of post-

hypopituitarism. Patients were treated with levothyroxine, hydrocortisone,

operative visual outcomes. In conclusion, data from our cohort demonstrates

sexual steroids, growth hormone and with desmopresine depending on the

improved endocrine outcome with increasing surgical experience over time.

type deficiency. At the time of the diagnosis, mean age was 40.2G18.7 and

It also highlights change in clinical practice in our centre with more patients

the average period of treatment was 15.9G11.4 years. The most common

undergoing surgery prior to the development of visual symptoms.

causes of hypopituitarism were pituitary macroadenomas

(53.3%) and

craniopharyngeomas (21.7%). Partial hypopituitarism with deficiency in

DOI: 10.1530/endoabs.49.EP1022

two or more functions was diagnosed in 64.4% subjects and panhypopitui-

tarism in 28.8%, deficiency of one function in 6,8%. Average body mass

index after the treatment was 27.8G6.5 kg/m². Blood pressure was in

normal range and without changes during the treatment. High levels of total

cholesterol and LDLcholesterol before the treatment showed statistically

significant decrease during the treatment (6.29G1.57 vs 5.32G1.38 mmol/l;

P%0.009 and 4.12G1.45 vs. 3.20G1.11 mmol/l; P%0.005 respectly).

Levels of HDLcholesterol and triglycerides were not changed significantly

EP1023

during the treatment. Crosslaps was decreased non-significantly and bone

Polyuria and diabetes insipidus after surgery for pituitary tumors

mineral density showed absence of osteopenia and osteoporosis during

Nerea Egan˜a Zunzunegui, Ismene Bilbao Garay, Cristina García Delgado,

treatment. Correlation analysis showed statistically significant negative

Izaskun Olaizola Iregui, Maite Perez de Ciriza Cordeu, Maria Luisa

correlation between LDL cholesterol and levothyroxine (rZK0.341). 10%

Antun˜ ano Lopez, Maite Aramburu Calafell, Nicolas Sampron,

of subjects had a cardiovascular event. One subject died because of sepsis.

Alfredo Yoldi Arrieta & Miguel Maria Goena Iglesias

We concluded that hypopituitarism in our region is commonest in the middle

Hospital Universitario Donostia, San Sebastian, Guipuzcoa, Spain.

aged population, the main cause being pituitary macroadenomas.

Cardiovascular risk factors of untreated hypopituitarism are reversible and

cardiovascular events are rare.

Introduction

DOI: 10.1530/endoabs.49.EP1024

Central diabetes insipidus (DI) is a common complication after pituitary surgery,

but is transient in the majority of patients. The aim of our study is to determine the

incidence and course of DI in the postoperative period and to characterize the

factors associated with this disease.

Methods

We performed a retrospective study of 44 patients (50% females) with a mean age

of 54 years (24-83), treated with transsphenoidal (TSS) or transfrontal surgery

(TFS) between January 2013 and December 2016. 26 were nonfuntioning

adenoma, 7 somatotrophinoma, 6 corticotrophinoma, 2 gonadotrophinoma, 1

tirotrophinoma, 1 Rathke’s cyst and 1 craniopharyngeoma. 93.2% underwent TSS

EP1025

(72% endoscopic) and 6.8% (3 patients) TSF. 18% were reinterventions. We

A novel DICER1 gene mutation in a 10-month-old boy presenting with

consider polyuria if diuresis is O200ml/h for 3 consecutive hours and DI if the

ACTH-secreting pituitary blastoma and lung cystic dysplasia

natremia is O145 mEq/l so that the patient is candidate for subcutaneous

Alexey Kalinin¹, Natalia Strebkova¹, Anatoly Tiulpakov¹,

desmopresine.

Eugene Vasiliev¹, Vasily Petrov¹, Anna Kolodkina¹, Maria Kareva¹,

Results

Nadezhda Mazerkina² & Valentina Peterkova¹

25 patients (56%) developed polyuria during early postoperative, 11 (25%)

¹Endocrinology Research Centre, Moscow, Russia;²Scientific Research

transient DI between 1 and 5th day and 10 (22%) SiADH between 3 and 10th day.

Neurosurgery Institute, Moscow, Russia.

15% of these patients presented 2 phases DiCSiADH, none of them 3 phases. DI

was permanent in only 3 patients (6.8%), all after TFS. There was no difference

comparing the DI group vs no DI in tumor size, pituitary function and surgery

technique. However, we found differences between transient and permanent DI

Hypercortisolism due to Cushing disease is an extremely rare condition in

groups in tumor size

(53!36!42 vs 18!16!15 P!0.05) and surgery

children under one year of age. We present a case of a 10-month-old boy

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

with lung cystic dysplasia and pituitary blastoma (ACTH-secreting). The

Klinikum der Universitat Munchen, Medizinische Klinik und Poliklinik IV,

disease manifested with symptoms of hydrothorax due to cystic dysplasia of

Munchen, Germany.

the right lung’s upper lobe. Surgical resection of the affected area has been

carried out. Symptoms of endogenous hypercortisolism appeared soon after

Introduction

lung surgery. Cushing disease due to pituitary macroadenoma has been

Acromegaly is characterized by chronic growth hormone (GH) excess and leads

diagnosed. Pituitary adenoma was surgically removed; pituitary blastoma

to numerous changes in bodily functions and comorbidity. We compared

with isolated ACTH-secretion was revealed by immunohistochemistry.

potassium homeostasis in patients with acromegaly to hypertensive controls.

A combination of lung cystic dysplasia and pituitary blastoma was

Methods

suspicious for a DICER1 gene defect. p.C199X mutation in DICER1 gene

We prospectively assessed serum potassium, urinary potassium excretion,

was found. He has been followed up for four years after the pituitary surgery.

aldosterone and renin, acid-base balance as well as glomerular filtration rate

The patient has been receiving replacement therapy with hydrocortisone,

according to the CKD-EPI formula in 71 patients with acromegaly (37 male, 34

levothyroxine and growth hormone. No other DICER1-related conditions

female; age 59G14 years) and 70 hypertensive age and gender matched patients

were detected during the last follow-up visit. The same mutation was found

(HP) in whom secondary hypertension was ruled out (37m, 33f; 59G14 year). Of

in the mother, who had a history of euthyroid multinodular goiter.

the acromegaly patients, 23 had active disease (AD) and 48 were biochemically

Conclusion

controlled (BC).

Combination of lung cystic dysplasia and ACTH- secreting macroadenoma

Results

should prompt to DICER1 gene analysis. We have shown the variable clinical

Serum potassium levels were more elevated in patients with acromegaly (4.2 vs

phenotype in DICER1 mutation carriers within a family.

4.0 mmol/l, PZ0.008). Urinary excretion of potassium was also elevated in

DOI: 10.1530/endoabs.49.EP1025

patients with acromegaly as compared to hypertensive controls

(53.3

35.3 mmol/l, P!0.001; 69.3 vs 52.9 mmol/g Creatinine, PZ0.004). Analysis

of variance in potassium excretion showed highly significant differences between

AD, BC and HP (P!0.001). Post-hoc comparison revealed higher excretion in

AD (66.3 mmol/l) as compared to BC

(47.1 mmol/l, PZ0.003) and HP

(35.3 mmol/l, P!0.001; BC vs HP PZ0.012). Mean arterial pressure was

higher in hypertensive patients (110 vs 104 mmHg, PZ0.009). There were no

statistically significant differences in GFR (PZ0.618), BMI (PZ0.549), sodium

EP1026

levels (PZ0.589), antihypertensive medications used (9 groups of antihyperten-

Pituitary insufficiency following traumatic thoracic injury in adolescent

sive drug classes; 0.117!P!1.0), aldosterone (PZ0.41) and renin (PZ0.161).

male patient-case study

Discussion

Aleksandra Gilis-Januszewska, Malgorzata Wilusz, Renata Turek-Jabrocka,

We observe higher serum potassium levels in patients with acromegaly compared

Jacek Pantoflinski, Malgorzata Trofimiuk-Muldner, Lukasz Kluczynski,

to patients with hypertension. Still, urinary excretion of potassium is also

Alicja Hubalewska-Dydejczyk & Dorota Pach

significantly higher despite comparable characteristics of both patient groups.

The University Hospital in Krakow, Krakow, Poland.

Higher intramuscular potassium levels have previously been shown in

acromegaly. Further research is warranted to elucidate potassium homeostasis

in acromegaly.

DOI: 10.1530/endoabs.49.EP1027

Traumatic thoracic injuries in children and adolescents are rare, but could be

connected with others traumas, often with traumatic brain injury (TBI).

Based on data in the current literature, approximately 15-20% of TBI

patients develop chronic hypopituitarism. Growth hormone

(GH) and

ACTH deficiency are the most common, followed by gonadotropins and

thyroid-stimulating hormone. The greatest challenge associated with

endocrine complications in individuals with polytrauma injury is early

recognition of these subtle problems. We present a case report of a 24-years-

old male. In 2007 (when he was 15-years-old) the patient underwent a traffic

accident, thoracic injury (hemothorax, dissection of the descending part of

EP1028

the aorta, aortic stent-graft implantation to the left subclavian artery) and

Russian hypothalamic and pituitary tumors registry (OGGO) data

concussion. During post traumatic period he had transient polydipsia and

analysis: acromegaly

polyuria. In

2013 gonadal axis deficiency was confirmed. Testosterone

Alexander Lutsenko, Elena Przhiyalkovskaya, Ekaterina Pigarova,

replacement therapy was started. During current investigation low growth

Zhanna Belaya, Liudmila Rozhinskaya & Irina Stanoevich

hormone level (GH) and insulin-like growth factor 1 (IGF-1) level were

Endocrinology Research Centre, Moscow, Russia.

found to be low. Patient’s hight is 160 cm, mothers 158 cm, fathers 182 cm.

Mid Parental Height (MPH)Z173.5 cm. An insulin tolerance test (ITT) was

performed. There was’t an adequate GH response-the insufficiency of

Objective

somatotropic axis was confirmed. There were no others hormonal

To analyze registry data on patients with acromegaly.

abnormalities. Further examinations e.g. NMR of the pituitary, genetic

Materials and methods

examination and DEXA are performed.

Russian hypothalamic and pituitary tumors registry database (on-line platform),

Conclusions

which contains data on 3719 patients with acromegaly.

Physical signs such as lack of progression through puberty, with decrease in

Results

testicular volume and libido, short stature and history of after trauma transient

According to the database, highest prevalence of acromegaly per

100 000

diabetes incipidus could suggest the presence of unrecognised hypopituitarism.

inhabitants is registered in: Penza region (7.3), Kirov region (7.3), Krasnoyarsk

Careful investigation and monitoring is necessary to unmask and treat such

region

(6.2). Most common clinical presentations in registered acromegalic

hormone deficiencies in the transition phase.

patients were: headaches (72%) maxillofacial changes (68%), arthralgias (48%)

excessive sweating (39%). Information about tumor size was available in 1543

DOI: 10.1530/endoabs.49.EP1026

patients: by the time of diagnosis, 516 (33.4%) had pituitary microadenomas and

1027

(66.6%) had macroadenomas. 59.5% of registered patients were prescribed

medical therapy: 65.9 and 34.1% were treated with somatostatin receptor ligands

(SRL) and dopamine agonists respectively. 29.9% of patients were primarily

treated surgically and remaining 10.6% underwent radiotherapy. Remission is

registered in 22% cases, 23% of patients have only partial disease control, 41%

have an active disease and 14% of records have no data regarding disease state.

Conclusions

Russian hypothalamic-pituitary tumors registry is a promising instrument for

EP1027

epidemiologic and clinical data acquisition. Data suggest that multimodal

treatment approach is essential to achieve higher remission rates in patients with

Potassium homeostasis in patients with acromegaly in comparison with

acromegaly.

hypertensive patients

Sylvère Stormann, Katharina Schilbach, Christine Pichl, Robert P Kosilek,

DOI: 10.1530/endoabs.49.EP1028

Hans-Joachim Anders & Jochen Schopohl

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1029

diameter of 15.9(11) vs 12.05(4.95) mm, respectively. After 6 months of SSA

therapy there was 51.2% decrease in IGF1 levels in No-Ha vs 72.3% in Ha. Six of

Adherence to hormone replacement therapy in patients with

the No-Ha had surgery and four of the Ha. The hormonal response in No-Ha was

hyp-opituitarism using the Morisky 4-item scale: results of a pilot,

complete in the 50% and partial in 20% of patients vs 83% and 17% in Ha,

prospective, cross-sectional study

respectively. O20% of tumour shrinkage occurred in 40% of the No-Ha vs 66%

Cesar Boguszewski, Simone Abe, Bruna Barbosa, Claudia Biondo,

of the Ha.

Debora Takito, Kamila Santos, Sayuri Hayashi & Victor Amarilla

Conclusions

SEMPR (Endocrine Division), Department of Internal Medicine,

Our results show the effectiveness of the pre-operative treatment with SSA in the

Federal University of Parana, Curitiba, Brazil.

acromegaly, in terms of hormonal but also anti-tumoral effects. T2-signal

intensity at diagnosis it’s a good prognostic marker of the effectiveness of SSA

Objective

therapy and it’s correlated with the tumour size-invasion and hormone levels at

To investigate adherence to hormone replacement therapy (HRT) in patients with

diagnosis.

hypopituitarism in a tertiary center outpatient clinic.

DOI: 10.1530/endoabs.49.EP1030

Patients and methods

Prospective, cross-sectional study of patients with hypopituitarism on HRT for at

least two pituitary deficiencies (independent of diabetes insipidus). Medication

adherence was assessed using a validated Portuguese version of four-item

Morisky scale, in which participants were asked to indicate the extent to which

they agreed with each of 4 statements (two related to unintentional and two with

intentional nonadherence) by rating on a 4-point scale (strongly agree, agree,

disagree, strongly disagree). Patients were categorized as nonadherent if they

indicated agreement (ie, reported either ‘strongly agree’ or ‘agree’) to either item

EP1031

of the subscale. Potential co-variables associated with adherence were tested.

Results

Ninety consecutive patients completed the survey, but five were excluded because

Abstract withdrawn.

they were on HRT with a single hormone. Of the remaining 85 patients (47 men,

age 48G16 year), 31 were on HRT with two hormones, 32 with three, 18 with

four and

4 with five. Levothyroxine, glucocorticoids, sex steroids, growth

hormone and desmopressin were prescribed to 81, 66, 64, 8 and 21 patients,

respectively. Mean number of prescribed medications (excluding HRT) per

patient was 3.1 (S.D. 2.4; range 0-9). The etiology of the hypopituitarism was non-

functioning pituitary tumors

(nZ19), functioning pituitary tumors

(nZ17),

craniopharyngeomas (nZ13), other tumors (nZ3), congenital (nZ14), vascular

(nZ13), trauma (nZ2), and idiopathic (nZ4). Fifty-six (65.9%) patients reported

unintentional nonadherence, while only

(10.6%) reported intentional

nonadherence. Complete adherence was reported by 29.4% of the patients,

while 5.9% showed both unintentional and intentional nonadherence. There were

no associations of adherence to gender, age, number of pituitary deficiencies and

EP1032

prescribed medications.

Conclusion

Does cyproterone acetate therapy contribute to the observed elevation

Self-reported unintentional nonadherence to HRT is a common finding in patients

in serum prolactin levels in trans women?

receiving HRT for hypopituitarism.

Justine Defreyne¹, Nienke Nota², Cecilia Perreira³, Schreiner Thomas⁴,

Fisher Alessandra Daphne⁵ & T’Sjoen Guy^1,6

DOI: 10.1530/endoabs.49.EP1029

¹Department of Endocrinology, Ghent University Hospital, Ghent, Belgium;

²Department of Endocrinology, Department of Internal Medicine, VU,

University Medical Center, Amsterdam, The Netherlands;³Department of

Endocrinology and Metabolism, San Juan de Dios Hospital, Santiago, Chile;

Department of Endocrinology, Oslo University Hospital, Oslo, Norway;

⁵Sexual Medicine and Andrology Unit, Department of Experimental,

Clinical and Biomedical Sciences, University of Florence, Florence, Italy;

EP1030

⁶Center for Sexology and Gender, Ghent University Hospital, Ghent,

Hormone and tumor responses to primary or pre-operative therapy

Belgium.

with somatostatin analogs in acromegaly and the relation with

T2-weighted MRI signal

Maria Picallo, Rogelio Garcia Centeno, Aurelio Lopez Guerra, Yoko

Objective

Lucia Olmedilla, Maria Arnoriaga, Maria Requena, Javier Agreda,

Hormonal treatment in trans women (MtF transgender persons) in Europe usually

Victor Andia, Marcel Sambo, Susana Monereo, Maria Angeles Velez,

consists of estrogens and anti-androgens, e.g. cyproterone acetate (CPA). After

Bettina Weber & Jose Atencia

initiation of cross-sex hormone therapy, an elevation in serum prolactin levels is

Gregorio Maran˜ on Hospital, Madrid, Spain.

frequently observed in trans women, which was previously attributed to estrogen

agents. This analysis evaluates whether CPA contributes to the elevation of

prolactin in trans women receiving cross-sex hormones.

Objective

Design

Study of the efficacy of SSA in the biochemical and tumour control and the

This study is part of the European Network for the Investigation of Gender

relation between the T2-weighted MRI signal intensity and the response to SSA.

Incongruence (ENIGI). Belgian data were selected for this substudy. Trans

Material and methods

women that initiated cross-sex hormone treatment (which consists of oral CPA

16 patients with GH-secreting pituitary adenomas (7_/9\) that received primary

50 mg in combination with estrogen substitution in Belgium) and underwent

or pre-operative treatment with SSA. We classified them according to baseline

orchiectomy were prospectively evaluated. Post-surgery estrogen was reinitiated

T2-weighted MRI sequences as Hypo-intense

(Ha) and No-Hypo-intense

in unchanged dose.

adenomas (no-Ha). Results expressed like media (S.D.).

Methods

Results

Sex steroids, gonadotropins and prolactin were compared at baseline, pre and post

Median age at diagnosis was 50.6 (18.5) years. 10 patients (9 macroademonas)

surgery (patients receiving orchiectomy) and after 12 and 18 months of cross-sex

had pre-operative therapy with SSA during 18.58 (26.9) months, with 47.2%

hormone therapy (patients not receiving orchiectomy).

decrease in IGF1 levels and 24.5% of tumour shrinkage. After neurosurgery three

Results

patients required medication for hormonal control. Only one patient had

Data was collected of 107 trans women, with a mean age of 31.5 years. After

postsurgical complications (hypopituitarism). Six patients (two macroadenomas)

1 year of cross-sex hormone therapy, there was an increase in serum prolactin

received exclusively medical treatment during 59.77(64.5) months. They showed

levels in all patients (9.65 mg/l), with a decrease after 18 months (14.10 mg/l) and

56.8% of reduction in IGF1 levels and 49% of tumour shrinkage. In the last

after orchiectomy (10.17 mg/l). However, serum prolactin levels post orchiectomy

consultation, 4 achieved hormonal control and two needed dose adjustment. From

were significantly lower than serum prolactin levels after 18 months of CPA

the whole group, ten were no-Ha and 6 Ha, showing at diagnosis: GH 20.13(16.5)

therapy, whereas there was no difference in serum estrogen levels between both

14.75(19.8) mg/l, IGF1

973.5(474) vs

703.7(243.5) mg/l and a maximum

groups.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

The observed elevation of serum prolactin levels in trans women is likely caused

The results of this study suggest that fetal exposure to cabergoline through early

by CPA (independent of estrogen therapy), as prolactin levels return to normal

pregnancy does not induce any increase in the risk of miscarriage or fetal

after CPA discontinuation, independent of serum estrogen levels.

malformation. According the results of the study in patients with hyperprolacti-

DOI: 10.1530/endoabs.49.EP1032

nemia risk of gestational diabetes mellitus is higher than in the population that

require further investigations.

DOI: 10.1530/endoabs.49.EP1034

EP1033

A rapidly resolving prolactinoma with cabergoline treatment

Goknur Yorulmaz¹, Aysen Akalin¹ & Esra Akcan²

EP1035

¹Division of Endocrinology, Eskisehir Osmangazi University School of

Clinical and hormonal characteristics of patients with different types

Medicine, Eskisekir, Turkey;²Radiology Department, Eskisehir State

hypophysitis: a single-center experience

Hospital, Eskisehir, Turkey.

Narin Nasiroglu Imga¹, Ali Erdem Yildirim², Ozden Ozdemir Baser¹ &

Dilek Berker¹

Department of Endocrinology and Metabolism, Ankara Numune Education

Introduction

and Research Hospital, Ankara, Turkey;²Department of Neurosurgery,

Prolactinomas are the most common pituitary tumors. Macroadenomas are rarely

Ankara Numune Education and Research Hospital, Ankara, Turkey.

seen. Dopamine agonists such bromocriptin and cabergoline are the preferred

treatments for prolactinomas. Herein, we report a patient with macroadenoma

whose adenoma has resolved rapidly with cabergoline treatment.

Background

Case

The inflammation of the pituitary gland known as hypophysitis. It is a rare disease

A 49 year old male patient evaluated for weakness and headache. After detection

accounting for approximately 0.24-0.88% of all pituitary diseases. Main forms of

of central hypothyroidism he was referred to our department. His prolactin level

hypophysitis are histologically classified as lymphocytic, granulomatous, IgG4

was more than

1925 ng/ml. His laboratory tests were concordant with

related and xanthomatous. We aim to present ourpatients of hypophysitis with

panhypopituitarism. Replacement therapy was initiated. A macroadenom with a

clinical,laboratoryand radiological features.

size of 28 mm was detected in pituiter MRI. Cabergolin treatment (3 mg/week)

Methods

was initiated. The size of the adenoma was decreased to 16 mm in the 3rd month

We retrospectively reviewed our database of 1293 patients diagnosed with

of the therapy. In the 6th month of the treatment the size of the adenoma regressed

pituitary diseases between 2010 and 2017. Demographical data, clinical features,

to 5 mm.

endocrinological dysfunction, magnetic resonance imaging findings, treatment

Conclusion

courses and follow-up periods were evaluated. Primary hypophysitis diagnosis

Prolactinomas are tumors with a good response to medical treatment. A rapid

was made by the exclusion of secondary causes of hypophysitis, consequently

response was detected in our patient but there is data about cabergolin resistance.

twelve patients with hypophysitis were identified.

So, a close follow up is required in patients with prolactinomas.

Results

DOI: 10.1530/endoabs.49.EP1033

The frequency of hypophysitis was found 0.93% in all cases of pituitary disease.

Twelve patients (nine females and three males); ages ranged between 17 and 61

years were evaluated. The characteristic features of our patients tend to be female

predominance and young population. Diagnosis of hypophysitis was made after

pituitary biopsy in 4 patients and in 8 patients after pituitary operation due to

adenoma. Headache (63%) and visual problems (18%) were the most frequent

nonendocrine symptoms. Anterior pituitary hormone deficiencies (63.7%) and/or

diabetes insipidus (16.7%) were seen amongpatients.According to histopatholo-

gical forms, 4 had lymphocytic, 6 had granulomatous and 1 had xanthogranu-

EP1034

lomatous types of hypophtsitis.

Pregnancy outcome in women with prolactinomas exposed to dopamine

Conclusion

agonists at early stages of gestation

Hypophysitis should be considered in the differential diagnosis of sellar masses.

Svetlana Vorotnikova, Darya Skuridina, Larisa Dzeranova,

It can mimic pituitary adenomas in radiological and endocrinological aspects.The

Ekaterina Pigarova & Zhanna Belaya

different patterns of anterior pituitary hormone deficiencies and diabetes insipidus

Endocrinology Research Centre, Moscow, Russia.

may be seen in the course of disease.

DOI: 10.1530/endoabs.49.EP1035

Introduction

Medical therapy with dopamine agonists is the best treatment for prolactinomas of

any size or invasiveness and restores ovulatory cycles in 80-90% of patients.

Cabergoline currently suggested nearly exclusively rather than other dopamine

agonists due to its excellent tolerability and long half-life. That is why the

question of safety using of this drug during pregnancy and embryo-fetal

development is actual.

EP1036

Aim

Comparative study of different methods for monomeric prolactin

The aim of the study is to assess the risk of pregnancy and fetal pathology in

determination in patients with hyperprolactinemia

patients with prolactin-secreting tumors treated with cabergoline at early stages of

Svetlana Vorotnikova, Larisa Dzeranova, Ekaterina Pigarova,

gestation.

Aleksandr Il’in, Nataliya Popova, Marina Vershinina, Olga Sukhanova,

Materials and methods

Nataliya Kadrina, Larisa Shibina & Ivan Dedov

The study included 24 patients from 24 to 38 years old with prolactin-secreting

Endocrinology Research Centre, Moscow, Russia.

tumors, who become pregnant during therapy with cabergoline

(Dostinex).

A retrospective analysis of the outcomes of 33 pregnancies based on available

medical records and questioning of the patients.

Introduction

Results

Prolactin exists in various forms including the monomeric biologically active

Of the 33 pregnancies 26 resulted in births (78.8%), in one patient a spontaneous

form (23 kDa) and a higher molecular weight form, bound most commonly to

miscarriage was registered at 7 weeks (3.0%), six women required medical

IgG, known as macroprolactin (O100 kDa). Macroprolactin lacks biological

abortions due to the non-developing pregnancy on terms from 4 to 7 weeks

activity but can interfere in standard prolactin immunoassays and is one of the

(18.2%). In

6% of cases (two pregnant) gestational diabetes mellitus was

causes of false-positive results. In Russian Federation the most common method

diagnosed. The average gestational age was 39.8 weeks (36-41 weeks). Preterm

for macroprolactin determination is PEG precipitation test.

delivery occurred in four women (15.3%). In total 27 children were born (in one

Aim

case - twins), 26 (96.3%) of them were healthy at the time of the birth. The growth

The aim of the study was an evaluation of the monomeric prolactin level

and development of the children did not differ from their peers in the general

measured by two methods: immunochemiluminescent (Cobas 6000) with manual

population.

PEG precipitation and immunofluorescent method (Brahms Cryptor).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Materials and methods

Objective

We had conducted a retrospective analysis of 41 samples of patients with

To evaluate the presence of glucose metabolism abnormalities and their impact on

hyperprolactinemia (3 of them were males). The mean age was 32G2.1 years.

IGF-1 levels in patients with acromegaly.

Prolactin was measured by the immune chemiluminescent

(after PEG

Methods

precipitation) and immunofluorescent methods.

Ninety-three acromegalic patients (52 male/41 female) were included in this

Results

study who were seperated into three groups as normal glucose tolerance (NGT),

The mean values found by immune chemiluminescent method with manual PEG

prediabetes and diabetes mellitus (DM). Insulin resistance (IR) was calculated

precipitation were 460.0 [334.0;807.2] mU/l, by immunofluorescent - 432,4

with homeostasis model assessment (HOMA). HOMA-IR O2.5 or %2.5 were

[338.8;700.0] mU/l. The number of patients with intrareference prolactin levels

defined as insulin resistant or noninsulin resistant groups, respectively. We

was 41% (17) for the first method and 48.8% (20) for the second one. At the same

compared the groups in terms of many factors that may be associated with glucose

time, six patients with equivocal results received by immune chemiluminescent

metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were

method and PEG precipitation had normal prolactin levels by immunofluorescent

used for impact of glucose metabolism abnormalities on IGF-1 levels.

method. The phenomenon of macroprolactinemia without elevated level of

Results

monomeric prolactin was registered in 24.4% (10) of patients. In one person of

Frequencies of NGT, prediabetes and DM were 25% (nZ23), 41% (nZ38) and

this group with clinical features of hyperprolactinemia, the increased hormone

34% (nZ32), respectively. Patients with DM were significantly older and with an

levels was revealed by Cryptor analyzer.

increased frequency of hypertension than NGT and prediabetes groups

Conclusion

(P!0.001, PZ0.01, respectively). IGF-1% ULN/GH ratio was significantly

Measurements of prolactin levels by the immunofluorescent method is useful for

lower in prediabetes group than in NGT group (PZ0.04). Similarly IGF-1%

correct diagnosis in patients with equivocal results received by immune

ULN/GH ratio was significantly lower in insulin resistant group than in

chemiluminescent method with PEG precipitation.

noninsulin resistant group (PZ0.04). Baseline and suppressed GH levels were

DOI: 10.1530/endoabs.49.EP1036

significantly higher in insulin resistant group than in noninsulin resistant group

(PZ0.024, P!0.001, respectively).

Conclusion

IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism

disorders and IGF-1 levels might be inappropriately lower in acromegalic patients

with IR or prediabetes. We suggest that IGF-1 levels should be re-evaluated after

the improvement of IR or glycemic regulation for the successful management of

EP1037

patients with acromegaly.

Pituitary Stalk Hemangioblastoma: a case report and review of the

DOI: 10.1530/endoabs.49.EP1038

literature

David Barbosa, Carolina Faria, Ana Sofia Osório, Ema Nobre &

Maria João Bugalho

Diabetes and Metabolism Department, CHLN - Hospital de Santa Maria,

Endocrinology, Lisbon, Portugal.

EP1039

Introduction

Monthly pasireotide provides clinical benefit over 12 months in patients

Hemangioblastomas (HBL) in the pituitary stalk are extremely rare. Most

with Cushing’s disease

pituitary stalk HBL reported in the literature were associated with von Hippel-

Rosario Pivonello¹, Marcello Bronstein², Jochen Schopohl³,

Lindau (VHL) disease.

Tuncay Delibasi⁴, Ariel Barkan⁵, Nori Suzaki⁶, Libuse Tauchmanova⁷,

Case report

Pritam Gupta⁸, Stefan Petersenn⁹ & André Lacroix¹⁰

We report the case of a 34-year-old female patient with VHL disease diagnosed at

¹Università Federico II di Napoli, Naples, Italy;²University of São Paulo

the age of 18 with multiple complications (bilateral retinal and cerebellum HBL,

Medical School, Sa˜o Paulo, Brazil;3Medizinische Klinik IV, University of

renal cell carcinoma). Brain magnetic resonance imaging (MRI) demonstrated an

Munich, Munich, Germany;⁴Hacettepe University, Ankara, Turkey;

hypointense suprasellar mass measuring 9!8!9 mm with marked homogenous

⁵University of Michigan, Ann Arbor, MI, USA;⁶Nagoya Medical Center,

contrast enhancement after gadolinium administration, originating from the

National Hospital Organization, Nagoya, Japan;⁷Novartis Pharma AG,

pituitary stalk, suggesting a pituitary stalk HBL. The initial hormonal workup was

Basel, Switzerland;⁸Novartis Healthcare Pvt Ltd, Hyderabad, India;

normal. A visual field defect evaluation was not feasible due to severely low

bilateral visual acuity. During the 4-year follow-up, a slight increase in the mass

⁹ENDOC Center for Endocrine Tumors, Hamburg, Germany;¹⁰Centre

hospitalier de l’Université de Montréal, Montreal, Canada.

volume and prolactin level was observed; depending on the clinical, radiological

and laboratory evolution, a future surgical approach cannot be disregarded.

Review of the literature

Introduction

The previously reported cases of HBL in the pituitary stalk were analyzed.

A monthly, long-acting formulation of pasireotide normalized or reduced mean

Seventeen cases have been reported, the majority (fourteen) being associated with

urinary free cortisol (mUFC) in most patients with Cushing’s disease (CD) in a

VHL disease and the remaining considered to be sporadic. Ten patients had no

multicentre, double-blind, Phase III study. The effects of long-acting pasireotide

visual symptoms or hormonal dysfunction, and therefore were kept on

on signs and symptoms of CD are reported here.

observation. A total of six patients were operated. Of the six surgical cases,

Methods

four patients developed panhypopituitarism, and two patients had visual field

Patients with persistent/recurrent (nZ123) or de novo (non-surgical candidates;

disturbances preoperatively with partial recovery after surgery. None of the

nZ27) CD and mUFCR1.5-5xULN were randomized to monthly pasireotide

patients were treated with radiotherapy.

10 mg (nZ74) or 30 mg (nZ76). Dose could be up-titrated (10-30 mg/30-

Conclusion

40 mg) at month (M) 4 if mUFCO1.5xULN and/or at M7, M9, or M12 if

To our knowledge, this is the 18th case of HBL in the pituitary stalk. According to

mUFCO1.0xULN. Primary endpoint was mUFC%ULN at M7, regardless of

our review, pituitary stalk HBL often remain asymptomatic and do not require

dose titration. Signs/symptoms of CD were evaluated at regular intervals. All data

treatment. Surgery can be reserved until associated signs or symptoms occur.

shown are mean (95%CI).

DOI: 10.1530/endoabs.49.EP1037

Results

mUFC reduction was accompanied by substantial clinical improvements. Mean

changes (95%CI) in clinical signs to M12 in the 10mg and 30mg groups included:

weight, K3.4 kg (K4.8,K2.0) and K6.5 kg (K8.3,K4.7); BMI, K1.3 kg/m²

(K1.8,K0.8) and K2.6 kg/m² (K3.3,K1.9); waist circumference, K4.5 cm

(K7.2,K1.8) and K6.2 cm

(K8.7,K3.6); health-related QoL score,

6.4

(1.3,11.6) and

7.0

(3.0,10.9). Clinically relevant decreases in systolic

EP1038

(K5.0 mmHg (K8.8,K1.3)) and diastolic (K3.1 mmHg (K5.7,K0.5)) BP

were reported in the

30 mg group; downward trends were also seen with

Impact of glucose metabolism disorders on IGF-1 levels in patients with

pasireotide

10 mg (systolic BP: K4.6 mmHg

(K9.9,0.7); diastolic BP:

acromegaly

K3.4 mmHg (K7.3,0.4)). A significant (P!0.0001) relationship was found

Sema Ciftci Dogansen, Gulsah Yenidunya Yalin, Seher Tanrikulu &

between change in mUFC and systolic/diastolic BP, after adjusting for

Sema Yarman

antihypertensive medication. Changes in other clinical parameters occurred

Division of Endocrinology and Metabolism, Department of Internal

irrespective of whether patients achieved mUFC%ULN at M7. The safety profile

Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul,

of long-acting pasireotide was similar to that of twice-daily pasireotide.

Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

patients complained of fatigue and lethargy; however five patients presented

Reductions in mUFC levels during 12 months’ long-acting pasireotide treatment

with hyponatraemia.

10 of the 19 patients had autoimmune illnesses;

were accompanied by improvements in clinical signs of CD. Long-acting

hypothyroidism was the most common autoimmune disease with eight

pasireotide is an effective treatment option for patients with CD, with a

patients suffering primary hypothyroidism. CRH stimulation testing was

convenient monthly administration schedule.

available in 6 of the 19 patients, five of these patients had a rise in ACTH

DOI: 10.1530/endoabs.49.EP1039

with CRH administration, indicating possible hypothalamic involvement.

Two patients had complete recovery of their HPA axis when repeat testing

was performed. IIAD is a rare, poorly defined disorder that typically presents

with insidious symptoms but can present with severe hyponatraemia. It is

associated with autoimmune diseases, in particular primary hypothyroidism.

Two patients in this case series had complete recovery of their HPA axis,

therefore repeat testing should be performed at intervals.

EP1040

DOI: 10.1530/endoabs.49.EP1041

Radiological study of clinically non-functioning pituitary

macroadenomas: a single institutional experience

Cristina Moreno, Miguel Paja, Aitzol Lizarraga, Eider Etxeberria,

Cristina Arrizabalaga, Estíbaliz Ugarte, Ana Izuzquiza, Fernando Go

˜i,

Natalia Iglesias & Laura Calles

Endocrinology Unit-Basurto University Hospital, Bilbao, Spain.

EP1042

Autonomic impairment in idiopathic diabetes insipidus

Introduction

Mattia Barbot¹, Filippo Ceccato¹, Marialuisa Zilio¹, Nora Albiger¹,

When facing with non-functioning pituitary macroadenomas

(NFPMA),

Marco Boscaro¹, Franca Bilora² & Carla Scaroni¹

radiological invasion is determinant to surgical approach, apart from histological

¹Endocrinology Unit, Department of Medicine, DIMED, Padova, Italy;

biomarkers of pituitary tumor aggressiveness (Ki-67; p53 and mitotic index).

²Vascular Medicine Unit, Department of Cardiovascular Sciences, Padova,

Invasive tumors usually need additional surgery and/or radiotherapy. There are no

Italy.

much studies describing epidemiological data on aggressive pituitary tumors in

clinical practice. We provide information regarding the radiological findings of

NFPMA in a single tertiary center during 17 years.

Introduction

Material and methods

Since DI was reported to be associated to increase mortality, the aim of this study

We evaluate retrospectively MR imaging of NFPMA diagnosed between 1999

is to evaluate the presence of autonomic dysfunction (AD) in patients with DI.

and 2016 in our Hospital. Evaluation includes infrasellar invasion, Knosp’s

Methods

classification in both cavernous sinus, measure in three dimensions, contact with

We enrolled 12 patients (six females) with central idiopathic DI and 12 controls,

quiasm, and intensity of signal in T2.

matched for age, sex and common cardiovascular risk factors, who were

Results

evaluated using the tilt, lying-to-standing, hand grip, deep breath, Valsalva

From 48 cases, we selected 41 with valuable presurgical MRI. 15 men and 26

maneuver and Stroop tests.

women, mean age 61 years (24-83). Infrasellar invasion ocurred in 19 (46.34%),

Results

Knosp III or IV in 21 of 82 cavernous sinus (25.6%). 3 patients (7.3%) presented

The tilt test showed a significant more pronounced decrease in both systolic

invasion of three areas. Mean craneocaudal diameter was 29.65 mm (8-52),

(K20.7G18 vs K1.92G7 mmHg, PZ0.0009) and diastolic blood pressure

transversal 21.5 mm (11-43) and anteroposterior 19.14 mm (11-51), with 80.5%

(K10.5G14.3 vs K1.5G5.5 mmHg, PZ0.02) in patients than in controls.

displacing optic quiasm. 22% were giant adenomas (O40 mm) and T2 secuences

Furthermore three patients with DI had to suspend the test because of the onset of

hiperintense, suggesting scarcely granulated tumour, was present in 19.5%.

syncope. The lying-to-standing test indicated a marked reduction in blood

Conclusions

pressure in patients with DI too (1.047G0.137 vs 1.533G0.144, PZ0.0001).

In our series, 56% of NFPMA had criteria of radiological invasión, infrasellar or

Similar results were find in Valsalva (ratio,

1.033G0.193 vs 1.431G0.109,

cavernous sinus invasion. This finding remarks the complex management of these

PZ0.00001) and deep breath tests (1.075G0.112 vs 1.33G0.083, PZ0.00002).

neoplasm and the need of a multimodal approach.

Discussion

DOI: 10.1530/endoabs.49.EP1040

All the principal autonomic tests performed were concordant, indicating that

patients with central DI have an impaired autonomic nervous system function

despite normal hydroelectrolytic balance under desmopressin therapy. This

impairment may reflect both a damage in the autonomic system and the absence

of the vasoactive effect of AVP on vascular smooth muscle which acts as a rescue

mechanism in case of rapid drop in blood pressure. Patients with central DI should

be educated on how to prevent orthostatic hypotension.

EP1041

DOI: 10.1530/endoabs.49.EP1042

Idiopathic isolated acquired ACTH deficiency- a case series from the

Irish National Pituitary Network

Anne marie Hannon¹, Diarmuid Smith¹, Mark Sherlock², Steven Hunter³ &

Chris Thompson⁴

¹Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin 9,

Ireland;²Department of Endocrinology and Diabetes, Adelaide and Meath

Hospital, Tallaght, Dublin, Ireland;³Department of Endocrinology and

EP1043

Diabetes, Royal Victoria Hospital, Belfast, UK;⁴Department of Endo-

Salivary and serum cortisol levels by liquid chromatography tandem

crinology and Diabetes, Cork University Hospital, Cork, Ireland.

mass spectrometry after standard dose ACTH test in the diagnosis of

central hypopituitarism

Valentina Morelli¹, Elisa Polledri², Rosa Mercadante², Beatrice Sonzogni¹,

Giovanna Mantovani¹, Serena Palmieri¹, Elena Malchiodi¹, Elisa Verrua¹,

Idiopathic Isolated ATCH deficiency (IIAD) is a rare cause of secondary

Anna Maria Barbieri¹, Emanuele Ferrante³, Maura Arosio¹,

adrenal insufficiency characterised by ACTH deficiency with otherwise

Silvia Fustinoni² & Iacopo Chiodini¹

intact pituitary function. Our objective was to describe the presentation, the

¹Unit of Endocrinology and Metabolic Disease, Fondazione IRCCS Cà

autoimmune associations and diagnostic findings observed in IIAD. We

Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy;

present a case series of 19 cases of idiopathic Isolated ACTH deficiency

²Department of Clinical Sciences and Community Health, University of

which were identified from the National Pituitary Register in Ireland.

Milano, Milan, Italy;³Unit of Internal Medicine 1, ASST Santi Paolo e

A chart and biochemical review was performed to identify the presentation,

Carlo, San Carlo Borromeo Hospital, Milan, Italy.

clinical features, diagnostic criteria and associated diseases of people with

IIAD. All patients had normal pituitary MRI imaging, (one patient refused,

however he had a normal CT brain) and other causes for ACTH deficiency

Objective

such as medication or traumatic brain injury were excluded. 19 patients were

The diagnosis of central hypoadrenalism (HPAI) is a major clinical challenge.

identified as meeting criteria (15 women and 4 men). The age at presentation

The gold standard procedure remains insuline tolerance test

(ITT). Liquid

ranged from 21 to 88 years, with a median age of 52 years. The majority of

chromatography tandem mass spectrometry (LC-MS/MS) is considered the best

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

procedure for the evaluation of cortisol levels. This study aimed to evaluate cut-

use to diagnose eucortisolism and avoid unnecessary replacement HC treatment

offs of serum (TM-SeC) and salivary cortisol (SaC) by LC-MS/MS and serum

in this patients.

cortisol by ECLIA assay (E-SeC) after Standard dose ACTH test (SDCT) in

DOI: 10.1530/endoabs.49.EP1044

diagnosing HPAI.

Design

In this study we performed SDCT in 52 consecutive patients (F/M, 33/19, age

42.9G13 yrs) referred to our Center to evaluate at specific time points E-SeC,

TM-SeC and SaC. In the same group of patients we also evaluated E-SeC after

ITT, to diagnose HPAI (using a cut off!500 nmol/l).

Results

HPAI was diagnosed in 8 out of 52 patients (five patients operated on for a

pituitary macroadenoma, and

3 with a pituitary microadenoma). Using the

EP1045

diagnosis of HPAI made by ITT as reference test, we found that after SDCT an

Nivolumab and pembrolizumab induced hypophysitis

E-SeCO348 nmol/l at 0-min, O671 nmol/l at 30-min or O756 nmol/l at 60-min

Marleen Vosjan-Noeverman, Rob van den Brom, Geke Hospers,

excluded HPAI, whereas an E-SeC !155 nmol/l at 0-min, !436 nmol/l at

Jeroen Hiltermann & Gerrit van den Berg

30-min or !527 nmol/l at 60-min confirmed HPAI. By using LC-MS/MS we

University Medical Center Groningen, Groningen, The Netherlands.

found that after SDCT a TM-SeC O378 nmol/l at 0-min, O1012 nmol/l at

30-min or O1021 nmol/l at

60-min excluded HPAI, whereas a TM-SeC

Introduction

!149 nmol/l at 0-min, !334 nmol/l at 30-min or !351 nmol/l at 60-min

Immune checkpoint blockade in cancer treatment causes frequent adverse events

confirmed HPAI. Similarly by LC-MS/MS we found that after SDCT a SaC

of auto-immune etiology. Ipilimumab

(anti-CTLA-4

antibody) causes a

O7.4 nmol/l at 0-min, O15.8 nmol/l at 30-min or O23.3 nmol/l at 60 min

hypophysitis in up to

10% of patients. In contrast, during treatment with

excluded HPAI, whereas a SaC!1.7 nmol/l at 0-min, ! 4.7;nmol/l at 30-min or

nivolumab and pembrolizumab (both anti-PD-1 antibodies), hypophysitis is rare

!7.3 nmol/l at 60-min confirmed HPAI.

(!1%).

Conclusions

Results

We can conclude that even evaluating TM-SeC and SaC, after SDCT there is

In the past year, we identified 4 cases of hypophysitis in patients treated with anti-

large gray area of indeterminate results.

PD-1 therapy (incidence 1% out of a total group of 395 patients). Two patients

DOI: 10.1530/endoabs.49.EP1043

(male aged 78, female aged 58) were treated with nivolumab for non-small cell

lung cancer and

patients

(male aged

61, female aged

69) received

pembrolizumab for metastatic melanoma. After 8-12 cycli, all patients developed

fatique, two patients developed edema and 1 patient developed nausea and a

blurry vision. There was no period of transient headache as typically found in

hypophysitis caused by ipilimumab. Laboratory examination revealed the

diagnosis. Brain magnetic resonance imaging showed a normal pituitary gland

in all patients. At diagnosis, pituitary failure was present for the thyroid and

adrenal axis in 2 and 3 patients, respectively. One patient developed failure of the

pituitary-gonadal axis.

EP1044

Discussion

Risk and diagnosis of hypocortisolism after transsphenoidal surgery for

In contrast to hypophysitis after ipilimumab treatment, anti-PD-1

induced

sellar tumors

hypophysitis seems characterized by an insidious clinical course, without typical

Milagros Sierra¹, David Males¹, Laura Perez-Olivares¹, Ana Maria Casta

˜ o-

symptoms or associated MRI abnormalities. In contrast, the pattern of endocrine

León², Jose Fernández², Igor Paredes², Alicia Serraclara¹ &

failure of the adrenal axis is immediately life threatening. Given the sharp

Maria Calatayud¹

increase in the number of patients treated with immune checkpoint inhibitors,

¹12 de Octubre University Hospital Endocrinology and Nutrition

more patients with this rare side effect are expected. Therefore, it is necessary to

Department, Madrid, Spain;²12 de Octubre University Hospital Neurosur-

screen for central hypocortisolism and hypothyroidism and be aware of the

gery Department, Madrid, Spain.

possibility of a varied clinical presentation.

DOI: 10.1530/endoabs.49.EP1045

Introduction

Transsphenoidal surgery (TS) is used for pituitary and suprasellar tumors. It has a

risk of damaging the pituitary axis and developing hypocortisolism, a potential

life threating risk.

Objetive

Incidence of hypocortisolism after TS, postsurgery cortisol (PSC) levels that

EP1046

predict hypocortisolism and potential risk factors for hypocortisolism after TS.

Heterogeneity of the patient pathway for adult growth hormone

Methods

deficiency: Perspectives from a CEE Endocrinologists expert panel

Prospective study in patients who underwent TS in

2016. Glucocorticoid

Ilan Shimon⁹, Corin Badiu¹, Artur Bossowski², Mirjana Doknic³,

replacement (GR) began in surgery with hydrocortisone (HC) 100 mg tid. We

Iveta Dzivite-Krisane⁴, Václav Hána⁵, Jana Kollerova⁶, Emil Natchev

defined hypocortisolism as PSC!10 mcg/dl (discharged with HC 20 mg/day),

Natchev⁷, Marija Pfeifer⁸, Nikolette Sz

˜cs10, Juliana Hey-Hadavi¹¹ &

possible hypocortisolism as PSC 10-20 mg/dl (discharged with HC 10 mg/day)

Roy Gomez¹²

and eucortisolism as PSC O20 mcg/dl 3 days after TS. Definitive eucortisolism

¹University of Medicine and Pharmacy, Bucharest, Romania;²Klinika

was defined as Cortisol O18 mcg/dl after 100 mcg ACTH stimulation or basal

Pediatrii,, Endokrynologii, Diabetologii z Pododdzialem Kardiologii,

cortisol O20 mcg/dl 5 weeks after TS.

Poland;³Klinicki Centar Srbije, Beograd, Serbia;⁴Bernu kliniska

Results

universitates slimnica, Riga, Latvia;⁵Charles University, Prague, Czech

Twenty-three (12 females) patients underwent TS, mean age 52 years (22-85):

Republic;⁶Univerzitna Nemocnica Bratislava, Bratislava, Slovakia;

56%nonfunctioning adenomas,

20%GH adenomas, 4%arachnoid cyst and

⁷Clinical Center of Endocrinology and Gerontology, Medical University,

8%craniopharyngioma. Preoperative features: tumor’s mean diameter: 25 mm

Sofia, Bulgaria;⁸University Medical Centre, Ljubljana, Slovenia;⁹Rabin

(5-65), involvement of cavernous sinuses (KNOSP gradeR2) 60%. Five patients

Medical Center, Petah Tiqva, Israel;¹⁰Semmelweis University, Budapest,

present preoperative hypocortisolism. Pituitary-adrenal axis (PAA) assessment:

Hungary;¹¹Pfizer, New York City, USA;¹²Pfizer Innovative Health,

After TS 9 patients were diagnosed of hypocortisolism, 13 of possible hypoC and

Brussels, Belgium.

of eucortisolism. Five week after TS:

were diagnosis of definitive

hypocortisolism and 15 of definitive eucortisolism. Mean PSC was 13.5 mcg/dl

(2.28-22.5) in definitive eucortisolism patients and 8.75 mcg/dl (1.2-14.35) in

Introduction

definitive hypocortisolism. 75% with definitive hypocortisolism patients had PSC

Effective identification, diagnosis and management of growth hormone (GH)

!12 mcg/dl. In patients with definitive hypocortisolism:

60% presented

deficiency in adults are crucial for treating endocrinologists to provide the best in

preoperative hypocortisolism,

30% preoperatory GH deficit, 60% cavernous

patient care. As such, it is important that we share our experiences to understand

sinuses involvement, with KNOSP grade O2 and 50% were O30 mm.

challenges and obstacles to enhance the patient journey. The objective of this

Conclusions

project was to start identifying these challenges and obstacles.

Hypocortisolism after TS is a mayor complication; large and invasive tumors

Methods and findings

have more risk to develop postsurgery pituitary hypofunction. Three days PSC

In November 2016, an expert panel of 10 endocrinologists from across 10 Central

can predict development of definitive hypocortisolism, PSC R15 mcg/dl may be

and Eastern European (CEE) countries met to discuss their standard of care and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

journey taken by adult GH-deficient

(AGHD) patients in their respective

24 h, and a MRI scan, in order to objectivate the diagnosis. Initial cooperation was

countries. Prior to the meeting the experts were asked to summarize in a

present. The anamnesis revealed diabetes insipidus diagnosed at age 30, treated

systematic way, the standard of care available for AGHD patients in their

with desmopressin spray 10 mcg two times a day, in the morning, and diabetes

countries and share this with their peers. The meeting was chaired by one of the

mellitus type II from age 60, treated with 4 shots of fast insulin, 42 U/day. Clinical

experts and each participant had adequate time to present their perspective

examination revealed signs of mild dehydration. Lab tests highlighted mild

followed by discussion. It was uncovered that there was a substantial degree of

hyperglycemia of

142 mg/dl and hyponatremia of

129 mol/l. Glycated

diversity in the management AGHD patient pathway across CEE. The main

haemoglobin was 7.3%. Plasmatic osmolarity was 272.3 mOsm. The patient

variations included: initial entry to the healthcare system and referral journey;

was uncooperative to stoping or changing the schedule of desmopressin treatment,

tests required to confirm diagnosis; availability of programmes to manage patients

so she was discharged with natremia of 139 mmol/l. Recent medical history

during transition to adulthood; limitations of who prescribes GH therapy,

showed a recent emergency admission with similar clinical and biochemical

medication re-imbursement by national healthcare services and, the frequency of

futures. Moreover, it was proved that the patient had many ER admissions in

follow-up visits and monitoring of patients. Although most countries represented

Bucharest’s hospitals, with same situation. In this respect, the diagnosis of diabetes

relied on international society-led, published guidelines, few countries have

insipidus itself can be put under question, complicated by the psihogenic adherence

developed national guidelines for patient management.

to desmopressin treatment of the patient. Frequent clinical manifestations of

Conclusion

hyponatremia due tu desmopressin abuse in our patient is highlighting not only the

This expert panel recognizes a high degree of diversity in the patient pathway

complexity of psihogenic association to organic abuse, but also the need for

across CEE. Sharing of local experiences with other colleagues may help in

cooperation between practitioners across EU.

understanding areas of high heterogeneity as well as facilitating the sharing of

DOI: 10.1530/endoabs.49.EP1048

best practice. Further work will be needed to identify differences in practice

patterns and AGHD patient management among other regions in the world.

DOI: 10.1530/endoabs.49.EP1046

EP1047

EP1049

Considerable delays to achieve adequate control in treating patients

Aggressive pituitary tumours: a multicenter study

with acromegaly

Ana Palha¹, Leonor Gomes², João Sequeira Duarte³, Concei

¸a˜o Marques3,

Marinella Tzanela, Olga Karapanou, Christianna Giatra, Efstathia Botoula,

Cláudia Amaral⁴, Ana Amado⁴, Fátima Borges⁴, Isabel Ribeiro⁴,

Elisabeth Tiaka, Lambraki Anastasia & Stylianos Tsagarakis

Eduardo Barreiros⁵, Luis Barreiros⁵, José Miguéns⁵, Maria João Bugalho⁵,

Department of Endocrinology and Diabetes, Evangelismos Hospital,

Adriana Lages², Isabel Paiva², Olinda Marques⁶, Rui Almeida⁶,

Athens, Greece.

Teresa Martins⁷, Luisa Cortez¹, Ana Agapito¹ & Fernando Fonseca¹

¹Centro Hospitalar Lisboa Central, Lisbon, Portugal;²Centro Hospitalar

Universitário Coimbra, Coimbra, Portugal;³Centro Hospitalar Lisboa

Ocidental, Lisbon, Portugal;⁴Centro Hospitalar Porto, Oporto, Portugal;

Acromegaly is a rare disease that leads to considerable morbidity and

⁵Centro Hospitalar Lisboa Norte, Lisbon, Portugal;⁶Hospital de Braga,

mortality, both reversible by adequate control of the disease. However,

Braga, Portugal;⁷Instituto Português de Oncologia de Coimbra, Coimbra,

patients that could be adequately controlled confront delays in achieving

Portugal.

treatment targets. The aim of the present study was to estimate the time to

disease control after diagnosis and the reason leading to control delays.

We retrospectively studied 119 acromegalic patients (aged 46.4G12.5; 71

Introduction

females). Following appropriate treatment modalities all achieved IGF-1

Pituitary tumours are considered benign, however some exhibit an aggressive

levels within normal limits for age (43 pts had GH !1.0 ng/ml, and 76 pts

behavior. Defining a timely treatment is challenging due to absence of accurate

had GH !2.5 ng/ml). Acromegaly was adequately controlled within 0-6

prognostic predictors.

months in 19 patients (15.9%), within 6-12 in 14 (11.8%), and within 12-24

Objective

in 21 (17.6%). In 65 patients (54.6%) disease control was achieved after 24

To evaluate radiological and histopathological features of aggressive pituitary

months (25-412, median 103 months). Earlier controlled patients were older

tumours.

(50G11.9 vs 43.5G12.3, PZ0.00434), and underwent surgery sooner after

Methods

the diagnosis (8.0G6.8 vs 19.8G30.9 months PZ0.0324). When under

Multicenter and retrospective study. Criteria for aggressiveness were: invasion to

medical treatment, the main reasons for delay control were the late referral

sphenoid and/or cavernous sinus; growth progression after treatment (surger-

and initiation of medical therapy

(5.4G5.0

124.6G117.1 months,

y/medical/radiotherapy); early recurrence (%12 months). Atypical features were

PZ0.0138), and the time elapsed to modify dosage and/or implementing

Ki-67O3%, p53 positivity, mitoses O2/10xHPF or brain/spinal/systemic

alternative treatment options (4.4G3.7 vs 16.1G11.1 months, PZ0.0138).

metastases.

Tumor size or extension, GH and IGF-1 had no impact to time to control.

Results

According to our audit a substantial proportion of patients remain

Forty-five patients

(28

men) were collected from seven tertiary endocrine

uncontrolled for several months despite the efficacy of available therapeutic

departments. Age at diagnosis was 41.2G12.2 years. In 35.6% of patients first

modalities in these patients. The main reason seems to be the delay to cease

symptoms occurred before 35 years. Symptoms related to tumour expansion,

early surgical intervention or to adjust the medical treatment options.

hypersecretion and deficiency of hormones were the first manifestations in 73.6,

DOI: 10.1530/endoabs.49.EP1047

13.2 and 13.2% of patients, respectively. Our cohort comprised nonfunctioning

adenomas (64.4%), somatotropinomas (9.0%), corticotropinoma (13.3%) and

prolactinomas (13.3%). All were macroadenomas and 82.2% showed radiological

signs of invasion. Of the 44 operated patients, 56.8% required three or more

surgeries. Complementary radiotherapy was used in 66.7% of patients, medical

therapy in 42.2% of patients, two of these with temozolomide. Histopathology

EP1048

was obtained in 42 patients. Imunohistochemichal staining was GH positive in

Hyponatremia - the other face of diabetes insipidus complications

9.5%; PRL 14.3%; ACTH 11.9%, TSH 2.4%, FSH/LH 19%; plurihormonal

Madalina Bucur & Carmen Barbu

14.3%; nonsecreting and null-cell 28.6%. Elevated mitotic index was observed in

Elias University Emergency Hospital, Bucharest, Romania.

20% (nZ25), Ki-67 labeling index S3% in 44.4% (nZ27) and p 53 nuclear

staining in

41.2% (nZ17). During a mean follow-up of 11.5G6.3 years,

8 patients died (5 ACTH-cell adenoma) one with extracranial systemic metastases

(carcinoma).

Diabetes insipidus is mainly associated with dehydration as a complication,

Conclusions

hyponatremia being very rare. We report the case of a 75 years old female,

In our cohort ACTH-secreting tumours presented a more aggressive clinical

from Switzerland, who presented with nausea and vomit, diarrhea, asthenia

course. One limitation of our study was incomplete histopathological data,

and general sickness at the emergency room, where blood tests revealed

however, the majority of patients who died, presented atypical features.

hyperglycemia of 320 mg/dl and hyponatremia of 115 mmol/l, the patient

A continuous multicenter collaboration could help to identify prognostic markers

knowing to have diabetes insipidus and diabetes mellitus type II, with

and enable a different approach.

insulin and desmopressin. Following emergency equilibration, we rec-

ommended monitoring water intake, urine excretion in the absence of

DOI: 10.1530/endoabs.49.EP1049

desmopressin, with control of glycemic profile every 4 hours, for the next

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1050

Methods

All women of this group diagnosed between 1996 and 2016 and followed-up in a

Effects of somatostatin analogs on glucose metabolism in acromegalic

large specialist centre were included in the study.

patients: a meta-analysis of prospective interventional studies

Results

Tiziana Feola¹, Alessia Cozzolino¹, Ilaria Simonelli², Emilia Sbardella¹,

We identified 17 women with diagnosis of prolactinoma after menopause (median

Giulia Puliani¹, Elisa Giannetta¹, Patrizio Pasqualetti², Andrea Lenzi¹ &

age at diagnosis 62 years, range 52-70). Headaches and/or visual deterioration

Andrea M Isidori¹

were the most commonly reported presenting signs (47%). Acute pituitary

¹Department of Experimental Medicine - Sapienza University of Rome,

apoplexy was diagnosed at presentation or during follow-up in

18%. Two

Rome, Italy;²Department of Neuroscience- Fatebenefratelli Hospital-Isola

prolactinomas were detected incidentally (12%). The median serum prolactin was

Tiberina-Rome, Rome, Italy.

18 553 mU/L (range 4153-238479). In all cases, IGF-I values were not consistent

with GH hypersecretion. Macroprolactinomas comprised 94% of the tumors and

Introduction

88% of them had parasellar extension. All patients with macroprolactinoma were

Glucose metabolism impairment is a common complication of acromegaly.

offered dopamine agonist therapy; the median duration of their follow-up,

Somatostatin analogs (SSAs) are used as both first and second line treatment. The

determined by the date of starting dopamine agonist until last serum prolactin

effect of SSAs on glucose metabolism in acromegaly is still debated.

measurement, was 91 (5-186) months. Normal prolactin was achieved in 94%

Aim

and adenoma shrinkage was observed in all women. Improvement or resolution of

To address the following questions: 1) do SSAs affect glucose metabolism?

the visual disturbances documented at presentation was observed in 86% of cases.

2) does the effect correlate with disease control? 3) do different SSAs - Lanreotide

Conclusions

(LAN) and octreotide LAR (OCT) - affect metabolism differently?

The clinical phenotype of prolactinomas diagnosed after menopause differs from

Methods

that of premenopausal women, possibly due to the lack of clinical signs and

We performed a meta-analysis of prospective interventional studies reporting the

symptoms of hyperprolactinemia in non-menstruating patients. Most tumours

use of SSAs for the treatment of acromegaly. We searched MEDLINE, EMBASE,

were macroadenomas, with frequent parasellar extension and a relative high rate

and SCOPUS for English-language studies. Inclusion criteria: minimum 6-month

of pituitary apoplexy. In this very rare group of tumours, response to dopamine

follow-up, glyco-metabolic outcomes before and after SSA treatment. The pooled

agonists is good.

estimate of a weighted mean was obtained for all outcomes using a random effects

DOI: 10.1530/endoabs.49.EP1051

model.

Results

Forty-one studies have been included, 20 for LAN (354 patients) and 21 for OCT

(569 patients). LAN treatment induced a significant decrease in fasting plasma

insulin (FPI) (effect size K8.32, 95% CI: K10.44 to K6.20; P!0.001) and

HOMAi (K2.11, 95% CI: K3.54 to K0.69; PZ0.004), without changes of

fasting plasma glucose (FPG), HbA1c, triglyceridemia, weight and BMI. OCT

induced a small increase in HbA1c (C0.146, 95% CI: 0.043-0.249; PZ0.005), a

borderline rise of glucose during OGTT (0.47, 95% CI: K0.01 to 0.95; PZ0.053)

and significant decrease in FPI (K6.78, 95% CI:K9.37 to K4.18; P!0.001),

triglyceridemia (K0.41, 95% CI K0.55 to K0.28; P!0.001), HOMAi (K1.44,

EP1052

95% CI:K2.54 to K0.34; PZ0.010) and HOMAb (K36.65, 95% CI:K63.21 to

Ipilimumab induced hypophysitis - an insight from a case series in the

K10.08; PZ0.007), without any change of FPG. Meta-regression analysis

United Kingdom

revealed an association between the degree of GH reduction and lowering of

Punith Kempegowda¹, Lauren Quinn², Anitha Vijayan Melapatte¹,

HbA1c (PZ0.03). Meta-regression also showed a worse post-therapy Hb1Ac

Ankit Jain¹, Neil Steven¹, Helena Gleeson¹ & Andrew Toogood¹

outcome with increasing pre-therapy IGF1 levels (PZ0.002). The percentage of

¹Queen Elizabeth Hospital Birmingham, Birmingham, West Midlands, UK;

patients at target for GH and baseline IGF1 explained up to 58% of variance of

²University of Birmingham Medical School, Birmingham, West Midlands,

HbA1c.

UK.

Conclusions

LAN and OCT induce a significant decrease in FPI and in HOMAi, without

adverse change in FPG. OCT seems to reduce HOMAb and increase HbA1c,

Aims

while reducing trygliceridemia. IGF1 and GH-response partially explain the

To assess the incidence of Ipilimumab associated hypophysitis and its common

metabolic effect of SSAs.

presentations.

Methods

DOI: 10.1530/endoabs.49.EP1050

All patients who developed Ipilimumab induced hypophysitis following

treatment for Malignant melanoma at a large tertiary care centre in West

Midlands, United Kingdom from 2012 to 2014 were included in the study.

Patients with known pituitary disease prior to treatment and/or received other

systemic immunotherapy following Ipilimumab treatment were excluded. All

surviving patients were followed up to December 2016. Relevant data - clinical

features, hormone profiles and radiological findings

- were extracted from

patients’ medical records.

Results

Overall,

59 patients were treated with Ipilimumab for malignant melanoma

EP1051

during the period of interest. The incidence of hypophysitis in the cohort was

Prolactinomas diagnosed after menopause: presentation and outcomes

15.3% (9/59). The median age for patients with hypophysitis was 64 years (IQR,

from a large specialist centre

60-68 years); 44.4% (4/9) were male. 66.7% (6/9) presented with mild to

Sandhya Santharam^1,2, Metaxia Tampourlou^1,2, Wiebke Arlt^1,2,

moderate symptoms and 33.3% (3/9) patients developed severe symptoms

John Ayuk², Neil Gittoes^1,2, Andrew Toogood², Rachel Webster³ &

secondary to Ipilimumab induced hypophysitis resulting in hospitalisation.

Niki Karavitaki^1,2

Fatigue (7/9; 77.8%) was the most common presenting symptom; headache and

¹Institute of Metabolism and Systems Research,College of Medical and

visual disturbance was reported by 33.3% (3/9) and 22.2% (2/9) respectively.

Dental Sciences University of Birmingham, Birmingham, UK,²Centre for

Secondary hypogonadism (5/9; 55.6%) and secondary hypoadrenalism (4/9;

Endocrinology, Diabetes and Metabolism, Birmingham Health Partners,

44.4%) were the most commonly affected pituitary systems. One patient

Birmingham, UK,³Department of Clinical Biochemistry, Queen Elizabeth

developed panhypopituitarism. 33.3% (2/6) patients developed diffuse enlarge-

Hospital Birmingham, Birmingham, UK.

ment of pituitary gland. All patients had clinical recovery following adequate

hormone replacement.

Conclusions

Introduction

Disturbances in pituitary axis are common with Ipilimumab treatment and can

Most prolactinomas in females are diagnosed during the years of reproductive age

present with subtle symptoms. Therefore, regular assessment of pituitary function

and the majority are microadenomas. Prolactinomas diagnosed after menopause

during Ipilimumab treatment is recommended. Affected patients should be

are very rare with limited published data on their presentation and outcomes.

managed jointly by oncology and endocrinology teams to prevent serious

Aim

complications and allow Ipilimumab treatment to continue.

The aim of our study was to assess the presenting clinical, biochemical and

DOI: 10.1530/endoabs.49.EP1052

imaging findings, as well as the outcomes of women diagnosed with a

prolactinoma in the post-menopausal period.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1053

R2 analysis fibrinogen itself accounted for

10% of the variance. Moreover,

T1-weighted coronal scans were inversely correlated with VES (PZ0.01).

Mammary duct ectasia due to prolactin-secreting pituitary adenoma

Conclusions

I¸ılay Kalan Sarı, Suheyla Gorar & Oykun Kola

˘ası

This study describes a reduction of pituitary volume and quantitative T1-weighted

Antalya Research and Training Hospital, Antalya, Turkey.

intensity in obese patients, that seems related to a low-grade inflammation. Data

could be explained by a relative change in pituitary stromal tissue in this cohort of

Introduction

patients.

Mammary duct ectasia (MDE) is an inflammatory breast disease characterised by

DOI: 10.1530/endoabs.49.EP1054

dilation of major ducts and periductal inflammation. MDE occurs commonly in

women undergoing menopause. The etiology has not been well defined but

previous studies described an association between high prolactin and MDE.

Case Report

A 42-year-old female was admitted to our hospital with complaints of

galactorrhea, amenorrhea, mammary gland tenderness and breast discomfort.

Tests revealed serum prolactin level of 85 ng/ml and breast ultrasound showed

EP1055

dilated anechoic ducts and marked cystic ectasia. A 15!12 mm complex cystic

Hypogonadotropic hypogonadism in a patient with long-term primary

lesion in right breast and several enlarged lymph nodes were found in right

hypothyroidism

axillae. Mammography revealed thickened breast tissue with diffuse MDE

Raquel Vaz de Castro¹, José Maria Aragués², Florbela Ferreira¹,

without any calcification. Pituitary MRI showed 5.5!5.0!2.5 mm pituitary

Vânia Gomes¹, Ana Wessling¹ & Maria Joa˜o Bugalho1

adenoma. Treatment with cabergoline 0.5 mg twice a week, warm compress and

¹Santa Maria Hospital, Lisbon, Portugal;²Beatriz Ângelo Hospital, Lisbon,

antibiotic started. Cabergolin dose is progressively increased to 2 mg per week.

Portugal.

Prolactin level reached to 20 ng/ml and tumor size reduced to 3!3!1.5 mm in

6 months. Although treatment with cabergoline, resulted in improvement of breast

symptoms and galactorrhea, diffuse MDE was reported in repeat ultrasound.

Abstract

Cabergoline dose is increased and the patient is still being followed up.

We report the case of a 65-year-old man who presented with erectile dysfunction

Discussion

to an appointment in our Endocrinology department. He referred fatigue, weight

In the present case, we hypothesize that there was an association between

gain and constipation as secondary complaints that had been steadily evolving

abnormal prolactin secretion and development of MDE. Shousha et al. discribed

throughout the past 4 years. He denied other symptoms such as visual impairment

three cases with marked MDE and chromophobe adenomas. Peters et al.

or headaches as well as the consumption of any medications or drugs. His past

concluded that MDE is due in part to increased prolactin secretion. They also

medical history was unremarkable. On examination, BMI was 25.8 kg/m², arterial

concluded that MDE may cause transient hyperprolactinemia. MDE induced by

blood pressure 112/64 mmHg, heart rate 71 BPM and temperature 36.4 8C. Neck

sulpiride-associated hyperprolactinemia was also discussed in literature. In our

palpation revealed a diffuse thyroid enlargement. Visual acuity and visual fields

case; diffuse MDE may have been developed as a result of changes in prolactin

were unaltered. Blood tests revealed elevated TSH (69.8 uU/ml) with low FT4

levels. We conclude that increased prolactin secretion leading to chronic

(0.18 ng/dl), consistent with the diagnosis of primary hypothyroidism, and

inflammation and fibrosis may cause to persistence of ductal dilatation.

hypogonadotropic hypogonadism (testosterone

74.3 ng/dl). PRL levels were

DOI: 10.1530/endoabs.49.EP1053

slightly elevated (38 ng/ml). Magnetic resonance imaging (MRI) of the pituitary

showed a 17!14!12 mm sellar mass, without compression of the pituitary stalk

or optic chiasm. The patient was started on levothyroxine 100 mcg per day. Three

months later, the erectile dysfunction had resolved and thyroid function and total

testosterone had returned to normal - TSH 0.90 uU/ml, FT4 1.16 ng/dl, and total

testosterone 522.8 ng/dl. The control MRI taken one year after starting therapy

revealed regression of the pituitary enlargement. This is a peculiar case of HH

EP1054

likely associated with pituitary hyperplasia, in the context of long standing

primary hypothyroidism, successfully treated with levothyroxine.

Quantitative analysis of the pituitary gland at magnetic resonance

imaging in obese patients

DOI: 10.1530/endoabs.49.EP1055

Giulia Puliani¹, Carla Lubrano¹, Marco Fiorelli², Emilia Sbardella¹,

Chiara Graziadio¹, Daniele Gianfrilli¹, Andrea Lenzi¹ & Andrea M Isidori¹

¹Department of Experimental Medicine - Sapienza University of Rome,

Rome, Italy;²Department of Neurology and Psychiatry - Sapienza

University of Rome, Rome, Italy.

Background

Hypothalamic-pituitary function and adipose tissue are deeply interconnected.

EP1056

Obesity has been linked to morpho-functional changes in several endocrine

Effects of pasireotide treatment on cardio-metabolic risk in patients

glands (thyroid, adrenal, gonads). No study has quantified the appearance of the

with Cushing’s disease: an Italian, multicenter study

pituitary gland in obese subjects.

Adriana Albani¹, Francesco Ferrau¹, Erika Messina¹, Rosario Pivonello²,

Aim

Carla Scaroni³, Carla Giordano⁴, Alessia Cozzolino², Marialuisa Zilio³,

To measure pituitary signal intensity, homogeneity and texture of the pituitary

Valentina Guarnotta⁴, Alessandro Ciresi⁴, Davide Iacuaniello²,

gland at magnetic resonance (MR) in obese subjects free of focal pituitary disease.

Angela Alibrandi⁵, Annamaria Colao² & Salvatore Cannavo⁶

Materials and Methods

¹Department of Clinical and Experimental Medicine, University of Messina,

Sixty-four overweight and obese patients were prospectively enrolled and

Messina, Italy;²Department of Clinical Medicine and Surgery, Endo-

underwent metabolic, hormonal, body composition (DEXA scan) and pituitary

crinology Unit, University of Naples Federico II, Naples, Italy;³Department

MR assessment. Texture of the pituitary gland was quantified recording pixel

of Medicine (DIMED), Division of Endocrinology, University of Padua,

density and distribution at sagittal and coronal non-enhanced T1-weighted images

Padua, Italy;⁴Biomedical Department of Internal and Specialist Medicine

using ImageJ software. Two operators independently placed the region of interest

(DIBIMIS), Section of Cardio-Respiratory and Endocrine-Metabolic

to entirely cover the pituitary gland, calculating mean intensity and its standard

Diseases, University of Palermo, Palermo, Italy;⁵Department of Econ-

deviation. All analyses were normalized for both white and gray brain matter

omics, University of Messina, Messina, Italy;⁶Department of Human

intensity. Pituitary volume (PV) was calculated using the ellipsoid formula.

Pathology of Adulthood and Childhood, University of Messina, Messina,

Results

Italy.

MR showed an empty sella in 12/64 (18.7%) patients. Mean PV was 384G

147 mm³ (427G120 mm³, excluding the empty sella). An inverse correlation was

found between PV and ultrasensitive C-reactive-protein

(PZ0.004) and a

borderline association between PV and BMI (PZ0.056). Pituitary intensity in T1-

Patients with Cushing’s disease (CD) have increased cardiovascular risk due to

weighted images was negatively correlated with BMI (PZ0.03) and truncal fat

metabolic alterations caused by glucocorticoids excess. Pasireotide, a multi-

(PZ0.04). Linear regression analysis revealed that, after adjusting for age and

receptor-targeted somatostatin analogue, is a therapeutic option in CD patients in

sex, the percentage of truncal fat and fibrinogen were significant predictors of the

whom surgery is not curative or not feasible. Pasireotide has been shown to be

mean intensity of coronal and sagittal T1-weighted scans (PZ0.001). The model

effective in controlling hypercortisolism and to improve metabolic features.

explained up to 29% of variance of pituitary signal intensity, and in a step-wise

Recently, the visceral adiposity index (VAI) has been proposed as a marker of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

visceral adipose tissue dysfunction (ATD) and of the related cardio-metabolic

¹Department of Endocrinology, Diabetes and Metabolism of Centro

risk. We aimed to assess the effects of 12-month pasireotide therapy on cardio-

Hospitalar de São João, Porto, Portugal;²Faculty of Medicine, University of

metabolic and cardiovascular risk in CD patients. In 16 CD patients (11 females),

Porto, Porto, Portugal;³Department of Pediatric Endocrinology, Hospital

referred to the Endocrine Units of four Italian University Hospitals, we assessed

Pediátrico Integrado, Centro Hospitalar de São João, Porto, Portugal;

anthropometric, clinical and biochemical parameters and calculated VAI, ATD

⁴Department of Pediatrics, Centro Hospitalar de Entre o Douro e Vouga,

severity, Framingham and Atherosclerotic CardioVascular Disease Risk Scores

Santa Maria da Feira, Portugal.

(FRS and ASCVD respectively), at baseline and after 6 and 12 months of therapy

with pasireotide

(1200-1800 mcg/daily). Before starting pasireotide therapy,

ATD was present in 8/16 patients (severe in 2/16, mild in 2/16, moderate in 3/16).

Introduction

After 12 months of treatment: i) UFC levels (PZ0.003), BMI (P!0.001), waist

During childhood and puberty, growth hormone(GH) is essential for linear

growth. Consequently, children with isolated GH deficiency(GHD) must receive

circumference

(PZ0.001), LDL-cholesterol

(PZ0.033), total-cholesterol

replacement therapy. GH has also important metabolic actions. GHD in adults is

(PZ0.032), triglycerides

(PZ0.03), VAI

(PZ0.015) and ATD severity

associated with altered body composition. However, long-term consequences of

(PZ0.026) were significantly decreased as compared to baseline; ii) ATD was

GH treatment in adults is not sufficiently known.

present in only 1/16 patients; iii) prevalence of diabetes (PZ0.015) and HbA1c

Objective

levels (PZ0.001) were significantly increased as compared to baseline; iv) FRS

To evaluate GH treatment during pediatric age in patients with isolated GHD.

and ASCVD scores were not statistically different from pre-treatment values. In

Methods

conclusion, twelve-month pasireotide treatment reduces cardio-metabolic risk in

Retrospective study of patients with isolated GHD followed in a tertiary hospital,

CD patients.

which had undergone reassessment after finishing growth period. Anthropometric

DOI: 10.1530/endoabs.49.EP1056

and analytical parameters before and after treatment were collected. SDS of

anthropometric variables were calculated according WHO curves. IGF1

(Immulite 2000^w) was analyzed considering SDS values adjusted for pubertal

stage.

Results

Sample composed by 27 patients, 63% males. Before treatment: mean age was

10.5G3.7 years, mean height-SDS K2.82G0.77, IGF1-SDS levels K2.41G

EP1057

1.59 ng/ml with a mean difference of 2G1.5 years between chronological and

DHEA-S as a marker of the secondary adrenal insufficiency following

bone age. All patients performed GH stimulation tests (clonidine, glucagon or

craniospinal irradiation

insulin tolerance test) - peak values !7.0 mg/l. Three patients had abnormal

Alla Yudina¹, Maria Pavlova¹, Tatiana Tselovalnikova¹,

pituitary MRI. Mean treatment duration was 5G3 years. Mean maximal dose

Nadezhda Mazerkina², Irina Arefyeva² & Olga Gheludcova³

administered was 0.03G0.01(mg/kg/day). No adverse effects were registered. At

¹Sechenov First Moscow State Medical University, Moscow, Russia;

the end, final height-SDS was K1.63G0.64 and IGF1-SDS K0.83G2.34. Final

²Burdenko Neurosurgery Institute, Moscow, Russia;³Russian Scientific

height and target height differed in K4.72G6.07 cm. Nine patients kept follow-

Center of Roentgenoradiology, Moscow, Russia.

up in Endocrinology: 3 performed insulin tolerance test, all having normal results.

Only 2 patients presented IGF-1 levels !-2 SDS (one of them proposed for

treatment).

Abstract

Discussion

The secondary adrenal insufficiency (SAI) is life-threatening disease. 30-50% of

As expected, patients with isolated GHD treated at our center showed good

patients have SAI following craniospinal irradiation (CSI). The “gold standard”

clinical outcomes, with mean final height reaching close target height. Current

of SAI diagnosis is the insulin tolerance test but it is demanding for patient and

recommendations consider to treat with GH, adults with documented persistent

medical staff. The simple and reliable test would allow to use ITT rarely. The aim

deficiency. In this series all patients with isolated GHD with normal MRI had a

was to evaluate probability of using DHEA-S in SAI diagnosis. 41 patient after

transitory deficit and did not required treatment in the adult age.

CSI non-pituitary brain tumors survivor and 23 healthy were included. The mean

DOI: 10.1530/endoabs.49.EP1058

age was 20.5G3,6 years (16-30), follow-up was more than 2 years. Cortisol,

DHEA-S, ACTH were determinate and then ITT was performed. The patients

were divided into SAI-group and without SAI (W-SAI) after ITT.

Results

18/41 had SAI by ITT. DHEA-S was significantly lower in SAE-group 2.65G

1.4 mmol/l than in W-SAI and healthy (5.2G2.1 and 7.6G4.4 mmol/l, PZ0.001).

Cortisol in SAI and healthy was the same (326G99.4 and 390.5G161 mmol/l,

PZ0.2) but lower that W-SAI (495.2G186 mmol/l, PZ0.05). ACTH was not

EP1059

differ. DHEA-S/cortisol ratio was lower in SAI (PZ0.002), ACTH/cortisol was

What should central diabetes insipidus and panhypopituitarism point

the same. There was the significant correlation between SAI and cortisol (rZ0.57,

out in a patient with lung adenocarcinoma in remission?

PZ0.02) and SAI and cortisol (rZ0.49, PZ0.02). There was not correlation

Sule Canlar, Caglar Keskin, Asena Gokcay Canpolat, Sevim Gullu &

between age and DHEA-S. DHEA-S did not have gender difference within SAI

Demet Corapcioglu

and W-SAI. AUC cortisol was 0.79; AUC DHEA-S 0.9; AUC DHEA-S/cortisol

Ankara University Faculty of Medicine, Ankara, Turkey.

0.67. All patients who had basal cortisol lower than 200 nmol/l or DHEA-S lower

than 2.0 mmol/l were in SAI-group, and who had cortisol or DHEA-S more than

500 and 3.7 respectively did not have SAI by ITT. Cut-off DHEA as 3.7 had Se

Objectives

73% and SP 100%. When linear regression has applied, AUC cortisolCDHEA-S

Pituitary gland is an uncommon site for metastasis of malignant tumors. Breast

was 0.96.

and lung are the most common cancer sites. Most pituitary metastases are

Conclusion

asymptomatic, with only 7% symptomatic and central diabetes insipidus is the

DHEA-S had higher sensitive and specificity that cortisol for diagnosis of SAI

most common symptom.

in patients younger than 30 years following craniospinal irradiation. DHEA-S

Case presentation

can used without gender accounting in this group. Combined examination by

A 54 year-old woman presented with nause, emesis and diplopia to emergency

DHEA-S and cortisol is optimal.

department. Her relatives stated that she had poliuria, nocturia, polidipsia for

DOI: 10.1530/endoabs.49.EP1057

three months. Her history revealed that she had been operated because of lung

adenocarcinoma and postoperatively had underwent adjuvant chemotherapy. She

was at follow-up in remission. Laboratory tests denoted hypernatremia and MRI

scan images demonstrated that hypointense contrasted hypophysis and

infundibular enhacement. She possesed central diabetes insipidus and desmo-

pressin treatment administered primarily. On observation, central hypothyroidism

and secondary adrenocortical defficiency developed. Medical oncology depart-

EP1058

ment assesed the patient, no metastatic lesion was detected in thoracoabdominal

CT additionally PET scan, so that they didn’t consider pituitary metastasis. We

Clinical and laboratorial reassessment of patients with isolated growth

didn’t reveal any autoimmune, infectious and inflammatory diseases that can

hormone deficiency during the transition phase

cause hypophyseal involvement. Transnasal-transsphenoidal hypophysis biopsy

Ana Saavedra^1,2, Juliana Oliveira³, Alexandra Martins⁴, Ana Azevedo⁴,

was occured, but histopathological sampling was insufficient. The patient refused

Rita Santos-Silva^2,3, Cíntia Castro^2,3, Elisabete Rodrigues^1,2,

second biopsy, so she was discharged with replacement therapy in clinical stable

Davide Carvalho^1,2 & Manuel Fontoura^2,4

state. But two weeks later, the patient applied with emesis-vomitting and diplopia

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

and MRI scans showed progression. Also she had seizures, periferal facial

hypophysitis as a result of performed tests is discussed hereby in the case report.

paralysis and drop foot. The progression of lesions necessitated exact diagnosis

A 30 year old male patient presented to out clinic with fatigue, malaise,

and transcranial biopsy was carried out by the same neurosurgeon. After biopsy,

somnolence and headache. It was learned that the onset of the complaints was

her clinical course worsened and she lost her life. Meanwhile, histopathological

three months before and they gradually increased since then. There was no

examination resulted as metastasis of lung adenocarcinoma to hypophysis.

chronic disease, medication, herbal agent or alcohol use in the patient anamnesis.

Conclusions

Overall medical condition of the patient was moderate with

36.78C body

A past history of cancer should be kept in mind in a patient presenting with sellar

temperature, 80/50 mmHg arterial blood pressure and 50/min heart rate. Physical

mass even if the cancer is in remission. Especially, presence of diabetes insipidus

examination revealed no abnormal finding other than icteric sclera. Due to the

and MRI scan findings are clues for metastatic disease.

pathologic findings of

0.05 ng/dl free thyroxine level,

2.04 pg/ml free

DOI: 10.1530/endoabs.49.EP1059

triiodothyronine level and

0.46 u/ml of thyroid-stimulating hormone, further

tests were performed on the patient for a pre-diagnosis of central hypothyroidism.

Tests performed for etiology resulted in

0.82 ug/dl cortisol,

0,1 mlu/ml

luteinizing hormone, 7.97pg/ml adrenocorticotropic hormone and 2.68 mlu/ml

follicle stimulating hormone. Panhypopituitarism was considered due to these

results. Levothyroxine and prednisolone treatment was initiated. Diagnostic

magnetic resonance (MR) imaging was performed. Imaging revealed height of

pituitary gland 14 mm higher than normal. No heterogeneity was observed at

pituitary gland level. Biopsy of pituitary gland was performed for establishing

EP1060

diagnosis and result was concordant with granulomatous hypophysitis. TORCH

Is there any relationship between nonfunctional pituitary adenoma and

panel, herpes simplex virus, Brucella, Epstein-Barr, parvovirus, varicella-zoster,

arterial stiffness?

T. pallidum tests were negative. Adenosine deaminase (ADA) level was 45, in the

Yavuz Cagir¹, Mustafa Altay², Erman Cakal³, Busra Betul Cagir⁴,

upper limit. Tuberculin skin test

(PPD) resulted in

22 mm induration and

Tolga Akkan¹, Murat Dagdeviren² & Esin Beyan¹

QuantiFERON-TB gold test was positive. Hypophysitis developed secondary to

¹Kecioren Education and Research Hospital, Internal Medicine, Ankara,

tuberculosis was considered. In addition to the current treatment, anti-tuberculosis

Turkey;²Kecioren Education and Research Hospital, Endocrinology and

(isoniazid, streptomycin, pyrazinamide, rifampin) treatment was initiated. The

Metabolism, Ankara, Turkey;³Diskapi; Education and Research Hospital,

dose of administered prednisolone was gradually (24 -O 18 -O 12 -O 8 -O 75

Endocrinology and Metabolism, Ankara, Turkey;⁴Diskapi; Education and

-O 5 -O 4 mg / day) increased along the course of treatment. The need for steroid

Research Hospital, Internal Medicine, Ankara, Turkey.

was completely eliminated by month 6 of tuberculosis treatment. In cases such as

tubercular hypophysitis developing due to secondary causes, early diagnosis is

very important given that panhypopituitarism may be completely eliminated in

Introduction

clinical terms following an effective anti-tuberculosis treatment. Therefore,

In a recent study, it was determined that morbidity rates due to cardiovascular

tubercular hypophysitis should be kept considered for cases referred with

diseases were affected as a result of long-term follow-up in patients with

hypopituitarism clinic and suggesting secondary hypophysitis.

nonfunctional pituitary adenoma. And cardio/cerebro vascular diseases were the

DOI: 10.1530/endoabs.49.EP1061

most frequent cause of mortality when mortality rates were examined. In the

literature, there are not enough studies evaluating this condition in patients with

nonfunctional pituitary adenoma without traditional cardiovascular risk factors.

The aim of our study was to determine the peripheral and central blood pressures

and arterial stiffness by Pulse Wave Analysis

(PWA) in patients with

nonfunctional pituitary adenoma without traditional risk factors.

Material & methods

In ourstudy, 60 participants (30 patients with nonfunctional pituitary adenoma

and 30 healthy volunteers) without traditional cardiovascular risk factors were

EP1062

evaluated. All participants were similar in terms of gender, age and body mass

T2-weighted MRI signal and response to somatostatin analogs in

index. Peripheral and central blood pressure and PWA measurements were

acromegaly

performed with a Mobile-O-Graph PWA / ABPM instrument (I.E.M. GmBH,

Luis Cerqueira, Ana Palha, Luisa Cortez, Amets Sagarribay,

Stolberg, Germany). In the nonfunctional pituitary adenoma group radiological

Fernando Fonseca & Ana Agapito

and biochemical data were obtained retrospectively.

Centro Hospitalar Lisboa Central, Lisbon, Portugal.

Results

In the nonfunctional pituitary adenoma group, systolic blood pressure (SBP),

diastolic blood pressure (DBP), mean arterial pressure (MAP), central SBP,

Introduction

central DBP, augmentation index that corrected based on pulse rate of 75 bpm

somatostatin analogs

(SSA) are largely prescribed in acromegalic patients,

(Aix@75) and pulse wave velocity (PWV) were significantly higher than control

whether as adjuvant or primary therapy. Response is variable and seems

group. There was no significant correlation between biochemical parameters and

dependent of histological subtype. Intensity T2 signal in MRI has been related to

arterial stiffness parameters in the group of nonfunctional pituitary adenoma.

granulation patern and accordingly with response to SSA.

Conclusion

Objective

Peripheral and central blood pressure and arterial stiffness parameters are

To evaluate whether T2 MRI signal is correlated with effectiveness of SSA

negatively affected in patients with nonfunctional pituitary adenoma known as

Material and methods

cardiometabolically innocent, without traditional cardiovascular risk factors.

Retrospective analysis of acromegalic patients treated with SSA and available T2

Measurement of arterial stiffness in this patient group will lead to early detection

MRI. We considered response as complete (normal GH and IGF1), partial (GH

of mortality and morbidity due to possible cardiovascular pathologies

and/or IGF1 reduction R50%) and no response (%50%). MRI were analysed by

DOI: 10.1530/endoabs.49.EP1060

one neuroradiologist blinded for clinical and pathological data. Visual assessment

only or direct measurements of signal intensity using ROI cursors on T2 coronal

sections classified adenomas as hypointense or hyperintense, according MRI

signal % temporal lobe white matter or R grey matter, respectively. Signal

intensity between grey and white matter defined isointensity.

Results

Fourteen patients (8 males) were treated with SSA for a minimum of 6 months.

All but 5 patients were surgically treated (3 refused, 1 approach failed due to

bleeding,

1 is waiting surgery). T2

MRI hypointensity was documented in

EP1061

8 patients (group 1) and hyperintensity in 6 (group 2). Group 1 included 3 non

A rare cause of hypophysitis: tuberculosis

responders, 3 with partial and 2 with complete response. Group 2 comprised 3 non

Ihsan Ates & Nisbet Yilmaz

responders, 2 with partial and 1 with complete response to SSA. Considering

Ankara Numune Training and Research Hospital, Ankara, Turkey.

isolated GH reduction (R 50%), hypointensity was more often observed (62,5%).

Comments

In this cohort of acromegalic patients we observed no relationship between T2

Hypophysitis is a heterogeneous inflammatory disease of pituitary gland. As it

signal intensity on MRI and hormonal response to SSA. One major limitation is

causes headache and visual defects, it mimics sellar tumors in clinical and

the small sample analysed.

radiological aspects. It may occur due to primary or secondary causes.

Tuberculosis is one of the rare secondary causes of hypophysitis. A young

DOI: 10.1530/endoabs.49.EP1062

male patient presented with fatigue and headache and diagnosed with tubercular

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1063

insufficiency documented in 3 of 4 patients tested by GHRH C Arginine (7%).

One patient displayed a concomitant GH insufficiency and low TSH level while in

“Toxic” Goiter Reveals Cushing’s Disease

another subject we found GH deficit and low FSH, LH and testosterone values

Madalina Musat^1,2, Dan Hortopan², Luciana Oprea², Andreea Duceac²,

even if his gonadotropin response was normal after LHRH test. Surprisingly, none

Dana Manda², Andra Caragheorgheopol², Carmen Iordachescu²,

of the patients displayed altered PRL values.

Claudiu Tupea² & Vasile Ciubotaru³

Conclusions

¹Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;

Mild to moderate TBI was followed by pituitary dysfunction documented in

²C.I.Parhon National Institute of Endocrinology, Bucharest, Romania;

13.3% of subjects. Higher frailty of GH and gonadotropin secretion by pituitary

³Emergency Clinical Hospital Bagdasar Arseni, Bucharest, Romania.

was confirmed, while altered PRL secretion was not documented.

DOI: 10.1530/endoabs.49.EP1064

Case presentation

Mrs. S presented in an endocrine clinic for fatigue, weight loss, restlessness and

goiter. She was obese with a BMI of 51 kg/mp, hypertensive and had a medium

size, nontender goiter. Lab test revealed hyperglycaemia, suppressed TSH

(!0.03mUI/L), on two separate occasions, mid-normal fT4 and T3. Thyroid

ultrasound revealed multinodular goiter. A diagnosis of polynodular goiter with

subclinical hyperthyroidism was made and patient was commenced on thiamazole

EP1065

30 mg/day. She was also scheduled for a RAIU. Three weeks later she was

The pseudo-tumoral adénohypophysitis: A rare disorder of the

admitted in the endocrine unit with a BMI of 47kg/mp. At presentation she had

postpartum

plethora, purpura on her breasts and bruised easily at venipuncture sites. FBC

Ghizlane El Mghari, Nassiba Elouarradi & Nawal El Ansari

revealed neutrophilia with lymphocytopenia, normal platelets. Thyroid function

Endocrinology and Diabetes Department, University Hospital Mohamed VI,

tests revealed suppressed TSH (0.0164 mUI/L) with low fT4. Thiamazole was

Marrckech, Morocco.

stopped. RAIU revealed low radioiodine uptake in the thyroid. Midnight plasma

and salivary cortisol were high, morning plasma cortisol was borderline high,

with increased ACTH. Urine cortisol was 10 fold upper limit of normal, low

Introduction

dexamethasone suppression test was negative. MRI of the pituitary revealed left

The pseudo-tumoral lymphocytic adénohypophysitis is an autoimmune disorder

sided pituitary microadenoma of 7,5/7 mm. Diagnosis of Cushing’s disease has

responsible for anterior hypophysis insufficiensy.It is a rare cause of pituitary

been made and transsphenoidal adenomectomy was perfomed. At 3 weeks

hypofunction which predominantly affects young women in the peripartum

postoperatively patient has returned to clinic with symptoms of cortisol

period. We report the case of a patient in whom the pseudo-tumoral lymphocytic

withdrawal while on 30 mg of cortisone daily. She had a BMI of 42 kg/mp, no

adénohypophysitis was the cause of a pituitary failure.

plethora and no purpura. Cortisol day curve was within the therapeutic range. Off

Case presentation

therapy, morning plasma cortisol was 8.89 mcg/dL, normal ACTH, midnight

The patient was a 44 year-old woman, who presented with headache and vomiting

plasma cortisol of 1.44 mcg/dL and lower normal range of urinary free cortisol.

without visual disturbance at the 7 th month of pregnancy. She was admitted to

Thyroid function tests were normal.

our institution in post-partum for secondary amenorrhea combined with the

Conclusion

absence of lactation without diabetes insipidus.In the hormonal evaluation, we

Hypercortisolism is known to alter pituitary hormones, however it is not usual that

have a ante-pituitary insufficiency with: cortisol Z0,01ug/dl, EstradiolZ16pg/ml

mild Cushing’s disease to suppress TSH to ‘thyrotoxic’ level. In this case of

FSHZ5.85 mUI/ml, LHZ0.4 mUI/ml, TSHZ0.008 uUI/ml, T4Z2.19 ng/dl and

unsuspected Cushing’s disease, thyroid function test alteration led to diagnosis.

a prolactinZ0.15 ng/ml. Magnetic resonance (MR) imaging of the pituitary

DOI: 10.1530/endoabs.49.EP1063

revealed a pituitary mass (18!14 mm) evoking a pituitary adenoma. The patient

is maintained on oral hydrocortisone and thyroxine. The evolution was favorable

and the controlled pituitary MRI, two years after, showed a normal pituitary gland

with disappearance of the pituitary mass.

Discussion

The pseudo-tumoral lymphocytic adénohypophysitis is a rare and previously

under-recognised disorder, most commonly affecting young females in the post-

EP1064

partum period. It presents clinically with symptoms and signs related to either a

pituitary mass or hypopituitarism, frequently mimicking a pituitary adenoma. It is

Low incidence of hyperprolactinemia following traumatic brain injury

difficult to distinguish lymphocytic hypophysitis from a pituitary adenoma on pre-

Anna Tortora¹, Domenico La Sala¹, Anna Luna Tramontano¹,

operative imaging and definitive diagnosis rests on histology which classically

Francesca Bisogno¹, Elisabetta Angrisani², Mario Carrano² &

demonstrates destruction of anterior pituitary acini by an inflammatory infiltrate

Mario Vitale^1,2

rich in plasma cells and T lymphocytes.

¹Department of Medicne, Surgery and Dentistry, University of Salerno,

Salerno, Italy;²AOU San Giovanni di Dio e Ruggi D’Aragona, Salerno,

DOI: 10.1530/endoabs.49.EP1065

Italy.

Background

Traumatic brain injury (TBI) is a major cause of disability and death, and a cause

of neuroendocrine dysfunction. Partial or complete pituitary dysfunction is a

EP1066

frequent event occurring in 25-50% of subjects after a TBI as result from damage

Clinically nonfunctioning pituitary adenoma: a case report

to either the pituitary or the hypothalamus. This large variability depends on the

Tugba Arkan, Gokcen Selma Kilic Halhalli & Seyyid Bilal Acikgoz

screening methods and on the difficulty to predict the effects of the trauma on

Kocaeli Derince Education and Research Hospital, Kocaeli, Turkey.

pituitary. Growth hormone deficiency and gonadotropin deficiency are the most

frequently documented pituitary dysfunctions after TBI. Also hyperprolactinemia

Objective and importance

has been documented as result of hypothalamic-pituitary stalk damage.

Clinically nonfunctioning pituitary adenomas (NFPA) are the most common

Aim of the study

pituitary tumors after prolactinomas. The absence of clinical symptoms of

Aim of our study was to determine the incidence of pituitary dysfunctions

hormonal hypersecretion can contribute to the late diagnosis of the disease.

following mild to moderate TBI.

Clinical presentation

Methods and patients

A 52-year-old man presented with muscle weakness, weight loss, fatigue and a

All subjects followed at the emergency room of our institution 12-6 months

long term history of depression. He had no headaches and no vision problems.

before were invited to a screening of pituitary function by measuring: FSH, LH,

Physical exam was unremarkable. Neck and thorax CT was performed because of

TSH, IGF-1, Testosterone (T) in (man), 17-beta-estradiol (in women) and PRL.

lung malignancy suspicious. Neck CT detected a cranial mass. Cranial MRI was

When IGF-1 was below the reference range a GHRH C Arginine test was

performed. Magnetic resonance imaging (MRI) revealed a pituitary macro-

performed to document a GH deficency. LHRH test was performed when FSH

adenoma (3.5 cm high, 2.5 cm wide and 2.3 cm deep). It extended up and out of

and LH and T or 17-beta-estradiol were below the reference range to document

the sella turcica, stretching the optic chiasm and optic nerves. The levels of

gonadotropin deficiency.

prolactin and the other pituitary hormones (except for testosterone) were normal

Results

and the lesion was given a diagnosis of a non-secreting pituitary adenoma.

Forty-five subjects aged 18-63 years joined the screening. Single or multiple

Endoscopic trans-nasal trans-sphenoidal pituitary adenoma resection was

pituitary failure was found in 14 patients (31%). Hypogonadotropic hypogonad-

performed. The tumour was completely removed, identified as a pituitary

ism was documented in 3 males (6.8%), low IGF-1 in 10 patients (22%) and GH

adenoma with intracapsular hematoma.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

Aim

Nonsecretory pituitary tumors are called null-cell tumors measuring a few

To determine and evaluate the clinical and hormonal characteristics of cases with

millimeters are common and found in up to 25% of autopsies. These may grow

Sheehan’s syndrome diagnosed and follow-up in our Clinic, during the last ten

slowly, destroying normal pituitary function, or they may compress nearby

years.

structures and cause neurologic problems. In our case report we discuss

Subjects and methods

asymptomatic pituitary macroadenoma.

We included, in this retrospective study, 13 patients, mean age 58G10.9 years,

DOI: 10.1530/endoabs.49.EP1066

diagnosed with Sheehan’s syndrome. Data about medical history, routine

laboratory determinations, hormonal parameters, pituitary imaging and therapy

were reviewed. All the cases presented a history of severe uterine bleeding after

last delivery.

Results

The age at diagnosis for these patients varied between 19 and 54 years. The period

of follow-up from the moment of diagnosis was between 3 and 48 years. All

except one of the cases had an assisted deliverance, but more than half of the cases

(53.8%) came from rural area. Due to severe uterine bleeding, hysterectomy was

EP1067

performed in 7 patients

(53.8%). In

12/13

subjects, breastfeeding was not

Nonfunctioning pituitary incidentaloma - delayed onset of acromegaly

possible. The diagnostic of Sheehan’s syndrome was established after 0.5 to 28

and concomitant primary adrenocortical insufficiency

years from pathological deliverance. The longest delay between the moment of

Serban Radian^1,2, Diana Deciu^1,2, Antonia Lefter^1,2 & Catalina Poiana^1,2

delivery and those of diagnostic was

years. All the cases presented

¹C. Davila University of Medicine and Pharmacy, Bucharest, Romania;

corticotropin, thyreotropin and gonadotropins deficiency in the moment of

²C.I. Parhon National Institute of Endocrinology, Bucharest, Romania.

diagnosis. Growth hormone deficiency was documented in 2 patients and one

subject was diagnosed with central diabetes insipidus. Hormonal substitution

therapy with thyroxine and glucocorticoids was used in all the cases.

Introduction

Gonadotropins deficiency was treated with estroprogestative in younger subjects

Pituitary incidentaloma (PitInc), defined as an unsuspected mass observed on

and GH replacement treatment was given in two cases. Desmopressin was given

imaging studies performed for unrelated conditions. Most such lesions are not

in one patient for ADH deficiency.

clinically significant at initial evaluation and current guidelines recommend

Conclusion

periodic follow-up.

Sheehan’s syndrome is still present in clinical practice, even in the condition of

Aim

assisted deliverance and well-managed uterine haemorrhage.

To present a rare case of delayed onset of acromegaly in a patient with a

nonfunctioning PitInc, raising the question of the utility of prolonged follow-up of

DOI: 10.1530/endoabs.49.EP1068

PitInc.

Methods

Clinical examination, biochemical and imaging studies.

Case report

Following a contrast head CT for headache, a 63 years old female presented with

EP1069

a 11!5 mm intrasellar pituitary mass, no clinical signs of pituitary hypersecre-

tion and normal serum prolactin and IGF-I. Subsequent follow-up showed non-

Mental disorders in the hospitalized patients with Cushing’s disease

progression of mass size on CT/MRI and normal prolactin/IGF-I. 10 years from

Denis Almaev¹, Elena Starostina³, Janna Belaya², Irina Komerdus³ &

initial diagnostic, unexplained hyperkalemia prompted re-evaluation, revealing

Aleksey Bobrov¹

mild skin hyperpigmentation, absence of other signs of adrenal failure, a small

¹Moscow Research Institute of Psychiatry, Moscow, Russia;²Endo-

increase in shoe size, without other acromegalic features. IGF-I was high (2.2-2.9

crinology Research Centre, Moscow, Russia;³Moscow Regional Research

xULN), the GH nadir during OGTT was diagnostic for acromegaly. Review of

and Clinical Institute, Moscow, Russia.

MRI scans revealed a minimal lesion size progression and cystic changes. Visual

fields were normal. The patient was offered surgery but chose to start cabergoline,

Objective

dose-titrated to 3 mg/week, leading to IGF-I normalization. ACTH was elevated

To study the frequency and features of mental disorders in hospitalized patients,

and increased progressively, 8 AM serum cortisol was normal, with subnormal

suffering from Cushing’s disease (CD).

response to Synacthen, suggesting subclinical primary adrenocortical failure. An

Materials and methods

adrenal CT scan excluded adrenal masses, but revealed a discrete left adrenal non-

We studied 70 patients (59 women and 11 men) with verified diagnosis of CD,

nodular hyperplasia. Serum

HO-progesterone was elevated, suggesting

aged 41G12 years. Their mental health was evaluated with ICD-10 criteria and

concomitant congenital adrenal hyperplasia. The patient is clinically well on

verified by the Mini-International Neuropsychiatric Interview questionnaire

glucocorticoid and mineralocorticoid replacement and hyperkaliemia resolved.

(MINI 6.0). 45 patients had overt hypercortisolism (untreated CD and relapse),

Conclusions

25 people had remission after treatment.

The current PitInc guideline

(Endocrine Society

2011) does not specify a

Results

maximum follow-up period. Prolonged clinical and hormonal evaluation may be

Majority of the patients with CD suffered from comorbid mental disorders

warranted, as delayed onset endocrine disease can occur. In our case, incidental

(88.5%). 61.6% of them had different forms of affective disorders including

hyperkalemia prompted endocrine re-evaluation revealing multiple endocrine

bipolar disorder in 22/70 (38%), hypomania in 8/70 (11.2%), depressive episode

abnormalities.

6/70

(8.4%), mania without psychotic symptoms

3/70

(4.2%), recurrent

DOI: 10.1530/endoabs.49.EP1067

affective disorder 3/70 (4.2%) and cyclothymia in 2/70 (2.8%) patients. The

frequency of neurotic, stress and somatoform disorders was 15/70 (21%), among

these, the frequency of obsessive-compulsive disorder (6/70, 8.4%) was higher

than population-based, while the frequencies of social phobia (3/70, 4.2%), panic

disorder

(2/70,

2.8%), agoraphobia without panic attacks

(2/70,

2.8%) and

adjustment disorder (2/70, 2.8%) were not increased. The rest of diagnoses did not

exceed population prevalence: unspecified dementia in 1 (1.4%), acute psychotic

disorder in 1 (1.4%), schizoid personality disorder in 1 (1.42%). Psychiatric

EP1068

comorbidity with presence of two or more mental disorders in the same patient

reached 37/70 (52.8%). The frequency of bipolar spectrum disorders and anxiety

Sheehan’s syndrome in clinical practice

disorders was similar in patients with active hypercortisolism and remission,

Mihaela Vlad^1,2, Ioana Golu^1,2, Daniela Amzar^1,2, Melania Balas^1,2,

although the lack of difference may be due to the small sample size.

Miruna Butaru², Ioana Milos^1,2 & Ioana Zosin^1,2

Conclusions

¹“Victor Babes” University of Medicine and Pharmacy, Timisoara,

Mental disorders in patients with CD are extremely high. A prominent frequency

Romania;²Emergency County Hospital, Timisoara, Romania.

of bipolar spectrum disorders and recurrent depression suggests, that the

dysregulation of biological cycles is an important mechanism of CD

Sheehan’s syndrome represents a rare cause of pituitary insufficiency, produced

development/recurrence. Besides, there are obviously specific psychological

by an ischemic pituitary necrosis due to a severe haemorrhage at deliverance.

adaptation patterns and a number of typical stress responses in such patients.

Epidemiologic data indicate that, nowadays, this disease is quite rare in developed

DOI: 10.1530/endoabs.49.EP1069

country.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1070

15 mm, P!0.001) and further suprasellar extension

(PZ0.015), cavernous

(PZ0.008) and sphenoidal sinus invasion (PZ0.006). Surgery occurred after a

Detailed assessment of hypothalamic damage in craniopharyngioma

median of 12 months (IQR 0-12), since imagiologic diagnosis and 26% (nZ25)

patients with obesity

required a second intervention. 13% (nZ12) were submitted to radiotherapy.

Sigridur Fjalldal¹, Cecilia Follin¹, Sanaz Gabery², Pia Maly Sundgren^3,4,

After surgery, 11 patients (16%) had hormonal deficiencies, while 8 (12%)

Isabella Bjorkman-Burtscher^3,4, Jimmy Lätt³, Peter Mannfolk³,

improved. In the EO group, we found de novo hypogonadism in 3 patients and

Carl-Henrik Nordstrom⁵, Lars Rylander⁶, Bertil Ekman⁷, Anna Pålsson¹,

hypothyroidism in 1. No significant tumour growth was observed and none

˚sa Petersén² & Eva-Marie Erfurth¹

suffered apoplexia.

¹Department of Endocrinology, Skåne University Hospital, Lund, Sweden;

Discussion

²Translational Neuroendocrine Research Unit, Department of Experimental

Patients that underwent surgery were in average 10 years younger, had more

Medical Science, Lund University, Lund, Sweden;³Department of Medical

neuro-ophthalmologic symptoms and bigger tumours at presentation. Those in

Imaging and Physiology, Skåne University Hospital, Lund, Sweden;

vigilant observation did not present significant tumour growth, new hormonal

⁴Department of Diagnostic Radiology, Clinical Sciences, Lund University,

deficiencies or apoplexy. Facing literature data, our population underwent fewer

Lund, Sweden;⁵Department of Neurosurgery, Skåne University Hospital,

surgeries. EO may be a valuable option in selected NFPAs.

Lund, Sweden;⁶Division of Occupational and Environmental Medicine,

Lund University, Lund, Sweden;⁷Department of Endocrinology and

DOI: 10.1530/endoabs.49.EP1071

Medical and Health Sciences, Linkoping University, Linkoping, Sweden.

Background/objectives

Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor

Craniopharyngioma (CP). Attempts have been made to predict the risk of HO

based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but

EP1072

none have included volumetry. Qualitative and quantitative (volumetric) analyses

Risk factors for progression of the surgical remnant of non-functioning

of HT damage was performed. The results were explored in relation to feeding

pituitary adenomas in patients treated with dopamine agonists

related peptides and body fat.

Elena Fernández González, Miguel Sampedro Nun˜ ez, Ana Ramos Leví, Ana

Subjects/methods

Rabé Caón, Isabel Hughet, Nerea Aguirre Moreno, Clara Marijuán Sánchez,

A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was

Bego

˜aPlaPeris,ÁngelesMailloNieto,AliciaVicun˜a Andrés, Pedro

performed at median 22 years after 1st operation. 41 CPs, median age 35 (range

Martínez Flores & Mónica Marazuela Azpiroz

18-56), of whom 23 had HT damage, were compared to 32 controls. After

Hospital Universitario La Princesa, Madrid, Spain.

exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome

measures were the relation of metabolic parameters to HT volume and qualitative

analyses of HT damage.

Introduction

Results

Surgery is the treatment of choice for non-functioning pituitary adenomas

Metabolic parameters scored persistently very high in vascular risk particularly

(NFPA), but remnants are frequently observed. Management of these remnants

among HT damaged patients. Patients had smaller HT volumes compared to

include observation (OBS), radiotherapy (RT) and/or dopamine agonist (DA)

controls 769 (35-1168) mm³ vs 879 (775-1086) mm³; P!0.001. HT volume

therapy. In this study, we evaluate the progression-free survival (PFS) of NFPA

correlated negatively with fat mass and leptin among CP patients (r_sZK0.67;

with postoperative remnant and the potential factors involved.

P!0.001; r_sZK0.53; PZ0.001), and explained 39% of the variation in fat mass.

Methods

For every 100 mm³ increase in HT volume fat mass decreased by 2.7 kg (95% CI:

We performed a single-center ambispective study of a cohort of 72 patients (age

1.5-3.9; P!0.001). Qualitative assessments revealed HT damage in 3 out of 6

56G15 years, 32 women), with NFPA and tumor remnant after transsphenoidal

patients with normal volumetry, but HT damage according to operation records.

(TS) surgery, followed-up between 1994 and 2015. We categorized patients as

Conclusions

stable (nZ36) or progression (nZ21), according to radiological criteria. No

A decrease in HT volume was associated with an increase in fat mass and leptin.

follow-up data were available for 10 patients and 5 cases died. We evaluated

We present a reproducible method with a high inter-rater reliability (0.94) that can

differences between patients according to the three postoperative approaches:

be applied by non-radiologist for the assessment of HT damage. The method may

OBS, DA and/or RT. Statistical analysis was performed with STATA v12.0. We

be valuable in the risk assessment of diseases involving the HT.

present data for progression-free time medians (p 25-75), correlation coefficient

DOI: 10.1530/endoabs.49.EP1070

(r) and Hazard Ratio (HR).

Results

Progression-free survival (PFS) of the total cohort of patients was 154 months

(77-184). Subgroup analysis suggested longer PFS in OBS patients (154m) vs.

RT(184m)

(PZ0.07). Univariate analysis indicates an increased risk of

progression in patients without RT (HR: 3.6; [0.8-15]; PZ0.09). Duration of

DA treatment was positively correlated with PFS (rZ0.60; P!0.05), and each

EP1071

additional month showed a favorable trend for an increased PFS (HR: 0.98; [0.95-

1.00]; PZ0.06). Sex, age, and postoperative tumor diameter were not associated

Surgery versus expectant observation in clinically non-functioning

with PFS. Subanalysis of the subgroup of patients who received DA(nZ20)

pituitary adenomas - a 20-year single centre experience

showed that the only influencing factor for progression was female sex (c²Z5.05;

Claudia Matta-Coelho¹, Rui Almeida² & Olinda Marques¹

PZ0.02).

¹Endocrinology Department, Braga Hospital, Braga, Portugal;

Conclusions

²Neurosurgery Department, Braga Hospital, Braga, Portugal.

RT of operated NFPA seems to be associated to a higher PFS in our cohort.

Prolonged treatment with DA also favored an increased PFS. Long-term follow-

Background

up and active management of patients with NFPA are important.

Clinically non-functioning pituitary adenomas (NFPAs) are among the most

DOI: 10.1530/endoabs.49.EP1072

common pituitary lesions. Its management includes surgery, radiation or

observation. The authors aim to compare clinical characteristics and outcomes

between patients submitted to surgery or expectant observation (EO).

Methods

Retrospective review of medical records from 1996 to 2016. In our centre, there is

only 1 pituitary surgeon and NFPAs patients are referred to surgery according to

EP1073

the presence of neurologic symptoms, mainly visual disturbances, and tumour

Aggressive macroprolactinoma - exception to the rule

growth. Statistical analysis: SPSSvs20.

Alina Daniela Belceanu¹, Georgiana Constantinescu¹, Iulia Crumpei¹,

Results

Anamaria Bursuc¹, Daniel Rotariu², Aurora Constantinescu³,

We found 179 patients, 52% (92 females), with a median follow-up time of 5

Vasile Ciubotaru⁴, Cristina Preda¹ & Carmen Vulpoi¹

years

(IQR 3-10), 54% (nZ96) underwent surgery. Besides indication for

¹Endocrinology Department, University of Medicine and Pharmacy Gr. T.

surgery, 2 patients refused and 3 did not have clinical conditions. Patients that

Popa, Iasi, Romania;²Neurourgery Department, University of Medicine and

underwent surgery were younger (58 vs 68 years, P!0,001), had more neurologic

Pharmacy Gr. T. Popa, Iasi, Romania;³Neurology Department, University

symptoms at diagnosis (62 vs 39%, PZ0.011) and visual disturbances (64 vs

of Medicine and Pharmacy Gr. T. Popa, Iasi, Romania;⁴Neurosurgery

22%, P!0.001) than patients in EO. There were no differences in hormonal

Department, University of Medicine and Pharmacy Carol Davila, Bucharest,

deficiencies (P!0.001). The surgery group presented larger adenomas (26 vs

Romania.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

cardiometabolic dysfunctions. Susceptibility to metabolic syndrome in IHH

Prolactinoma is the most frequent pituitary tumour. However, peculiar aspects

patients on HRT should be further investigated.

may induce difficulties in their evolution and management. Malignant

DOI: 10.1530/endoabs.49.EP1074

prolactinoma is exceptionally rare and it cannot be diagnosed on histological

grounds alone. We report the case of a recurrent, possibly malignant

macroprolactinoma.

Case report

46 years old female, addressed for bitemporal hemianopia, without other clinical

signs. MRI confirmed a pituitary macroadenoma (22/19/35 mm) with suprasellar

evolution. Hormonal profile revealed hyperprolactinemia with secondary thyroid

EP1075

and gonadal insufficiency, for which Cabergoline was started, with initial good

The E in POEMS syndrome: what to expect?

evolution. Three years later she presented pituitary apoplexy with acute

Francisca Caimari¹, Shirley D’Sa², Michael Lunn³ &

intracranial hypertension, solved by partial transcranial adenomectomy.

Stephanie E Baldeweg¹

Gamma knife radiation completed the treatment, with succeeding adrenal and

¹Department of Endocrinology, University College London Hospitals,

thyroid insufficiency. After 4 years of stationary evolution under Cabergoline and

London, UK;²Haematology Department, University College London

substitutive treatment, an aggressive tumour progression imposed a new surgical

Hospitals, London, UK;³Neurology Department, University College

intervention

(transsphenoidal adenomectomy). One year later, intensive

London Hospitals, London, UK.

vertiginous syndrome enforced reinvestigations. MRI identified two cerebral

tumours (meningioma?), one of them at the cranio-spinal junction, which needed

urgent excision. Pathology identified pituitary adenoma cells and a Ki-67 index of

Introduction

2%. Post-operatory, the patient complained of gait dysfunction, nausea and

POEMS syndrome is a rare multisystemic disorder including polyneuropathy,

headache. Left cranial nerves paresis X, XI, and XII was objectified. The patient

organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder and

underwent six cycles of Temozolomide chemotherapy, with no improvement, last

skin changes. We aim to describe the course of the endocrine disease in the

MRI revealing further tumour evolution.

context of this paraneoplastic syndrome.

Conclusion

Methods

Elucidating the pathogenesis of aggressive prolactinomas remains largely

69 patients with POEMS have been under the MDT care in our hospital. Data is

unknown and continues to mesmerize the physicians. The diagnosis of pituitary

currently available for 32 patients who attended the joint haematological/neur-

carcinoma is confirmed only in the presence of metastasis. After initial good

ological/endocrine clinic from 06/1999 to 01/2017. All patients had regular

response to Cabergoline, our patient developed a rapid aggressive progression of

endocrine screening including pituitary, thyroid and calcium metabolism. Median

the tumour, with little effect of surgery and radiotherapy. Temozolomide was not

and interquartile range and meanGS.D. were used for quantitative variables and

efficient in controlling tumour evolution. In spite of the longer survival (9 years)

percentage for qualitative variables.

and the low proliferation index, we believe that new markers are needed in order

Results

to assess the aggressiveness of malignant prolactinoma.

Seventy-two patients were male. The age at diagnosis was 49.4(38.2-59.8) years

DOI: 10.1530/endoabs.49.EP1073

and the median follow-up was 4.6(2-7.4) years. At diagnosis, all patients

presented with polyneuropathy, 25% had hyperhidrosis and 50% endocrinopathy.

From those with endocrinopathy, 36.7% had thyroid disease, 26.7% hypogonad-

ism, 3.3% type 2 diabetes mellitus (2DM) and 6.5% Addison disease. None of

them had parathyroid disorders. 60% had more than one endocrinopathy at

diagnosis. During surveillance 90.3% of patients developed endocrinopathy.

68.8% of patients had hyperprolactinemia with a fold increase 1.8G0.99 above

the upper limit of the normal. Hyperprolactinaemia was transient in 72.7%. One

patient with hyperprolactinaemia had an empty sella on MRI.

59.4% had

hypothyroidism (37.5% clinical, 21.9% subclinical). This was transient in 27.8%

EP1074

of patients. Addison disease was diagnosed in 18.8% of patients and none of them

Body composition and bone mineral density in male patients with

recovered their adrenal function. 15.6% presented with type 2DM. 78.6% had

isolated hypogonadotropic hypogonadism

hypogonadism (19.1% secondary, 38.1% primary, 42.9% subclinical primary).

Małgorzata Kałuz˙na1, Magdalena Człapka-Matyasik2, Dorota Przeorska2,

Gonadal function recovered in 3 patients.

Katarzyna Ziemnicka¹ & Marek Ruchała¹

Conclusion

¹Department of Endocrinology, Metabolism and Internal Diseases, Poznan

Endocrinopathy in POEMS was described in 90% of our cohort. The MDT team

University of Medical Sciences, Poznan, Poland;²Department of Human

should include an endocrinologist. Patients should be systematically assessed for

Nutrition and Hygiene, Poznan University of Life Sciences, Poznan, Poland.

endocrinopathy. The most common deficiencies were hypogonadism, hyperpro-

lactinemia and hypothyroidism. Normalisation of the endocrinopathy was

Isolated hypogonadotropic hypogonadism (IHH) is known to decrease bone

common and should be considered when treating these patients.

mineral density due to lack of pubertal surge of gonadotropins and deficiency of

DOI: 10.1530/endoabs.49.EP1075

sex steroid hormone. Gonadal steroid hormones imbalance affects body

composition. Nineteen Caucasian men, 22-48 year old (meanGS.D. 33G7.65)

diagnosed with IHH (8 normosmic, 11 anosmic or hyposmic) were enrolled into

the study. 14 patients were on hormone replacement therapy (HRT), 5 patients

were started with HRT treatment. Nineteen healthy male volunteers (CON) with

matched age and BMI were also included. Body composition and bone mineral

density measurements were conducted with use of Air Displacement Plethysmo-

EP1076

graphy (BOD POD, Cosmed) and dual-energy x-ray absorptiometry DEXA

Pituitary adenoma and elevated ACTH: not always corticotrophinoma

(Lunar Prodigy,GE Healthcare), respectively. Hormonal status, lipid profile,

Mariana Cabac¹, Alina Daniela Belceanu¹, Iulia Crumpei¹,

calcium and phosphorus levels, 25-hydroxy vitamin D concentration were also

Mirela Tirnovan¹, Georgiana Constantinescu¹, Anamaria Bursuc¹,

measured. There was significant difference between fat-free-mass (FFM; kg) in

Aurora Constantinescu², Voichita Mogos¹ & Carmen Vulpoi¹

IHH and matched controls (60.1 vs 66.0; PZ0.012), related to Gynoid FFM

¹Department of Endocrinology, University of Medicine and Pharmacy ‘Gr.

distribution (IHH vs CON: 9.1 vs 10.3 kg; PZ0.003). IHH patients have marked

T. Popa’, Iasi, Romania;²Department of Neurology, University of Medicine

decreases in total bone mineral density compared to CON (1.21 vs 1.31 g/cm²,

and Pharmacy ‘Gr. T. Popa’, Iasi, Romania.

PZ0.009). Total bone mineral content, T-score and Z-score were also decreased

in IHH subjects (2982 vs 3271 g/cm, PZ0.05; 0.08 vs 1.06, PZ0.016; K0.40 vs

0.54, PZ0.013). High-density lipoprotein cholesterol (HDL) level was correlated

Introduction

with waist-to-height ratio

(WHtR) (rZK0.81, P!0.05) in IHH patients.

Hypothalamic-pituitary-adrenal (HPA) axis activation is the main neuroendo-

Significant correlations between insulin-like growth factor-1

(IGF-1) and

crine response to an environmental challenge. Drug abuse may activate HPA axis

WHtR were observed in IHH (rZK0.81, P!0.05; rZK0.82, P!0.05).

by interaction with neuromodulation systems.

Testosterone and 25Hydroxy vitamin D concentrations were not correlated with

Case report

body composition and densitometry measurements. To conclude, IHH patient are

28 year old man, was admitted in the Neurology Department for persistent

at increased risk for osteoporosis. Long testosterone deficiency in IHH resulted in

headache with spinal irradiation. With suspicion of multiple sclerosis, MRI

body composition changes related to fat free mass and distribution. WHtR, IGF-1

revealed pituitary macroadenoma (14 mm diameter) and subcortical, paraventric-

and HDL correlations in IHH patients might suggest their link with

ular and frontal white matter demyelinating lesions. Neurological examination

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

excluded multiple sclerosis and he was addressed to the Endocrinology

EP1078

Department. Anamnesis revealed a history of drug abuse (cocaine), alcoholism,

Inferior petrosal sinus sampling: experience of a terciary hospital

chronic smoking (1 pack of cigarettes/day) and depression. Clinical examination

Maria Manuel Costa^1,2, José Luís Castedo¹, Eduardo Vinha¹,

revealed moderate weight excess (BMIZ27.14 kg/m²) and normal high blood

Josué Pereira^2,4, Irene Bernardes⁵ & Davide Carvalho^1,3

pressure (148/100 mmHg). Hormonal axes were normal, with the exception of the

¹Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-

HPA axis: high levels of ACTH (89.2 pg/ml), DHEAS (491.3 mg/dl) and free

talar de Sa˜o João, Porto, Portugal;2Faculty of Medicine, University of Porto,

urinary cortisol (216 mg/24 h), with normal morning and evening cortisol. 1 mg

Porto, Portugal;³Instituto de Investigac¸ão e Inovação da Saúde da

DXM overnight test was negative (cortisolZ4.28 mg/dl). It was re-evaluated after

Universidade do Porto, Porto, Portugal;⁴Department of Neurosurgery,

one month: persistency of normal cortisol values with constantly moderate high

Centro Hospitalar de São João, Porto, Portugal;⁵Department of

ACTH and good response to 1 mg DXM (1.12 mg/dl). The discordance between

Neurorradiology, Centro Hospitalar de São Joa˜o, Porto, Portugal.

ACTH, DHEAS and the rest of HPA axis suggested another possible etiology than

an ACTH secretion adenoma (cocaine use, smoking, depression). One year after,

biological parameters were constant, with insignificant increase of adenoma

Introduction

(16 mm diameter). Patient denied any further cocaine use for approximately 1

Inferior Petrosal Sinus Sampling (IPSS) is the gold standard test to distinguish

year, but admits that he is still smoking.

between Cushing Disease and ectopic ACTH secretion (EAS), mostly when the

Conclusions

biochemical tests are discordant and/or there is no lesion in MRI.

The dysregulation of HPA axis may increase vulnerability to depression and

Aim

numerous other psychiatric disorders, which can be puzzling for the

To evaluate the results of IPSS in the diagnosis of ACTH-dependent Cushing

endocrinologists in the diagnosis process. The peculiarity of the case is the

syndrome.

association of a pituitary macroadenoma with persistent increased levels of

Methods

ACTH. Investigations had not confirmed the suspicion of an ACTH secreting

Retrospective study that analysed IPSS results performed in the last decade in our

pituitary adenoma, and oriented to multiple ethology - drug abuse (cocaine,

centre and integrated in the clinical context of each patient. Basal central-

smoking) and depression.

to-peripheral ratioO2 or after CRH testO3 were considered diagnostic of CD.

DOI: 10.1530/endoabs.49.EP1076

Results

We analysed 31IPSS performed in 26 patients with biochemical diagnosis of CS.

Nine patients were excluded. Seventeen patients (2 Male) with a mean age of

38.4(11.8) years were included. One patient had to repeat IPSS due to haemolysis

and other had done 3 IPSS due to be on interfering medication. Eleven patients

had central-to-peripheral ACTH ratio suggestive of CD(6basal and 11after CRH

stimulation). The ratio was maximal at 5⁰ in 45.4%(5/11) patients and at 2-3⁰ in

36.3%(4/11). Pituitary MRI revealed microadenoma in 8 patients, macroadenoma

in one and 2 patients did not present any lesion. Three patients had a lesion on the

other side of pituitary when compared to the intersinus gradient. Immunohisto-

EP1077

chemical result revealed an ACTH expression adenoma in 6 patients, and

Pituitary apoplexy - presentation, management and outcome in 35 cases

expression of ACTH and GH in 2. There was no positivity for ACTH in 3 patients

Maria Manuel Costa^1,2, Bruno Carvalho⁴, José Luís Castedo¹,

who had MRI lesions, but one was cured after surgery and 2 underwent adjuvant

Eduardo Vinha¹, Josué Pereira^2,4, Irene Bernardes⁵ & Davide Carvalho^1,3

therapy. Of the remaining 6 patients, 3 had results suggestive of ectopic EAS,

¹Department of Endocrinology, Diabetes and Metabolism of Centro

one of which was submitted to lobectomy and had bilateral adrenalectomy

Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, University of

by occult ectopic, but underwent pituitary surgery with a histological result

Porto, Porto, Portugal;³Instituto de Investiga

¸a˜o e Inovação da Saúde da

revealing ACTH expression. Of the other 3 patients, all with pituitary MRI lesion,

Universidade do Porto, Porto, Portugal;⁴Department of Neurosurgery,

2 patients underwent surgery that revealed CD and in the other the result was

Centro Hospitalar de São João, Porto, Portugal;⁵Department of

normal and patient underwent adrenalectomy. There were no significant adverse

Neurorradiology, Centro Hospitalar de São João, Porto, Portugal.

effects.

Conclusion

This study reinforces the utility of IPSS in identifying aetiology of SC, which was

Introduction

obtained in more than half of the patients, with no associated adverse effects. The

Pituitary apoplexy is a rare disease which results of haemorrhage and/or infarction

IPPS catheterization was not possible in 1 patient.

of pituitary gland. The optimal management of this problem still remains

DOI: 10.1530/endoabs.49.EP1078

controversial between surgery and conservative treatment.

Aims

To characterize the clinical presentation, diagnostic workup, treatment and follow

up of patients with apoplexy. Methods:Retrospective study of

35 pituitary

apoplexy followed in a portuguese hospital from 2006 to 2016.

Results

Thirty-five patients (21 males; mean age, 55.1(15.6) years) were identified. Three

patients had subclinical pituitary apoplexy and

9(28%) had more than one

EP1079

emergency evaluation until the diagnosis has been correctly made. Commonest

Cushing syndrome and pregnancy: a systematic review including three

presenting features were acute headache (84.4%), visual impairment (62.5%) and

new cases

vomiting

(15.6%). Five patients were known to have pituitary tumour at

Diogo China¹, Ana Isabel Oliveira², Sandra Belo^2,3 & Davide Carvalho^2,3

presentation, one of them was a Cushing Disease which became cured after PA,

¹Faculty of Medicine, Porto, Portugal;²Department of Endocrinology,

and

3 were nonfunctioning adenomas. Nineteen patients had at least one

Diabetes and Metabolism Centro Hospitalar S. João, Porto, Portugal;

precipitating factor with antiaggregation being the most common (nZ4). Twenty

³Instituto de Investiga

˜o e Inova

¸a˜o em Saúde, University of Porto, Porto,

patients had hypopituitarism at presentation, 14 had hyponatraemia, 9 had a

Portugal.

decreased in level of consciousness and 21 had visual impairment. 78.1% patients

proceeded to pituitary surgery and 3 developed diabetes insipidus after that. When

we compared those who underwent surgery and those treated conservatively,

Cushing’s Syndrome

(CS) is an uncommon disease worldwide, being

visual deficits were more common in first group (76% vs 28%, PZ0.032) and

characterized by an increased production of glucocorticoids, and if left untreated

hyponatremia in the second one (32% vs 86%; PZ0.027). There were no more

can lead to serious consequences and women with CS rarely get pregnant. The

differences between groups in other evaluated factors, namely in Pituitary

aim of our work is to make a systematic review of the cases of pregnancy in

Apoplexy Score (1.68 (1.21) vs 0.86 (1.21); PZ0.124). During follow-up 6(3)

patients with previously diagnosed CS, being performed an extensive research of

years,

1 patient had hypopituitarism reversal after surgery and

11 patients

the Medline and Web of Knowledge databases, and add three new cases observed

recovered from neuro-ophthalmologic deficits. Three patients passed away and 21

in our institution. We compared two different groups: the ‘active disease’ one and

have a MRI without lesion.

the ‘non-active disease’ and we found 17 pregnancies that were included in the

Conclusion

first group while other 20 pregnancies were in the second category. We observed

The diagnosis of pituitary apoplexy is often delayed as occurred in our

two spontaneous abortions and one ectopic pregnancy in the ‘active’ group, while

population.It is associated with a high rate of anterior hypopituitarism that does

in the ‘non-active’ category we found the same number of spontaneous abortions

not typically recover, unlike the visual symptoms. Patients with visual defects

besides a placental abruption and a medical interruption of the pregnancy.

were more likely to be managed surgically.

Cushing disease (CD) was the main cause behind CS (28 pregnancies), with

transsphenoidal surgery the preferred treatment. Within the ‘active’ category, we

DOI: 10.1530/endoabs.49.EP1077

reported nine full-term and five pre-term pregnancies and in the ‘non-active’

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

category we observed 11 full-term and three pre-term pregnancies, while two in

Introduction

this last group were non-specified. Hypertension was diagnosed in eight cases (six

The endocrine system is often affected in the course of HIV infection. However,

and two in the ‘active’ and ‘non-active’ group respectively) and gestational

hypopituitarism and diabetes insipidus are uncommon disorders in these patients

diabetes in four patients

(three and one in the

‘active’ and

‘non-active’

and have been related to drugs, infections of the central nervous system and

categories). Inability to breastfeed was one of the main perinatal events reported,

neoplastic infiltration, in extremely rare cases.

as a logical consequence of the treatment regimen adopted for CS. A major

Case report

concern in these patients refers to the medical control of CS activity, because

We present a case of a 42-year-old man with HIV infection known since 2005, but

hypercortisolism occurs physiologically during pregnancy. This is a topic with

undergoing antiretroviral therapy only since 2010 (emtricitabine/tenofovir and

extreme clinical significance since it is rare that a CS women conceives.

raltegravir), when he was diagnosed with hepatitis C, left parotid MALT-

DOI: 10.1530/endoabs.49.EP1079

lymphoma, and cerebral toxoplasmosis (treated with pyrimethamine/sulfadia-

zine). He has also a history of smoking, drug addiction, in a methadone

replacement program for 10 years, and hypothyroidism diagnosed for 1 year,

medicated with L-thyroxine. The patient was referred to the Endocrinology

department by bilateral gynecomastia, loss of libido and erectile dysfunction.

When specifically asked he also complained of polydipsia-polyuria. Breast,

testicular and thyroid ultrasonography showed no relevant changes, but the

hormonal study revealed: central hypothyroidism and hypogonadotropic

hypogonadism; normal prolactin levels; slightly decreased IGF-1 and GH levels;

EP1080

normal ACTH, cortisol and tetracosactide test; insulin-induced hypoglycemia test

20-year retrospective study of clinically non-functioning pituitary

showed normal glucocorticoid reserve. Plasma osmolality was 300 mOsmol/kg

adenomas - a single center experience

and urine osmolality 136 mOsmol/kg. Water deprivation test confirmed central

Claudia Matta-Coelho¹, Rui Almeida² & Olinda Marques¹

diabetes insipidus. Pituitary MRI showed lack of neurohypophyseal bright signal.

¹Endocrinology Department, Braga Hospital, Braga, Portugal;

He was started on testosterone therapy (250 mg, 3/3 weeks), desmopressin

²Neurosurgery Department, Braga Hospital, Braga, Portugal.

lyophilisate (0.06 mg bid) and maintained L-thyroxine (0.088 mg/day). Currently,

he refers a global clinical improvement, but still complains of erectile

Background

dysfunction, and was recently medicated with avanafil (100 mg).

Clinically non-functioning pituitary adenomas (NFPA) are the most common

Conclusion

pituitary adenomas but their treatment remains challenging. Our aim is to describe

The authors describe a rare case of hypopituitarism and diabetes insipidus in a

clinical, imagiological and hormonal characteristics of patients with NFPA

patient with HIV infection of possible multifactorial etiology

- uncommon

presenting at our department.

complication of cerebral toxoplasmosis and/or side effects of antiretroviral drugs.

Methods

This case reveals the need to keep in mind the possibility of hypopituitarism in

Retrospective review of medical records of patients with NFPA at our centre from

HIV-treated patients and a history of cerebral infection.

1996 to 2016. Exclusion criteria: prolactin O100 ng/ml or histologic evidence of

DOI: 10.1530/endoabs.49.EP1081

prolactinoma. Statistical analysis: SPSSv20.

Results

179 patients included, 52% (nZ92) female, with a median age of 61 years (IQR

48-73) and follow-up time of 5 years (IQR 3-10). The diagnosis were more

frequent in the last 10 years (nZ114, 64%). 40% (nZ62) had hypertension and

15% (nZ24) were diabetic. The initial presentation was neuro-ophthalmologic

symptoms (nZ87, 52%), incidentally discovered adenomas

(nZ36, 21%),

pituitary apoplexy (nZ30, 18%) and endocrine disorders (nZ16, 9%). Pituitary

function assessment showed that half

(nZ69) had at least one hormonal

deficiency, specifically; LH/FSH deficiency was detected in 45%, ACTH in 25%,

Steroid Metabolism C Action

TSH in 30% and GH in 15%. Hyperprolactinemia was present in 22% (nZ30).

EP1082

Five patients

(3%) had diabetes insipidus. The NFPA were mainly macro-

Social stress stimulates glucocorticoid regeneration in lymphoid organs

adenomas (nZ146, 89.5%) with suprasellar extension

(nZ89, 70%), 36%

Jiri Pacha, Peter Ergang, Anna Mikulecka, Karla Vagnerova & Ivan Mikšík

(nZ43) had sphenoidal and 30.3% (nZ36) cavernous sinus invasion. Surgery

Institute of Physiology, Czech Academy of Sciences, Prague, Czech

was performed in

54% patients

(nZ96), while the remaining maintained

Republic.

expectant observation. Immunohistochemical analyses showed 42 null-cell, 34

gonadotrophs, 1 silent thyrotroph, 2 silent corticotroph and 2 plurihormonal

adenomas.

The presence of the enzymes of local metabolism of glucocorticoids in lymphoid

Discussion

organs and many other tissues suggests that the local glucocorticoid signal is not

As in other series, our patients also presented with visual disturbances and

determined only by plasma level of glucocorticoids but also by the local activity

pituitary dysfunction at diagnosis, but we found and older population. We

of these enzymes. Using resident-intruder test the present study determined if

emphasize that a quarter of patients had ACTH and 30% TSH deficiency that can

chronic social stress modulates local metabolism of corticosterone and

cause a significant morbidity and had not been suspected before. Hence, earlier

11-dehydrocorticosterone in rats of Fisher 344 (F344) and Lewis (LEW) strains,

diagnosis of hypopituitarism and prompt treatment are imperative.

which differ in their response to social stressors and inflammation. We

DOI: 10.1530/endoabs.49.EP1080

demonstrated that social defeat significantly increased regeneration of corticos-

terone from

11-dehydrocorticosterone in thymus, spleen and mesenteric

lymphatic nodes (MLN) but not pituitary of both strains. When compared with

F344 strain, LEW rats showed lower corticosterone regeneration in pituitary of

unstressed and stressed animals and higher corticosterone regeneration in thymic

and MLN mobile cells after chronic stress. In contrast, stress-induced increase of

corticosterone regeneration in stroma tissues of all lymphoid organs was similar

in both strains. Social defeat was also associated with changes in expression of

enzymes participating in local metabolism of glucocorticoids: 11b-hydroxy-

steroid dehydrogenase type 1 (11HSD1), 11b-hydroxysteroid dehydrogenase type

EP1081

(11HSD2) and hexose-6-phosphate dehydrogenase (H6PDH). Whereas F344

Hypopituitarism and central diabetes insipidus in an HIV patient - a

rats exhibited significant upregulation of 11HSD1 mRNA, 11HSD2 mRNA and

late complication of cerebral toxoplasmosis and/or antiretrovirals?

H6PDH mRNA expression in thymus and 11HSD1 mRNA in spleen, LEW rats

Sofia Castro Oliveira^1,2, Pedro Souteiro^1,2, João Sérgio Neves^1,2,

showed an apparent insensitivity to stress in all lymphoid organs and neither of

Cláudia Nogueira³, Celestino Neves^1,2, Paula Freitas^1,2 &

the transcripts was upregulated by stress. Our results indicate that social stress

Davide Carvalho^1,4

amplifies glucocorticoid regeneration in the lymphoid organs including the

¹Department of Endocrinology, Diabetes and Metabolism of São Jo

˜o

expression of genes involved in local metabolism of glucocorticoids and that this

Hospital Center, Porto, Portugal;²Faculty of Medicine, University of Porto,

process is partly determined by the genetic background. The study was supported

Porto, Portugal;³Department of Endocrinology, Diabetes and Metabolism

by Czech Science Foundation.

of Trás-os-Montes e Alto Douro Hospital Center, Vila real, Portugal;

DOI: 10.1530/endoabs.49.EP1082

⁴Instituto de Investigac¸ão e Inovaçao em Saúde, University of Porto, Porto,

Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Bone & Osteoporosis

heterogeneous and conflicting. The aim of this study was to investigate the effect

of HRT and tibolone on Lp(a) concentrations in post-menopausal women.

EP1083

Methods/design

Effects of male hypogonadism treatment on the bone mineral density

MEDLINE, Scopus, EMBASE and Cochrane databases were searched (up to

Mário Rui Mascarenhas^1,2, Ana Paula Barbosa^1,2, Ana Raquel

February 2016). Two researchers identified randomized controlled studies and

Coelho Gomes², Catarina Silvestre², David Barbosa², Raquel Paix

˜o²,

extracted data. Potential controversies were resolved by a third reviewer.

Carolina Faria², Ana Sofia Osório², Vânia Gomes², Joana Ferreira¹,

Results

Manuel Bicho¹ & Maria João Bugalho²

In 24 eligible studies, HRT caused a significant reduction in Lp(a) concentrations

¹Endocrinology and Metabolic Diseases, Faculty Medicine of Lisbon,

compared with placebo or no treatment (mean relative difference: K20.35%, 95%

Lisbon, Portugal;²Endocrinology, Diabetes and Metabolism Department,

CI: K25.33% to K15.37%, P!0.0001), with significant heterogeneity between

Santa University Maria Hospital-Chln, Epe, Lisbon, Portugal.

studies (I²Z98.5%), but without evidence of publication bias. No significant

effect was found for tibolone (nZ7) (mean relative difference: K23.84%, 95%

CI: K63.43% to 15.74%, PZ0.238) (I²Z98.7%, but without publication bias).

Increased recognition of the morbidity and mortality due to osteoporosis in men

Oral estrogen caused greater reduction in Lp(a) concentrations than transdermal

are main issues of public health. Ageing and the propensity to falls are the main

estrogen (nZ10) (mean relative difference: 37.66%, 95% CI: 16.84% to 58.48%,

risk factors for osteoporotic fractures in men; moreover, hypogonadism is an

P!0.0001), with significant heterogeneity between studies (I²Z99%), but no

important secondary cause of low bone mineral density (BMD), but very little is

evidence of publication bias. No difference was observed when continuous was

known about the effect of hypogonadism treatment on the BMD.

compared with cyclical HRT, conventional with low estrogen dose, and estrogen

Objective

monotherapy with combination with progestogen. No difference was observed

The aim was to study the impact on BMD of the treatment of male hypogonadism.

between HRT and tibolone regarding their effect on Lp(a).

Material and methods

Conclusions

A group of 26 men were devided in the hypogonadotrophic hypogonadism

HRT significantly decreases Lp(a) concentrations, with oral being more effective

(nZ17) and hypergonadotrophic hypogonadism (nZ9) groups. The BMD at

than transdermal estradiol. The type of HRT, dose of estrogen and addition of

several skeletal sites (assessed by DXA scans) was evaluated before and during

progestogen do not seem to modify the Lp(a)-lowering effect of HRT.

treatment (duration from 1 to 8 years, on average 3.1 (G2.3) years). Adequate

statistical tests were used (statistical significance P!0.05).

DOI: 10.1530/endoabs.49.EP1084

Results

The treatment did not improved significantly the mean BMDs at several skeletal

sites (Table 1). Moreover the BMDs were similar before and during the treatment

in the hypergonadotrophic hypogonadism group; nevertheless, in the hypogona-

dotrophic hypogonadism group the mean BMDs were significantly higher at the

Clinical Case Reports - Pituitary/Adrenal

lumbar spine, at the hip, at the forearm and at the whole body during therapy.

Conclusions

EP1085

After more than three years of treatment there was no improvement on the BMD

CHARGE Syndrome: a rare case of hypogonadotropic hypogonadism

significantly in the total hypogonism group. The treatment of male hypogonadism

Ana Sofia Osório, Carolina Faria, David Barbosa, Ema Nobre &

has improved the BMD at several skeletal regions just in the hyponadotrophic

Maria Joa˜o Bugalho

group.

Serviço de Endocrinologia, Diabetes e Metabolismo, Hospital de Santa

Maria, Centro Hospitalar de Lisboa Norte, Lisboa, Portugal.

Table 1 BMD qualification in hypogonadism before and during therapy.

Introduction

Hypogonadism before

Hypogonadism during

CHARGE Syndrome (CS) is a rare cause of hypogonadotropic hypogonadism

BMD

treatment nZ26 (100%) treatment nZ26 (100%)

(HH), usually diagnosed in paediatric age when pubertal development is

compromised. Herein, we report a case that presented a major criterion and

Normal

(23.1%)

(30.8%)

three minor criteria.

Reduced

(46.1%)

(42.3%)

Case report

Osteoporosis

(30.8%)

(26.9%)

At age ten, the patient was referred to the paediatric endocrinology unit due to

phenotypic alterations and psychomotor and cognitive impairment. She had no

DOI: 10.1530/endoabs.49.EP1083

family history of consanguinity, inherited or genetic disorders. At 8 years of age

she was diagnosed with semicircular channels bilateral agenesis with consequent

profound bilateral deafness. At physical examination there was a normal stature

and weight, facial asymmetry and dysmorphia, low ear implantation, cleft palate

and dorsocifoescoliosis. Genital examination revealed normal morphology and a

Tanner 2 stage. Pelvic ultrasonography was consistent with small ovaries and

uterus, without evidence of follicular activity. Basal FSH and LH were below the

normal range without response to LHRH stimulation. CHARGE syndrome was

considered and genetic tests were performed. The karyotype was 46 XX and a

Cardiovascular Endocrinology and Lipid Metabolism

missense mutation in the CHD7 gene was identified (c.484COT/p.Q162X). The

EP1084

patient initiated treatment with an estradiol/norgestrel combination at the age of

15 with marked improvement of pubertal development.

The effect of hormone replacement therapy and tibolone on lipoprotein

Conclusion

(a) concentrations in postmenopausal women: a systematic review and

CS should be considered in the differential diagnosis of HH particularly in

meta-analysis of randomized controlled studies

presence of an abnormal phenotype. Mutations in the CHD7 gene cause more than

Panagiotis Anagnostis¹, Petros Galanis², Vasileia Chatzistergiou¹,

half of all cases of CS and most of the times are new mutations as occurred in the

John Stevenson³, Ian Godsland⁴, Irene Lambrinoudaki⁵, Mamas Theodorou⁶

current case. Different malformations may be present but the pattern varies among

& Dimitrios Goulis¹

affected individuals justifying a long term follow up.

¹Unit of Reproductive Endocrinology, First Department of Obstetrics and

Gynecology, Medical School, Aristotle University of Thessaloniki,

DOI: 10.1530/endoabs.49.EP1085

Thessaloniiki, Greece;²Center for Health Services Management and

Evaluation, Department of Nursing, National and Kapodistrian University

of Athens, Athens, Greece;³National Heart and Lung Institute, Imperial

College London, Royal Bromptonand Harefield NHS Foundation Trust,

London, UK;⁴Diabetes Endocrinology and Metabolic Medicine, Faculty of

EP1086

Medicine, Imperial College London, St Mary’s Campus, London, UK;

Combination of turner syndrome and congenital adrenal hyperplasia:

⁵Second Department of Obstetrics and Gynecology, National and

a rare case report

Kapodistrian University of Athens, Athens, Greece;⁶Health Policy and

Ivana Ságová^1,2, Dušan Pávai¹, Matej Stančík², Helena Urbánková¹,

Management Department, Open University of Cyprus, Nikosia, Cyprus.

Juliana Gregová¹, Anton Va

ˇuga^1,3 & Peter Vanˇ uga1

¹Department of Endocrinology, National Institute of Endocrinology and

Introduction

Diabetology, Lubochna, Slovakia;²Department of Internal Medicine I,

Data on the effect of hormone replacement therapy (HRT) and tibolone on

University Hospital Martin, Martin, Slovakia;³Alpha Medical, s.r.o.,

lipoprotein(a) (Lp(a)), an independent risk factor for cardiovascular disease, are

Lubochna, Slovakia.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Combination of Turner syndrome

(TS) and classical congenital adrenal

Functional hypogonadism has been described in association with acute severe

hyperplasia (CAH) is rare worldwide. Incidence of CAH - autosomal recessive

medical or surgical illness, subacute recovery and chronic disease. We present a

disorders characterized by enzyme defect of steroidogenic pathway, of which

case of transitory hypogonadism manifested during a peri-surgical period. A

90% ocuurs in the CYP21A2 gene coding 21-hydroxylase is 1:10000-16000.

42-year-old patient was sent to the endocrinology clinic due to hypertension and a

Incidencie of Turner syndrome is 1:2500 worldwide. Phenotypically, females

solitary adrenal mass. He was treated with bisoprolol and telmisartan, that he

with TS may present with a wide spectrum of clinical features. They may exhibit

maintains until today. The evaluation favoured non-functional adenoma but

short stature, virilization, premature ovarian failure and compromised fertility.

during the follow-up new complaints arose. He was diagnosed heart failure

We present a 57-year-old women suffering from both 45X0/46XX mosaic Turner

NYHA class-I related to aortic valve dysfunction and thoracic aortic aneurysm

syndrome and salt wasting form of CAH. After birth she was misdiagnosed as a

with surgical indication. He had recently visited the urologist due to complaints of

male. She had short stature and ambiguous genitalia - presence of the phallus with

erectile dysfunction and mentioned a normal scrotal US evaluation and the

perineoscrotal hypospadias and incomplete urogenital opening. Laparoscopy at

prescription of a phosphodiesterase inhibitor. These complaints started during the

age of six showed female sex organs. After this examination clitoroplasty and

pre-surgical period. He mentioned timed puberty (13 years old) and one daughter

vaginoplasty was done. Karyotyping revealed a 45X0/46XX pattern without sex

but declared reduced libido, reduced spontaneous erections, reduced turgor and

determining region Y on gene analysis. The presence of virilizing feature at

reduced need of shavings. He had BMI 21 kg/m², no gynecomastia, normal sense

puberty could not explain the diagnosis of Turner syndrome. She had amenorhea,

of smell and adult volume testicles. His previous total testosterone

(TT)

marked hirsutism and was of short stature (height 130 cm). Laboratory tests

evaluations were within reference range (265 and 310 ng/dl). The new laboratory

revealed elevated level of 17-hydroxyprogesterone, dehydroepiandrosterone and

analyses showed low TT on two separate evaluations, 104 and 181 (RI 249-836)

low cortisol concentrations. Congenital adrenal deficiency was then suspected.

ng/dl with inappropriately normal LH 3.12 U/l and FSH 5.18 U/l. Prolactin, IGF1

With the genomic analysis, CYP

21A2 mutation in IN2G and united

and ACTH were normal. MRI could not be performed because of the new

deletion/conversion was detected. She was treated with hydrocortisone. In

prosthetic valve. He was started on monthly testosterone enanthate achieving

adolescent hydrocortisone was replaced by dexamethasone. Fludrocortisone was

normal TT levels (267 ng/dl) and remission of clinical complaints. After a period

added to the treatment, because laboratory tests revealed increased plasma renin

of 5 months, approximately 2 months after the heart surgery the patient felt he had

concentration. Under a continuous treatment, her state improved.

regained shaving frequency and sexual turgor, withdrawing both the phospho-

Keywords: Turner syndrome, congenital adrenal hyperplasia, 21-hydroxylase

diesterase inhibitor and the testosterone substitution. After 5 months of no therapy

deficiency, CYP21A2

he revisited the clinic and laboratory tests were performed with the finding of

normal TT 295 ng/dl, normal FSH and LH.

DOI: 10.1530/endoabs.49.EP1086

DOI: 10.1530/endoabs.49.EP1088

EP1087

EP1089

A rare case of short-term postpartum primary adrenal insufficiency

Myriam Briner¹, Christina Gattlen², Gunther Kaindl², Martin

Congenital adrenal hyperplasia: case series, describing results of initial

Lukas Kaufmann², Nic Zerkiebel¹ & Natalia Rudovich^1,3

dexamethasone therapy

¹Department of Internal Medicine, Spital Bulach, Bulach, Switzerland;

Dragan Tesic¹, Edita Stokic¹, Milica Medic-Stojanoska¹, Milena Mitrovic¹,

²Department of Obstetrics and Gynaecology, Spital Bulach, Bulach,

Dragana Tomic-Naglic¹, Tijana Icin¹, Ivana Bajkin¹, Djordje Popovic¹,

Switzerland;³German Institute of Human Nutrition Potsdam-Rehbruecke,

Vuleta Dusan² & Jovan Vlaski³

Nuthetal, Germany.

¹Clinic of Endocrinology, Diabetes and Metabolic Diseases, Novi Sad,

Institut for

Serbia;²Obstetrics and Ginecology Clinics, Novi Sad, Serbia;³

Child and Youth Health Care, Novi Sad, Serbia.

Aims

Polyglandulare Autoimmune Sydnrome

(PAS) is a rare disease and the

development during pregnancy is seen even less often. PAS Type II presents

Introduction

with autoimmune adrenalitis and thyroiditis. Symptoms of adrenalitis such as

Congentital adrenal hyperplasia (CAH) comes to adult endocrinologist wheather

hypotension and hyperpigmentation are overlapping with physiological mani-

as transition from pediatritian (Case 3) or as still without diagnosis (Case 1, 2, 4).

festations during pregnancy making the diagnosis difficult.

The aim of this work is to describe typical forms of CAH initially sucessfuly

Clinical presentation

treated with dexamethasone therapy.

We are reporting the case of a 28-year old prima para prima gravida presenting

Case descriptions

two weeks postpartum (spontaneous preterm birth at 36 completed weeks of

Case 1: female, 1972y., presented in 1995y. (23y.) as severe hirsutism and

pregnancy) with hypotension, orthostatic presyncopal events and adynamia.

infertility managed by team of gynecologists. She refused any additional

Laboratory tests showed a low cortisol level, while adrenocorticotropic hormone

investigations and was severily depressed. Ex iuvantibus 0.5mg dexamethason

was augmented. Steroid-21-hydroxylase-antibodies and active renin were

therapy was followed with pregnancy. Case 2: female, 1990.y, presented in

increased. The medical history was significant for chronic lymphocytic thyroiditis

2008.y.(18y.). Non-classic CAH. Hirsutism, primary amenorrhoea. Dexametha-

with subclinical hyperthyroidism under L-thyroxin substitution. Synopsis of all

sone therapy 0.5 mg at night. After 4 month estabished menstruation, after 18m.

findings led us to the diagnosis of PAS type II.

became pregnant with healthy male baby born. Case 3: female, 1994y, presented

Conclusion

2012.y. (18y.) Classic CAH, salt wasting form. At birth classical low sodium,

The aim of this case report was to show that during pregnancy or postpartum we

high potassium. Established therapy with fludrocortison and hydrocortison, at

should take symptoms of adrenalitis in women with known autoimmune

night dexamethason 0.5 mg. Still primary amenorrhoea. On CT sevear vaginal

thyroiditis seriously and test for PAS.

stenosis. Case 4: male, 1980y, presented in 2014.y.(34y. old), when he was

diagnosed for the first time! Classic CAH, simple virilising form and

DOI: 10.1530/endoabs.49.EP1087

glucocorticoid-remediable aldosteronism, suprarenal hyperplasia on one gland

and incidentaloma on the other. Unilateral testicular adrenal rest tumour (TART),

azoospermia. Therapy hydrocortisone and dexamethasone at night. Soon he

normalised aldosterone, ACTH, 17-OH progesterone but lowered testosterone.

After 2y. CT of testes confirmed enlargement and the regression of TART.

Discussion

We have described two cases of CAH which solved the problem of fecundity

EP1088

(Cases 1 and 2). One treatment confirmed the need for additional surgical

Hypogonadotropic hypogonadism, functional and transitory

treatment of developmental abnormality on external genitalia(Case 3). Finally the

Catarina Roque, Filipa Serra, Francisco Sousa Santos, Catia Ferrinho,

problem of TART has been solved without any invasive intervention (Case 4),

Ricardo Capita˜o, Carlos Bello & Carlos Vasconcelos

wheather diagnostic or therapeutic, which are not the rare case even in these

Endocrinology Unit, Hospital de Egas Moniz, C.H.L.O. E.P.E., Lisbon,

years.

Portugal.

DOI: 10.1530/endoabs.49.EP1089

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Clinical Case Reports - Thyroid/Others

Developmental Endocrinology

EP1090

EP1092

A rare cause of a 46, XY disorder of sex development diagnosed in an

Age and developmental stage dependent relationship between plasma

adult patient

concentrations of leptin, luteinizing hormone, follicle stimulating

Katrin Feller¹, Christa Fluck², Laura Audi³, Mónica Fernández-Cancio³ &

hormone, prolactin, testosterone and inhibin B in boys between the age

Christoph Stettler¹

of 1 and 20 years

¹Department of Diabetology, Endocriniology, Clinical Nutrition and

Afzaal Ahmed Naseem¹, Mazhar Qayyum¹, Maleeha Akram¹,

Metabolism, University Hospital of Bern, Bern, Switzerland;²Department

Zubaria Iqbal¹, Fahim Tahir², Kiran Afshan³, Sarwat Jahan³ &

of Pediatrics, Divsion of Pediatric Endocrinology and Diabetology,

Syed Shakeel Raza Rizvi¹

University Hospital of Bern, Bern, Switzerland;³Pediatric Endocrinology

¹Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University

Research Unit Vall d’Hebron Institut de Recerca, Universitat Autonoma de

Rawalpindi, Rawalpindi/Punjab, Pakistan;²Reproductive Physiology,

Barcelona, Barcelona, Spain.

Public Health Laboratories Division, National Institute of Health (NIH),

Islamabad, Pakistan;³Department of Animal Sciences, Quaid-i-Azam

University, Islamabad, Pakistan.

The defective conversion of testosterone to dihydrotestosterone due to a steroid

5-alpha-reductase 2 deficiency results in a unique form of 46, XY disorder of

sexual development (DSD). Dihydrotestosterone is essential for the embryonic

Leptin is regarded as an essential adipokine for controlling energy homeostasis,

differentiation of the external male genitalia and the prostate. Steroid 5-alpha-

caloric intake reduction and increase of caloric expenditure by negative feedback

reductase 2 deficiency is an autosomal recessive disorder in which genetic males

mechanisms via receptors in the hypothalamus. Puberty is said to be triggered by

have a predominantly female phenotype with female external genitalia but male

leptin, which signals the hypothalamus that adequate fat reserves are available for

internal urogenital tract. We describe the case of an adult patient having migrated

initiation of energetically costly process of reproduction. Leptin activates

from Pakistan to Switzerland in whom a steroid 5-alpha-reductase 2 deficiency

gonadotropin releasing hormone (GnRH) system, which stimulates luteinizing

was diagnosed at the age of

29. Molecular genetic analysis identified a

hormone (LH) and follicle stimulating hormone (FSH) secretion from pituitary

homozygous point mutation in exon 4 of the 5-alpha-reductase 2 gene, leading

gonadotropes and subsequent secretion of testosterone (T) from testes. Never-

to an amino acid change from glutamic acid to lysine. To our knowledge, this is

theless, it is not clear whether leptin has any association with the secretion of

the second case of this mutation in the steroid

5-alpha-reductase

2 gene

FSH, prolactin (PRL) and inhibin B during puberty. This study examined possible

(SRD5A2) which was first described in 1997 (Anwar et al.).

associations between plasma concentrations of leptin and LH, FSH, PRL, T, and

DOI: 10.1530/endoabs.49.EP1090

inhibin B at different ages and developmental stages in boys between 1 and 20

years (27 boys/age group). The concentrations of leptin, LH, FSH, PRL, T and

inhibin B were determined using specific ELISA. Data were analyzed using

Student’s t-test, ANOVA and Pearson correlation r. The concentrations of leptin

and LH were positively correlated at 1st, 4thK10th, 12th, 16th, 20th year and at

infancy and early puberty. Leptin and FSH concentrations were positively

correlated at 1st-3rd, 8thK10th, 12th, 13th, 15th, 16th, 18th, 20th year and at

infancy, pre-puberty and early puberty. Leptin and PRL levels were positively

correlated at 1st, 3rd, 5th, 6th, 9th, 10th, 12th-14th, 19th year and at infancy, pre-

puberty and early puberty. Leptin and T concentrations were positively correlated

at 1st, 3rd, 6th, 7th, 9th, 10th, 12th and 16th year and at infancy and early puberty.

Leptin and inhibin B levels were positively correlated at 1st, 3rdK8th, 10th, 12th,

15th-19th year and at infancy, early and late puberty. Thus, leptin and LH, FSH,

PRL, T and inhibin B are positively correlated only at early puberty.

DOI: 10.1530/endoabs.49.EP1092

EP1091

Association of short stature, microcephaly, secondary amenorrhea and

consanguinity: clinical case report

Claudia Matta-Coelho & Selma B Souto

Endocrinology Department, Braga Hospital, Braga, Portugal.

Background

Endocrine Tumours and Neoplasia

In 1985, Mikati et al., described a new syndrome, which included microcephaly,

EP1093

hypergonadotropic hypogonadism, short stature, mental retardation and minor

Molecular mechanisms underlying progesterone-enhanced breast

anomalies in four out of nine siblings of consanguineous parents. No genetic

cancer cell proliferation

disorder was associated to the disease. No further references to this syndrome

Hui-Chen Wang

have been found in literature. The authors present a new possible case of Mikati-

Taipei Medical University, Taipei Taiwan, Taiwan.

Naijjar and Sahli syndrome (MNJS).

Clinical case

Forty-two-year-old female referred to the Endocrinology Department due to

Previously, we demonstrated that progesterone (P4) could enhance breast cancer

secondary amenorrhea for 6 years. History of menarche at eighteen with regular

cell migration through increasing formation of the p27-RhoA complex and RhoA

menstrual cycles. No access to prenatal and neonatal history. Personal history of

activation caused by the cSrc/AKT-mediated phosphorylation of p27 at T198.

primary hypothyroidism medicated with levothyroxine 50 mg. She was able to

Here, we further examined the effect of P4 on breast cancer cell proliferation. Our

help in some household duties, but lacked capabilities for satisfactory results at

results show that P4

(12.5-100 nM) concentration-dependently enhanced

school. Parents are 1st degree relatives. Two healthy brothers and one other with

proliferation in breast cancer cell lines (T47D and MCF-7). We also found that

microcephaly, not further investigated. Physical examination Microcephaly

increases of cytoplasmic p27 localization are responsible for the P4-enhanced

(46 cm), weight 50 kg, height 129 cm. Also, narrow forehead, synophrys and

breast cancer cell proliferation. Our results demonstrated that P4 activated the

micrognathia. Tanner V. Unremarkable neurological exam. No relevant findings

cSrc/PI3K/AKT signaling pathway, subsequently activating RSK1, which in turn

in biochemical study besides hypergonadotropic hypogonadism. She had normal

increased phosphorylation of p27 at T198. PI3K/AKT activation also increased

prolactin, dehydroepiandrosterone sulphate, delta-4-androstenedione, sex hor-

phosphorylation of p27

at T157. Both p-p27T157

and p-p27T198

caused

mone-binding globulin and total testosterone. Normal uterus and ovary

cytoplasmic mislocation of p27 protein. In addition, P4 induced KIS activation,

ultrasound. Karyotype 46, XX.

which in turn increased phosphorylation of nuclear p27 at S10, subsequently

Discussion

causing p-p27S10 translocation from the nucleus to the cytosol. The decreased

The patient presented with multiple congenital abnormalities, which do not

level of nuclear p27 protein reduced its inhibition in the cyclin-CDK2 system,

occur in any known syndrome to our knowledge, besides MNJS. However, our

subsequently increasing phosphorylation of CDK2 at T160 and p27 at T187,

patient presented with secondary amenorrhea unlike the female patient in

hence causing translocation of p-p27T187 from the nucleus to the cytosol. In the

MNJS kindred with primary amenorrhea and Tanner II. Like the genetic defect

cytosol, both p-p27S10

and p-p27T187

were degraded by the ubiquitin-

was not studied in MNJS it will be challenging to ascertain if it is the same

proteasome pathway. Importantly, the P4-enhanced proliferation in breast cancer

syndrome.

cell lines was abolished when p27 was knocked-down or phosphorylation of 27

DOI: 10.1530/endoabs.49.EP1091

was inhibited. Taken together, our results demonstrated that P4 enhanced breast

cancer cell proliferation through increasing p27

degradation due to its

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

cytoplasmic mislocation. The findings from the present study highlight the

(ALT) and levels of total bilirubin. Furthermore, treatment with INH, RIF and

molecular mechanisms underlying P4-enhanced proliferation in breast cancer cell

PZA significantly (P!0.05) reduced the levels of luteinizing hormone, estrogen

lines.

and prolactin. In contrast, there were no significant differences (PO0.05) in the

DOI: 10.1530/endoabs.49.EP1093

levels of follicle stimulating hormone and progesterone in rats treated with anti-

TB drugs when compared to controls. Moreso, INH, RIF, EMB and PZA caused

significant (P!0.05) increase in the uterine malondialdehyde (MDA) levels by

281, 214, 273 and 190%, respectively, while INH and EMB increased the ovarian

MDA levels by 111% and 129%, respectively. All the anti-TB drugs significantly

(P! 0.05) decreased the activities of ovarian glutathione-S-transferase and

uterine glutathione peroxidase, superoxide dismutase and catalase. Histopatho-

logical examinations showed severe erosion of uterine mucosa, cellular debris in

EP1094

lumen of uterus and under-developed follicles in ovary of the rats. These results

Study of CYP17 and PSA G158A polymorphisms in prostate cancer

confirmed that the first line anti-TB drugs elicited reproductive toxicity in female

Suzana Vladoiu¹, Dana Manda¹, Sabina Oros¹, Sorina Schipor¹,

rats via mechanism that involved oxidative stress.

Adrian Preda³, Ismail Gener³, Catalina Picu¹, Roxana Rosca^1,2 &

DOI: 10.1530/endoabs.49.EP1095

Corin Badiu^1,2

¹‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;

²‘Carol Davila’ University of Medicine and Farmacy, Bucharest, Romania;

³Clinical Institute Fundeni, Bucharest, Romania.

The relationship between the level of genetic variation in CYP17, PSA genes and

prostate cancer has been extensively studied but the results are still unclear. A

EP1096

450c17a

(CYP17) polymorphism A1/A2 was described to be significantly

Development of hepatic steatosis and inflammation by chronic insulin

associated to prostate cancer. A SNP in the promotor PSA gene is an A to G

and hCG exposure in female rats: possible implications in PCOS

substitution at position K158 (G158A) was proposed to interact differently with

patients with NAFLD

AR, thereby modifying the expression pattern and occurrence of prostate cancer.

Ruijin Shao¹, Yuehui Zhang^1,2, Min Hu¹ & Håkan Billig¹

Objective

¹The Sahlgrenska Academy at the University of Gothenburg, Goteborg,

The aim of the study was to investigate the association between CYP17 and PSA

Sweden;²First Affiliated Hospital, Heilongjiang University of Chinese

gene polymorphisms with advanced prostate cancer.

Medicine, Harbin, China.

Subjects and methods

The study was conducted on 48 patients with advanced prostate cancer (Gleason

score O 7) and 13 benign prostate hyperplasia subjects. Patients were enrolled

Accumulating clinical data suggest that women with polycystic ovary syndrome

after they gave their informed consent. DNA was isolated from prostatic tissue

(PCOS) are at high risk for nonalcoholic fatty liver disease (NAFLD). However, it

with PureLink Genomic DNA (Invitrogen). Genotyping of the A1/A2 and G/A

is not clear whether hyperinsulinemia and hyperandrogenism act concomitantly

polymorphisms in the promoter region of CYP17 and the PSA, respectively, were

or independently to induce hepatic steatosis and inflammation, and the molecular

determined by a PCR-RFLP assay. PCR product was digested with restriction

mechanisms behind the interactions between insulin resistance and hyperan-

enzyme NheI (PSA G-158A) and MspA1I (CYP17). Preoperatory serum PSA was

drogenism in the female liver remain largely unexplored. To achieve

assayed by immunochemiluminescence.

hyperinsulinemia, insulin resistance, and hyperandrogenism, we treated rats

Results

chronically with insulin, human chorionic gonadotropin (hCG), or a combination

Genotype distribution differ for PSA G-158 between the prostate cancer and the

of insulin and hCG. We showed that the different treatments induced varying

control group (25% GG, 25% AA, 50% AG vs. 8% GG, 23% AA, 69% AG) and

degrees of hepatic steatosis in rats. While hCG-treated rats had strongly

for CYP 17 (36% A1, 45% A1A2, 19% A2 vs. 22% A1, 64% A1A2, 14% A2).

aggravated hepatic inflammation, insulinChCG-treated rats exhibited the

The frequency of A1 allele was 0.41, and 0.59 for A2 allele. In control group the

hallmarks of metabolic alterations and hepatocyte cell damage. Further

frequency of A1 allele in population was 0.46, for A2 allele the frequency was

mechanistic study revealed that the expression of a number of genes (Srebp-1,

0.54. Neither CYP17 nor PSA polymorphisms associated with prostate cancer.

Srebp-2, Gpam, Ppara, Pparg, Lxra, E2f1, Il-6, Mcp1, Tgfb, and Ctgf) and

Serum levels of PSA did not differ between genotypes.

proteins (AceCS1, p-ACL, IRb, p110-PI3K, p-Akt (T308), AS160, p-GSK3b,

Conclusion

p-JNK, TNFa, and IL-1b) was significantly different in the liver between

In our study groups CYP17 and PSA gene polymorphisms did not significantly

treatment and control groups. In parallel, we observed that expression of genes in

associated with prostate cancer or serum PSA levels. Further studies are needed

adipose tissues that are related to M1/M2

macrophages was differentially

on larger cohorts.

regulated by the different treatments. In summary, our study presents several lines

Acknowledgement

of in vivo evidence that hyperinsulinemia and hyperandrogenism, either alone or

This work was funded by UEFISCDI grant no. 192/2014

in combination with insulin resistance, alter hepatic lipid metabolism, liver and

DOI: 10.1530/endoabs.49.EP1094

adipose tissue inflammatory responses, and cellular function and that the effects

of the different conditions are distinct from each other. By deciphering the

metabolic, endocrine, and molecular alterations along with morphological

changes, our findings offer a new understanding of how hyperandrogenism itself

or combined with insulin resistance contributes to liver damage in women with

PCOS.

DOI: 10.1530/endoabs.49.EP1096

Female Reproduction

EP1095

Administration of first line anti-tuberculosis drugs induces ovarian and

uterine oxidative stress and disruption of endocrine balance in rats

Oluwatosin Adaramoye, Olayinka Adebayo, Omolola Adesanoye,

Amos Abolaji & Aderemi Kehinde

EP1097

University of Ibadan, Ibadan/South West, Nigeria.

Frequency of nodular goiter and autoimmune thyroid disease and

association of these disorders with insulin resistance in polycystic

The first line anti-tuberculosis (anti-TB) drugs; isoniazid (INH), rifampicin (RIF),

ovary syndrome

ethambutol (EMB) and pyrazinamide (PZA) were effective in the treatment of

Mellia Karakose¹, Sema Hepsen², Erman Cakal¹, Muyesser Arslan¹,

pulmonary tuberculosis. However, the toxicity of these drugs has been of great

Esra Tutal¹, Safak Akin¹, Ilknur Unsal¹ & Mustafa Ozbek¹

concern in clinical settings. This study was designed to evaluate the toxic effects

¹Diskapi Training and Research Hospital, Department of Endocrinology and

of anti-TB drugs on reproductive system in female rats. Thirty-five female Wistar

Metabolism, Ankara, Turkey;²Diskapi Training and Research Hospital,

rats were assigned into five groups of seven animals each. The control received

Department of Internal Medicine, Ankara, Turkey.

normal saline, while others received INH (5 mg/kg), RIF (10 mg/kg), EMB

(15 mg/kg) and PZA (15 mg/kg) via gavage thrice in a week for eight consecutive

Background and aim

weeks. Results showed that anti-TB drugs significantly (P! 0.05) reduced both

Polycystic ovary syndrome (PCOS) is one of the most common endocrine

uterine and ovarian weights, and relative weight of uterus relative to controls. In

disorder in women with reproductive age. Nodular goiter and autoimmune thyroid

addition, anti-TB drugs increased the activities of alanine aminotransferase

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

disease (AITD) are frequently seen endocrinological abnormalities. The aim of

EP1099

this study was to identify the prevalence of AITD and nodular goiter in PCOS

Serum sclerostin and dickkopf-1 levels in polycystic ovary syndrome

patients and investigate whether PCOS related hormones and metabolic factors

patients

affect these thyroid disorders.

Ogun Bilem, Yildiz Bilem, Mustafa Eroglu, Hakan Turkon,

Methods

Yasemin Sefika Akdeniz & Mehmet Asik

Ninety-seven with PCOS and seventy-one healthy female volunteers were

Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale,

recruited in the present study. Serum free thyroxine (fT₄), thyroid stimulating

C¸ anakkale, Turkey.

hormone

(TSH), anti-thyroperoxidase antibody

(anti-TPO Ab), and anti-

thyroglobulin antibody (anti-Tg Ab) were measured. Thyroid ultrasonography

was performed and thyroid volume (TV) was calculated.

Introduction

Results

Polycystic ovary syndrome (PCOS) is the most common endocrine pathology in

The BMI, waist/hip ratio, fasting blood glucose, fasting insulin, HOMA-IR, TG

premenopausal women and it is a complex syndrome affecting various systems.

and LDL-C were significantly higher in PCOS patients (P!0.05). HDL-C were

Numerous studies have been made about how the PCOS effects on bone

significantly higher in control group (PZ0.005). The mean thyroid volume was

metabolism, but currently there is no clear information. Wnt pathway plays

11.4G4.7 ml in PCOS patients while 9.9G2.8 ml in controls (PZ0.022). Twenty

important role in the regulation of bone metabolism. The sclerostin(Scl) and

nine PCOS patients (29/97; 29.9%) had thyroid nodule whereas only eleven

Dickkopf-1

(DKK1) inhibit this pathway and they has recently become a

control subjects had thyroid nodule (11/71; 15.5%) (PZ0.043). The frequency of

therapeutic target of osteoporosis. In this study, we aimed to show the Scl and

AITD was significantly higher in PCOS patients

(PZ0.001). Statistically

DKK1 levels in women with PCOS.

significant relationship was found between thyroid volume and age, BMI, fasting

Methods

glucose, fasting insulin, HOMA-IR (P!0.05). Participants with thyroid nodule

This study was conducted in C¸ anakkale Onsekiz Mart University Endocrinology

were older and had higher BMI, fasting glucose, fasting insulin and HOMA-IR

department. Thirty-six women with PCOS and 35 healthy volunteers were

values compared to participants without thyroid nodule (P!0.05).

examined in this study. Both groups were compared in terms of respect

Conclusion

demographic, anthropometric, biochemical and Scl and DKK levels.

Our study showed that TV and frequency of nodular goiter were increased in

Results

PCOS patients. This result has been associated with insulin resistance. Therefore

PKOS grubunda sklerostin duzeyi 42.68G13.28 pg/ml, kontrol grubunda ise

we recommend PCOS patients must be monitored for the development of nodular

45.69G11.79 pg/ml olarak olçulmu¸ olup iki grup arasında istatistiki anlamlı fark

goiter and AITD.

olmadıg˘ı tespit edilmi¸tir. DKK1

duzeylerinin ise PKOS’lularda

1444.73G

DOI: 10.1530/endoabs.49.EP1097

611.30 pg/ml, kontrol grubunda 1204.26G660.88 pg/ml oldug˘u gosterilmi¸ olup

iki grup arasında anlamlı fark olmadıg˘ı saptanmı¸tır. The proportion of clinical

hirsutism (FGSR8) in PCOS group were significantly higher than the control

group. PCOS group compared to the control group in BMI and WHR were found

to be high, although the difference is not statistically significant.

Conclusions

This is the first study on this subject. C¸ alı¸mamızda PKOS’lu kadınlarda

sklerostin ve DKK1 duzeylerinin de

˘i¸medig˘i gosterilmi¸tir. PKOS’lu hastaların

EP1098

KMY olçumleriyle olan çalı¸malarda da çeli¸kili sonuçlar çıkmı¸tır. Her ne kadar

Association of basal and post-synacthen stimulated 17-hydroxypro-

amenore bu hastalarda kemik kaybına yol açıyorsa da, hiperandrojenemi ve

gesterone levels with insulin resistance in polycystic ovary syndrome

hiperestrojenemi gibi durumlar kemik uzerine olumlu etkiler yaparak bu etkiyi

Eleni Kandaraki¹, Georgios Papadakis², Sofia Tsirona³,

dengeliyor gorunmektedir.

Athina Asimakopoulou⁴, Nikolaos Chiotinis⁵, Genovefa Chronopoulou⁵,

Keywords: Polycystic Ovary Syndrome, Osteoprosis, Sclerostin, Dickkopf-1

Georgia Kassi⁴ & Evanthia Diamanti-Kandarakis³

DOI: 10.1530/endoabs.49.EP1099

¹Endocrinology Department, Red Cross Hospital, Athens, Greece;²STEPS

Stoffwechselzentrum, Biel/Bienne, Switzerland;³Department of Endo-

crinology, Diabetes and Metabolic Diseases, Euroclinic Hospital, Athens,

Greece;⁴3rd Department of Internal Medicine, Endocrinology Unit, Sotiria

Hospital, Athens, Greece;⁵Biochemical Department, Euroclinic Hospital,

Athens, Greece.

Objective

EP1100

17-alpha-hydroxyprogesterone caproate therapy during pregnancy has been

associated with insulin resistance. The aim of this study was to highlight any

Phthalates induce ovarian failure through disturbance in

folliculogenesis and steroidogenesis

possible association of 17OHP with insulin resistance in women with PCOS.

Dinh Nam Tran, Jae Hwan Lee, Changhwan Ahn, Jin Yong An,

Design

Seon Young Park & Eui-Bae Jeung

Forty-five women with PCOS underwent 75 g OGTT test and short Synachten test

Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

with sampling of stimulated 17OHP. Women were divided into two subgroups

according to basal 17OHP cut-off level of 0.8 ng/ml.

Results

Introduction

Women with basal 17OHP more than 0.8 ng/ml had significantly higher glucose

Phthalates are chemicals used to improve the plasticity of industrial polymers and

levels at 60⁰ min: Glu₆₀: 111.36G22.37 mg/dl vs 133.11G32 mg/dl, PZ0.047,

used in commercial products such as toys, paints, packaging materials, medicals

and at 90⁰ min Glu₉₀: 93.50G13 mg/dl vs 113.50G27 mg/dl, PZ0.038 and more

devices and personal care items. Phthalates, endocrine disrupting chemicals, have

often polycystic ovarian morphology in ultrasound compared to those with basal

been documented to cause adverse effects to the human health such as breast

17OHP levels below 0.8 ng/ml. The mean percentage increase of 17OHP at 60⁰

cancer in female, reduced uroogenital distance and changed the expression of

after Synachten test was 223%. According to this, women were subdivided into

steroidogenesis and folliculogenessis. In this study, we investigated the impact of

two categories depending on whether the intraindividual percentage increase of

di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl

post-Synachten 17OHP levels was higher or lower than the mean percentage

phthalate

(BBP) on loss of ovarian function through folliculogenesis and

increase. A total of 26 women with hyperresponsiveness of 17OHP at 60⁰ minutes

steroidogenesis. 4-Vinylcyclohexene diepoxide (VCD), a disruptor of ovarian

appeared with significant higher insulin resistance and post glucose challenge

small pre-antral follicles, was used as a positive control.

hyperinsulinemia when compared to 19 women with lower percentage increase of

Methods

17OHP, i.e. their mean insulin levels at 30⁰ minutes were: Ins₃₀: 130.9G98.7 vs

Female Spargue-Dawley rats (8 weeks of age, 160-180 g bodyweight) were

59.3G30.9 mU/ml, PZ0.05, at 60⁰

minutes: Ins₆₀:

182.4G124.9 vs 74.4G

administered VCD

(80 mg/kg) by intraperitoneal, DEHP

(25 mg/kg), BBP

32.1 mU/ml, PZ0.01, at 90⁰ minutes: Ins₉₀: 177.2G128.2 vs 67.9G34.1 mU/ml,

(250 mg/kg) and DBP (250 mg/kg) by oral gavage in 0.3 ml of corn oil at LOAEL

PZ0.01, and at

120⁰

minutes: Ins₁₂₀:

121.6G65.2

67.1G45.8 mU/ml,

during 6 weeks. Vaginal smear was collected at 9 a.m every day to check estrus

PZ0.05.

cycle. Blood, pituitary, uterine and ovaries were collected after

24 h final

Conclusions

injection.

17OHP could possibly be related to the metabolic abnormalities in women with

Results

PCOS and this should me taken into account especially during pregnancy when

There was significantly increased in body weight of DEHP groups compared to

insulin resistance increases.

other groups. Estrus cycle in DEHP and DBP groups showed no difference

DOI: 10.1530/endoabs.49.EP1098

comparing with vehicle group. However, diestrus phase in VCD and BBP groups

drew out compared to vehicle group. The transcriptional levels of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

folliculogenesis-related genes (Foxl2, Kitl and Amh) and steroidogenesis-related

found. No significant relation between age, BMI, w_h, E2, T, SHBG

genes (Star and Cyp11a1) were changed.

concentrations, duration of E2

use and FSFI domains in TS patients was

Conclusion

detected. 41% (nZ11) of TS used NE2, 26% (nZ7) were on COCs and 33%

Our findings suggest that these phthalates can induce premature ovarian failure by

(nZ9) were in no_E group. NE2 or COCs users had higher total FSFI score

disturbance in folliculogenesis and steroidogenesis and failure in hormone

(25.36G9.10 vs 17.89G13.62; PZ0.008) and reported better lubrication (4.60G

regulation.

1.84; PZ0.031), satisfaction (4.83G1.72 vs 3.20G2.57; PZ0.008), pain (4.67G

DOI: 10.1530/endoabs.49.EP1100

1.69 vs 2.97G2.46;Z0.03) during sexual intercourse compared with no_E. NE2

users had better desire (3.81G1.36 vs 2.01G2.15,Z0.005), lubrication (4.58G

1.78 vs 2.35G2.48; PZ0.014), arousal (4.03G1.63 vs 2.37G2.33; PZ0.009),

orgasm (3.85G1.86 vs 2.20G2.37; PZ0.05), satisfaction (4.54G1.81 vs 2.71G

2.83; PZ0.001), pain (4.90G1.73 vs 2.26G2.46; PZ0.011) and total FSFI score

(25.74G9.33 vs 14.09G14.38; PZ0.001) when compared with COCs users.

Conclusion

Sexual function in TS did not differ compared with controls. Higher FSFI score

EP1101

was found in E2 users compared with untreated patients and in NE2 users

Efficacy comparison of oral rosuvastatin versus oral progesterone and

compared with COCs users.

bevacizumab on regression of surgically endometriotic implants in rats

DOI: 10.1530/endoabs.49.EP1102

Ayse Gul Kebapcilar, Tolga Tuyan Ilhan, Duygu Dursunoglu, Kubra Kurt,

Suleyman Hilmi Ipekci, Suleyman Baldane, Mustafa Gazi Ucar,

Cem Onur Kirac, Levent Kebapcilar & Cetin Celik

Selcuk University, konya, Turkey.

Aim

Thirty female Wistar albino rats with surgically endometriotic implants were

randomly randomized into three treatment groups: oral rosuvastatin (20 mg kg per

day; oral rosuvastatin group 1; nZ10), oral progesterone (Dienogest group 2;

EP1103

nZ10), and intraperitoneal bevacizumab (2.5 mg/kg of single intaperitoneal

BMP8 sustains expansion and survival of cumulus cells in vitro

injection of bevacizumab; group 3; nZ10) respectively, for 10 day and post-

Fang-Ju Wu & Ching-Wei Luo

treatment variables were compared.

National Yang-Ming University, Taipei, Taiwan.

Results

The endometrium foci as were measured on days 1 and 10. Rosuvastatin group

showed higher reduction for the glandular epithelium and uterine vessels of

histopathological scores values than progesterone group

(both, P!0.017;

Cumulus cells are a group of specialized granulosa cells that surrounds

respectively). The median glandular epithelium and uterine vessels and

oocytes and are critical for female fertility. During ovulation, cumulus cells

histopathological scores values did not show statistically significant difference

need to be expanded systematically in order to support the maturation,

among group 1 and group 3 (PO0.017). No significant different reduction was

ovulation and fertilization of oocytes, whereas their apoptosis will result in

observed in between the three groups for the myometrium, endometrial stroma, in

the decline of fertilization rate and pregnancy outcome. However, the

histopathological scores (PO0.017). Endometrial thickness and uterine volume

molecules as well as their signalings involved in the control of cumulus cell-

values analyzed in all treatment groups. Endometrial thickness values and uterine

oocyte complex (COC) expansion are complicated and await more studies.

volume values was more significantly reduced in the oral rosuvastatin medication

By analyzing several microarray and RNA-seq datasets, we intriguingly

than oral progesterone group

(both, P!0.017; respectively). Moreover,

noticed that BMP8 expression in cumulus cells was positively correlated to

endometrial thickness and uterine volume values were not different in groups I

human oocyte maturation and zygote developmental competence. Using a

compared with group 3 (PO0.017).

rat superovulation model, we found that Bmp8 transcripts were up-regulated

Conclusion

by the luteinizing hormone signaling and were abundant in cumulus cells of

In conclusion, rosuvastatin and intaperitoneal injection of bevacizumab may

pre-ovulatory follicles. Furthermore, BMP8 treatment can induce COC

causes more significant regression of surgically endometriotic implants in rats

expansion as well as the expression of COC expansion-related genes.

than oral progesterone medications.

Hoechst-propidium iodide double staining further revealed that BMP8 can

decrease cumulus cell apoptosis in ovulated COCs. BMP8 can induce the

DOI: 10.1530/endoabs.49.EP1101

phosphorylation of both SMAD1/5/8 and SMAD2/3 in isolated COCs.

Signaling dissection by inhibitors further indicated that blockage of

SMAD2/3 pathway can impair BMP8-induced COC expansion, whereas

blockage of either SMAD1/5/8 pathway or SMAD2/3 pathway dampens the

protective role of BMP8 against cumulus cell apoptosis, indicating that both

pathways are needed for BMP8-mediated cumulus cell survival. Taken

together, our data demonstrated that BMP8 sustains both expansion and

survival of cumulus cells through different SMAD downstreams. With these

EP1102

capabilities, BMP8 can contribute to the maintenance of oocyte quality and

The relation between sex hormones and sexual function in women with

this may have clinical applications when doing in vitro fertilization.

Turner syndrome

DOI: 10.1530/endoabs.49.EP1103

Ruta Kriksciuniene, Birute Zilaitiene, Justina Sematonyte &

Rasa Verkauskiene

Lithuanian University of Health Sciences, Kaunas, Lithuania.

Objectives

To evaluate sexual function in women with Turner syndrome (TS) in the relation

with sex hormones.

Methods

The study was undertaken in Lithuanian University of Health Sciences. 65 women

EP1104

with genetically confirmed TS (18-45 years) were enrolled and compared with 65

Serum concentrations of betatrophin and its association with indirect

age-matched healthy controls. Sexual function was evaluated using The Female

indices of insulin resistance and beta cell function in women with

Sexual Function Index (FSFI). Risk for sexual dysfunction was defined as FSFI

polycystic ovary syndrome

score % 26.55. BMI, waist-hip ratio (w_h), concentrations of estradiol (E2),

Agnieszka Adamska¹, Agnieszka Lebkowska¹, Malgorzata Jacewicz¹,

testosterone (T), sex hormone binding globulin (SHBG) were evaluated. TS

Anna Krentowska¹, Justyna Hryniewicka¹, Slawomir Wolczynski²,

patients were divided into 3 groups: natural estrogens users (NE2), combined oral

Maria Gorska¹ & Irina Kowalska¹

contraceptives users (COCs) and untreated (no_E).

¹Department of Endocrinology, Diabetology and Internal Medicine,

Results

Medical University of Białystok, Bialystok, Poland;²Department of

38% (nZ27) TS had sexual intercourse and filled out FSFI. 33% (nZ9) of TS and

Reproduction and Gynecological Endocrinology, Medical University of

42% (nZ25) of controls were at risk for sexual dysfunction (PO0.05). No

Białystok, Bialystok, Poland.

difference in FSFI score depending on karyotype (classic or mosaicism) was

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1106

The accumulated data underline the role of betatrophin in glucose

The functional state of hypophysis - gonad axis in patients with

homeostasis. Polycystic ovary syndrome (PCOS) is characterized by insulin

polycystic ovary syndrome (PCOS)

resistance and high risk of developing prediabetes and diabetes. The aim of

Yulduz Urmanova^1,2, Feruza Khodgaeva^1,2, Dinara Alieva^1,2,

our study was to investigate the relationship of serum betatrophin

Salim Sodikov^1,2, Nazira Rikhsieva^1,2 & Maryam Abduvakhabova^1,2

concentrations with indirect indices of insulin resistance and insulin

¹Paediatric Medical Institute, Tashkent, Uzbekistan;²Center of the

secretion in women with PCOS, comparing to the control group. The

Scientific and Clinical Study of Endocrinology, Tashkent, Uzbekistan.

study group comprised 43 women with PCOS and 16 controls matched for

BMI and age. An oral glucose tolerance test (OGTT) with estimation of

serum betatrophin concentrations was performed. Insulin resistance was

The aim

assessed by HOMA-IR and Matsuda index. Insulin secretion was evaluated

To study the functional state of axis of hypophysis-gonads for women with PCOS.

by HOMA-B. Glucose load resulted in an increase of serum betatrophin

Material and methods of investigation

concentrations only in the control group (PZ0.02). Consequently, serum

Under our supervision in the department of neuroendocrinology of The Center of

betatrophin concentrations at 120⁰ of OGTT were lower in women with

Endocrinology of PHM of Republic of Uzbekistan ambulatory in a period from

PCOS in comparison to the control group (PZ0.02). We observed a positive

September 2015 for July, 2016 120 patients of fertile age were inspected with

relationship between baseline serum betatrophin concentrations and

polycystic ovary syndrome (PCOS). Middle age of patients - 25.5G4.3 years.

baseline serum insulin concentrations

(rZ0.42, PZ0.004) in PCOS

The remoteness of disease hesitated in limits from 7 months to 9 years. 20 healthy

group. Additionally, correlations between baseline serum betatrophin

women of corresponding age made a control group. The complex of researches,

concentrations and HOMA-IR (rZ0.39, PZ0.008), HOMA-B (rZ0.38,

including clinical, biochemical hormonal, ultrasound investigations of uteri/o-

PZ0.01) and Matsuda index (rZK0.31, PZ0.004) were observed in

varies, pituitary MRI was executed all patients.

women with PCOS. We found relationship between D betatrophin and

Results

serum total testosterone concentration in the entire group

(rZK0.32,

Patients were divided into two groups: 1 g - patients with primary sterility are 94

PZ0.01). Multiple regression analysis revealed that HOMA-B (bZ0.47,

cases, 2 r. - patients with secondary sterility are 26 cases. In a 1 group of patients

PZ0.001) was an independent factor connected to serum betatrophin levels

with primary sterility the reliable decline of both pituitary and ovarian hormones

in women with PCOS. Serum concentrations of betatrophin is connected

was marked on a background hyperandroenemiya and hyperprolactinemiya. In

with insulin resistance and beta cell function and did not change after

the second group of patients the reliable decline of pituitary hormones was also

glucose load in women with PCOS.

educed on a background hyperandroenemiya and hyperprolactinemiya. While an

DOI: 10.1530/endoabs.49.EP1104

ovarian function was within the limits of norm.

Conclusions

In both groups of patients took place hypogonadotropinemiya combining

moderate hyperprolactinemiya and hyperandrogenemiya.Thus, the most

expressed violations of the system of pituitary - ovarian function were found

out in the first group of patients with PCOS with primary sterility, at that the

reliable decline of the functional state of pituitary-gonads was marked, namely

decline of LH, FSH, estradiol and progesterone of plasma of blood on 14 day of

menstrual cycle.

DOI: 10.1530/endoabs.49.EP1106

EP1105

Short term intervention with liraglutide and metformin increased

fertility potential in a subset of obese PCOS proceeding IVF

Vesna Sˇ alamon2, Mojca Jensterle1, Andrej Janež1 & Eda Vrtačnik Bokal2

¹Department of Endocrinology, Diabetes and Metabolic Diseases,

University Medical Centre Ljubljana, Ljubljana, Slovenia;²Department of

Human Reproduction, Division of Obstetrics and Gynecology, University

Medical Centre Ljubljana, Ljubljana, Slovenia.

EP1107

Efficacy of FSH alone, FSH C LH, hMG or FSH C hCG on ART

outcomes in the ‘personalized’ medicine era: a meta-analysis

Objective

Daniele Santi^1,2, Livio Casarini^2,3, Carlo Alviggi⁴ & Manuela Simoni^1,2

Obese PCOS have poor IVF outcomes. The aim of this study was to evaluate the

¹Unit of Endocrinology, Department of Biomedical, Metabolic and Neural

impact of weight reduction with metformin alone or in adjunct with liraglutide on

Sciences, University of Modena and Reggio Emilia, Modena, Italy;²Unit of

oocyte maturity and embryo quality in infertile obese PCOS population.

Endocrinology, Department of Medicine, Endocrinology, Metabolism and

Design/participants/main outcome measure

Geriatrics, Azienda USL of Modena, Modena, Italy;³Center for Genomic

A 12-week prospective randomized study was conducted with 40 infertile PCOS

Research, University of Modena and Reggio Emilia, Modena, Italy;

(30.77G3.742 aged years, BMI 36.69G3.51 kg/m², mean G SD) who had been

⁴Department of Neuroscience, Reproductive Science and Odontostomatol-

previously poor responders to lifestyle intervention. They were assigned to

ogy, University of Naples Federico II, Naples, Italy.

metformin (MET) 1000 mg BID or MET 1000 mg BID and liraglutide 1.2 mg QD

S.C.

(COMBI) or to controls (CON). CON direclty proceeded with ovarian

stimulation protocol, whereas MET and COMBI started with stimulation after 4

Background

weeks medication free period.

Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) act on the

Results

same receptor, activating different signal transduction pathways. The role of LH

Eleven women on MET, 13 on COMBI and 11 CON completed the study.

or hCG addition to follicle stimulating hormone (FSH) as well as menopausal

Patients in MET lost 6.70G6.70 kg (P?0.001) compared with 7.68G3.74 kg loss

gonadotropins (hMG) in controlled ovarian stimulation (COS) is debated.

in COMBI (P!0.001), COMBI not being superior to MET (PZ0.103). COMBI

Aim

resulted in a reduction of visceral adipose tissue area

(K20.65G7.40 cm²;

To compare FSHCLH, or FSHChCG or hMG vs FSH alone on COS outcomes.

PZ0.028). More than 5% of weight reduction was achieved in 76.9% in COMBI

Design

and 45.5% of patients in MET. In high responders who lost more than 5% of body

A meta-analysis according to PRISMA statement and Cochrane Collaboration

weight numbers of blastocysts/patient were greater in both treatment arms than in

was performed, including prospective, controlled clinical trials published until

CON (3.67G4.82 in COMBI; 3.60G6.95 in MET; vs 2.09G2.07 in CON). High

July 2016, enrolling women treated with FSH combined with other gonado-

responders in COMBI had the highest numbers of oocytes/patient 14.67G9.59

tropins. Trials enrolling women with polycystic ovarian syndrome were excluded.

and of mature oocyte 11.22G9.27 (PZNS). In COMBI 3 patients became

Results

spontaneously pregnant before IVF in medication free period.

Considering 70 studies, the administration of FSH alone resulted in higher

Conclusion

number of oocytes retrieved than FSHCLH or hMG. The MII oocytes number did

Women who lost more than 5% of body weight before IVF had increased fertility

not change when FSH alone was compared to FSHCLH, FSHChCG or hMG.

potential. COMBI resulted in the highest number of high responders and was

Embryo number and implantation rate were higher when hMG was used instead

associated with the highest number of blastocysts/patient. The high rate of

of FSH alone. Pregnancy rate was significantly higher in FSHCLH-treated group

spontaneous pregnancies in COMBI implies the potential role of GLP-1 in

versus others. Only twelve studies reported live birth rate, not providing protocol-

reproduction.

dependent differences. Patients’ stratification by age (medianZ32.5 years) and/or

DOI: 10.1530/endoabs.49.EP1105

by GnRH agonist/antagonist identified patient subgroups benefiting from specific

drug combinations.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

cigarette smoke extract

(CSE) affects the cell proliferation, migration and

In COS, FSH alone results in higher oocyte number. However, hMG improves the

endocrine hormone activity of JEG-3 human placental cancer cells. JEG-3 cell

collection of mature oocytes and embryos and increases implantation rate,

proliferation was significantly reduced by all CSEs in a concentration-dependent

although the final increased pregnancy rate is evident only in GnRH agonist

manner. Moreover, CSEs decreased proliferating cell nuclear antigen (PCNA)

protocol. On the other hand, LH addition leads to higher pregnancy rate. This

levels in JEG-3 cells in western blot. Increased migration or invasion ability of

study supports the concept of a different clinical action of gonadotropins in COS,

JEG-3 cells following CSE treatment was also confirmed by a scratch or

reflecting previous in vitro data.

fibronectin invasion assay in vitro. Additionally, protein levels of E-cadherin as

DOI: 10.1530/endoabs.49.EP1107

an epithelial maker were down-regulated, while the mesenchymal markers

N-cadherin, snail and slug were up-regulated in a time-dependent manner. The

metastasis marker, cathepsin D, was also down-regulated by CSE. Finally, CSEs

significantly reduced the expression of hCG-b protein in JEG-3 cells. Overall,

these results indicate that exposure of placental cells to CSE deregulates the cell

cycle by altering the expression of cell cycle-related proteins and stimulates cell

metastatic ability by altering EMT markers and cathepsin D expression. CSE

exposure may also decrease hCG-b production as an endocrine marker, implying

that cigarette smoke has adverse effects during pregnancy. (This research was

EP1108

supported by a grant (14182MFDS977) from the Ministry of Food and Drug

May thiol/disulfide homeostasis predict adult PCOS?

Safety, Republic of Korea, in 2016.)

Hakan Sevimli¹, Cemile Koca², Mahmut Senyurt¹, Ozcan Erel²,

Keywords: Cigarette smoke extract, placental cells, cell cycle, metastasis, human

Esra Laloglu³ & Ayse Carlioglu¹

chorionic gonadotropin beta subunit

¹Regional Training and Research Hospital, Erzurum, Turkey;²Yildirim

DOI: 10.1530/endoabs.49.EP1109

Beyazit University Faculty of Medicine, Ankara, Turkey;³Public Health

Laboratory, Erzurum, Turkey.

Purpose

The purpose of this study was to evaluate the relation polycystic ovarian syndome

(PCOS) and the thiol/disulfide balance, used as a marker of oxidative stress, by

measuring that exchange using a novel technique.

Material/methods

EP1110

Fourty nine subjects diagnosed with PCOS and 44 healthy were included in the

Hyperandrogenism and overweight/obesity, independently and inter-

study. Thiol/disulfide homeostasis concentrations were measured by a newly

actively, increase the risk of metabolic syndrome and type 2 diabetes in

developed method. After native thiol, total thiol and disulfide levels were

women - a Prospective, Population-based Cohort Study

determined; measures such as disulfide/native thiol, disulfide/total thiol, and

Meri-Maija Ollila¹, Kari Kaikkonen², Sirkka Keinanen-Kiukaanniemi^3,4,

native thiol/total thiol were calculated.

Katri Puukka⁵, Aimo Ruokonen⁵, Marjo-Riitta Järvelin^3,6,

Results

Juha Tapanainen^1,7, Steve Franks⁸, Terhi Piltonen¹ &

Lipid accumulation product

(LAP) index

(P!0.001), total testesterone

Laure Morin-Papunen¹

(P!0.001), insulin

(PZ0.003), total cholesterol

(PZ0.02), triglyceride

¹Department of Obstetrics and Gynaecology, University of Oulu and Oulu

(PZ0.004), disulfide (PZ0.007), disulfide/native thiol ratio

(P!0.001) and

University Hospital, Medical Research Center, PEDEGO Research Unit,

disulfide/total thiol ratio (P!0.001) were significantly higher and native thiol

Oulu, Finland;²Division of Cardiology, Department of Clinical Medicine,

(PZ0.01), total thiol (PZ0.04) and native thiol/total thiol ratio (P!0.001) were

Medical Research Center, University of Oulu and Oulu University Hospital,

sig-nificantly lower in patients with PCOS compared to control subjects.

Oulu, Finland;³Institute of Health Sciences, University of Oulu, Oulu,

Correlation analysis reveals negative correlation of FGS, cycles, WC, LH: FSH

Finland;⁴Unit of General Practice, Oulu, Finland;⁵NordLab Oulu,

ratio and Tg with native thiol and total thiol in cases. Also there was a significant

Department of Clinical Chemistry, University of Oulu and Oulu University

negative correlation between LAP index, BMI and native thiol. DHEA-S had a

Hospital, Medical Research Center Oulu, Oulu, Finland;⁶Department of

positive correlation between disulphide. Stepwise logistic regression model

Epidemiology and Biostatistics, MRC-PHE Centre for Environment and

showed that significantly high disulfide levels, disulfide/native thiol ratio and

Health, School of Public Health, Imperial College London, London, UK;

disulfide/total thiol ratio in patients with PCOS were found to be independent of

⁷Department of Obstetrics and Gynaecology, University of Helsinki and

age and BMI. Receiver operating characteristic curve analysis showed that areas

Helsinki University Hospital, Helsinki, Finland;⁸Institute of Reproductive

under the curve for native thiol, total thiol, native thiol/total thiol ratio and

and Developmental Biology, Imperial College London, London, UK.

disulfide, disulfide/native thiol ratio, disulfide/total thiol ratio were

0.660

(PZ0.008),

0.601

(PZ0.096),

0.714

(P!0.001),

0.663

(PZ0.007),

0.701

(PZ0.001), 0.701 (PZ0.001), respectively.

The significance of hyperandrogenism (HA) as a metabolic risk factor in women

Conclusion

is controversial. HA can be defined as either clinical (hirsutism) or biochemical

It can be concluded that oxidative stress is increased in patients with PCOS, can

(elevated androgen levels). We aimed to investigate whether HA at age 31

play a pathophysiological role in the development of PCOS and this increase is

associates with metabolic syndrome (MetS), type 2 diabetes mellitus (DM2) or

not associated age and BMI. However, studies with larger sample sizes are needed

carotid intima media thickness (CIMT) by age 46. In a prospective, general

in this area.

population-based follow-up birth cohort (nZ5889 women) blood samples were

DOI: 10.1530/endoabs.49.EP1108

collected at age 31 in 3127 women and at age 46 in 3280 women. HA was defined

as presence of hirsutism, serum testosterone O2.3 nmol/l

(determined by

LC-MS/MS) or free-androgen-index (FAI) O5.6 at age 31. MetS was defined

according to IDF criteria. An oral glucose tolerance test (OGTT) was performed

at age 46 in 2780 women. Glucose metabolism was defined according to the

WHO standards. Diagnosis of DM2 was also verified and completed from the

national drug and hospital discharge registers. Regression models were used to

study if HA associates with cardiovascular risk factors at age 46. As expected,

EP1109

women with HA had significantly greater BMI at age 46 (27.54G6.2 vs 26.58G

Effects of cigarette smoke extracts on proliferation, migration, and

5.23 kg/m², PZ0.018), compared to controls. HA at age 31 was significantly

hCG-b protein expression of JEG-3 human placental cancer cells

associated with MetS (ORZ1.5, 95%CI: 1.1-2.0) and DM2 (ORZ3.1, 95%CI:

Cho-Won Kim, Hae-Miru Lee & Kyung-Chul Choi

1.8-5.2) at age 46. The significance remained in the multivariate regression

Laboratory of Biochemistry and Immunology, College of Veterinary

analysis including BMI at age 31 (for MetS: HA: ORZ1.4, 95%CI: 1.1-2.0;

Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic

BMI: ORZ4.0, 95%CI: 3.1-5.2; for DM2: HA: ORZ2.7, 95%CI: 1.6-4.6; BMI:

of Korea.

ORZ4.1, 95%CI: 2.4-7.0). There were no significant differences in the CIMT

between women with HA compared to controls. These results indicate that HA

Maternal smoking during pregnancy is known to be related to adverse pregnancy

per se may increase the prevalence of MetS and DM2 in a general population.

results associated with trophoblast proliferation and cell cycle progression.

However, BMI seems to have a greater impact on the presence of these metabolic

Moreover, many previous studies have shown that cigarette smoke is correlated

risks, with two-fold higher odds ratios than HA.

with human chorionic gonadotropin beta

(hCG-b) subunit produced from

DOI: 10.1530/endoabs.49.EP1110

syncytiotrophoblasts during pregnancy. Thus, we further investigated whether

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1111

Conclusion

Our study suggests that S1PRs play a role in ovarian follicle growth and oocyte

Natural history of the Swyer Syndrome

maturation.

Katarzyna Doroszewska¹, Tomasz Milewicz¹, Marta Kialka¹ &

Sandra Mrozinska²

DOI: 10.1530/endoabs.49.EP1112

¹Department of Gynecological Endocrinology UJ CM, Cracow, Poland;

²Department of Metabolic Diseases UJ CM, Cracow, Poland.

We present a case of a eighteen-year-old woman admitted to the Gynecological

and Endocrinological Department because of primary amenorrhea. Physical

examination showed excessive pubic hair and clitoral hypertrophy. Laboratory

EP1113

tests showed the increased level of foliculotropina (FSH) 90 mIU/ml (normal

range 3.5-12.5 mIU/ml) and the estradiol level below 10 pmol/l (normal range

Polycystic ovary syndrome and euthyroid hashimoto’s thyroiditis:

46-607 pmol/l). An ultrasound-imaging of the abdomen and pelvis showed the

possible influence of thyroid autoantibodies

uterus of normal size and shape. Bands of connective tissues were present at the

Mustafa Utlu, Ozge Timur & Ayse Carlioglu

Regional Training and Research Hospital, Erzurum, Turkey.

site of ovaries. Because of the clinical presentation a genetic test was done which

revealed the XY karyotype. Based on the results the Swyer syndrome was

diagnosed. A hormonal substitution therapy was introduced and the surgical

Thyroid disorders and polycystic ovary syndrome (PCOS) are two of the most

removal of the streak gonads was planned because of the risk of malignancy. The

common endocrine disorders in general population. Autoimmune thyroid diseases

patient did not give consent for the operation and did not report for the follow up

are common autoimmune disorders that affect about 5% to 20% of women in

visits. Three years later, the woman reported back to the Clinic because of acute

childbearing age. In this study, we evaluate the comorbidity rate of euthyroid

pain in the lower back, dyspnoea and increasing abdominal circumference. The

Hashimoto’s Thyroiditis (HT) in PCOS patients and possible influence of thyroid

computer tomography of the minor pelvis showed the presence of lumpy mass in

autoantibodies on clinical and laboratory findings of PCOS. This study includes

the pelvic cavity. The patient underwent an operation. Intraoperatively numerous

285 PCOS patients attending to our outpatient Endocrinology Clinic at Erzurum

metastasis were found in the abdomen and pelvis. Radical hysterectomy was

Region Training and Research Hospital. The control group include 32 age and

performed. Histopathological examination of the streak gonads showed

body mass index matched healty women. In PCOS group 88 of 285 (%30.87)

dysgerminoma and gonadoblastoma on the left gonad and dysgerminoma on

patients have euthyroid Hashimato’s disease where as in control group 2 of 32

the right one. After operation the patient was given 4 cycles of chemotherapy.

(%6.25) have disease. These findings are statistically significant (PZ0.003).

This case presents the natural history of the Swyer syndrome.

None of the euthyroid Hashimato’s patients take L-thyroxine replacement therapy.

DOI: 10.1530/endoabs.49.EP1111

Anti-TPO and anti-TG were significantly higher in patients with PCOS

(PZ0.000; PZ0.01; respectively). Anti-TPO had a significantly positive

correlation between PCOS presence (rZ0.119; PZ0.036), and clinical indicators

of PCOS such as cycle time (rZ0.709; PZ0.000), Ferriman-Gallwey score (rZ

0.376; PZ0.001), DHEAS

(rZ0.132; PZ0.04), testosterone

(rZ0.124;

PZ0.043), and LH/FSH

(rZ0.136; PZ0.025). TPO was seen to be an

independent risk factor from body mass index, age and TSH in PCO patients.

EP1112

Anti-TPO and anti-Tg were also sensitive and spesific in diagnosing PCOS. AUC

value of Anti-TPO was 0.843 (PZ0.000) and Anti-Tg was 0.843 (PZ0.000). In

Biological activity mediated by sfingosine-1-phospate receptors in

ROC analysis, TPOR4.9 had 99.6% sensitivity and 71% specificity, anti TG R18

human primary granulosa cells and immortalized granulosa cell line

had 94.8% sensitivity and 75% specificity in predicting PCOS. In our study

in vitro

thyroid autoantibodies were significantly higher in patients with PCOS. We think

Livio Casarini^1,2, Giulia Fornari¹, Manuela Simoni^1,3 & Francesco Potì⁴

that thyroid autoantibodies can affect the clinical and laboratory course of PCOS.

¹Unit of Endocrinology, Department Biomedical, Metabolic and Neural

We have found that the euthyroid HT may be observed at higher rates in PCOS

Sciences, University of Modena and Reggio Emilia, Modena, Italy;²Center

patients, independent of the thyroid function tests.

for the Genomic Research, University of Modena and Reggio Emilia,

Keywords: polycystic ovary syndrome, Hashimoto’s Thyroiditis, thyroid

Modena, Italy;³Azienda Ospedaliero-Universitaria di Modena, Modena,

autoantibodies

Italy;⁴Department of Neurosciences, University of Parma, Parma, Italy.

DOI: 10.1530/endoabs.49.EP1113

Introduction

Sphingosine-1-phosphate (S1P) is a sphingolipid mediating proliferative signals

in human ovarian follicles, acting through five receptors

(S1PR1-5). We

characterized the effects of S1PR1 and S1PR3 in vitro, as those mostly expressed

in human primary granulosa cells

(hGLC) and immortalized, tumor-like

granulosa cell line (hGL5).

Methods

The S1P-mediated signaling, as well as the activity of S1PR1- and S1PR3-specific

agonists (SEW281 and CYM5541, respectively), was evaluated in hGLC and

EP1114

hGL5 cells. Dimethyl-sulfoxide-, cholera toxin- and phorbol-12-myristate-

Novel insulin resistance index using C-peptide is reliable predictor of

13-acetate

(PMA)-treatments served as controls. The kinetics of pERK1/2,

insulin resistance in women with PCOS

pAKT and pCREB activation were evaluated over 2 h by Western blotting, while

Ivana Bozic-Antic¹, Dusan Ilic¹, Jelica Bjekic-Macut²,

total cAMP production was measured by ELISA. The downstream cell viability

Danijela Vojnovic-Milutinovic³, Sanja Ognjanovic¹, Tamara Bogavac¹,

was measured by MTT assay over 72 h, GFSH. Differences were significant for

Bojana Popovic¹, Tatjana Isailovic¹, Valentina Elezovic¹,

P!0.05 (two-way Anova; nZ2-12).

Olivera Stanojlovic⁴ & Djuro Macut¹

Results

¹Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of

Dose-response experiments revealed that 0.1 mM S1P, 1.0 nM SEW2871 and

Medicine, University of Belgrade, Belgrade, Serbia;²CHC Bezanijska

1.0 nM CYM5541 are the most effective concentrations, in terms of pERK1/2 and

Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia;

pAKT activation. In hGLC, pERK1/2 activation occurs within 5-60 min by S1P,

³IBISS, University of Belgrade, Belgrade, Serbia;⁴Institute of Physiology,

and, in a lesser extent, within 15-30 min by SEW2871 and CYM5541. In hGL5

Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

cells, SEW2871- and CYM5541-dependent pERK1/2 activation is prolonged

until

2 h. We describe for the first time S1P- and, to a lesser extent,

SEW2871/CYM5541-mediated pCREB activation in both cell models, occurring

Introduction

in spite of no pAKT and cAMP recruitment. All the agonists increased cell

Recently, it was suggested that insulin resistance index using C-peptide (CIR)

viability in hGL5 cells, an effect reverted in the presence of 50 nM FSH. Only S1P

could be a better marker of insulin resistance than homeostasis model assessment

mediated anti-apoptotic effects in hGLC, while the treatment by SEW2871 and

(HOMA-IR) in patients with type 2 diabetes mellitus. The aim of this study was to

CYM5541 impacts negatively cell viability.

investigate performance of CIR index in PCOS subjects.

Discussion

Methods

We found S1PRs-mediated cAMP-independent steroidogenic potential and

We evaluated 187 PCOS women (PCOS: 25.38G6.32 kg/m²; 26.01G5.16 years)

different signaling kinetics in hGLC and hGL5 cells, revealing opposite effects

diagnosed using ESHRE/ASRM criteria and

42 healthy women (Controls:

on the downstream cell signaling, depending on the cell model.

22.56G5.46 kg/m²; 28.33G5.62 years). In follicular phase of menstrual cycle

total testosterone, SHBG, lipids, glucose, insulin and C-peptide were determined.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Novel CIR index (20/(fasting C-peptide!fasting plasma glucose)) and HOMA-

EP1116

IR (fasting plasma glucose! fasting insulin)/22.5 were calculated in all subjects.

Hirsutism in reproductive aged Korean women

Euglycaemic hyperinsulinemic clamp (EHC) was performed in PCOS group and

Yeon Ah Sung¹, Sei Hyun Baik² & Dong Sun Kim³

the whole body disposal rate (M, mg/kg per min) was determined as the mean of

¹Ewha Womans University School of Medicine, Seoul, Republic of Korea;

the glucose infusion rate during the last 30 min of EHC. Insulin sensitivity index

²Korea University College of Medicine, Seoul, Republic of Korea;

(M/I) was calculated by dividing M by the steady state plasma insulin level during

³Hanyang University College of Medicine, Seoul, Republic of Korea.

the last 30 min of EHC. All analyses were adjusted for BMI and age.

Results

In comparison to controls, PCOS had significantly lower CIR index (14.72G2.21

Hirsutism, excessive terminal hair growth in a male-like pattern as a marker of

vs 9.65G1.02, respectively; PZ0.040) and higher HOMA-IR (2.91G0.36 vs

hyperandrogenism, affects 5-10% of reproductive-age women worldwide. The

3.70G0.16, respectively; PZ0.047). CIR index strongly correlated with HOMA-

frequency of hirsutism seems to decrease in Asians and the lower cut-off modified

IR (rZK0.447, P!0.001), M/I (rZ0.461, P!0.001), BMI (rZK0.381,

hirsutism score is suggested. We performed the study to estimate the frequency,

P!0.001) and waist circumference (WC)(rZK0.335, P!0.001). HOMA-IR

bio-metabolic characteristics, correlates and determinants of hirsutism in

correlated with M/I (rZK0.404, P!0.001), BMI (rZ0.349, P!0.001), WC

reproductive aged Korean women. A total of

2682

female volunteers of

(rZ0.348, P!0.001) and, unlike CIR index, also with SHBG (rZK0.411,

reproductive age (15-39 years) were recruited for the genetic study of PCOS.

P!0.001).

Menstrual history was taken and hirsutism was diagnosed when modified

Conclusion

Ferriman-Gallway

(mFG) score S8 was noted. Anthropometric features,

Novel CIR index could be a good surrogate marker of IR in PCOS. The absence of

hormones (total testosterone, SHBG, 17OH progesterone, prolactin, and TSH)

liver clearance of C-peptide is the reason for stronger correlation of CIR index

and metabolic parameters (glucose, insulin and lipids) in blood were measured.

with M/I in comparison to HOMA-IR.

The frequency of hirsutism is 133 (4.96%) in a total 2682 subjects. Fifty nine %

DOI: 10.1530/endoabs.49.EP1114

(1582) of subject had m-FG score of zero; 30.0% (805) had m-FG score between 1

and 4; 6.0% (162) were between 5 and 7. The m-FG values of 25th, 50th, 75th,

and 95th percentiles were 0, 0, 2, and 7 respectively. m-FG score significantly

correlated to age, waist circumference, serum total and free testosterone, SHBG,

postprandial plasma glucose, fasting and postprandial plasma insulin, and

HOMA-IR. Logistic regression analysis showed younger age, increased fasting

insulin and free testosterone levels were associated with mFG score. In conclusion

the estimated frequency of hirsutism among reproductive aged Korean women

was 4.96%, which is comparable to other races. Hirsutism is associated with

fasting plasma insulin, serum free testosterone level and younger age.

EP1115

DOI: 10.1530/endoabs.49.EP1116

Omentin-1, a potential link between chronic low grade inflammation,

metabolic and reproductive features of polycystic ovary syndrome

Soulmaz Shorakae^1,2, Sally Abell^1,2, Barbora de Courten^1,2,

Gavin Lambert^3,4, Danielle Hiam⁵, Nigel Stepto^1,5, Eveline Jona¹,

Lisa Moran¹ & Helena Teede^1,2

¹Monash Centre for Health Research and Implementation, Monash

EP1117

University, Melbourne, Australia;²Diabetes and Vascular Medicine Unit,

Monash Health, Melbourne, Australia;³Human Neurotransmitters Labora-

Pharmacokinetics and bioavailability of non-polar phytocomponents of

tory, Baker IDI Heart & Diabetes Institute, Melbourne, Australia;

Aloe vera gel and their role as an endocrine modulator in letrozole

⁴Department of Physiology, Monash University, Melbourne, Australia;

induced PCOS rat model

⁵Institute of Sport Exercise and Active Living (ISEAL), Victoria University,

Arpi Dey, Shweta Vasoya & Laxmipriya Nampoothiri

Melbourne, Australia.

The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.

Background

Background and aim

Polycystic ovary syndrome

(PCOS) is associated with features linked to

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in

metabolic syndrome including visceral adiposity, dyslipidemia and impaired

women of reproductive age with an estimated prevalence of 5-10%, is one of the

glucose homeostasis. Adipose tissue produces adipocytokines which contribute to

most common causes of female infertility. The therapeutic options for PCOS are

regulation of insulin sensitivity and reproduction. Omentin-1 is an adipokine with

limited. Thereby, traditional knowledge of Ayurveda has been exploited to

anti-inflammatory and insulin sensitizing roles produced by adipocytes. The exact

identify an herbal therapeutic target for PCOS. Pharmacokinetic (PK) studies on

role of mentin-1 in PCOS remains unclear as studies have reported reduced or

bioactive constituents of herbal drugs provide valuable information on bio-

unchanged levels in PCOS.

transformed metabolites, dosage form, doses and potential herb-drug

Methods

interactions. Thereby, the aim of the study was to study the pharmacokinetics

To determine the relationships between PCOS status, adipocytokines including

and bioavailability of the non-polar phytocomponents of Aloe vera gel and their

omentin-1 and etiological features of PCOS we measured serum omentin-1,

role as an endocrine modulator in PCOS pathology.

interleukin-6 (IL-6), high sensitivity CRP (hs-CRP), androgens, SHBG, fasting

Methodology

glucose and insulin levels in an observational study of community recruited

PCOS was induced in rat using letrozole and validated for structural and

PCOS and controls.

metabolic characteristics of PCOS. Blood and tissues

(ovaries, adrenal,

Results

hypothalamus, pituitary, uterus and liver) were collected upto

48 h after

49 women with PCOS (age 29.8G5.9 years, BMI: 29.0G5.4 kg/m²) and 25

petroleum ether extract of dried Aloe vera gel (1.0 g) were administered orally

healthy controls (age 37.6G7.8 years, BMI: 28.9G4.0 kg/m²) were recruited.

to rats. Metabolites of Phytosterols were identified using GC/MS and quantified

Homeostatic model assessment for insulin resistance (HOMA-IR) (PZ0.006),

using HPLC. Progesterone and estradiol were analysed using ELISA.

free androgen index (FAI) (PZ0.01) and Ferriman-Galway score (P!0.001)

Steroidogenic enzymes as well as important enzymes responsible for

were higher in PCOS. Women with PCOS had lower omentin-1 (median (IQR):

biotransformation were evaluated along with the toxicity parameters.

68.76(67.17) vs 112.45(67.42)) (PZ0.005) independent of obesity. Omentin-1

Results

correlated significantly with hs-CRP, IL-6, HMW-adiponectin, BMI, percentage

PCOS animals demonstrated altered estrus cyclicity, serum testosterone levels

of body fat, insulin, low density lipoprotein (LDL), triglycerides and total ovarian

and oral glucose tolerance test profile when compared to controls. An increase in

volume in women with PCOS. Multiple regression analyses revealed omentin-1

the estradiol (P!0.01) and progesterone levels (P!0.05) were observed in the

was explained by triglycerides (Beta: K0.177, PZ0.03) and total ovarian volume

plasma after

24 h. Several phytosterols and their modified oxysterols were

(Beta: K0.009, PZ0.025).

identified in the plasma and tissues which could be well-correlated with the

Conclusion

functional changes observed in hormone profile.

Omentin-1

is significantly lower in women with PCOS and correlates

Conclusion

significantly with other inflammatory markers, metabolic parameters and total

This study elucidates the bioavailability and functionality of phytosterols/

ovarian volume. This finding suggests omentin-1 as a potential link between

oxysterols obtained from Aloe vera gel towards management of PCOS. This study

metabolic and reproductive features of PCOS and chronic low grade

will be helpful in identification of a naturally derived drug target and add to its

inflammation.

economic viability at national and international level.

DOI: 10.1530/endoabs.49.EP1115

DOI: 10.1530/endoabs.49.EP1117

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1118

clinical symptoms of hyperandrogenism was observed - hirsutism, assessed

according to the Ferriman-Gallwey scale, as compared to the control group

Influence of peroxisome proliferator-activated receptor (PPAR)-g exon

(PZ0.048). Full-blown PCOS was diagnosed in 6.52% of the girls from the study

(Pro12Ala) and exon 6 (His447His) and Gly972Arg insulin receptor

group, whereas none of the patients from the control group met all the criteria for

substrate (IRS)-1 polymorphisms on insulin resistance (IR) and beta cell

the diagnosis of PCOS (P!0.05). There were no significant differences in plasma

function in Southern Mediterranean women with polycystic ovary

concentrations of leptin, adiponectin and apelin-36 between the study and control

syndrome (PCOS)

groups.

Giuseppina T Russo¹, Maria Angela Pappalardo², Annalisa Giandalia¹,

Conclusions

Elisabetta L Romeo¹, Angela Alibrandi³, Flavia Di Bari¹, Roberto Vita¹,

Hormonal disorders such as hyperprolactinemia, hyperandrogenaemia and PCOS

Domenico Cucinotta¹ & Salvatore Benvenga^1,4

are more frequently diagnosed in girls with oligomenorrhea. In girls with

¹Department of Clinical and Experimental Medicine, University of Messina,

oligomenorrhea, elevated levels of leptin and decreased levels of adiponectin may

Messina, Italy;²Centro Polispecialistico Rizzo, Torregrotta, Messina, Italy;

be considered as new biomarkers for insulin resistance and hyperandrogenaemia.

³Department of Economicsm University of Messina, Messina, Italy;

⁴Interdepartmental Program of Molecular and Clinical Endocrinology, and

DOI: 10.1530/endoabs.49.EP1119

Women’s Endocrine Health, University hospital Policlinico G. Martino,

Messina, Italy.

The Pro12Ala and His447His polymorphisms of PPAR-g, and Gly972Arg

polymorphism of IRS-1 have been implicated in insulin resistance (IR) and

adiposity. In this study, we investigated the possible influence of these

polymorphisms on metabolic features of 53 PCOS women compared with 26

EP1120

healthy women (controls). All women underwent a clinical, anthropometric and

Global methylation pattern and endocrine-metabolic profile during

biochemical evaluation, including a 75-g oral glucose tolerance test; insulin

early infancy and puberty in sons born to women with polycystic ovary

secretion and sensitivity indices were calculated. In the two groups, frequencies of

syndrome (PCOS)

PPARg polymorphisms did not differ from those predicted by the Hardy-

Teresa Sir-Petermann¹, Nicolas Crisosto¹, Barbara Echiburu¹,

Weinberg equilibrium. Instead, the IRS-1 Gly972Arg allele was significantly

Manuel Maliqueo¹, Francisco Perez-Bravo², Daniel Sandoval³ &

more frequent in the PCOS group compared to controls. The frequency of

Sergio Recabarren³

different allelic combinations was unequal in the two groups, with IRS1^C/ex-

¹Laboratory of Endocrinology and Metabolism, University of Chile,

on2^K/exon6^K detected in 66% of PCOS and IRS-1^K/exon2^K/exon6^K in 73% of

Santiago, Chile;²Nutrigenomic Laboratory, Department of Nutrition,

controls. In PCOS women, the IRS-1 Gly972Arg allele was associated with lower

University of Chile, Santiago, Chile;³Laboratory of Animal Physiology and

E₂

levels

(PZ0.030), while the PPARg Pro12Ala allele with lower free-

Endocrinology, University of Concepcion, Concepcion, Chile.

testosterone levels

(PZ0.021). No other relationships were noted. When

compared with wild-type women, in PCOS group, IR was: 1) trendwise greater

in carriers of the variant allele in IRS-1 gene (borderline higher HOMA-IR,

Prenatal and postnatal environment can regulate gene expression through multiple

insulinogenic and disposition indices); 2) trendwise lower in carriers of the

epigenetic mechanisms, being DNA methylation among the most relevant.

variant PPAR-g exon6 allele (lower HOMA-IR and higher Matsuda index, lower

Metabolic and reproductive function may be modified by this mechanism. Sons

insulinogenic and disposition indices); 3) lower (P!0.01) in carriers of the

born to women with PCOS show altered markers of metabolic and reproductive

PPAR-g exon2 variant (lower HOMA-IR values and higher insulinogenic and

function during childhood and adulthood. However, these functions have not been

disposition indices). Furthermore, within the IRS-1^C/PPAR-g-exon2^K PCOS

studied during puberty. The aim of the present study was to assess the global

women, PPAR-g- exon6^C women had higher Matsuda index

(PZ0.03)

methylation pattern and its possible association with anthropometrics, endocrine

compared with the noncarriers

(PPAR-g-exon6^K). Our data support the

and metabolic variables in a cohort of early infants and peripubertal boys born to

protective influence of PPAR-g-exon2 and exon6 variants on IR and beta-cell

women with PCOS. Global DNA methylation was measured from blood

function, whereas IRS-1 polymorphism is associated with a more unfavorable

leucocytes, in 21 sons born to control women (C-Sons) and 15 born to women

metabolic profile. However, these associations do not fully explain the high

with PCOS (P-Sons) at early infancy (2-3 months old). In addition, 50 P-Sons (12

metabolic risk PCOS-associated.

prepubertal (Tanner I), 28 pubertal (Tanner II-IV) and 10 late pubertal (Tanner

V)) and 61 C-sons (13 prepubertal, 30 pubertal and 18 late pubertal) were studied.

DOI: 10.1530/endoabs.49.EP1118

Weight, height and waist circumference were determined. A 75-gr oral glucose

tolerance test with insulin and glucose measurements was performed. HOMA-IR

and ISI composite were calculated. In the fasting sample circulating AMH,

17-OH-Progesterone, androstendione, testosterone, estradiol and lipids were

measured. P-Sons showed lower global methylation at early infancy (PZ0.027),

whereas at pubertal age a higher global methylation was found (PZ0.035). No

differences were observed during pre and late puberty. At early infancy, no

EP1119

differences were observed in anthropometric variables between C-Sons and

Hormonal disturbances and adipokines levels in girls with

P-Sons. In prepubertal age, fasting and 120-min glucose were higher in P-sons

oligomenorrhea

compared to C-Sons (PZ0.038 and 0.046, respectively). At puberty, waist

Violetta Skrzypulec-Plinta, Agnieszka Drosdzol-Cop & Dominika Sajdak

circumference and androstenedione levels were higher (PZ0.032 and 0.006,

Medical University of Silesia in Katowice, Katowice, Poland.

respectively) and cholesterol tended to be higher (PZ0.06) in P-Sons compared

to C-Sons. At late puberty, no differences were observed between groups. These

results suggest that the methylation pattern can be modified from early infancy to

Aim

the pubertal age in sons born to PCOS women. During puberty, global

The aim of this study was to evaluate hormonal disturbances and adipokines

methylation increased concomitantly with circulating androstendione levels and

levels in girls with oligomenorrhea.

waist circumference suggesting that the endocrine and metabolic milieu may be

Materials and methods

associated with DNA methylation in these boys.

The study comprised a group of 46 girls, aged 16-18 years, who were diagnosed

with oligomenorrhea, and a control group with 37 healthy girls, aged 16-18 years,

DOI: 10.1530/endoabs.49.EP1120

with no diagnosed menstrual disorders. In the first stage of the study, all girls had

their medical history assessed. Subsequently, anthropometric measurements

(height, weight) were measured, severity of hirsutism -according to the Ferriman-

Gallwey score - was assessed and a pelvic ultrasound was conducted. In the blood

serum, the following parameters were determined: LH, FSH, estriadol, TSH,

SHBG, total and free testosterone, androstenedione, DHEA-S, prolactin, insulin

and glucose. Assessment of adipokines in plasma included: leptin, adiponectin

and apelin-36. Insulin resistance was assessed using the indirect method, setting

EP1121

HOMA-IR and on the basis of a standard model, free androgen index (FAI) was

Natural history of autoimmune primary ovarian insufficiency

also calculated.

progresses through several stages from normal ovary function to

Results

clinically overt ovary dysfunction

The incidence of hyperprolactinemia in the study group is 32%, while there was

Giuseppe Bellastella¹, Ofelia Casciano¹, Mariluce Barrasso¹,

no disturbance among any of the girls from the control group. Furthermore,

Maria Ida Maiorino¹, Dario Giugliano¹, Katherine Esposito²,

among the group of girls with oligomenorrhea, a significantly greater increase in

Lorenzo Scappaticcio¹ & Annamaria De Bellis¹

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Endocrinology and Metabolic Diseases Unit, Department of Medical,

Conclusion

Surgical, Neurological, Metabolic Sciences and Aging, University of

Our study indicate that no association between E2 levels and existence of benign

Campania ‘L. Vanvitelli’, Naples, Campania, Italy;²Diabetes Unit,

lesions in different organs according to the radiologic investigations in

Department of Medical, Surgical, Neurological, Metabolic Sciences and

premenopausal women. And, TSH levels were found related to upper BIRADS

Aging, University of Campania, ‘L. Vanvitelli’, Naples, Campania, Italy.

grades in premenopausal women.

DOI: 10.1530/endoabs.49.EP1122

Context

Women with autoimmune Addison’s disease with normally ovulatory cycles but

positive for steroid cells antibodies

(StCA) have been considered at risk of

premature ovarian insufficiency (POI).

Design

Thirty-three women younger than 40 years, with subclinical-clinical Addison’s

disease but with normally ovulatory menses, were followed-up for 10 years to

EP1123

evaluate the long-term time-related variations of StCA, ovarian function and

Heterogeneous hCG and hMG commercial preparations result in

follicular reserve. All patients and 27 control women were investigated at start

biased intracellular signaling but induce similar progesterone response

and every year for the presence and titer of StCA (by indirect immunofluores-

in vitro

cence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian

Laura Riccetti¹, Danièle Klett², Mohammed Akli Ayoub^2,3, Thomas Boulo²,

function along four consecutive menses every year.

Julie Mariot², Elisa Pignatti^1,4, Simonetta Tagliavini⁵, Manuela Varani⁵,

Results

Tommaso Tranti⁵, Alessia Nicoli⁶, Giovanni Battista La Sala⁶,

At start of the study StCA were present in 16 women (group 1), at low/middle titer

Yves Combarnous², Eric Reiter², Manuela Simoni^1,5 & Livio Casarini^1,4

(%1:32) in seven of them (43.75%, group 1A), at high titer (O1:32) in the

¹Unit of Endocrinology, Department Biomedical, Metabolic and Neural

remaining nine patients (group 1B, 56.2%), while they were absent in 17 patients

Sciences, University of Modena and Reggio Emilia, Modena, Italy;

(group 2). During the follow-up period, all women in group 1A persisted StCA

²Biologie et Bioinformatique des Systèmes de Signalisation (BIOS) group,

positive at low/middle titer with normal ovulatory menses and normal

INRA, UMR85, Unité Physiologie de la Reproduction et des Comporte-

gonadotropin and AMH levels, while all patients in group 1B showed a further

ments; CNRS, UMR7247, F-37380 Nouzilly, Nouzilly, France;³Biology

increase of StCA titers (1:128-1:256) and progressed through three stages of

Department, College of Science, United Arab Emirates University, Al Ain,

ovarian function. None of patients in group 2 and controls showed appearance of

United Arab Emirates;⁴Center for Genomic Research, University of

StCA or ovary dysfunction during the follow-up.

Modena and Reggio Emilia, Modena, Italy;⁵Azienda Ospedaliero-

Conclusions

Universitaria di Modena, Modena, Italy;⁶Unit of Obstetrics and

The presence of StCA at high titers could be considered a good predictive marker

Gynecology, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.

of subsequent development of autoimmune POI. To single out the stages of

autoimmune POI may allow a timely therapeutic choice in subclinical and early

Human chorionic gonadotropin (hCG) is the pregnancy hormone marketed as a

clinical stage.

drug for assisted reproduction technologies to support follicle-stimulating

DOI: 10.1530/endoabs.49.EP1121

hormone action. Several hCG formulations are commercially available, differing

in source, purification methods and biochemical composition. In this study, we

investigated the molecular features and the intracellular signaling mediated by

five urinary and recombinant hCGs. The drug comparisons were performed by

quantifying the hormones by immunoassay, calibrated against the hCG standard

(5^th IS; NIBSC

07/364). Immunoreactivity pattern, isoelectric point and

oligosaccharide content of hCGs were evaluated by reducing and non-reducing

Western blotting, capillary isoelectric-focusing immunoassay and lectin-ELISA,

respectively. Functional studies were performed in order to evaluate intracellular

and total cAMP, progesterone production, as well as b-arrestin two recruitment by

EP1122

ELISA and BRET, in both human primary granulosa lutein cells (hGLC) and

LH/hCG receptor (LHCGR)-transfected HEK293 cells stimulated by increasing

Relationship between anabolic hormones and benign lesions in different

hormone doses. Heterogeneous profiles were found among preparations,

organs in premenopousal women

revealing hormone-specific molecular weight patterns

(20-75 kDa range),

Zeynep Nilufer Tekin¹, Berçem Ayçic¸ek1 & Tuna Demirba¸2

isoelectric points (4.0-9.0 pI range) and lectin binding (Two-way ANOVA and

¹Darıca State Hospital, Kocaeli, Turkey;²Tekirdag˘ State Hospital,

Bonferroni post-test; P!0.05; nZ5). These drug-specific compositions are

Tekirdag˘, Turkey.

linked to different potencies on cAMP production (EC₅₀ 1.0-400 ng/ml range)

and partial agonism on b-arrestin 2 recruitment (EC₅₀ 0.03-2.0 mg/ml) in hGLC

Objective

and transfected HEK293 cells (Mann-Whitney’s U test; P!0.05; nZ3 or 5).

We aim to detect co-occurence of uterine myomas, thyroid nodules and breast

However, the treatment of hGLC with hCGs resulted in similar progesterone

lesions in premenoposual women with menstruel disorders and investigate

production after 24 h of exposure (Mann-Whitney’s U test; PR0.05; nZ3).

association between these benign tumors with anabolic hormon levels.

Therefore, although hCG preparations consist of different glycosylated isoforms

Design

and mediate drug-specific early signaling, they result in similar downstream

Records of 8008 premenopausal women were analyzed who had been admitted to

steroidogenesis in vitro. Commercial gonadotropins calibration relies on their

the hospital for routine breast image investigation which was performed by the

in vivo activity (Pharmacopea), which can be reached with different mixtures of

same radiologist in between 2010 and 2015.

isoforms with various half-lives and receptor binding activities. Here, we

Study and Methods

demonstrate that commercial hCG preparations, likely with different assortments

251 patients who had both Thyroid Ultasound (US), Pelvic Ultrasound (US) and

of isoforms, exhibit similar steroidogenic activity in vitro, by triggering biased

Breast Imaging Reporting and complain about menstruel disorders in the same

intracellular signaling pathways.

year, were extracted from 8008 premenapousal woman. All data were obtained

DOI: 10.1530/endoabs.49.EP1123

from file records and ICD-10 diagnosis code of electronic database of the hospital.

For breast examination, Breast Imaging Reporting and Data System (BIRADS)

terminology had been used. Tiroid stimulating hormone (TSH) and Estrodiol (E₂)

levels were recorded for investigate of situation of anabolic hormon levels, which

had been taken from premenopousal women at the time of third day of menstruel

cycle.

Results

EP1124

The mean age of the patients at the admission to the hospital was 32G5.7 years.

Etiopathogenetical aspects of endocrine infertility

From 251 patients only 9 patients had benign lesions in all three organs, whereas

Gulyamova Xilola & Ibragimova Kamilla

63 patients had both thyroid nodules and breast lesions and 5 patients had thyroid

Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan.

nodules and uterine myoma, and seven patients had BIRADS 2,3 lesions and

uterine myoma, respectively. There was only found a relationship between age

and existence of myoma uteri and thyroid nodule. (PZ0.008, for both). Only TSH

Urgency

levels were found lower in patients with BIRADS 2,3 lesions than with BIRADS

According to WHO the frequency of infertile unions is high amount 25-30% in

(PZ0.017).

developed countries. There are following reasons of infertility by women: 1) tubal

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

infertility; 2) endocrine infertility-it takes the 2^nd place among the reasons of

expression and promoter methylation of the particular CpG sites of follicle

infertility; 3) anomalies of the vagina and uterus; 4) immunological reasons, that

maturation involved genes.

are caused by sensibilisation of female organism, also there are patients, the

Keywords: GATA6, FST, Gene Expression, Promoter Methylation, Prenatal

reason of infertility of that is not ‘explainable’, when there not obvious violations

androgenisation

of reproductive system, it is called ‘unexplained infertility’ - 8-10% and an

DOI: 10.1530/endoabs.49.EP1125

emotional form of infertility.

Research aim

Studying etiological and pathogenetic mechanisms of infertility’s development

by women.

Materials and methods

Retrospective analyses of scientific literature from 2010 to 2016 years.

Results of the research

EP1126

Endocrine infertility- complex of hormonal disorders, that follow irregular

ovulation or its absence. By every 3^rd infertile woman the reason is the pathology

Graduated response to pulsatile GnRH therapy in hypothalamic

of endocrine system. These are:

1) unovulation;

2) hypothalamic-pituitary

amenorrhea

Natacha Germain^1,2, Anais Fauconnier¹, Jean-Philippe Klein^3,4,

dysfunction; 3) hyperandrogenism of ovarial or adrenal henesis; 4) function

Amelie Wargny², Yadh Khalfallah¹, Chrysoula Papastathi-Boureau¹,

disorders of thyroid; 5) estrogen and progesterone deficiency; 6) severe somathic

Bruno Estour^1,2 & Bogdan Galusca^1,2

pathology; 7) obesity; 8) resistance ovary syndrome, when there is an insensivity

¹Endocrinology Department, University Hospital of Saint Etienne, Saint

to the gonadotrophini, that stimulates an ovulation, that is manifested with

Etienne, France;²EA 7423, Jean Monnet University of Saint Etienne, Saint

amenorrhea;

9) premature menopause in younger women to

35-38

y.o;

Etienne, France;³Histology and Embryology Department, University

10) mutations of sex chromosomes. Abortions and infections, that cause tube-

hospital of Saint Etienne, Saint Etienne, France;⁴UMR INSERM 1059,

peritoneal forms of infertility among to 50% of all patients with infertility.

Jean Monnet University of Saint Etienne, Saint Etienne, France.

According to WHO more than 20% of patients with infertility have expressed

anatomical changes of fallopian tubes. Obstruction of FT we can see by 11-15%

of observing, 30% of cases-endometrioid heterotopia.

Introduction

Conclusions

Pulsatile GnRH therapy is currently used to restore LH pulse and induce

For prophylaxis of endocrine infertility: 1) preventing of child infections, chronic

physiological ovulation, with effectiveness demonstrated in all types of

tonsillitis, rheumatism;

2) preventing the developing of patholodical birth,

hypothalamic amenorrhea (HA). Anorexia nervosa (AN) is characterized by

abortion, inflammatious infections of women reproductive system; 3) proper

self-starvation-induced undernutrition leading to functional hypothalamic

maintenance of pregnancy, judicious use of hormones during the pregnancy.

amenorrhea (HA). Weight recovery does not always restore menses despite no

DOI: 10.1530/endoabs.49.EP1124

apparent clinical and biological undernutrition residual signs. Only few specific

studies on persistent amenorrheic weight-recovered AN (Rec-AN) have evaluated

pulsatile GnRH therapy, including small number and under nourished patients.

Comparison data on hormonal response of the different causes of HA (weight-

recovered AN, primary and secondary HA non-related to eating disorders) is also

lacking. Therefore, this study was designed to evaluate hormonal and clinical

responses to GnRH pulsatile treatment in three groups of HA patients: weight-

EP1125

recovered anorexia nervosa patients

(Rec-AN) with persistent functional

hypothalamic amenorrhea (HA), secondary and primary HA.

Prenatal androgen exposure alters gene expression and promoter

Patients and method

methylation of two ovarian follicle maturation factors

This retrospective, observational ambulatory study included

41 females: 15

Marziyeh Salehi Jahromi^1,2, Fahimeh Ramezani Tehrani¹ &

secondary HA without any eating disorders patients (SHA), seven primary HA

Jennifer W Hill³

patients (PHA), and 19 Rec-AN (BMIO 18.5 kg/m² without menses recovery),

¹Reproductive Endocrinology Research Center, Research Institute for

who underwent GnRH pulsatile therapy. Baseline Estradiol

(E), LH and

Endocrine Sciences (RIES), Shahid Beheshti University of Medical

Progesterone plasma level and their changes during induction cycles were

Sciences, Tehran, Iran;²Cellular and Molecular Endocrine Research Center,

evaluated. Ovulation, follicular recruitment and pregnancies rate were also

Research Institute for Endocrine Sciences (RIES), Shahid Beheshti

studied.

University of Medical Sciences, Tehran, Iran;³Center for Diabetes and

Results

Endocrine Research (CeDER), Department of Physiology and

Rec-AN displayed higher basal E and LH plasma levels after GnRH injection

Pharmacology, College of Medicine and Life Sciences, University of

compared to SHA and to PHA. WE observed higher E and LH levels during

Toledo, Toledo, Ohio, USA.

induction cycles in Rec-AN compared to SHA and PHA. PHA displayed the

lowest hormonal plasma levels. Follicular recruitment was higher in Rec-AN.

Background

Ovulation rate was higher in Rec-AN and SHA compared to PHA.

Follicles imaturation, as the hallmark of polycystic ovarian syndrome caused by

Conclusions

prenatal androgen exposure, is suspected to be effected through expression

This study showed increased gonadal status and higher Estradiol response to

changes of related genes. The aim of this study was to evaluate gene expression

pulsatile GnRH therapy in persistent amenorrheic weight-recovered AN

and promoter methylation of GATA6 and Follistatin (FST), two factors involved

compared to SHA and PHA. Pulsatile GnRH therapy seems less efficient in

in follicle maturation, in adult female rats prenatally exposed to androgen excess

primary hypothalamic amenorrhea.

by comparing them with non-treated rats.

DOI: 10.1530/endoabs.49.EP1126

Material and methods

Eight pregnant Wistar rats in the experimental group were treated by

subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while

controls (nZ8) received 500 ml of solvent. DNAs and RNAs were extracted from

ovarian theca cells of adult female off-springs of PNA (nZ24) and controls

(nZ24). Relative expression and promoter methylation levels were measured

using Cyber-green Real-Time PCR and bisulfite sequence PCR (BSP) methods,

EP1127

respectively.

Relationship between steroid hormones and metabolic profile in women

Results

with polycystic ovary syndrome

Compared to the control group, the relative expression of GATA6 and FST genes

Zora Lazúrová², Jana Figurová², Simona Ujházi², Jana Mašlanková¹,

in the treated group was 2.08 fold (95% CI: 1.62-2.55; P!0.0001) for GATA6

Silvia Toporcerová¹ & Ivica Lazúrová¹

and 0.85 fold (95% CI: 0.73-0.97; PZ0.058) for FST. Along with decrease in the

¹Medical Faculty, Košice, Slovakia;²University Hospital, Košice, Slovakia.

methylation percentage of 11 CpG sites of GATA6 promoter in the PNA group in

comparison with controls, the methylation of K480 position, was significantly

decreased by 6.72G4.66 and 41.69G15.78 percent for PNA and the controls,

Background

respectively (PZ0.03). No significant difference was seen in methylation of FST

There is evidence that polycystic ovary syndrome

(PCOS) is commonly

promoter although the percentage of 17 CpG sites increases slightly in PNAs.

associated with higher cardiometabolic risk. Aim of the study was to compare

Conclusions

various sex streoids in PCOS women with overweight or obesity (BMI O27) and

These results reveal that manifestation of PCOS-like phenotype following

those with lower BMI. Second aim of the study was to determine the relationship

prenatal exposure to excess androgen is associated with alteration in the

of various sexual setroids to cardiovascular risk in PCOS women.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Subjects and methods

¹Erzincan University, Department of Medical Genetics, Erzincan, Turkey;

Study included 64 Caucasian women with PCOS. Fasting blood samples were

²Erciyes University, Department of Medical Genetics, Kayseri, Turkey;

collected in an early follicular phase and were analyzed for metabolic parameters

³Erciyes University, Department of Endocrinology, Kayseri, Turkey.

and sexual steroid hormones

(androgens, estrogens and adrenal androgen

precursors).

Results

Introduction

Women with BMI R 27 had worse metabolic profile and higher serum free

Hirsutism affects

5-8% of the whole female population. In most patients,

testosterone (FT), free androgen index (FAI), estrone (E1) (PZ0,014 for FT,

hirsutism is associated with hyperandrogenemia and the most common cause of

PZ0.02 for FAI and PZ0.01 for E1) and slightly higher dihydrotestosterone

androgen excess is polycystic ovary syndrome; however, the clinical presentation

(DHT) with borderline significance

(PZ0.06). There were no significant

of non-classical congenital adrenal hyperplasia(NCAH) in females is often

indistinguishable from other hyperandrogenic disorders because of common

differences in total testosterone (TT), androstenedione (ASD) and dehydroepian-

clinical signs with hirsutism and poly cystic ovary syndrome(PCOS).

drosterone sulphate (DHEAS). E1 positively correlated with BMI (PZ0.0067),

Objective

serum insulin (PZ0.0046) as well as HOMA IR (PZ0.0125) and negatively

The aim of the study is to evaluate the prevalence of NCAH in woman presenting

correlated with HDL-cholesterol (PZ0.009). FAI was in positive correlation with

with hirsutism and distinguish the underlying causes.

total cholesterol (PZ0.0457), TAG (PZ0.0001), HOMA IR (PZ0.037), serum

Subject and Method

insulin (PZ0.0428) and glycemia (PZ0.0001) and negatively correlated with

122 women admitted to the Endocrinology Clinic at Erciyes University Hospital

HDL cholesterol (PZ0.029). In multiple linear regression model E1 most

with hirsutism enrolled the study voluntarily between January

2013

and

significantly predicted HOMA IR, whereas FT predicted HDL-cholesterol and

December 2014. All protein encoding exons and exon-intron boundaries of

BMI.

CYP21A2, CYP11B1, HSD3B2 and CYP21A2 promoter changes determined by

Conculsion

direct gene sequencing from genomic DNA isolated from peripheral blood

We conclude that PCOS women with marked overweight or obesity have

leukocytes.

significantly worse cardiometabolic profile than those with lower BMI. They also

Results

have higher FT, FAI, E1 and slightly higher DHT. Among steroid hormones E1

Detailed clinical, hormonal and DNA sequencing analyses of the volunteers have

and FT predicted cardiometabolic risk, whereas other sexual steroids were not in

resulted in 91 (74.6%) PCOS, 12 (9.8%) IHA, 14 (11.4%) IH and 5 (4.1%)

relationship to CVD risk.

NCAH. All NCAH were steroid 21-hydroxylase deficient and there was neither

DOI: 10.1530/endoabs.49.EP1127

11B-hydroxylase nor 3-beta-hydroxysteroid dehydrogenase deficient NCAH.

Sequencing analyses revealed 5 novel mutations; A89V (c.266 COT), M187I

(c.571 GOA) and G491S (c.1471 GOA) located on CYP21A2 and V188I (c.562

GOA) and G87A (c.260 GOC) located on CYP11B1 gene in homozygous and

heterozygous states.

EP1128

Conclusion

Secondary amenorrhea after bone marrow transplantation and

NCAH prevalence in Turkish woman with hirsutism found higher compare to

adjuvant chemotherapy misdiagnosed as disorder of sex development: a

similar studies. It might be because of not only doing sequencing analyses of

case report

CYP21A2 but also promoter region since 3 of them have promoter changes in

Mouna Elleuch, Mouna Ammar, Faten Hadj Kacem, Dorra Ghorbel,

addition to protein coding. However, the study confirmed that promoter region of

Nabila Rekik, Nadia Charfi, Mahdi Kalthoum, Mouna Mnif &

the CYP21A2 should be sequenced as well for true genetic diagnosis and genetic

Mohamed Abid

counselling.

Department of Endocrinology and Diabetes Hedi Chaker, Sfax, Tunisia.

DOI: 10.1530/endoabs.49.EP1129

Introduction

Disorders of sex development (DSD) is a congenital condition in which the

development of chromosomal, gonadal or genital sex is atypical. A female

appearance patient with secondary amenorrhea and 46 XY karyotype seems to be

EP1130

solid evidences to diagnose Y-chromosome-related DSD diseases, while it is not

Effects of photoperiod on estrous cycle in the Mongolian gerbil

necessarily the accurate diagnosis. We here report a case of a 16- year-old girl

(Meriones unguiculatus)

with secondary amenorrhea and

XY karyotype after bone marrow

Nayeli Ortega¹, Marcela Arteaga² & Pilar Duran¹

transplantation (BMT) and adjuvant chemotherapy misdiagnosed as DSD.

¹Universidad Nacional Autonoma de Mexico, Mexico City, Mexico;

Case report

²Universidad Autonoma Metropolitana, Mexico City, Mexico.

A 16-year-old lady who gets her first period at age 13, was referred with a 3 years

history of secondary amenorrhoea. The patient presented female appearance. She

had normal female genitalia and she was at Tanner stage 3. Her medical history

Gerbil

(Meriones unguiculatus) a non traditional laboratory model with

included BMT and chemotherapy because of acute leukemia (AL) when she was

reproductive state influenced by photoperiod, was used to analyze those

13 years old. So far there is no sign of AL recurrence. Laboratory examination

photoperiodic mechanisms involving reproductive regulation. The

14:10

showed a 46 XY karyotype, elevated follicle stimulating hormone and luteinizing

photoperiod has been widely used for reproductive research since 1950 (Everett).

hormone, low estrogen, and normal prolactin. Perineal and pelvic ultrasound

As is well known gerbils locomotor activity cycle has been reported to be

scans showed developed uterus and vagina, and two small ovaries with no

crepuscular and reproductive cycle presents two annual peaks. As for the estrous

follicular activity. Furthermore, we found that she received BMT from her brother

cycle (EC), it has been analyzed mainly under a12hr:12hr light (L)dark(D)

and adjuvant chemotherapy 3 years ago. Her karyotype changed from normal

photoperiod, and reported as mostly irregular. In this research, female gerbils

were exposed to 8:16, 12:12, 14:10 and 16:8 LD conditions. The EC were

female to a karyotype of donor

(her brother) origin after BMT. Adjuvant

monitored by cytology via vaginal smears every four hours (ZT) for 3 consecutive

chemotherapy for AL may impair her ovarian function and finally bring about

cycles, where ZT2 was the first (ZT0 was the light onset). Under the 14:10

primary ovarian insufficiency.

photoperiod, the EC was the most stable. Cycles lengthen in between to five and

Conclusion

four days and stable phase duration. When the other photoperiods were analyzed

The present case serves as a reminder that a correct diagnosis depends on the

the EC showed not only less stability (3-9 days) but also variability in the phase

comprehensive collection of present and past medical history, complete physical

duration, i.e. diestrus increased its duration under 8:16 and12:12 LD, meanwhile

examination, and careful evaluation of related adjuvant tests.

16:8 photoperiod diestrus and estrus, showed a significant increase when

DOI: 10.1530/endoabs.49.EP1128

compared with 14:10 LD. In a period of 15 days an average of 2 cycles on 16:8,

12:12 and 8:16 and 3 EC for 14:10 were presented. Proestrus and metaestrus did

not show a significative variance under any condition. A shift in the time of the

day when estrus phase become settled was reported; vaginal smear showed

predominantly cornified cells under 12:12 and 14:10 LD at ZT6; for 6:8 LD ZT2,

EP1129

and under 8:16 photoperiod a shift to the dark phase was found starting at ZT22.

NCAH prevalance with novel CYP21A2 and CYP11B1 mutations in

As cytological examination of vaginal smears is a good indicator for endocrine

hirsut turkish women

condition of the female, the estradiol and progesterone level are being analyzed

Seher Polat¹, Sulbiye Karaburgu³, Kursad Unluhizarci³, Munis Dundar²,

by ELISA.

Yusuf Ozkul², Zuleyha Karaca³ & Fahrettin Kelestimur³

DOI: 10.1530/endoabs.49.EP1130

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1131

met-group was smaller. BMI levels have reached a plateau after 3 months of

metformin treatment. TSH levels decreased (7.2C/K 1.6 mUI/ml vs. 4.8C/K

The regulation of LHCGR-dependent signaling is linked to circadian

2.2 mUI/ml) significantly in the metformin group, compared to a smaller decrease

gene expression

in the non-metformin group (5.6C/K2.2). Significant decrease was registered for

Lisa Gilioli¹, Marco Marino^1,2, Manuela Simoni^1,3 & Livio Casarini^1,2

the LH/FSH ratio (5,10C/K0.9 vs. 2,1C/K0.45), AMH (9.80C/K1.6 vs. 7.9C/

¹Unit of Endocrinology, Department Biomedical, Metabolic and Neural

K1.2 ng/ml) and testosterone levels; antral follicle count and ovarian volume

Sciences, University of Modena and Reggio Emilia, Modena, Italy;²Center

improved in met-group (in a similar fashion to the gross ultrasound appearance),

for Genomic Research, University of Modena and Reggio Emilia, Modena,

while in non-met group, the 3 and 6 months values were similar to baseline.

Italy;³Azienda Ospedaliero-Universitaria, Modena, Italy.

Conclusion

Metformin treatment administered in high doses (3000 mg/day) on a 6 months

Introduction

period was useful for weight loss, improvement of ovarian function and decrease

Reproduction exhibit a regular cyclicity and is regulated by complex interactions

of androgen levels in obese PCOS patients with hypothyroidism. It also improved

between circadian signals, gonadotropins and sex steroid hormones. Peripheral

supplementary the thyroid function parameters. AMH can be used a prognostic

circadian rhythm is generated upon cyclic transcription of clock genes expressed

marker for metformin response in PCOS obese patients with thyroid dysfunction,

in several cells, e.g. granulosa cells in the ovary. Here we investigated whether

especially if (transvaginal) ultrasound scanning is not available.

cyclic intracellular events occurring in response to gonadotropins are linked to

DOI: 10.1530/endoabs.49.EP1132

expression of clock genes.

Methods

Primary human granulosa cells (hGLC), naturally expressing luteinizing hormone

(LH)/chorionic gonadotropin (hCG) receptor (LHCGR), were maintained under

continuous exposure to LH/hCG over 24 h, and the expression of clock genes

(PER1, PER2, ARNTL, CLOCK), gonadotropin receptors (LHCGR and LHCGR-

exon

6A variants, FSHR) and genes regulating steroidogenesis

(STARD1,

EP1133

CYP19A1, etc.) was analysed by real-time PCR. Cyclicity of cAMP production,

Influence of thyroid stimulating hormone (TSH) level in in-vitro

G proteins and b-arrestins and ERK1/2 phosphorylation were evaluated by

fertilization (IVF) success

ELISA, Western blotting and immunofluorescence.

Carolina Faria, Ana Gomes, Joaquim Nunes, Sandra Sousa, Aguiar Ana,

Results

Rodrigues Cátia, Sampaio Joaquim & Calhaz-Jorge Carlos

Treatments by gonadotropins de-synchronize CLOCK and ARNTL gene

Hospiyal de Santa Maria, Lisboa, Portugal.

expression, as well as LHCGR mRNA isoforms, STARD1 and CYP19A1 gene

expression (two-way Anova; P!0.05; nZ3). Immunostainings revealed a 4-5 h-

rhythmic, up- and down-regulation of Gas protein and b-arrestin1/2, as well as G

Introduction

protein coupling/uncoupling to LHCGR upon gonadotropin treatment. 17 h-

Prevalence of hypothyroidism is 2-5% in women in the reprodutive age group.

treatment is linked to rounded shape of the cells and intracytoplasmic vacuoles,

Hypothyroidism can affect fertility due to anovulatory cycles, luteal phase

LHCGR internalization and translocation of Gas protein to cytoplasm. These

defects, hyperprolactinemia and sex hormones imbalance. Some data also report

gonadotropins-induced changes are accompanied by

3-5 h-oscillatory intra-

that TSH levels are inversely proportional to the fertilization rate at ART (assisted

cellular cAMP production over 24 h, in spite of LHCGR internalization.

reproductive technologies).

Discussion

Objective

We found a link between circadian rhythm, LHCGR up-/down-regulation and

To evaluate if a relationship exists between pregnancy rates in women undergoing

interaction with Gas protein and b-arrestin1/2, resulting in the modulation of

in vitro fertilization (IVF) and their basal thyroid stimulating hormone (TSH)

cAMP-dependent signalling.

levels.

Conclusions

Study design

These data suggest that the kinetics of LHCGR activation and downstream events

We performed a retrospective cohort study in which women with known TSH

are influenced by circadian rhythm, which modulates the cell response to

level who were submitted to IVF in our Hospital during 2014 and 2015 were

gonadotropins and secondary waves of cell signalling activation.

included. They were divided in two groups, according to their initial TSH level:

DOI: 10.1530/endoabs.49.EP1131

O or ! 2.5 mU/l. Pregnancy was defined by ultrasound visualization of

gestational sac.

Results

A total of 132 women met inclusion criteria. The mean age was 34.6 years old.

75.7% of women with TSH data had oligomenorrhea. Thyroid autoantibodies

were requested only in 6 cases. 36.3% of the patients had a TSH O2.5 mU/l. In

that group 39% of the women had pregnancy compared to 42.8% in the group

EP1132

with TSH !2.5 mU/l (PZ0.636).

Conclusion

High dose metformin effect on weightloss, androgen levels and thyroid

No statistically significant difference was observed between the two groups

function in obese hypothyroid patients with PCOS

concerning pregnancy rates after IVF. We cannot exclude that it is the presence of

Aurelian-Emil Ranetti^1,2 & Anca-Pati Cucu¹

thyroid autoantibodies and not the TSH value per se that is associated with lower

¹“Dr. Carol Davila” Central University Emergency Military Hospital,

pregnancy rates. Further studies are needed to confirm this hypothesis.

Bucharest, Romania;²Carol Davila University of Medicine and Pharmacy,

Bucharest, Romania.

DOI: 10.1530/endoabs.49.EP1133

Objective

to evaluate the effects of metformin use on weight loss, improvement of ovarian

and thyroid function in obese women with polycystic ovarian syndrome.

Material and Methods

30 obese (BMI 30-34.99 kg/m²) hypothyroid (TSH 6-10 mIU/ml) women of

EP1134

age

25-35

years old were included. The patients received appropriate

The efficiency of metformin in polycystic ovarian syndrome is not

levothyroxine treatment according to TSH levels and body weight. A number

necessarily attributable to the improvement of insulin resistance

of 15 patients added metformin gradually increased from a starting dose of

Zsuzsanna Szanto & Adelina Micheu

500 mg/day to a final dose of 3000 mg/day over a period of 6 months. Baseline

University of Medicine and Pharmacy, Targu Mures, Romania.

levels, 3 months and 6 months levels of TSH, fT4, T3, AMH, LH/FSH ratio,

testosterone, along with BMI and ultrasound ovarian volume and antral follicle

count were determined. No adverse events that might have led to discontinuation

Insulin resistance has a pivotal role in the pathogenesis of polycystic ovarian

of the treatment were recorded. Mild nausea was registered in 8 patients after

syndrome (PCOS), thus insulin sensitizer therapy is beneficial. Purpose. Our

2 weeks of treatment with 3000 mg/day of metformin, respectively softer stools

purpose was to study the effectiveness of metformin in PCOS women, including

(but no diarrhoea) in 5 patients in the first week of treatment (500 mg/day), but the

those without insulin resistance. Matherials and methods. This study was

symptoms relieved with disappearing within the mentioned time frame.

conducted on 24 pacients (12 obese or overweight and 12 lean women), aged 21-

Results

31 years, diagnosed and treated with PCOS at the Clinical Department of

BMI levels decreased significantly in the first 3 months in metformin group

Endocrinology Targu-Mure, during January

2013-March 2015. All patients

(32.5C/-1.65 kg/m²

vs.

28.4C/K 1.95 kg/m²). BMI variation in the non

received metformin therapy, including those without insulin resistance.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

EP1137

Menstrual cycle disturbances

(anovulation, bradi-oligomenorrhoea) before

Oxidative status imbalance in patients with polycystic ovary syndrome

metformin therapy appeared in 91.6% of the obese or overweight women, and

Alina Crenguta Nicolae¹, Cristina Manuela Dragoi¹,

83.3% of the lean women (21 cases from the 24). In 15 cases insulin level,

Andreea Letitia Arsene¹, Nicoleta Petruta Burlacu¹, Crina Filisan²,

glycaemia were measured, and HOMA-IR calculated. Mean insulin level was

Alice Albu^1,2 & Carmen Gabriela Barbu^1,2

13.06G14.53 mIU/l in the obese group, and 6.82G1.92 mIU/l in the lean group,

¹University of Medicine and Pharmacy Carol Davila, Bucharest, Romania;

and the corresponding mean HOMA-IR was 4.23G3.42 vs. 1.29G0.43. Among

²Elias Hospital, Bucharest, Romania.

the

21 women (11 obese and 10 lean) with menstrual disturbance before

metformin therapy these disturbances improved or pregnancy occurred in 11

cases (5 obese and 6 lean) during metformin treatment alone, which means a

Polycystic ovary syndrome (PCOS) is one of the most frequently encountered

significant improvement (PZ0.0085, RRZ3.16, 95% CIZ1.12-8.87). During

endocrine pathologies in women of reproductive age, being regarded as a chronic

metformin treatment alone, 14 women from the 24 presented normal menstrual

systemic disease instead of the simple local one. It is frequently associated with

cycle, normalized progesterone level or pregnancy occurrence (PZ0.002, RRZ

insulin resistance, hyperandrogenemia and chronic inflammation. PCOS reunites

3.83,

95% CIZ1.33-11.03). Conclusion. Metformin therapy might resolve

multiple and diversified pathological combinations like: ovulatory functional

menstrual cycle disturbances not only in insulin resistant obese PCOS women, but

disorders directly impacting on the reproductive system, carbohydrate and lipid

also in those with normal weight and/or without insulin resistance.

metabolism disorders which can be explained at least partially through an

DOI: 10.1530/endoabs.49.EP1134

increased oxidative stress. Oxidative stress occurs due to an imbalance between

the generation of reactive oxygen species (ROS) and the antioxidant defense

systems. In women, oxidative stress may be a major cause of infertility. In this

clinical study, comprising 55 PCOS patients and age-matched healthy subjects,

we aimed to assess the relationship among different metabolic risk factors, such as

triglycerides, cholesterol and glycaemia, and the reactive oxygen species levels in

patients diagnosed with polycystic ovary syndrome. For an accurate determina-

tion of the biochemical markers, diagnostic kits (Dialab, Austria) have been used,

EP1135

whereas for the determination of the reactive oxygen species

(ROS)

Serum Vitamin D status in women with the polycystic ovary syndrome

concentration, the chemiluminescent method was chosen. The triglycerides,

Justyna Kuliczkowska-Plaksej¹, Andrzej Milewicz¹, Renato Pasquali²,

glycaemia and cholesterol levels were significantly higher in the group of patients

Agnieszka Lenarcik-Kabzda¹, Lukasz Laczmanski¹, Felicja Lwow³,

compared with the control group (P!0.05), suggesting a considerable imbalance

Diana Jedrzejuk¹ & Marek Bolanowski¹

in patients with polycystic ovary. The serum concentration of the reactive oxygen

¹Department of Endocrinology, Diabetology and Isotope Therapy, Wroclaw

species

(ROS) represents a marker of the global oxidative stress. The

Medical University, Wroclaw, Poland;²Department of Medical and

experimental results obtained following the assessment of the ROS concentration

Surgical Sciences, Division of Endocrinology, University of Bologna,

revealed a significantly higher value in the patient group with polycystic ovary as

Bologna, Italy;³Department of Health Promotion, University School of

compared to the control group, which translates into an enhanced oxidative stress

Physical Education, Wroclaw, Poland.

in patients diagnosed with polycystic ovary syndrome. Correcting oxidative stress

with antioxidants along with monitoring the antioxidant status could have a

beneficial effect on oxidative stress induced insulin resistance and hyperan-

Objective

drogenism in the PCOS diagnosed women.

To measure the levels of 25-hydroxyvitamin D (25(OH)D) and vitamin D binding

protein (VDBP) and assess their relationships with metabolic features in patients

DOI: 10.1530/endoabs.49.EP1137

with the polycystic ovary syndrome (PCOS).

Methods

267 women, aged 20-35 years (24.7G4.9): 167 with PCOS, 100 healthy women

as a control group were studied. Study groups were divided according to body

mass index (BMI). Biochemical and hormonal parameters, 25(OH)D, VDBP

were measured. Free and bioavailable

25(OH)D were calculated using the

mathematical equations. The percentage of body fat and visceral fat deposit were

EP1138

assessed by DXA.

Utility of oral glucose tolerance test (OGTT) in patients with polycystic

Results

ovary syndrome (PCOS)

In the normal weight control group total, free and bioavailable 25(OH)D were

Oana Alexandra Petre¹, Ivona Gheorghe¹, Irina Nicolaescu¹, Dragos Albu^2,3

significantly (P!0.001 for all) higher than in its overweight/obese counterpart. In

& Alice Albu^1,2

women with PCOS both total 25(OH)D (P!0.001), and VDBP (P!0.001) were

¹Elias Hospital, Endocrinology and Diabetes Department, Bucharest,

lower in the overweight/obese subgroups than in the normal weight one. VDPB

Romania;²Carol Davila University of Medicine and Pharmacy, Bucharest,

was negatively correlated with fasting insulin, positively with SHBG in control

Romania;³Medlife, Maternal Fetal Medicine and Human Reproduction,

group. In PCOS group, VDPB was negatively correlated with abdominal fat

Bucharest, Romania.

deposit, BMI, fasting glucose and insulin and positively with HDL and SHBG.

Conclusions

Background

Despite lower total 25(OH)D in obese PCOS women, all women with PCOS (lean

PCOS patients associate an increased risk of glucose metabolism abnormalities.

and obese) had comparable free and bioavailable 25(OH)D which might be a

Although Hb A1c was suggested as a good diagnostic test for prediabetes/

result of concomitantly lowered serum VDBP levels in obese PCOS women.

diabetes, in PCOS patients its diagnostic value could be inferior to OGTT as

VDBP might play important role in the regulation of availability of active

previously suggested. Aim of the study was to evaluate which are the clinical and

fractions of 25(OH)D in PCOS women. VDBP is strongly associated with cardio-

paraclinical parameters associated with impaired glucose tolerance (IGT) in order

vascular risk factors such as BMI, waist circumference, visceral fat, fasting

to identify the profile of the patients that will benefit from OGTT.

insulin in women with PCOS.

Material and methods

449 patients (mean age years, mean body mass index (BMI) kg/sqrm) diagnosed

DOI: 10.1530/endoabs.49.EP1135

with PCOS based on Rotterdam criteria evaluated with OGTT were retro-

spectively selected from our PCOS database.

Results

From the 449 patients included in the study 23 (5.1%) had impaired fasting

glycemic (IFG) and 28 (6.2%) IGT. Patients with prediabetes (IGT and IFG) were

older, had higher BMI, waist circumference (WC), insulinemia (fasting and 2 h),

HOMA-IR in comparison to patients with normal glucose. Patients with IFG were

EP1136

not different from those with IGT with respect to age, clinical and biochemical

hyperandrogegism, adiposity, HOMA-IR, fasting insulinemia and metabolic

parameters, except the 2 h insulinemia and serum FSH level which were higher

Abstract withdrawn.

and lower respectively in patients with IGT (P!0.05).

Conclusion

Our patients with IGT and IFG were similar in terms of clinical and paraclinical

baseline parameters, making impossible their identification without an OGTT.

DOI: 10.1530/endoabs.49.EP1138

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1139

Following vitamin D supplementation for 3 months, significant improvement of

BMI and metabolic parameters like FPG, 2 hr glucose, HOMA IR, HOMA B, TG

Diagnostic performance of non-invasive markers for the presence of

levels and TC was observed in women who followed LSM. However, there was

nonalcoholic fatty liver disease in premenopausal women with and

no change in serum testosterone.11/30 patients in the supplementation group who

without polycystic ovary syndrome

did not comply with LSM also showed significant decrease in FPG, 2 hr PG, and

Evangeline Vassilatou¹, Sophia Lafoyianni², Dimitra-Argyro Vassiliadi³,

HOMA IR.

Dimitrios Ioannidis², Stavroula Paschou¹, Maria Mizamtzidi¹ &

Conclusion

Andromachi Vryonidou

Vitamin D supplementation has beneficial effect on insulin resistance and

¹‘Red Cross’ Hospital, Athens, Greece;²‘Amalia Fleming’ General

metabolic parameters in vitamin D deficient PCOS women. Both vitamin D

Hospital, Athens, Greece;³‘Evangelismos’ Hospital, Athens, Greece.

supplementation and LSM have complementary effects in improving BMI and

HOMA indices, glucose and lipid metabolism in the setting of PCOS with vitamin

Introduction

D deficiency, suggesting a role of vitamin D in the management of PCOS.

Several markers based on anthropometric and biochemical parameters like fatty

DOI: 10.1530/endoabs.49.EP1140

liver index (FLI), lipid accumulation product (LAP) index and visceral adiposity

index (VAI), have been proposed for the detection of nonalcoholic fatty liver

disease (NAFLD).

Objective

To evaluate the diagnostic performance of FLI, LAP and VAI as markers of

NAFLD in premenopausal women with and without polycystic ovary syndrome

(PCOS), assessed for hepatic steatosis (HS) by ultrasonography.

Design

Prospective, cross-sectional study.

Patients and methods

EP1141

Anthropometric measurements, biochemical testing and abdominal ultrasono-

graphy after excluding causes of secondary liver disease were performed in 145

Epigenetics of female hypogonadotropic hypogonadism: analysis of

premenopausal women with PCOS (Rotterdam criteria) and 145 BMI-matched

mRNA expression of engaged in IHH genes

healthy controls. The three markers VAI, FLI and LAP were calculated and their

Anna Loktionova¹, Irena Ilovayskaya¹, Natela Eneva²,

diagnostic performance for predicting HS was evaluated with receiver operating

Karina Khusniyarova², Lidia Nefedova², Alexander Kim² &

characteristic (ROC) analysis.

Alexander Dreval¹

Results

¹M.F. Vladimirsky Moscow Regional Research and Clinical Institute,

HS by ultrasonography was detected in 132/290 (45.5%) women, while the

Moscow, Russia;²Lomonosov Moscow State University, Moscow, Russia.

prevalence of HS was increased in PCOS women compared to controls [78/145

(54%) kai 54/145 (37%), PZ0.01]. FLI, LAP and VAI values were higher in

Hypogonadotropic hypogonadism is a syndrome which may be manifested

HS(C) compared to HS(K) women [68.7G26.7 vs 26.5G24.8, P!0.001,

clinically by low sex steroids because of low

(or inappropriately normal)

61.1G39.3 vs 23.7G15.2, P!0.001 kai 2.4G1.8 vs 1.2G0.6, P!0.001),

gonadotropins. To date, more than 30 genes were reported as possible reason for

respectively] as well as in PCOS women compared to controls. The area under the

this condition, but genetic basis is still unknown for w60% of HH cases. Due to

curve (AUROC) for FLI, LAP and VAI were 0.87G0.02, 0.84G0.02 and 0.77G

this fact we decided to analyze mRNA expression of several HH-related genes

0.03, respectively, in the whole group of women. When AUROCs of the three

which can be found in leukocytes of peripheral blood: GNRHR and GNRH1

indices were calculated separately for PCOS women and controls, no statistical

(which are necessary for adequate biological effect of GnRH); PROK2 and

differences were observed.

CHD7 (which are responsible for the migration of GnRH neurons), WDR11 and

Conclusions

DUSP6 (which are involved in normal sexual development). A quantitative

FLI, LAP and VAI can detect NAFLD in premenopausal women with a similar

determination of mRNA expression of these genes were comlpeted in the fresh

diagnostic performance. The presence of PCOS has no effect on the diagnostic

peripheral blood sample by PCR in real time.

performance of these indices.

Examined patients

DOI: 10.1530/endoabs.49.EP1139

Ten women with hypogonadotropic hypogonadism (age from 18 to 53 y.o.); 4 of

them suffer from amenorrhea I and 6 - amenorrhea II. Reasons of amenorrhea II

were: stress, excessive exercises, rapid body weight loss, past use of oral

contraceptives. The control group: 19 healthy women; age from 19 to 37 y.o.;

with regular ovalutory menstrual cycle, some of them have children.

Results

mRNA expression of examined genes differed from normal patterns in each case

of hypogonadotropic hypogonadism. Changes in GNRHR, GNRH1 and DUSP6

mRNA expression were found in most of cases. However variations of mRNA

expression were multidirectional in each case and there was no similarity among

EP1140

expression profiles of patients according to anamnestic factors; but some affinities

Complementary effect of Vitamin D supplementation and lifestyle

were found among patients who suffer from primary amenorrhea. According to

modification on anthropometric and metabolic parameters in young

our preliminary results, in women with hypogonadotropic hypogonadism the

polycystic ovary syndrome women with Vitamin D deficiency: a

functional activity damage of ‘reproductive-responsible’ genes could be found in

3-month prospective interventional study

each case. Probably mRNA expression measuring could be a perspective method

Ramesh Jayanthy¹ & Prasanna Belgundi²

for proving hypothalamo-pituitary level of reproductive disorders and may help to

¹Sai’s Institute of Endocrinology, Hyderabad and Visakhapatnam, India;

determine which genes should be tested for DNA impairment.

²Osmania Medical College, Hyderabad, India.

DOI: 10.1530/endoabs.49.EP1141

Background

PCOS women usually have metabolic disturbances particularly insulin resistance.

Previous studies suggest that vitamin D deficiency may contribute to the

development of insulin resistance. Our aim is to study the effect of vitamin D

supplementation on clinical and biochemical parameters in vitamin D deficient

PCOS women.

Methods

EP1142

At baseline, 50 PCOS women were enrolled (37 vitamin D deficiency and 13

How far is possible to make a diagnosis of infertility

vitamin D sufficiency). Thirty-seven PCOS women on LSM (low-calorie diet

Daniela Dias, Joana Simo˜es-Pereira, Sara Donato & Conceição Pereira

1000-1200 kcal/d and aerobic exercise walking 3.2 km/d, 5 days/wk) received

Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon,

60 000 IU cholecalciferol weekly for 8 weeks followed by once a month. Clinical,

Portugal.

anthropometric and biochemical parameters were performed at baseline and after

12 weeks.

Results

Introduction

Thirty PCOS women completed the study.

25(OH) D levels significantly

Chemotherapy may be an important cause of primary infertility, especially in girls

increased from

7.55G4.10 at baseline to

34.16G4.14 ng/ml at

3 months.

submitted to this therapy at very young ages.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Clinical case

EP1144

A 20-year-old female was diagnosed with acute lymphoblastic leukaemia at the

Serum activities of dipeptidyl peptidase-4 and adenosine deaminase and

age of 1. She was submitted to chemotherapy: intrathecal methotrexate and

parameters of oxidative stress in polycystic ovary syndrome: association

cyclophosphamide and i.v. doxorubicin, vincristine, mercaptopurine, asparagi-

with obesity

nase and bone marrow transplantation at the age of 2. She was referenced to

Seda Kahraman¹, Alev Eroglu Altinova¹, Serenay Elgun Ulkar², Mehmet

Endocrine Rehabilitation Clinics at the age of 6.75 years-old. Her auxology

Muhittin Yalcin¹, Banu Aktas Yilmaz¹,

¸ igdem Ozkan¹, Mujde Akturk¹ &

evidenced: height 109.8 cm (p3-10); predicted adult stature: 155 cm (p10); and

Fusun Balos Toruner¹

identical bone and chronological ages. In terms of puberty, her Tanner stages

¹Faculty of Medicine, Gazi University, Ankara, Turkey;²Faculty of

were A1P1B1. Blood analysis evidenced IGF1 of 344 ng/ml (p90) and normal

Medicine, Ankara University, Ankara, Turkey.

thyroid and gonadal axes. At the age of 11, she remained pre-pubertal, with

increased levels of FSH (76.3 mUI/ml) and LH (17.2 mUI/ml). Her bone age was

11 years. At this time, we started inducing puberty with oestradiol. After 2 years,

Dipeptidyl peptidase 4 (DPP-4) is thought to play a role in the pathophysiology of

Tanner stages were A4P4B3. Menarche was achieved at 13.41 years old. At the

metabolic and inflammatory diseases. Increased ADA activity has been suggested

age of 18, she reached A5P5B5, after 7 years of estradiolCnorgestrel. She

to induce insulin resistance and inflammation. We investigated DPP-4 and ADA

withdrawal this therapy when she was 20 and scarce menses were observed.

activities, serum nitric oxide (NO) level and nitric oxide synthase (NOS) activity

Blood tests evidenced FSH of 84.1 mUI/ml and LH of 26.7 mUI/ml and pelvic

which are the oxidative stress parameters in patients with PCOS. Fifty two women

ultrasound was normal. At this age, given her desire to become pregnant, she

with PCOS and 41 healthy women were included in this study. Serum ADA

underwent ovarian stimullation, which was unsuccessufull. However, 12 months

activity (0.33 (0.17-0.67) vs 0.26 (0.12-0.60) IU/l; PZ0.006), NO level (24.5

later she became pregnant.

(13.25-58) vs 12.25 (6-24.50) mmol/l; P!0.001) and NOS activity (5.46 (3.38-

Discussion

12.71) vs 4.54 (2.55-10.13) IU/ml; P!0.001) were significantly higher in PCOS

This case reports the complex and not fully understood process of gonadal

group while there was no difference in serum DPP-4 activity (19.54G7.01 and

function after chemotherapy gonadotoxicity. We believe that the fortunate

18.24G6.73 IU/l; PZ0.369) between the groups. The groups were divided into

pregnancy result in our patient was probably due to previous gonadotrophins

subgroups as obese and nonobese. In obese PCOS group; ADA, NO and NOS

stimulation performed in a very young woman, which enabled the reactivation of

were significantly higher than obese controls

(PZ0.044, P!0.001

and

the gonadic axis.

P!0.001), while there was no difference in DPP-4 activity (PZ0.356) between

DOI: 10.1530/endoabs.49.EP1142

the groups. In nonobese PCOS group; NO and NOS were significantly higher than

nonobese controls (P!0.001 and PZ0.006), while there were no differences in

DPP-4 and ADA activity (PZ0.802 and PZ0.128). There was a negative

correlation between ADA and DPP-4 activity in PCOS group (PZ0.047). A

positive correlation was observed between ADA and BMI in the whole group

(PZ0.022). In conclusion, we found that there was no significant change in serum

DPP-4 activity in women with PCOS. However, we demonstrated increased

serum ADA activity as well as its association with obesity in PCOS. Also, our

finding that increased NO level and NOS activity in PCOS which is independent

of obesity may result from a compensatory mechanism for the oxidative stress

in PCOS.

DOI: 10.1530/endoabs.49.EP1144

EP1143

Physiological changes of adipokines and selected steroids during the

menstrual cycle

Monika

ˇ rámková^1,2, Michaela Dušková¹, Jana Vítk

˚¹, Josef Vcˇelák1,

Petr Matucha¹, Olga Bradnová¹, Jose Cordeiro¹ & Luboslav Stárka¹

¹Institute of Endocrinology, Prague, Czech Republic;²Faculty Hospital

Motol, Prague, Czech Republic.

EP1145

Context

Oocyte donation in women with Turner’s syndrome: successful outcome

The cyclical effects of hormones during the menstrual cycle (MC) are responsible

can be achieved with a specialist multidisciplinary approach

for driving ovulation. The information about roles of adipokines within the scope

Matilde Calanchini^1,3, Kathy Baker², Andrea Fabbri³, Ashley Grossman¹,

of MC are not definite. Leptin plays a role in sexual function and regulating the

Elizabeth Orchard⁴, Tim Child² & Helen Turner¹

onset of puberty. Thin girls often fail to ovulate or release an egg from an ovary

¹Oxford Centre for Diabetes, Endocrinology and Metabolism - Churchill

during menstruation cycles. Leptin also acts on specific receptors in the

Hospital, University of Oxford, Oxford, UK;²Oxford Fertility Institute of

hypothalamus to inhibit appetite. Levels of leptin are increased in women

Reproductive Sciences, Oxford, UK;³Department of Endocrinology CTO

suffering from premenstrual syndrome. The aim of our study was to describe

Alesini & S. Eugenio, University of Rome Tor Vergata, Rome, Italy;

physiological changes of selected steroids and adipokines at healthy women

⁴Cardiology Unit, John Radcliffe Hospital, Oxford, UK.

during the MC.

Introduction

Methods

Although oocyte donation (OD) is increasingly utilised in women with Turner’s

Twenty-seven women with regular menstrual cycles were included in the study,

syndrome

(TS) few data are available. Reported clinical pregnancy rates

and their hormonal spectrum and adipokines were measured in regular intervals

following OD range from 17 to 40%. Complications of 2% death from aortic

starting from the first day of their MC.

dissection and severe hypertension are reported.

Results

Aim

Classical changes in gonadotropins, estrogens and progesterone during the

To analyse the OD-pregnancy success rate and materno-fetal outcomes in women

menstrual cycle are accompanied by less striking but significant changes in

followed in a TS-dedicated centre.

17-hydroxyprogesterone and testosterone. No significant changes show dehy-

Methods

droepiandrosterone and its

7-oxygenated metabolites. Adipokines show a

A retrospective study of 114 adult TS patients analysed cardiovascular risk

tendency to increase during ovulation, while ghrelin and resistin decrease.

factors, feto-maternal morbidity and mortality in women undergoing OD (1997-

There is also a remarkable association of sex hormone-binding globulin on the

2015). Data were compared with spontaneous pregnancy (SP) 14/114 patients,

day of the cycle.

mean age 24 years (Calanchini et al. 2016, for SP data comparison).

Conclusion

Results

Our results demonstrate that changes to adipokines dutiny the menstrual cycle are

Eleven patients underwent egg donation cycles (total 27) using fresh (16) or

not substantial, but nonetheless can play a role in the changes of food intake

frozen (3) donated eggs or embryos frozen and stored from a previous egg

described in the literature. Precise descriptions of physiological changes in

donation cycles (8). Endometrial preparation achieved endometrial thickness

healthy women are important in helping us understand the significance of the

R7.3 mm, mean 10.2 mm. 1 or 2 embryos were transferred between day 2 and 5.

changes accompanying various pathological states.

Mean recipient age at first IVF was 32.5 years (24-41) and at delivery 33.8 years

DOI: 10.1530/endoabs.49.EP1143

(26-41). 3/11 were 45X, 3/11 were 45X/46XY and 5/11 other TS-karyotypes.

Five had cardiovascular malformations (4 bicuspid aortic valve, 1 treated aortic

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

coarctation), four treated hypertension, and two pre-existing aortic dilatation.

underlying this association are incompletely clarified. The aim of the present

12/27 (44%) cycles had positive pregnancy-tests and 5/27 (19%) resulted in live

study is to evaluate the factors associated with thyroid autoimmunity in patients

births. The cumulative live birth rate per patient undergoing treatment was

with PCOS. We performed a retrospective study which included 126 PCOS

therefore 5/11(46%). Increased aortic diameter occurred in 1/5, and gestational-

patients (mean age 24G4.5 years, mean body mass index, BMI 27G7.33 kg/sqm)

diabetes 1/5. No patient developed gestational-hypertension compared with 7%

diagnosed based on Rotterdam criteria between January 2015 and January 2016.

SP. No cardiovascular or fetal complications were noted. One emergency

We found that anti-thyroid peroxidase antibodies (ATPO) serum levels were

caesarean section (37C1w, twin pregnancy).

positively correlated with HOMA-IR

(rZ0.234, PZ0.019), fasting insulin

Conclusions

(rZ0.218, PZ0.025), waist circumference (WC, rZ0.267, PZ0.007) and BMI

OD showed a 19% live birth rate per cycle and 46% per patient in TS, was safe

(rZ0.203, PZ0.04). We found no association between ATPO and total

even in women with cardiac risk factors, and unassociated with increased feto-

testosterone, free androgen index, gonadotropins, TSH, leptin and adiponectin

maternal complications compared with TS SP. This emphasises the importance of

serum levels. In a multivariate linear regression model with ATPO as dependent

early discussion of assisted reproductive technology and alongside monitoring in

variable only HOMA-IR was an independent predictor of ATPO values after

a TS-dedicated multidisciplinary centre.

adjustment for adiposity markers. In conclusion, in PCOS patients insulin

DOI: 10.1530/endoabs.49.EP1145

resistance seems to be the main factor involved in thyroid autoimmunity.

DOI: 10.1530/endoabs.49.EP1147

EP1146

The features of young women reproductive health with type 1 diabetes

Kateryna Kondratiuk¹, Nazarii Kobyliak¹, Iryna Nikitina²,

Valentyna Kondratiuk³ & Petro Bodnar¹

EP1148

¹Bogomolets National Medical University, Kyiv, Ukraine;²Sumy State

Metformin treatment decreased free androgen index among

University, Sumy, Ukraine;³State Institution ‘Institute of Pediatrics,

PCOS women

Obstetrics and Gynecology of NAMS of Ukraine’, Kyiv, Ukraine.

Sandra Mrozinska^1,3, Anna Wajda², Patrycja Czekanska²,

², Marta Kialka^2,3 & Tomasz Milewicz^2,3

Barbara Zdzierak

Background

¹Department of Metabolic Diseases, Jagiellonian University, Medical

Leading position among endocrine pathology of adolescence and young women is

College, Krakow, Poland;²Department of Gynecological Endocrinology,

type 1 diabetes (T1D), which in recent years had been proved to have a strong

Jagiellonian University, Medical College, Krakow, Poland;³University

association with reproductive dysfunction among such patients. The purpose was

Hospital, Krakow, Poland.

to investigate the features of reproductive health in 120 young women (18-22

years old) with T1D.

Methods

Hyperinsulinemia is one of biochemical features of polycystic ovary syndrome

Retrospectively we studied the features of puberty and prospectively examined

(PCOS). Metformin is a common drug used in PCOS. Recent studies have shown

level of blood glucose and HbA_1c, levels of gonadotropin (LH, FSH) and sex

that metformin has impact on clinical and biochemical parameters in PCOS

hormones (prolactine, estradiol, progesterone, testosterone) (ELISA, France) and

patients. The aim of our study was to assess retrospectively the influence of

determined antibodies to ovarian tissue (Euroimmune, Germany) in peripheral

metformin on total testosterone, sex hormone binding globulin (SHBG) and free

blood, held pelvic ultrasonography (MyLabSeven, Italy).

androgen index (FAI) in women with PCOS in polish cohort. A total of 54

Results

patients with PCOS and irregular menses were examined. The duration of

The proportion of patients with delayed puberty and physical development of type

metformin treatment between the baseline and final blood results was about six

1 diabetes with the debut in the pre-puberty was in 62.5%, in the early puberty

months. There were statistically significant differences in the total testosterone

(3-7 years) - 15.0%, in the active adolescence (11-14 years) - 11.7% of post-

(1.9

(1.4-2.6) vs 1.2 (0.6-2) ng/ml), SHBG (34.8 (27.2-53.1) vs 49.4 (35.9-81.7)

puberty (over 14 years) - 10.8%. Ovarian failure occurred in 76.7% of the

nmol/l) levels and FAI (5.3 (3.2-9.8) vs 2.3 (1.3-4.3) before and after the

patients, and was expressed in the increased LH, estradiol and free testosterone

metformin administration (all P!0.0001). In addition the patients were divided

levels. The positive correlation relationships were detected between blood levels

into two groups according to FAI. There was no difference in age (29 (26-32) vs

of estradiol (rZ0.77, P!0.05), testosterone (rZ0.56, P!0.05) and level HbA_1c;

(25-31) years, PZ0.7) and BMI (22.5 (19-24.1) vs (22 (20.7-28.1) kg/m²,

negative correlation relationship were revealed between progesterone blood level

PZ0.35) between group with FAI!5 and group with FAIO5, respectively. Our

(rZ0.67, P!0.05) and level of HbA_1c. Fiction revealed correlations between the

study showed that metformin therapy ameliorates the total testosterone and FAI

levels of sex hormones and the regime of insulin therapy. Autoimmune ovarian

both in women with FAI greater and lower 5 but improves SHBG levels only

failure was detected in the 4.2% cases. The presence of ovarian insufficiency was

among patients with FAIO5. The groups did not differ in difference between

accompanied by an increase in ovarian volume and number of antral follicles

baseline and final testosterone and SHBG levels but differed in FAI change. Our

in them.

study suggest that metformin effectiveness could differ between PCOS patients

Conclusion

according to the phenotype.

Type 1 diabetes adversely affect the formation of future reproductive health of

girls, realized at hormonal dysfunction, ovarian failure and pathological changes

DOI: 10.1530/endoabs.49.EP1148

in the structure of the ovaries.

DOI: 10.1530/endoabs.49.EP1146

EP1147

The determinants of thyroid autoimmunity in patients with polycystic

ovary syndrome

EP1149

Alice Albu^1,2, Oana Petre², Irina Nicolaescu², Ivona Gheorghe² &

Dragos Albu¹

¹Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;

Abstract withdrawn.

²Elias Hospital, Bucharest, Romania.

It was suggested that polycystic ovary syndrome

(PCOS) patients have an

increased risk for autoimmune thyroid disease. However the mechanisms

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1150

normal BP; excessive hair on chin, forearms and lower abdomen; no striae, no

acanthosis nigricans, normal thyroid. High levels of insulin, LH, total

Biochemical and clinical characteristics of polysystic ovarian syndrome

testosterone, androstendione and low levels of SHBG and progesterone in the

(PCOS) in women with and without type 1 diabetes (TID)

luteal phase were found. An oral glucose tolerance test, fasting lipid profile and

Anjuli Gunness¹, Agnieska Pazderska¹, Mohamed Ahmed¹, Niamh Phelan¹,

concentrations of TSH, prolactin, 17OHP were normal. A pelvic ultrasound

Gerard Boran¹, AE Taylor², MW O’Reilly², Wiebke Arlt², Kevin Moore¹,

confirmed polycystic ovaries. The clinical and lab. tests were consistent with

Lucy-Ann Behan¹, Mark Sherlock¹ & James Gibney¹

PCOS. Therapy with life style changes (weight reduction) and metformin was

¹Department of Endocrinology and Clinical Chemistry, Adelaide and Meath

started (500 mg bid). After 10 months of treatment, she lost 8 kg, menstrual cycles

Hospital, Tallaght, Dublin 24, Ireland;²Institute of Metabolism and Systems

were regular (26-28 days), concentrations of LH, testosterone, progesterone and

Research (IMSR), University of Birmingham, Edgbaston, Birmingham B15

insulin were normal. The patients with PCOS are treated according to their

2TT, UK.

symptoms, risks and desire for pregnancy. The OCs are the mainstay of

pharmacologic therapy for women with PCOS for managing hyperandrogenism

Abstract

and menstrual dysfunction. The case has showed impact of the OC on the

PCOS prevalence is reported to be increased in reproductive-age women with

pituitary-ovarian suprresion. There are relatively few publications examining the

type-1 diabetes (T1DM) but measurement of androgens, crucial for diagnosis, has

effect of the OC on ovarian function in women and it’s less clear whether the

been with inaccurate immunoassays. No studies have been reported using liquid-

pituitary-ovarian suppression induced by the OCs has any impact on functional

chromatography-mass-spectrometry (LCMS). Reproductive-age T1DM women

ovarian reserve, so we need further evaluation. Although, the use of metformin in

attending a single centre were evaluated for PCOS (NIH criteria). Women with

the treatment of PCOS is off-label, in this case, metformin had showed as safe and

T1DM and PCOS (T1/PCOS) were compared to T1DM women without

effective. Benefit was made on oligomenorrhea, fertility and obesity.

hyperandrogenism (T1/no HA), and to two groups of non-diabetic women with

DOI: 10.1530/endoabs.49.EP1151

PCOS - one group BMI-matched (PCOS-lean) and the other overweight (PCOS-

overweight). 16 (18%) of T1DM women had PCOS. TIDM women with PCOS

compared to the overall group were younger (26.5 vs 29) and had a lower BMI

(23.4 vs 25.3). Compared to T1/no HA, testosterone (1.3 vs 0.8 nM, PZ0.004)

and androstenedione (7.1 vs 4.6 nM, PZ0.0016) were elevated but no differences

in DHEA-OX, DHEAS, SHBG or free testosterone was noted. They had an older

age of menarche (13 vs 12.5 years, PZ0.024), and were more likely (PZ0.024)

to have a positive family history of PCOS. There were no differences in androgen

levels between T1/PCOS and PCOS-lean women, but both of these groups

demonstrated greater androstenedione levels (7.1 vs 5.5 nM, PZ0.0247) than

PCOS-overweight women. In summary, PCOS is common in T1DM. Women

with T1/PCOS are leaner than T1 women without PCOS but are more likely to

have a family history of PCOS. They have a similar biochemical phenotype to

lean women with PCOS but differ from overweight women with PCOS. The

mechanisms underlying PCOS in T1DM and its clinical significance are

EP1152

unknown.

Does radioactive ıodine therapy affect fertility?

DOI: 10.1530/endoabs.49.EP1150

Berna Evranos Ogmen¹, Sevgul Faki², Sefika Burcak Polat²,

Nagihan Bestepe¹, Reyhan Ersoy² & Bekir Cakir²

Ataturk Education and Research Hospital, Department of Endocrinology

and Metabolism, Ankara, Turkey;²Yildirim Beyazit University, Faculty of

Medicine, Ataturk Education and Research Hospital, Department of

Endocrinology and Metabolism, Ankara, Turkey.

Introduction

Thyroid carcinoma is common in young women. Radioactive iodine (RAI)

therapy has been confirmed as a useful treatment in the management of

differentiated thyroid carcinoma (DTC). For women with DTC, the effect of RAI

therapy on gonadal and reproductive function is an important consideration. We

aimed to evaluate effects of RAI therapy on ovarian function.

Method

Women younger than 40 years old and diagnosed with thyroid cancer that

required RAI treatment were enrolled in this study.Patients with ovarian

insufficiency were excluded. Early follicular phase serum follicle stimulating

EP1151

hormone (FSH) and anti-mullerian hormone (AMH) levels were measured before

A case of polycystic ovary syndrome (PCOS)

and 3-6 months after RAI therapy. Friedman test is used to detect changes in FSH

Kristina Kljajic Babic, Dubravka Majic Milotic, Kristijan Peros &

and AMH levels by RAI therapy with time.

Lea Smircic Duvnjak

Results

Clinical Hospital Merkur, Zagreb, Croatia.

Eighteen patients with a mean age of 31.9G4.9 years were enrolled in this study.

Median AMH levels were 4.2 (2.96-17.42) ng/ml, 2.21 (0.84-3.69) ng/ml, 2.08

(0.86-6.12) ng/ml before and 3-6 months after RAI therapy, respectively. Median

FSH levels were 5.5 (3.78-15.5) mIU/ml, 5.32 (4.19-35.36) mIU/ml, 6.07 (4.24-

Polycystic ovary syndrome (PCOS) is one of the most common endocrine

13.69) mIU/ml before and 3-6 months after RAI therapy, respectively. AMH

disorders in women of reproductive age. It’s a heterogeneous functional disorder

levels before RAI were higher than after RAI (PZ0.021).AMH levels after

of unclear etiology. The features of PCOS are disorders of ovulation, androgen

RAI at 3 and 6 months were not different. FSH levels were similar before and

excess, polycystic ovaries; it’s associated with presence of associated risk factors

after RAI.

for cardiovascular disease

(obesity, glucose intolerance, dyslipidemia). The

Conclusion

diagnosis of PCOS is made using the Rotterdam 2003 criteria. 23yo female

Anti-mullerian hormone (AMH) is considered an important marker of ovarian

patient was evaluated for oligomenorrhea. At the age of 17, she consulted for the

reserve. Ovarian reserve decreases in first 6 months after RAI therapy. Further

first time her gynecologist because of irregluar menstrual cycles since the

large prospective studies are necessary to determine its predictive interest for

menarche (age 14) and excessive hair growth. A diagnosis of PCOS was made and

post-treatment residual fertility.

oral contraceptives (OC) were introduced in therapy. After 1.5 yrs, OC were

excluded because of undetectable levels of LH and FSH. Without them, the

DOI: 10.1530/endoabs.49.EP1152

menstrual cycle length was 40-120 days. Examination revealed high BMI 25;

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1153

P!0.01. In PCO group, it was higher before (3.54G0.58 ng/ml) than after

treatment (2.79G0.39 ng/ml), with P!0.01.

Androgen profiling by liquid chromatography-mass spectrometry

Conclusion

(LC-MS) in reproductive-age women with and without diabetes

AMH is higher in PCO subjects and its levels decreases significantly with the

Anjuli Gunness¹, Agnieska Pazderska¹, Mohamed Ahmed¹, Niamh Phelan¹,

insulin sensitizer metformin and it can be used as a marker for treatment efficacy

Gerard Boran², AE Taylor³, MW O’Reilly³, Wiebke Arlt³, Kevin Moore¹,

with metformin.

Lucy-Ann Behan¹, Mark Sherlock¹ & James Gibney¹

Keywords: PCO, Anti-Mullerian hormone (AMH), Metformin.

¹Department of Endocrinology, Adelaide and Meath Hospital, Tallaght,

Dublin 24, Ireland;²Department of Clinical Chemistry, Adelaide and Meath

DOI: 10.1530/endoabs.49.EP1154

Hospital, Tallaght, Dublin 24, Ireland;³Institute of Metabolism and Systems

Research (IMSR), University of Birmingham, Edgbaston, Birmingham B15

2TT, UK.

Abstract

The prevalence of hyperandrogenism has been reported to be increased in

EP1155

reproductive-age women with type-1

diabetes

(T1DM). This observation

Influence of BMI in response to ovarian stimulation and live birth in

however is based on findings using inaccurate immunoassays. No studies have

IVF

been reported in diabetes using liquid-chromatography-mass-spectrometry

Patrícia Tavares¹, Catarina Machado¹, Lucinda Calejo², Gustavo Rocha¹,

(LCMS). We compared LCMS-measured androgens in T1DM-women with

Ana Margarida Póvoa², Sandra Soares², Sónia Sousa² & Maria João

age-/ BMI-matched normal women, and compared findings with those in women

Oliveira¹

with type-2 diabetes (T2DM) also compared to a matched control group (Table

¹Centro Hospitalar Vila Nova de Gaia/Espinho, Endocrinology Department,

Below). Compared to non-diabetic women, androstenedione and SHBG were

Vila Nova de Gaia/Porto, Portugal;²Centro Hospitalar São João,

greater in T1DM while estimated free-testosterone was lower. In contrast,

Reproductive Medicine Department, Porto/Porto, Portugal.

compared to non-diabetic women, androstenedione, DHEA-OX and SHBG levels

were lower in T2DM while free-testosterone and DHEAS were greater. Total

testosterone did not differ between groups in either comparison. T1DM and

Introduction

T2DM are associated with differing effects on androgen levels. These differences

The deleterious effects of obesity on spontaneous reproduction are well

are likely to reflect differences in insulin sensitivity and differing effects of

recognized, although the literature on obesity and assisted reproductive

exogenous insulin administration. Their clinical significance requires further

technology outcome remains heterogeneous and inconsistent.

investigation.

Objective

Mean (G SEM); P-value vs matched non-diabetic.

To estimate the effect of BMI on ovarian stimulation response and live birth in

Median (range); P-value vs matched non-diabetic.

women underwent in vitro fertilization (IVF).

Methods

Retrospective observational study that included women submitted to a first IVF

Non-diabetic

cycle in an infertility center of a public hospital in 2015.

TID (NZ63; median

(NZ42; median

T2D TID (NZ32;

(NZ55; median

Results

age Z32; median

age Z34.5; median

median age Z38;

age Z34; median

BMIZ25.5)

BMIZ27.4)

median BMIZ36)

BMIZ35.1)

We included 102 women with a mean age of 33.2 years (G3.7). 69 (67.6%) were

in normal weight range, 22 (21.6%) were overweight and 11 (10.8%) were obese.

Androsten-

5.1

(1.4-13.1)

3.6

(0.0-16.9)

2.5

(0.0-14.1)

3.8

(0.4-15.5)

dione (nM)

PZ0.0005

PZ0.0035

The mean values of basal serum FSH and LH were 6.6 mIU/ml (G2.7) and

DHEA-OX

10.1

(2.0-44.0)

12.0

(1.3-43.7)

5.7

(0.0-15.3)

13.5

(1.1-51.0)

5.9 mIU/ml (G3.8) respectively. The antral follicles count (AFC) on day 2-3 of

(nM)

P !0.0001

the cycle was on average 14.2 (G6.9). 46 (45.1%) women underwent IVF cycle

DHEAS

(1.3-14.3)

5.0

(1.1-14.7)

6.0

(2.2-13.9)

4.3

(1.3-13.1)

(uM)

PZ0.0045

and 56 (54.9%) underwent IVF with intracytoplasmic sperm injection. The

FT (%)

1.1

(G SEM 0.05)

1.4

(G SEM 0.07)

2.0

(G SEM 0.11)

1.6

(G SEM 0.056)

average duration of stimulation and dose of FSH administered was 9.8 days

PZ0.0015

PZ0.0005

(G2.3) and

1622.1UI

(G647.7) respectively. There were no statistically

significant differences in the 3 groups of BMI in relation to the women’s age,

FSH levels, AFC and neither in relation to the number of oocytes obtained. In our

sample, age and AFC were the factors that correlated with the number of oocytes

DOI: 10.1530/endoabs.49.EP1153

(P!0.001). Obese women had significantly fewer live births than overweight

women (PZ0.027) and this last BMI group (average BMI 26G0.9) had more live

births. There were no differences in embryo quality or number of embryos frozen

in these three groups.

Conclusions

Increased age and decreased AFC are negative determinants in the number of

oocytes obtained. Although BMI groups had no difference in the number or

EP1154

quality in the oocytes collected, obese women had a significant lower probability

Anti-mullerian hormone a marker for metformin therapy efficacy in

of having a live birth after IVF.

PCO: a pilot study on Egyptian population

DOI: 10.1530/endoabs.49.EP1155

Nermin Sheriba, Mona Mohamed Abdelsalam, Bassem Mourad,

Madiha Mamdouh & Eltohamy Samia

Ain Shams University, Cairo, Egypt.

Background

Polycystic ovarian syndrome (PCO) is the most common endocrinopathy in adult

women, and is emerging as a common cause of menstrual disturbance in the

EP1156

adolescent population. Insulin resistance, which is considered one of its

Anti-Mullerian hormone level is independently affected only by the

underlying causes, has increased substantially in the past decade, putting more

ovarian factor among clinical and endocrinological factors in polycystic

adolescent girls at risk for PCOS and its complications. Anti - Mullerian hormone

ovary syndrome

(AMH) is secreted by the granulose cells of ovarian follicles and correlated with

Toshiya Matsuzaki, Munkhsaikhan Munkhzaya, Takeshi Iwasa,

count of small antral follicles and it is expressed throughout folliculogenesis.

Altankhuu Tungalagsuvd, Kiyohito Yano, Yiliyasi Mayila &

Objective

Minoru Irahara

Evaluation of AMH in Egyptian women with PCOS and if it might serve as a

Tokushima University, Kuramoto-cho, Tokushima, Japan.

prognostic marker for treatment efficacy with metformin.

Patients and methods

The study included 30 women with PCOS (group 1) and 30 healthy women

without PCOS (group 2). AMH is measured in both groups and before and after

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 6-10% of

treatment with metformin (2550 mg) for 3 months in group I.

women. We evaluated the correlations between the serum AMH level and various

Results

endocrine and metabolic features in PCOS. Serum AMH level was compared

AMH levels was higher in PCO groups before (3.54G0.58 ng/ml) and after

between 114 PCOS patient (PCOS group) and 95 normal menstrual cycle women

treatment (2.79G0.39 ng/ml) than the control group (2.14G0.49 ng/ml) with

(Control group). Correlations between serum AMH level and various endocrine

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

and metabolic factors were analysed in PCOS group. The serum AMH level was

Aim

significantly higher in the PCOS group (8.35G8.19 ng/ml) than in the Control

Has testosterone undecanoat 1000 mg injection (Nebido^R; Bayer), 1/3month

group (4.99G3.23 ng/ml). The serum AMH level was independently affected by

negative effect on prostate?

age and the presence of PCOS on multiple regression analysis. Ovarian volume

Material and method

per ovary (OPVO) showed the strongest positive correlation (rZ0.62) with the

i) PSA (ng/ml) was registred retrospective (from files) and prospective analysis

serum AMH level among clinical factors. OPVO was the only independent factor

(onset 2010). ii) Patients: PSA analysis was done before treatment and recorded at

that affected the serum AMH in PCOS on multiple regression analysis. Serum

T1 to T12 [2 weeks to 9 years] (see Pisoschi, this Congress). iii) Statistical

AMH level is determined only by ovarian morphological factor and the other

analysis: Student test, simple correlation, multiple regression.

pathophysiological factors such as androgen, severity of anovulation and insulin

Results

resistance are not determinant factors in PCOS even if significant relationship

A. Patients at onset: 160 men, 18-96 years, average: 60.38; median: 60; no

exists.

prostatic cancer. B. Prostatic volume (cmc): average: 34.81. C. Average PSA (no

DOI: 10.1530/endoabs.49.EP1156

patients): before treatment Z1.60 (160); 1yZ1.69 (110); 2yZ1.4 (83); 3yZ1.85

(57); 4yZ2 (46); 5yZ1.86 (34); 6yZ1.51 (30); 7yZ2.86 (2); 8yZ1.99 (11);

9yZ1.90 (4). D. Statistical difference of increasing average: nonsignificant for all

times from 2 weeks to 9 years. E. Correlation between age and PSA was 1.

significant at: T0: rZ0.29; 1y: rZ0.35; 2y rZ0.28. 2. nonsignificant for 3 to 9

years (rZ0.14-0.73). F. Correlation between PSA and prostatic volume was

significant, both before and after treatment

(depending on group size).

G. Observations: 7 patients died; 1 during treatment, Klinefelter, 41 y, cerebral

tumor; remaining 6 after 2 years stoping tretament, 60& 83-91 y, most cardiac

stop. H. Multiple regression test shows p values /0.001 for all years (examples):

Male Reproduction

1y: R² Z0.58, FZ50.24 / 9y: R² Z1, FZO1000.

EP1157

Conclusions

i) Testosterone undecanoat 1000 mg injectable i.m. at 3 months did not increased

Analysing by decade, testosterone undecanoat depot injectable does not

PSA level after up to 9 years administrations. ii) PSA level post testosterone does

increases prostate volume. Study during up to 9 years on hypogonadic

not depend on testosterone administration but on age, prostatic volume, before

patients. (December 2016)

and after treatment, and initial PSA level, i.e. before testosterone administration.

Matei Pisoschi¹, Dana Cristina Staicu² & Dan Peretianu²

¹Hospital CF2, Department of Urology, Bucharest (Bucuresti), Romania;

DOI: 10.1530/endoabs.49.EP1158

²Medical Center Povernei, Department of Endocrinology, Bucharest

(Bucuresti), Romania.

Aim

Re-analyzing

(study starting in

2007) the effect of injectable testosterone

undecanoat depot (TUD) in hypogonadic patients.

Materials and Methods

A. Patients: at onset 231 men with hypogonadism (median: 62 y). B. Distribution:

by decade (starting with 20y); no Z4, 14, 24, 61, 63, 49, 17, 1. C. TUD (Nebido^R-

Bayer) 1000 mg injected one/3 months i.m. D. Prostate volume (PV) appreciated

EP1159

by per-abdominal ultrasound:

3.5-5 MHz probe, elliptical/3D

(cm³). E.

patients were opperated before starting testosteron, 2 patients were opperated

Induction of male puberty in patients with hypogonadism hypogona-

during treatment. F. Analysis Time: before starting testosterone (T0), after 1/2

dotrope with subcutaneous gonadotropin

month (T1Z231), 3m (T2Z182), 6m (T3Z149), 1y (T4Z123), 2y (T5Z90), 3y

Paloma Moreno-Moreno, Concepción Mun˜ oz-Jiménez, María

(T6Z62), 4y (T7Z48), 5y (T8Z40), 6y (T9Z33), 7y (T10Z22), 8y (T11Z11),

Rosa Alhambra-Expósito & María Ángeles Gálvez-Moreno

9y (T12Z4). G. Maximum increment from T0 noted D M %. Average increment

Management Unit of Clinical Endocrinology and Nutrition, University

noted D A %. H. Statistical analysis: Student test.

Hospital Reina Sofía, Córdoba, Andalucia, Spain.

Results

I. All average prostatic volume for decade - tabulated (see pdf). Maximum

Objective

increment (D M %) per decade, including the moment (D M % at) and average

The most used therapeutic guidelines for the induction of male puberty in

increment (D A %) - tabulated (see pdf). II. PV at T0 increases with age, from

hypogonadotropic hypogonadism (HH) are GnRH in subcutaneous pulsatile

minimum 15.38

(19-29y) to maximum

45.5

(80-89y), PZ0.0007. III.

infusion and HCG in monotherapy or combined with FSH in intramuscular

Considering all observations, TUD did not increase PV significantly; in fact the

injection. The objective of this study was to evaluate the efficacy of subcutaneous

average of increment in all patients was negativeZK22.38%. D M % per decade:

HCG with or without FSH in induction of male puberty in patients with HH.

45.95; 31.82; 56.41; 55.77; 45.45; 64.41; 42.11; 20 IV. Inside a specific decade no

Patients and methods

significant increased in PV was registered: all PO0.05; exception: 80-89 decade,

Descriptive study of patients with HH treated with HCG subcutaneously (s.c.)

PZ0.002, from 3 to 5 y. V. In some patients, especially from 40-79 years, TUD

with or without FSH, for induction of male puberty (2004-2015). The Treatment

could decrease slightly prostatic volume.

was initiated with HCG 500 UI/72h s.c., periodic monitoring of testosterone,

Conclusions

testicular volume and semen analysis was realized, adjusting doses up to 2500

Considering the risk for prostate (in elderly), testosterone undecanoat 1000 mg

UI/72h. If no answer obtained after one year, combined treatment with FSH s.c.

depot injectable is a safe treatment, even after

9 years of administration.

was started.

Precautions should be accorded to men over 80 y old, after the 2nd year

Analyzed data

administration.

Cause of HH, age, testosterone levels, testicular volume, semen, dose of HCG and

DOI: 10.1530/endoabs.49.EP1157

FSH treatment. Pubertal development assessed by testosterone levels, testicular

volume and normalization of spermatogenesis.

Results

Nine patients. 17.2G1.8 years old (15-20). Cause of HH: four Idiopathics, four

craniopharyngiomas and one adenohypophysis hypoplasia. Dose of HCG: 1666G

821.6U/72 h. Two patients required combined treatment with FSH. Treatment

period: 32.2G9.5 months. Testosterone levels were normalized in 100% of cases

(7.34G5.1 ng/ml). 95% increased testicular volume: 13.5G4.4 ml (10-20). The

spermiogram was performed in 80% of cases at the end of treatment, with

oligospermia in all cases. No presence of side effects.

Conclusions

EP1158

Subcutaneous gonadotropin therapy is effective in induction of male puberty in

After 9 years observation, testosterone undecanoat 1000 mg at 3 months

HH. Treatment with subcuataneous HCG alone is successful. No presence of side

did not increased Prostatic Specific Antigen level (December 2016)

effects.

Matei Pisoschi

DOI: 10.1530/endoabs.49.EP1159

¹Department of Urology, Hospital CF2, Bucharest (Bucuresti), Romania;

²Medical Center Povernei, Bucharest (Bucuresti), Romania.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1160

Conclusion

Patients with lymphoma have an increased risk for poor semen quality before any

Semen quality in young, healthy men is not related to serum

treatment.

74% of these men in our study had abnormal semen parameters

concentration of vitamin D (AndroLS)

according to the WHO. Generally, all patients with newly diagnosed lymphoma’s

Pawel Jozkow¹, Aleksandra Zagrodna¹, Marek Medras^1,2, Felicja Lwow³ &

need counselling about their reproductive function and semen cryopreservation

Malgorzata Slowinska-Lisowska¹

should be offered before undergoing gonadotoxic treatment.

¹Department of Sports Medicine and Dietetics, University School of

Physical Education, Wroclaw, Poland;²Department of Endocrinology,

DOI: 10.1530/endoabs.49.EP1161

Diabetology and Isotope Therapy, Wroclaw Medical University, Wroclaw,

Poland;³Department of Health Promotion, University School of Physical

Education, Wroclaw, Poland.

Introduction

Relationships between vitamin D and male fertility are not fully elucidated.

EP1162

Studies in infertile/subfertile subjects suggest that vitamin D status may be

associated with semen parameters (1, 2). Data from healthy men is inconclusive

(3,

4). Our purpose was to evaluate the andrological status and a range of

biochemical, dietary and lifestyle variables in healthy men aged 18-35, living in

Abstract withdrawn.

the region of Lower Silesia (Poland) (AndroLS).

Material and methods

We invited

5000

subjects to participate in the study. From among

500

respondents, we acquired necessary material (semen and blood) from 177 men.

The specimens were collected in autumn and winter. The semen samples were

evaluated according to WHO 2010 criteria by a single experienced medical

analyst.

Results

Only minority of the studied subjects (18%) had serum 25(OH)₂D₃ concentration

above the lower limit

(20 ng/ml).

39% had severe vitamin D deficiency

(!10 ng/ml). Mean (GS.D.) 25(OH)₂D₃ was 13.7G8.9 ng/ml. Mean (GS.D.)

semen volume in the volunteers was: 3.1G1.5 ml, sperm concentration: 60G

44!10⁶/ml, total sperm count: 170G137!10⁶/ejaculate, percent of normal

forms: 14.7G6.5%. None of the studied semen parameters correlated with serum

concentration of

25(OH)2D3. We did not observe any correlations after

adjustments for: alcohol consumption, cigarette smoking, carrying a mobile

EP1163

phone in pants’ pockets, body mass index, caffeine consumption and physical

Gonadal profile in men with early-onset androgenetic alopecia: does a

activity, either.

male PCOS-equivalent syndrome exist?

Conclusions

Rossella Cannarella¹, Rosita A Condorelli¹, Sandro La Vignera¹, Laura

Our data suggest that serum concentration of 25(OH)₂D₃ cannot indicate semen

M Mongioì¹, Enzo S Vicari¹, Giuseppe Micali² & Aldo E Calogero¹

quality in healthy men.

¹Department of Clinical and Experimental Medicine, University of Catania,

DOI: 10.1530/endoabs.49.EP1160

Catania, Sicily, Italy;²Dermatology Clinic, University of Catania, Catania,

Sicily, Italy.

Importance

Early-onset androgenetic alopecia (AGA) has been suggested as a phenotypic

sign of the male polycystic ovary syndrome (PCOS)-equivalent since men with

this feature have a PCOS-like hormonal pattern. No study has evaluated the

gonadal function of these men.

Objective

EP1161

To study the gonadal function of men with early-onset AGA and to identify

suggestive criteria of male PCOS-equivalent.

Semen quality in patients with newly diagnosed lymphoma’s

Kristijan Peros, Dubravka Majic Milotic, Tomislav Bozek, Mia

Design

Sunjic Stakor, Kristina Kljajic Babic, Vesna Dermanovic Dobrota &

This case-control study was conducted from January 2014 to June 2016.

Sasa Magas

Setting

Vuk Vrhovac University Clinic, Clinical Hospital Merkur, Zagreb, Croatia.

The study was carried out on patients referring to hospital for andrological

check-up.

Participants

Objective

Forty-four men with early-onset AGA (19-30 years) and 37 aged-matched

To analyse the semen quality in patients with newly diagnosed lymphoma’s

healthy men (controls) were enrolled. A subgroup of patients was assumed to

before starting the treatment.

have the male PCOS-equivalent (sAGA) when at least one of the following

Materials and methods

parameter was present: BMI O25 kg/m², insulin-resistance (IR) (HOMA index

We evaluated semen quality in 131 patient with lymphoma who underwent sperm

O2.5), SHBG !25 nmol/l. The remaining patients were considered to have AGA

banking in our clinic over a

14-year period.

102 patients had Hodgkin’s

alone (aAGA).

lymphoma, and 29 had non-Hodgkin’s lymphoma. Semen samples were collected

Main outcome(s) and measure(s)

by masturbation after 2-7 days of sexual abstinence. Age at banking, semen

The primary outcome was to evaluate the gonadal function and the

volume, sperm concentration, and total and progressive sperm motility were

metabolic/hormonal features of men with early-onset AGA. The secondary

recorded. Semen parameters were compared to established World Health

outcome was to identify which parameters may be used to suspect the male

Organisation

(WHO) reference values

(WHO Laboratory Manual for the

PCOS-equivalent syndrome among men with early-onset AGA.

Examination and Processing of Human Semen, Fifth Edition, 2010).

Results

Patients had higher mean (GS.D.) BMI (25.5G3.8 vs 23.7G3.0 kg/m²; P!0.05)

The median age of these patients was 26 years (range 17-43); median semen

and 17aOH-progesterone (2.05G0.90 vs 1.51G0.62 ng/ml; P!0.05) compared

volume was 2.0 ml (range 0.1-6.5); median sperm concentration was 63.8!106

to controls. sAGA had higher levels of insulin (11.8G1.7 vs 6.0G0.4 mU/ml;

per ml (range 0-413); median total and progressive sperm motility were 40%

P!0.01) and LH (4.9G2.1

3.8G1.4 mIU/ml; P!0.05), lower total

(range 0-84) and 24% (range 0-69), respectively. According to the reference

testosterone (TT) levels (5.2G1.7 vs 6.3G1.6 ng/ml; P!0.05) and left testicular

values of the WHO 34 patients (26%) in this series had a semen quality within the

volume (TV) (12.3G2.8 vs 15.4G4.1 ml; P!0.05) compared to aAGA. sAGA

normal range, and 97 patients (74%) had abnormal semen quality. In 2 patients

also had higher fat-mass percentage

(17.6G4.1

13.2G5.3%; P!0.05),

(1.5%) the semen samples were not frozen because of azoospermia

(no

DHEAS (323.3G112.6 vs 257.8G107.1 mg/dl; P!0.05) and seminal fluid

spermatozoa in the ejaculate).

patients

(52.7%) had single damages

volume (4.2G2.8 vs 2.8G1.3 ml; P!0.05), lower TT (5.16G1.70 vs 6.47G

(oligozoospermia or asthenozoospermia) and 26 patients (19.8%) had combined

4.30 ng/ml; PZ0.016) and left TV

(12.3G2.8 vs 15.0G4.3 ml; P!0.05)

damages (oligoasthenozoospermia).

compared to controls.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion and relevance

Introduction

Men with early-onset AGA and at least one among the following parameters BMI

The prevalence of cardiometabolic disorders such as type 2 diabetes mellitus,

O25 kg/m², IR, SHBG !25 nmol/l had a borderline-low left TV and a impaired

dysipidemia and metabolic syndrome is increased in patients with Klinefelter

gonadal steroidogenesis. Hence, they might have a greater risk to develop a

syndrome (KS). The mechanism by which cardiometabolic risk increases in

gonadal dysfunction later in life. These criteria may be used to suspect the male

patients with KS remains to be completely elucidated. We investigated the

PCOS-equivalent.

presence of inflammation, insulin resistance and endothelial dysfunction in an

DOI: 10.1530/endoabs.49.EP1163

unconfounded population of KS.

Methods

A total of 31 patients with KS (mean age 21.59G1.66 years) and 33 healthy

control subjects (mean age: 22.15G1.03 years) were enrolled. The demographic

parameters, Asymmetric dimethylarginine (ADMA), high sensitive C reactive

protein

(hs-CRP) and homeostatic model assessment of insulin resistance

(HOMA-IR) levels were measured in patients and controls.

Results

The patients had higher insulin, HOMA-IR and ADMA levels (P! 0.001 for all)

and lower HDL-C (PZ0.002) and total testosterone (P! 0.001) levels, compared

to the healthy controls. There were significant negative correlations between the

total testosterone levels and ADMA (rZK0.479, P! 0,001), hsCRP (rZK

0.291, PZ0.034), and significant positive correlation with HDL-C (rZ0.429,

EP1164

PZ0.001) levels. The multivariate analysis has shown that total testosterone

Improved conception of the normative values of testosterone in men

(bZK0.412, PZ0.001) and TG (bZ0.332, PZ0.009) levels were the significant

with type 2 diabetes

independent determinants of the plasma ADMA levels.

Irina Khripun¹, Sergey Vorobyev¹, Elizaveta Dzantieva¹, Igor Belousov¹,

Conclusion

Michail Kogan¹ & Michael Zitzmann²

The results of the present study show that endothelial dysfunction and insulin

¹Rostov State Medical University, Rostov-on-Don, Russia;²University

resistance are prevalent even in the very young subjects with KS, who have no

Clinics Muenster, Muenster, Germany.

metabolic or cardiac problems at present.

DOI: 10.1530/endoabs.49.EP1165

Background

Men with type 2 diabetes mellitus (T2DM) have significantly lower levels of

testosterone (T) than nondiabetic controls. But androgen deficit symptoms may be

detected in males with normal T levels.

Aim

To analyze parameters of lipid, carbohydrate metabolism and endothelial function

in diabetic males with low normal and middle-to-high normative T levels.

Patients and methods

We examined 86 men with T2DM and serum T levels higher than 12.1 nmol/l.

Parameters of total T, lipid metabolism, HbA1c, biochemical markers of

EP1166

endothelial function

- NO, endothelial NO synthase type

(NOS3) were

Testosterone is poorly related to erectile dysfunction in young/middle

analyzed. The patients were divided into two groups: 1-23 men with T levels

aged human immunodeficiency virus-infected men

12.1-14.9 nmol/l, 2-63 patients with T levels S15.0 nmol/l. Statistic analysis

Sara De Vincentis¹, Daniele Santi¹, Maria Chiara Decaroli¹,

was performed using Mann-Whitney U-test and Spearmen rank correlation

Flaminia Fanelli^2,3, Marco Mezzullo^2,3, Alessia Fazzini^2,3, Anna Ansaloni¹,

method.

Uberto Pagotto^2,3, Giovanni Guaraldi⁴ & Vincenzo Rochira¹

Results

¹Unit of Endocrinology, University of Modena and Reggio Emilia, Modena,

The HbA1c value was 8.7% (6.7; 9.8) in 1st group and 7.7% (6.4; 9.2) in 2nd

Italy;²Unit of Endocrinology, University of Bologna, Bologna, Italy;

group (PO0.39), but the proportion of patients with HbA1c levelO7% was

³Center for Applied Biomedical Research, University of Bologna, Bologna,

higher in group 1 (71% vs 58.6%) as compared to group 2 (PZ0.002). In patients

Italy;⁴Unit of Infectious Diseases, University of Modena and Reggio

with T levels lower than 15.0 nmol/l, higher levels of serum cholesterol (38.1% vs

Emilia, Modena, Italy.

27.6%), triglycerides (40.0% vs 24.1%) and low density lipoproteins (26.3% vs

17.2%) as compared to the 2nd group were found (P!0.01). There was a

significant correlation in the T concentrations with NOS3 levels jrjZ0.350 in 1st

Background

and jrjZ0.266, (P!0.05) in 2nd group. Vascular endothelial dysfunction as

human immunodeficiency virus (HIV)-infection is strongly associated to erectile

assessed by ultrasonographic measurement of the dilatation of the brachial artery

dysfunction (ED) in men. Preliminary data suggests that ED is poorly associated

was more frequent in patients of group 1 compared to group 2 (55.6% vs 23.8%,

with serum T in HIVC men.

PZ0.02).

Aim

Conclusion

To investigate in HIV-infected men the relationship between sexual function as

Males with T2DM and low-normal T level are at higher risks of dyslipidemia,

assessed by the validated International Index of Erectile Function (IIEF-15) and

endothelial dysfunction and progression of T2DM as compared to men with

T deficiency using Liquid Chromatography-tandem Mass Spectrometry

serum T higher thanO15 nmol/l.

(LC-MS/MS).

Acknowledgments

Methodology

Supported by RSF, grant No. 14-25-00052.

Prospective, cross-sectional, observational study on HIV-infected male patients

DOI: 10.1530/endoabs.49.EP1164

with ongoing Highly Active Antiretroviral Therapy (HAART), attending the

Clinic of Infectious Diseases. IIEF-15 and IIEF-5 questionnaires were used to

define ED, while LC-MS/MS was used for hormonal assays.

Results

233 consecutive HIV-infected patients were enrolled (mean age 45.29G5.33

years). Eight patients (3.4%) had total T !300 ng/dl, while 142 patients (61.5%)

had ED (score %25). Age, hormonal data and duration of HIV-infection and

HAART did not differ among groups of patients according to the degree of ED.

The direct comparison of each ED cluster showed that months of infection were

EP1165

significantly higher in men with severe ED compared to mild ED (PZ0.037). The

Endothelial dysfunction, inflammation and insulin resistance in patients

erectile function domain at IIEF-15 was directly correlated with IIEF-5 score

with Klinefelter Syndrome

(0.778, P!0.001), as expected. Moreover, the IIEF-15 score was inversely

Cem Haymana¹, Aydogan Aydogdu¹, Ibrahim Demirci¹, Mustafa Dinc¹,

related to months of infection (K0.147, PZ0.026), but not to months of HAART

Orhan Demir¹, Deniz Torun², Fatih Yesildal³, Coskun Meric¹,

therapy (K0.121, PZ0.071).

Yalcin Basaran¹, Alper Sonmez¹ & Omer Azal¹

Conclusions

¹Gulhane Training and Research Hospital, Department of Endocrinology

To the best of our knowledge, this is the first, properly-designed prospective study

and Metabolism, Ankara, Turkey;²Gulhane Training and Research

aiming to investigate the relationship between erectile function and serum T,

Hospital, Department of Medical Genetics, Ankara, Turkey;³Selahaddin

assessed by LC-MS/MS in HIV-infected men. In our cohort, i) IIEF-5 is reliable

Eyyubi Public Hospital, Department of Biochemistry, Diyarbakir, Turkey.

as IIEF-15 for ED diagnosis, ii) ED is not associated with serum T, iii) erectile

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

function is not influenced by T and HAART, but only by HIV-infection duration.

EP1169

In conclusion, several specific factors, such as the duration of HIV infection, are

Can salivary testosterone be used in the monitoring of men using

involved in erectile function in HIV-infected men and should be carefully

transdermal testosterone replacement therapy?

considered in this setting, while hormonal status seems to be less important.

Tomas Ahern¹, Jo Adaway², Phillip Monaghan¹, Peter Trainer¹ &

DOI: 10.1530/endoabs.49.EP1166

Brian Keevil²

¹The Christie NHS Foundation Trust, Manchester, UK;²University Hospital

of South Manchester, Manchester, UK.

In community-dwelling men, salivary testosterone (Sal-T) concentrations are

thought to represent tissue hormone levels and correlate strongly with serum free-

T levels. Measurement of salivary glucocorticoid concentrations is a non-invasive

and objective means of assessing cortisol exposure in users and non-users of

hydrocortisone therapy. We assessed relationships of Sal-T with transdermal

testosterone replacement therapy (TD-TRT) and with markers of testosterone

EP1167

exposure. In 40 men aged 50.7 (G13.9) years who were attending a university

Early arterial stiffness and chronic inflammation in male equivalents of

hospital endocrinology clinic, we measured serum and salivary androgen

polycystic ovary syndrome

concentrations by immunoassay and liquid chromatography tandem mass

Mehmet Sozen¹, Suleyman Baldane², Sedat Abusoglu³, Levent Kebapcilar²,

spectrophotometry (LC-MS/MS) respectively. In our unit, TD-TRT (Tostran

Aysegul Kebapcilar⁴, Fatma Akyurek⁵, Ali Unlu³ & Suleyman

2% Gel at an initial dose of 30-60 mg of testosterone once daily) is offered to men

Hilmi Ipekci²

with sexual symptoms and low fasting serum testosterone (Ser-T) concentrations

¹Deparment of Internal Medicine, Selcuk University Faculty of Medicine,

on at least two consecutive occasions. Ser-T concentrations did not differ between

Konya, Turkey;²Division of Endocrinology and Metabolism, Selcuk

users

(nZ23) and non-users

(nZ17) of TD-TRT (16.6G10.2 vs

11.4G

University Faculty of Medicine, Konya, Turkey;³Department of

4.4 nmol/l, PZ0.131). Sal-T concentrations, however, differed greatly (17.14G

Biochemistry, Selcuk University Faculty of Medicine, Konya, Turkey;

15.25 vs 0.23G0.15 nmol/l, P!0.001) as did salivary androstenedione (Sal-A4)

⁴Department of Obstetrics and Gynecology, Selcuk University Faculty of

concentrations (2.57G4.50 vs 0.17G0.04 nmol/l, P!.001) and Sal-T/Sal-A4

Medicine, Konya, Turkey;⁵Department of Dermatology, Selcuk University

(16.26G14.25

1.45G0.94, P!0.001). Haematocrit and serum prostate

Faculty of Medicine, Konya, Turkey.

specific antigen concentrations (PSA) did not differ significantly between the

two groups (0.44G0.05 vs 0.43G0.05 l/l, PZ0.563 and 1.06G0.66 vs 0.79G

0.53 ng/ml, PZ0.170 respectively). With TD-TRT, there was a rise in blood

Introduction

testosterone (4.7G4.2 to 7.9G5.7 nmol/l, PZ0.162), haematocrit (0.42G0.05 to

There is some evidence that a rise in the androgen hormone levels increases the

0.44G0.04 l/l, PZ0.049) and PSA (0.68G0.33 to 1.06G0.76 ng/ml, PZ0.021)

risk for the development of a cardiovascular disease, obtained from the studies

levels. Two hours after a dose of TD-TRT, Ser-T rose modestly (10.5G13.2 to

conducted on women with polycystic ovary and on men with androgenic alopecia.

16.6G11.0 nmol/l, PZ0.003) and Sal-T rose tremendously (7.7G8.1 to 17.0G

Inflammatory substances tend to increase in polycystic ovary syndrome and in

16.9 nmol/l, PZ0.004). Despite normal Ser-T, haematocrit and PSA concen-

androgenic alopecia. On this basis, we conducted a study that aimed to evaluate

trations, Sal-T concentrations are 75-fold greater than normal in men using

the early cardiovascular and metabolic effects in male patients with androgenic

TD-TRT. This is unlikely due to contamination (Sal-A4 concentrations are also

alopecia.

high) and may be due to a conduit between skin, the lymphatic system and

Methods

salivary ducts. Measurement of Sal-T is unlikely to be useful in the monitoring of

A total of 81 people, of whom 41 were patients with androgenic alopecia and 40

men using TD-TRT.

were healthy controls, were included in the study. Aged from 25 to 45, none of

DOI: 10.1530/endoabs.49.EP1169

them had any cardiovascular risk factors, malignancy, any active infections and

any liver or kidney diseases. Ambulatory blood pressure was measured for 24 h

and sensitive CRP and galectin-3 were studied so as to assess the cardiovascular

and metabolic risk.

Results

There were no differences between the patient and control groups in terms of

ambulatory blood pressure of 24 h, sensitive CRP and galectin-3. A positive

correlation was found in the patient group between sensitive CRP and waist and

neck circumferences. While there was a positive correlation in the patient group

between galektin-3 and HOMA-IR, waist and neck circumferences, a negative

correlation was seen with free testosterone. Alopecia level correlated positively

with daytime pulse wave velocity and night time reflection magnitude.

Conclusion

EP1170

We did not find any difference in our study in terms of arterial stiffness and

Changes of dihydrotestosterone within the life in men

chronic inflammation in the early period when the control and androgenic

Hana Pospíšilová, Michaela Dušková, Martin Hill & Luboslav Stárka

alopecia groups were compared; however, a positive correlation between alopecia

Institute of Endocrinology, Prague, Czech Republic.

level and daytime pulse wave velocity and night time reflection magnitude may be

considered as an early signal for atherosclerosis.

DOI: 10.1530/endoabs.49.EP1167

Abstract

Dihydrotestosterone (DHT) is the most powerful naturally occurring androgen

with three to six times higher biopotency than testosterone. Time onset of benign

prostatic hyperplasia and alopecia in middle life could be the result of an

imbalance between androgens. The decline of testosterone during lifespan is well

known, controversial data can be found concerning the age dependence of DHT

levels. We analysed the levels of testosterone, dihydrotestosterone and SHBG

from 3076 men and we observed changes of their relationship and the ratio of total

and free fraction of T and DHT, depending on age in men. We found that the

DHT/T and fDHT/fT ratios during the life of adult males are constant, and that

there is no evidence of a reversal in ratios of these hormones after puberty. Given

EP1168

that the ratio DHT/T remains constant during the age, the role in the development

of androgenetic alopecia and benign prostatic hyperplasia is rather unlikely. The

question remains, however, local status in androgen-dependent tissues, which

Abstract withdrawn.

would change the expression of enzyme, it could be caused just by local change in

this ratio. This study was supported by the project MZCR for conceptual

development of research organization 00023761 Institute of Endocrinology and

grant 17-28692A.

DOI: 10.1530/endoabs.49.EP1170

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1171

dose, form or duration of intake were included in the review. Main outcomes were

AAS effects on the reproductive system of athletes, as assessed by medical

Male pseudohermaphroditism with 45,X/46,X,idic(Y) karyotype: a case

history, clinical examination, hormone analysis and/or semen analysis.

presenting with dysgenetic testis on one side and almost normally sized

Results

testis on the other side

Twenty-six studies were included in the review, involving 963 participants, with

Flavia Di Bari¹, Roberto Vita¹ & Salvatore Benvenga^1,2

the median (25th-75th percentile) duration of AAS intake being 16 (8-100.8)

¹Department of Clinical and Experimental Medicine, University of Messina,

weeks. Most studies showed that gonadotropin and testosterone levels decreased

Messina, Italy;²Interdepartmental Program of Molecular & Clinical

during the period of AAS intake, whereas following AAS cessation, they

Endocrinology, and Women’s Endocrine Health, University hospital

gradually returned to normal levels. The majority of AAS users demonstrated

Policlinico G. Martino, Messina, Italy.

prolonged hypogonadism with persistently low gonadotropin and testosterone

levels, lasting for several weeks to months after AAS withdrawal. Most studies

have also shown that AAS use results in structural and functional sperm changes,

Dicentric Y chromosome [idic(Y)] is the most common structural abnormality of

reduction of testicular volume, as well as clitoromegaly and menstrual

this chromosome, and generally results from altered meiotic breakage and reunion

irregularities. Only 2 out of 26 studies determined AAS effects on fertility and

of sister chromatids. Since this rearrangement is unstable, idic(Y) may be lost in

only 2 studies involved female athletes.

subsequent cell cycles, resulting in a mosaic 45,X cell line. Variable are the

Conclusion

phenotype and gonads (from streak gonads to ovotestes or dysgenetic testes). Few

AAS use results in profound and lasting effects on the reproductive system of

cases of 45,X/46,X,idic(Y) male pseudohermaphroditism with testes have been

athletes and potentially on fertility. Targeted education about AAS abuse and

reported. We report the case of a 26-yr-old 45,X/46,X,idic(Y) male born at 38

thorough monitoring are needed to prevent negative long-term effects.

weeks’ uncomplicated gestation who consulted us for infertility. At 3 years, he

DOI: 10.1530/endoabs.49.EP1172

presented with cryptorchidism, micropenis and scrotal hypospadias. Congenital

adrenal hyperplasia was excluded (17OH-progesterone 0.7 ng/ml, testosterone

!20 ng/ml). Scrotal ultrasound revealed the absence of the right testis (RT). RT

was eventually found in the pelvis, where uterus and ovaries were absent.

Hypospadias repair was performed. The undescended RT, which histologically

was described as testicular tissue with fibrosis, was surgically fastened inside the

scrotum. At age 26, the patient was slightly overweight (BMI 25.8 kg/sqm), with

a male phenotype, normal androgenization and no gynecomastia. He had a

satisfactorily engagement with her partner. The RT was hardly palpable, while the

left testis was reduced in volume and consistency. At ultrasound, RT was atrophic

(1.4 ml), while the left was 10 ml, and both had a hypoechoic and inhomogeneous

texture. FSH, androstenedione and 17OH-progesterone were high (30 mU/ml, 4.1

and 3.4 ng/ml), LH high-normal (9.6 mU/ml), total testosterone low-normal

(348 ng/dl), and calculated free-testosterone low (6.1 ng/ml). The response of

17OH-progesterone after cosyntropin stimulation was normal. E2, progesterone,

EP1173

and SHBG were within the female reference range (53 pg/ml, 3.4 ng/ml, and

Gonadal status in males with acute coronary syndrome and the extent of

37.7 nmol/L). Azoospermia was detected at semen analysis. Considering the risk

coronary artery disease: a comparative cross-sectional analysis

of malignancies within the dysgenetic gonad

(10-15%), we advised right

Adriana Bednárová, Tomáš Koller, Martin Kužma & Juraj Payer

gonadectomy.

Comenius University Faculty of Medicine, 5th Department of Internal

DOI: 10.1530/endoabs.49.EP1171

Medicine, University Hospital Bratislava, Bratislava, Slovakia.

Introduction and aims

Association between coronary artery disease (CAD) and male gonadal status has

been previously suggested, but still remains inconclusive. Aims of our study in

males with recent acute coronary syndrome

(ACS) were to evaluate the

prevalence of hypogonadism, to compare their gonadal status with non-ACS

matched controls and to evaluate gonadal status by the extent of CAD.

Subjects and Methods

A cross-sectional retrospective study included all consecutive males with recent

ACS and age and BMI matched non-ACS controls. Basic demography and

standard CAD risk factors were recorded as well as fasting serum levels of total

testosterone (TT), sex hormone binding globulin (SHBG), estradiol, follicle-

stimulating and luteinizing hormone (FSH and LH) and calculated free androgen

index (FAI). First, we evaluated the prevalence of hypogonadism (TT! 7 nmol/l

and FAI!24%). Second, we compared patients and control group for ACS

associated factors on univariate and multivariate analysis. Third, using the same

analysis in patients undergoing coronary angiography we aimed at identifying

EP1172

factors associated with CAD extent (0-1 vessel vs 2-3 vessel disease).

Effects of anabolic androgenic steroids on the reproductive system of

Results

athletes

96 patients and 49 controls were included. Hypogonadism was confirmed in

Maria Christou^1,2, Panagiota Christou¹, Georgios Markozannes²,

20.8% of patients. Patients had lower levels of TT (12.638G6.138 vs 15.702G

Agathocles Tsatsoulis¹, George Mastorakos³ & Stelios Tigas¹

4.903, P!0.01), FAI (30.292G12.489 vs 36.902G9.816, P!0.01) and higher

¹Department of Endocrinology, University of Ioannina, Ioannina, Greece;

levels of LH (5.58 IQR 4.4-8.21 vs 5.0 IQR 3.64-6.35, PZ0.04) compared with

²Department of Hygiene and Epidemiology, Ioannina, Greece;³Endocrine

controls. In multivariate analysis, smoking, hypertension, dyslipidemia and FAI

Unit, Aretaieion Hospital, National and Kapodistrian University of Athens,

were identified as factors independently associated with ACS.

73 patients

Athens, Greece.

underwent coronary angiography,

had findings of

2-3

vessel disease.

Hypertension, BMI and FAI were found as associated factors with CAD extent

and FAI as its single independent risk factor.

Background

Conclusion

Anabolic androgenic steroids (AAS) are widely used to improve performance

Lower gonadal status was found common (20.8%) in males with recent ACS.

and/or enhance appearance. The aim of this study was to assess the impact of AAS

It was independent on standard ACS risk factors and was independently

on the reproductive system of athletes.

associated with CAD extent.

Methods

DOI: 10.1530/endoabs.49.EP1173

An electronic literature search was conducted, using the databases MEDLINE,

CENTRAL, Scopus and Google Scholar. Studies including AAS use in any type,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1174

EP1176

An unusual karyotype in a young adult with a clinical phenotype

Methylation of the CPG islands from MTHFR promoter in male

suggesting a Klinefelter syndrome

infertility

Lourdes Garcia-Garcia-Doncel, Isabel Torres-Barea,

Suzana Vladoiu¹, Anca Botezatu², Daniela Dinu Draganescu¹,

Manuel Cayón-Blanco, Rosa Marquez-Pardo, Rosario Lopez-Velasco &

Dana Manda¹, Sabina Oros^1,3, Diana Paun³, Roxana Rosca^1,3,

Gloria Baena-Nieto

Corin Badiu^1,3 & Gabriela Anton²

Jerez Hospital, Jerez, Spain.

¹‘C.I. Parhon’ National Institute of Endocrinology, Bucharest, Romania;

²‘Stefan S. Nicolau’ Institute of Virology, Bucharest, Romania;³‘Carol

Davila’ University of Medicine and Farmacy, Bucharest, Romania.

Introduction

46 XX testicular DSD (disorder of sex development) is a rare syndrome

characterized by 46 XX karyotipe, male external genitalia, azoospermia, sterility

and usually hypergonadotropic hypogonadism in adulthood. Approximately 85%

A large number of studies are now focused on the causes of male infertility.

of individuals present after puberty with normal penile size, small testes and

Among these are epigenetic modifications, which are important contributors to

gynecomastia.

reproductive pathology in the male by providing dynamic changes of the

Case report

phenotype according to the environmental and metabolic factors. The most

We present a 34-year-old male who was referred for endocrine evaluation due to

known epigenetic modification is DNA methylation and alterations in this pattern

slightly high prolactin levels. He underwent surgical correction of bilateral

in several genes could induce male infertility. Alterations in DNA methylation

inguinal hernia at the age of 1.8 years old. Three years later, surgery was needed

patterns in several genes may lead to abnormal male sexual development and

to descend trapped right testicle, showing testicular atrophy. At age 33, the patient

infertility. MTHFR is an enzyme involved in the folate pathway and in de novo

requested medical evaluation after one year unsuccessfully attempting to father a

nucleotide biosynthesis but also a good example for gene-environment interaction

pregnancy. Erectile dysfunction and lack of libido were not present. Semen

in phenotype development. This study investigates the promoter methylation

analysis revealed azoospermia. Serum hormone evaluation detected high

status of MTHFR in infertile men from by quantitative methylation-specific PCR

gonadotropines, low-normal testosterone and normal prolactin levels: LH

in order to investigate possible correlations with sperm abnormalities. Our study

13,9 mIU/ml, FSH

32.11 mIU/ml, prolactin

15 ng/ml

[4-15], testosterone

includes patients (nZ27, median age 31 years, range 26-41 years) recruited from

311.20 ng/dl [250-836]. Physical examination revealed a descended left testicle

men seeking advice for couple infertility and control group (nZ11, median age

of 12 cm³ and a right testicle unnoticed to palpation. There was no hypospadias

30.5 years, range 24-37 years). DNA was isolated from sperm samples and

and penile size was within the normal range. Patient’s height and weight was

promoter methylation of MTHFR was quantified in qMS-PCR using bisulphite

177 cm and 70 kg, respectively. Klinefelter syndrome was suspected. Cytogenetic

treated DNA samples (EpiTect Bisulfite Kit - Qiagen). Were detected significant

procedures demonstrated a 46 XX kariotype, and the presence of SRY gene on

correlations that indicate a tendency towards promoter hypermethylation in

one of the X comosomes was detected by fluorescent in situ hibrydization.

spermatozoa with low motility

(PZ0.0130, r²Z0.3886), poor morphology

Conclusions

(PZ0.0138, r²Z0.3833) and with low sperm count (PZ0.0092, r²Z0.4184).

46 XX testicular DSD SRY-positive should also be considered in the differential

Our data suggest that the methylation patterns of the promoter of MTHFR is

diagnosis of adult hypergonadotropic hypogonadism with small testes and

linked with sperm anomalies of motility, morphology and sperm count, which

sterility. Adult diagnosis can be challenging because of normal sexual

could lead to male infertility.

development and phenotypic similarities between patients with 46 XX DSD

DOI: 10.1530/endoabs.49.EP1176

and Klynefelter syndrome, althought the latter are usually taller and show less

incidence of cryptorchidism.

DOI: 10.1530/endoabs.49.EP1174

EP1177

How relevant are the complications associated with testosterone

treatment in men with hypogonadism?

Ricardo Capitão¹, Raquel Castro², Cátia Ferrinho¹, Francisco Santos¹,

Catarina Roque¹, Carlos Bello¹, João Sequeira¹, Catarina Saraiva¹ &

Carlos Vasconcelos

EP1175

¹Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal;²Centro Hospitalar

A case with taurodontism and Klinefelter syndrome

Lisboa Norte, Lisboa, Portugal.

Isilay Taskaldiran¹, Tulay Omma¹, Anara Karaca¹, Alper Taskaldiran² &

Nese Ersoz Gulcelik¹

Introduction

¹Ankara Education and Research Hospital, Endocrinology and Metabolism,

Testosterone treatment in patients with hypogonadism has been associated with

Ankara, Turkey;²Balgat Dental Public Hospital, Ankara, Turkey.

cardiovascular and prostatic complications.

Objective

To describe the evolution of analytical parameters associated to the complications

In this paper we present an 18-year-old patient with Klinefelter syndrome who has

of testosterone treatment in a male population with hypogonadism treated with

taurodontism. Klinefelter syndrome is the most common abnormality of sex

testosterone. Methods A retrospective, longitudinal study in which the clinical

chromosomes. It is characterized by hypogonadism, gynaecomastia, azoospermia

data of male adults with hypogonadism under intramuscular testosterone therapy

or oligospermia, and increased levels of gonadotropins. Associated medical

were analysed in 2 tertiary centres. The duration and doses of testosterone were

disorders can be categorized as follows; cancer, autoimmune disorders,

recorded. Haematocrit (Hct), total cholesterol (TC), LDL cholesterol (c-LDL),

intellectuel and psychiatric disorder, osteoporosis, endocrine disorders, venous

total prostate-specific antigen (PSA) and total testosterone levels were assessed at

disease and taurodontism. Taurodontism is a developmental anomaly of a tooth

the beginning and at the end of follow-up. Paired-t-test was used to compare

characterized by large pulp chamber and short roots. It affects 0.5-3% of the

means and the results are shown in mean and standard deviation.

general population. Taurodontism is observed with several syndromes and

anomalies including Klinefelter syndrome. Endodontic treatment of taurodont

teeth is tend to be complex and difficult because of the complexity in the tooth

morphology, extraction of the taurodont teeth may be difficult and these teeth

C-LDL

have risk for early decay. This feature can be seen in permanent and primary teeth,

Hct (%)

TC (mg/dl)

(mg/dl)

PSA (ng/ml)

in a single tooth, or in several molars, and can be unilateral or bilateral.

Taurodontism must be the part of comorbidity evaluation and patients with

First

42.9G5.0

194.3G41.5

114.1G37.3

1.4G1.7

Klinefelter syndrome should have regular dental examination and care in order to

measurement

provide long term oral health and improve quality of life of patients with

Final

44.0G4.4

191.7G30.2

110.8G28.3

1.7G2.4

Klinefelter syndrome.

measurement

Difference

1.1G4.4

K2.6G38.2

K3.4G34.8

0.3G1.6

DOI: 10.1530/endoabs.49.EP1175

P-values

0.01

0.68

0.60

0.30

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

¹Department of Microscopy, Laboratory of Cell Biology, Abel Salazar

We analysed 128 patients, 35% primary and 65% secondary hypogonadism. The

Institute of Biomedical Sciences (ICBAS), University of Porto, Porto,

mean age was 49.6G17.3 years. The follow-up time was 2.6 years (0.6-9.4 years).

Portugal;²Unit for Multidisciplinary Research in Biomedicine, Abel Salazar

The mean interval between injections was 4.4G2.3 weeks. The final testosterone

Institute of Biomedical Sciences (UMIB-ICBAS), University of Porto,

was 392.0G112.7 ng/dl. The results are summarized in the table below:

Porto, Portugal;³Department of Anatomy, Abel Salazar Institute of

Treatment with testosterone resulted in increased Hct and PSA values, however

Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal;

only the Hct difference proved statistically significant. Spearman correlation test

⁴i3S - Instituto de Investiga

¸a˜o e Inovação em Saúde, University of Porto,

revealed a positive and statistically significant correlation between the increase of

Porto, Portugal.

testosterone levels and the increase of Hct (rZ0.21; PZ0.03). No hospital-

izations for cardiovascular events were reported.

Discussion

Current lifestyle, characterized by physical inactivity and a poor diet, is

The rise of Hct, although statistically significant, was low. The remaining

heavily linked with an increased incidence of metabolic diseases. One of the

parameters did not show statistically significant increases so testosterone therapy

most serious silent co-morbidities of those diseases is infertility. The

appears to be safe from a cardiovascular and prostatic perspective.

hormonal link between food intake and energy homeostasis is mediated by

the leptin ghrelin axis. Compelling evidence suggests that direct leptin’s

DOI: 10.1530/endoabs.49.EP1177

action regulates cellular glucose homeostasis and mitochondrial biogenesis.

We have recently shown that leptin modulates the nutritional support of

spermatogenesis, which may be related with obesity-related male

subfertility/infertility. Herein, we hypothesized that leptin directly affects

mitochondrial function, dynamics and biogenesis of Sertoli cells (SCs). Rat

Sertoli cells (Ser-W3) were treated (nZ5 for each group), during 24 h at

378C 5% CO₂, with different concentrations of leptin (5 ng/ml as reported in

EP1178

normal mice, 25 ng/ml as reported in obese mice and

50 ng/ml as a

Evolution of healthcare demand in a public gender identiy clinical

supraphysiological concentration) and the results were compared to a

center in Valencia (spain)

condition without leptin. Western Blot was performed to determinate

Victor Atienza Moya¹, Marcelino Gomez Balaguer¹, Felipe

protein levels of mitochondrial complexes. qPCR was performed to

Hurtado Murillo², Santiago Garcia Torres¹, Eva Maria Riera Sabater¹,

determinate expression levels of several genes involved in mitochondrial

Christian Salim Vendrell¹ & Antonio Hernandez Mijares^1,3

biogenesis and to assess mitochondrial DNA copy number. Mitochondrial

¹Endocrinology Service, Doctor Peset University Hospital, Valencia, Spain;

membrane potential was determined by JC-1. Direct leptin exposure did not

²Sexual psychology and reproductive health unit, Doctor Peset University

alter SCs proliferation rate, though all leptin concentrations decreased SCs

Hospital, Valencia, Spain;³Medicine department, University of Valencia,

metabolic activity. That was accompanied with alterations in the expression

Valencia, Spain.

levels of the different mitochondrial complexes and also of genes involved

in mitochondrial biogenesis. In addition, the highest concentration of leptin

decreased mitochondrial membrane potential. Finally, mitochondrial DNA

Introduction

copy number was not sensitive to the treatment with the different leptin

The prevalence of transsexuality in Europe is uncertain in absence of

concentrations. Overall, the results show a direct action of leptin on Sertoli

epidemiological studies, so it’s difficult to implement public healthcare strategies.

cells mitochondrial function and biogenesis with implications in the

Aim

nutritional support of spermatogenesis, which is a novel mechanism by

To describe healthcare demand evolution in a gender identity clinical service in

which leptin can affect the reproductive potential of males.

our country.

DOI: 10.1530/endoabs.49.EP1179

Methods

Our center is a public university hospital placed in Valencia (Spain). It is a

reference center on gender dysphoria from two provinces

(Valencia and

Castellon), with a target population of 2.646.801 inhabitants R14 years old

(50.8% women and 5.5% adolescents). We reviewed medical records of patients

referred from 2008 to 2016, excluding gender-non conforming people without

demand of hormonal or surgical intervention.

Results

EP1180

We attended 331 transsexual people with eligibility criteria for pubertal block,

Study of CDX-2 VDR gene polymorphisms in male infertility

cross hormonal treatment or surgery; 41.7% transsexual men (FxM) and 58.3%

Suzana Vladoiu¹, Daniela Dinu Draganescu¹, Anca Botezatu³,

transsexual women (MxF). 6% in FxM and 30% in MxF had previously started

Dana Manda¹, Sabina Oros^1,2, Roxana Rosca^1,2, Gabriela Anton³,

any kind of treatment. 82% FxM and 56% MxF were living in desired role at the

Diana Paun² & Corin Badiu^1,2

initial evaluation. Before 2011 no adolescent was referred while between 2012

¹‘C.I. Parhon’ National Institute of Endocrinology, Bucharest, Romania;

and 2016 were attended 82 of them. In adolescents, sex ratio was favoring natal

²‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania;

males before

2014

(2.9:1) and it changed in

2015 and 2016 (1.7:1-1:1.5,

³‘Stefan S. Nicolau’ Institute of Virology, Bucharest, Romania.

respectively) favoring natal female. Minors represented 16% of patients in 2012-

2014 and 52% nowadays. We performed 34 hysterectomies (34.6% of patients

older than 18 years), 25 mastectomies (25.5%) and implanted 20 breast prosthesis

The CDX2 VDR polymorphism (rs11568820) is located in the promoter region of

(13.1%), surgeries preformed in private centers were not accounted. For

exon 1 in the 5⁰ -untranslated region of the VDR gene.

genitoplasty surgery they were referred to another national surgery center.

Objective

The current investigation examines the association between CDX2

VDR

Conclusions

polymorphism and male infertility.

Demand for transexual care shows an important increase in our geographical area.

Subjects and methods

This increase is due to adolescent population. There is a significant variation of

The study was conducted on 69 infertile men, aged between 20 and 50 years,

sex ratio favoring transsexual men. This results can be explained by sociocultural

divided into three groups, based on spermatic parameters: group with

phenomena. Only one-third of FxM choose to perform hysterectomy and

azoospermia (19 subjects), group with severe oligospermia (38 subjects), group

adnexectomy.

with oligospermia (12 subjects), and 37 age-matched controls. CDX-2 VDR gene

DOI: 10.1530/endoabs.49.EP1178

polymorphisms were performed by PCR-RFLP. Vitamin D was assessed by

electrochemiluminiscent method.

Results

The evaluation of Vitamin D levels was found to be significantly decreased in

infertile patients group versus controls (PZ0.0198). The lowest Vitamin D levels

were characteristic for azoospermia patient group

(medianZ18.34 ng/ml,

rangeZ14.89-19.6 ng/ml), than controls

(medianZ24 ng/ml, rangeZ18.2-

EP1179

36.10 ng/ml). The analyses for CDX2 VDR polymorphism in infertile patients

Leptin modulates Sertoli cells mitochondrial function and biogenesis

showed that six cases were homozygote (GG), 28 heterozygote (GA) and 35

with implications for the nutritional support of spermatogenesis

homozygote (AA). The frequency of G allele was 0.29, and 0.71 for A allele,

Bruno M Moreira^1,2, Ana D Martins^1,2, Mariana P Monteiro^2,3,

c2Z0.014. In control group the analyses of CDX2 VDR polymorphism revealed

Mário Sousa^1,2, Marco G Alves² & Pedro F Oliveira^2,4

that 10 cases were homozygote for G allele (GG), 19 were heterozygote (GA) and

8 were homozygote (AA). The frequency of G allele in population was 0.53, for A

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

allele the frequency was 0.47, c²Z0.033. The controls and infertile groups were

Introduction

compared using c²-test and the difference was significant (PZ0.0229). The GG

Dysgonosomies are abnormalities of the number of gonosomes X and Y. They

genotype was found in a low percentage in patients group than controls (8.7% vs

have fewer Phenotypic repercussions than the aneuploidies involving autosomes,

27.03%), and the percentage of AA genotype was higher in infertile group

and are mostly viable. The 47 XYY are generally boys with normal phenotype.

(50.72% vs 21.62%).

The prevalence is around 1 per 1000 birth boy but undoubtedly under diagnosed

Conclusion

given the often normal phenotype associated with this chromosomal formula, in

Despite numerous publications, the influence of Vitamin D on reproductive health

addition to the lack of large-scale studies. There is no gonadal dysgenesis and

remains ambiguous. Our study showed that infertile patients present low levels of

often no infertility or criminality in the past.

Vitamin D. According the results the A allele may represents a potential risk for

Case report

male infertility.

Our case is a 48 years old patient consulting for primary hypofertility. The

DOI: 10.1530/endoabs.49.EP1180

anamnesis finds a type 2 diabetes, High blood pressure, orchi-epididymitis at the

age of 34 and bilateral unaccompared varicosele and hydrocele. The patient is an

active smoker. Clinically, he is an over weighted patient (BMI: 27 kg/m square)

with 180 cm height. No other dysmorphia is noted. In the Spermogram, we find an

azoospermia (00 SPZ), with 1 CC of ejaculation volume. Scrotal ultrasound

shows a normal-sized testicles with micro calcifications in the epididymis tail

with varicocele and bilateral hydrocele. An Epididymis Cytoponction recovering

SPZ (without cryopreservation).

EP1181

The hormonal status is:

CHARGE syndrome - late diagnosis in adulthood

FSH: 1.65 mIU/ml (0.95-11.95)

Maria Manuel Costa^1,2, César Esteves^1,2, JoséLuís Castedo¹,

LH: 2.40 mIU/ml (0.57-12.07)

Duarte Pignatelli¹ & Davide Carvalho^1,3

Testosterone: 5.65 ng/ml (1.42-9.23) or a correct gonadal assessment

¹Department of Endocrinology, Diabetes and Metabolism of Centro

Inhibin B 215.4 ng/ml (11.5-368.9) predicting the presence of SPZ in the biopsy

Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, University of

Caryotype 46 XY/47 XYY

Porto, Porto, Portugal;³Instituto de Investiga

¸a˜o e Inovação da Saúde da

The clinical examination and the exploration of the 31 years old partner is without

Universidade do Porto, Porto, Portugal;⁴Service of Medical Genetics,

anomalia. The patient is programmed for testicular biopsy in the optic of a

Centro Hospitalar de São João, Porto, Portugal.

possible ICSI.

Conclusion

Introduction

It appears that many men with 47, XYY syndrome will likely have decreased

CHARGE syndrome is a rare autossomal dominant genetic disorder with an

fertility potential. These patients may ultimately require assisted reproductive

estimated birth incidence of 1:10000. It affects multiple organ systems and can

techniques in order to achieve pregnancy.

have a variable phenotypic expression.

DOI: 10.1530/endoabs.49.EP1182

Case report

34-years-old man, referred to Endocrinology in the context of bilateral

gynecomastia. He had an acute corneal hydrops which was treated by

ophthalmology. Physical examination showed short stature (149 cm), obesity

(BMI 31.5 kg/m²), micropenis and cryptorchidism. He presented other problems:

coloboma of the iris, bilateral hearing loss, anosmia, craniofacial dysmorphisms

(abnormal ear shape, microstomia) and intellectual disability. Patient’s

Neuroendocrinology

investigation included among others: breast ultrasound which revealed bilateral

EP1183

gynecomastia; testicular ultrasound that demonstrated an empty scrotal sac with

the atrophic testes in the inguinal canals; biochemical evaluation showed

Prenatal intervention by P271 reduces LH pulsatility and testosterone

hypogonadotrophic hypogonadism

(FSH 0.42 mUI/ml

(n:1.5-12.4), LH!

levels in PCOS condition

0.10 mUI/ml (n:1.7-8.6), total testosterone 0.08 ng/ml (n:2.8-8.0) and a low

Sareh Zeydabadinejad¹, Fahimeh Ramezani Tehrani¹, Azita Zadeh-Vakili²

IGF-1 12 ng/ml (n:140-405). Pituitary had a 3 mm height on MRI; Karyotype

& Mahsa Noroozzadeh¹

result was normal male (46, XY); He started monthly 250 mg/ml enanthate

¹Reproductive Endocrinology Research Center, Research Institute for

testosterone with poor compliance. Otolaryngology evaluation excluded choanal

Endocrine Sciences (RIES), Shahid Beheshti University of Medical

stenosis/atresia (peri-nasal sinuses CT showed only exuberant deviation to the left

Sciences, Tehran, Iran;²Cellular and Molecular Endocrine Research Center,

of the nasal septum) and confirmed moderate sensorineural hearing loss

Research Institute for Endocrine Sciences (RIES), Shahid Beheshti

(audiogram with about

50 dB hearing threshold bilaterally and normal

University of Medical Sciences, Tehran, Iran.

tympanogram) but the patient refused auditory prosthesis. His echocardiogram

was normal. Family history was irrelevant for congenital malformations,

Background

intellectual disability, deafness or vision loss and endocrinological problems.

Polycystic ovary syndrome

(PCOS) is a frequent endocrine and metabolic

CHARGE Syndrome was suspected and molecular study of CHD7 gene was

disorder and the most common cause of infertility occurring in 5-10% of women

requested. A heterozygous pathogenic variant was identified

[c.3106COT,

of reproductive age. The characteristic endocrine abnormalities of PCOS involve

(p.Arg1036Ter)] and clinical suspicion was confirmed.

hypersecretion of androgens and LH (as a consequence of increased GnRH

Conclusion

frequency). Although PCOS signs generally become obvious at puberty, clinical

CHARGE acronym stands for C-coloboma, H-heart disease, A-atresia choanae,

and experimental evidence suggests an intrauterine origin for the syndrome. On

R-retarded growth and retarded development and/or CNS anomalies, G-genital

the other hand, kisspeptin antagonists have been shown to reduce LH pulse

hypoplasia, and E-ear anomalies and/or deafness. Diagnostic criteria currently

frequency and amplitude.

combined major and minor features are used. Pathogenic variants in CDH7 gene

Methods

are found in around 80% of CHARGE patients. We present CHARGE Syndrome

RNAs were extracted from hypothalamus of prenatally androgenized (PNA)

referred to our clinic due to gynecomastia. Most of CHARGE syndrome patients

(nZ18) and non-PNA female rats (nZ14) thought estrus cycle. The ability of

are diagnosed in childhood infancy and rarely in adulthood. With this clinical

prenatal administration of kisspeptin antagonist P271, to alter GnRH mRNA

report we would like to alert that in the presence of hypogonadotrophic

expression and gonadotropin and steroid hormone levels, was tested using Cyber-

hypogonadism associated with suggestive features, this diagnosis should be

green Real-time PCR and ELISA methods, respectively.

considered.

Results

DOI: 10.1530/endoabs.49.EP1181

Hypothalamic GnRH mRNA levels fluctuated in a cyclic-dependent manner, with

a robust increase in the afternoon of proestrus phase. P271 treated animals showed

reduced GnRH expression and gonadal steroid and gonadotropin levels.

Conclusion

PNA animals had increased GnRH mRNA expression and LH levels in diestrous

phase than controls, which reduced in response to prenatally administered P271.

This pilot study, for the first time, shows that prenatal intervention by P271 reduce

EP1182

LH pulsatility and T levels associated with PCOS.

Azoospermia revealing the uncommon Jacob’s syndrome

Keywords: Kisspetin, P271, Gene Expression, Prenatal androgenisation

Abdelkader Yahi, Zakaria Haouchine & Samia Ould-Kablia

DOI: 10.1530/endoabs.49.EP1183

Endocrinology Service, HCA, Algiers, Algeria.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1184

EP1186

Prenatal testosterone exposure increases anxiety-like behavior in

The dynamics of anthropometric data in fertile age women by various

female rats

types of the treatment

Aleksandra Rasic-Markovic¹, Djuro Macut², Dragan Hrncic¹,

Saidganikhoja Ismailov & Maryam Abduvakhabova

Valentina Cirkovic¹, Bojana Rankov-Petrovic¹, Nikola Sutulovic¹ &

Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan.

Olivera Stanojlovic¹

¹Institute of Medical Physiology, Faculty of Medicine, University of

The aim

Belgrade, Belgrade, Belgrade, Serbia;²Clinic for Endocrinology, Diabetes

To study efficiency of pathogenetic therapy and dynamics of anthropometric

and Metabolic Diseases, Faculty of Medicine, University of Belgrade,

indexes for women with obesity of fertile age at different endocrinopathies to and

Belgrade, Serbia.

through 6 months after treatment.

Material and research methods

On the etiologic factor of patient with obesity were up-diffused on three groups:

Polycystic ovary syndrome (PCOS) is characterized by excessive androgen

1 g. are patients with obesity at the polycystic syndrome of ovaries (PCOS) - 30

secretion and women with PCOS are at risk of developing anxiety disorders.

patients, 2 g. are patients with hypothalamic obesity - 21 cases and 3 g. - patient

Maternal testosterone levels in humans have been shown to affect brain

with endocrine obesity (at a primary hypothyroidism) - 20 patients. Age of

development and to be correlated to mental function. During pregnancy,

patients in a 1th group hesitated 39 from 20 to and 28.3G0.64 averaged year. To

women with PCOS display high circulating androgen levels that may affect

all patients have been conducted spectrum of investigations, which include

the fetus and increase the risk of mood disorders in offspring. This study

clinical, biochemistry, hormonal analysis of the blood. Besides of this,

investigated whether maternal androgen excess causes anxiety-like behavior

electrocardiography, ultrasound investigation of uteri and ovarium during 11-

in offspring. Ten pregnant Wistar rats were injected s.c. with 100 mg/kg

14 days of periods, and MRY of pituitary. For the

1 g. we administered

testosterone undecanoate (TU) on gestational day 20, while control (C) rats

combination of Syofor 1000 mgs C spironolacton 100 mgs C yodmarinum

received only solvent. To investigate the presence of anxiety-like behavior

100 mgs CL-thyroxine 50 mgs in the morning C antiandrogens C antidepress-

in female offspring of TU and C dams, the elevated plus maze (EPM) and

ants. For the 2 group: combination of Syofor 1000 mgs C spironolacton 100 mgs

open field (OF) test was performed. In the EPM test, offspring of TU dams

C Yodmarin 100 mgs CL-thyroxine 50 mgs iC methaboliks C Reduxine

displayed decrease in the number of open arm entries and in the percentage

(Sibutramin)

15 mgs C antidepressants. For the 3 groupo: combination of

of time spent on open arms. OF test showed altered pattern of locomotor

Yodmarin 100 mgs CL-thyroxine 50 mgs.

activity in female TU offspring. Numerous data demonstrate that the early

The results

life environment, including in utero plays a key role in later life behavior.

In 1 and 2 groups of patients marked reliable decline of BMI 1 and 2 degrees after

The results of our research suggest that prenatal testosterone exposure

6 months of treatment, while for patients 3 groups of reliable changes of BMI

increases anxiety-like behavior in female offspring.

through 6 months of treatment were not attained at none of degree of BMI Thus,

DOI: 10.1530/endoabs.49.EP1184

for patients 1 and 2 groups with BMI 3 degrees through 6 months a tendency was

attained to the decline of BMI. In addition, renewal of fecundity and pregnancy

was attained for the patients of a 1 group - in 19,5%% cases (at 10 patients).

Conclusions

Optimization of treatment of obesity for the women of reproductive age is based

on drafting of the individual programs, the choice of that is determined by the

values of anthropometric indexes, state of hormonal and metabolic status, features

of food behavior and personality-emotional sphere, state of menstrual and

reproductive function.

Obesity

DOI: 10.1530/endoabs.49.EP1186

EP1185

Placental maternal and fetal vascular circulation in healthy non obese

and metabolically healthy obese pregnant women

Marina Shargorodsky^1,2, Jacob Bar^1,2 & Michal Kovo^1,2

¹Wolfson Medical Center, Holon, Israel;²Tel Aviv University, Holon,

Israel.

Background

EP1187

Obesity in pregnancy is associated with hyperinsulinemia, impaired endothelial

The disorder of secretion of somatotropic hormone in women with

function, inflammatory up-regulation and higher risk of placental pathological

obesity in the polycystic ovaries syndrome (PCOS) by comparison to

lesions. However not all obese individuals demonstrate similar metabolic profiles.

patients with the non-functional pituitary adenomas (NFPA)

The present study was designed to investigate placental histopathology in lesions

Saidganokhoja Ismailov & Maryam Abduvakhabova

that are associated with maternal and fetal circulation abnormalities, in nonobese

Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan.

and obese women with and without metabolic alterations.

Methods

332 pregnant women were divided into three groups according to presence of

Aim

obesity and metabolic risk factors: Group 1 included 163 non-obese metabolically

To study the disorder of secretion of growth hormone for women with obesity in

normal (NOMN); Group 2 included 106 obese metabolically normal (OMN);

PCOS by comparison to patients with NFPA.

Group 3 consisted 63 obese metabolically abnormal (OMA) subjects.

Materials and methods

Results

Under our supervision in the department of neuroendocrinology of the Center of

Placental weight was significantly higher in OMN compared to NOMN

Endocrinology of PH Ministry of RUz ambulatory in a period from September

(P!0.000). Maternal vascular supply (MVS) abnormalities of the placental

2015 for December, to 2016, 15 adult patients of fertil age were observed with

bed differed significantly across groups, and increased from Group 1 to Group 3 in

obesity in PCOS and 15 - with NFPA. Middle age of patients to make 25.5 and

a continuous fashion (31, 38 and 54% respectively, P!0.005). Fetal vascular

28.9 accordingly. The remoteness of disease hesitated in limits from 7 months to

supply (FVS) abnormalities rate increased from group 1 to group 3, and was

9 years.

significantly higher in obese subjects with and without metabolic abnormalities,

Results

compared to non-obese subjects (9, 20 and 22% respectively, P!0.021). Willous

It was set that in both groups there were neuroendocrine violations peculiar to

maturation defect (WMD) rate was higher in OMN subjects compared to NOMN

each of pathologies. So, in a 1 group of patients with PCOS such violations, as

(P!0.018). In the logistic regression analysis, obesity emerged as a significant

obesity, met most often, strium, acanthosis, acne, hyperandrogenemiya.

predictor of fetal vascular supply abnormalities

(PZ0.001) and WMD

hyperpolymenorheya, and in the second is secondary amenorrheya, hyperpro-

(PZ0.011).

lactinemiya, pahhypopituitarism. In both groups there was anovulation, and also

Conclusion

decline of secretion of STH, IGF- 1. In addition, in the group of patients with

We demonstrated that obesity, per se, is associated with an increased rate of fetal

NFPA the most for certain mionectic basale levels of trope hormones of

vascular malperfusion abnormalities, Willuos maturation defect, as well as higher

hypophysis were educed - STH, LH, FSH on a background hyperprolactinemiya

placental weight and lower FPR, compared to non-obese subjects.

and normal values of IGF- 1, while for patients with PCOS the decline of STH,

DOI: 10.1530/endoabs.49.EP1185

LH, FSH, was marked on a background hyperandrogenemiya and declines of

IGF- 1.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

cells such as POU5F1, SOX2, and NANOG. Next, we investigated whether

1) It is set that in the group of patients with PCOS the most reliable decline of

female sex steroid hormones such as 17b-estradiol (E2) and progesterone (P4)

basale levels of IGF- 1 was educed, while the deficit of STH met rarer.

could alter the protein expression of epithelial-mesenchymal transition (EMT)

2) For patients with NFPA took place panhypopituiarism, namely combined

related markers as well as pluripotency markers such as POU5F1, SOX2, and

deficiency of STH, LH, FSH, TSH, while the deficit of IGF- 1 met rarer.

NANOG in human ES cells. The protein expressions of N-cadherin, SNAI1, and

3) The secretions of STH and IGF- 1 educed in our research of violation confirm

SNAI2 were increased while E-cadherin expression was decreased by treatment

these literatures that for patients with PCOS the decline of levels of STH and IGF-

of E2 or P4 and that the expressions of POU5F1, SOX2, and NANOG were

1 takes place on a background of hyperinsulinemiya and hyperandrogenemiya,

decreased by the treatment of E2 or P4. When E2 and P4 were treated in the

that requires further research.

combination with estrogen receptor inhibitor (ICI 182,780) and progesterone

DOI: 10.1530/endoabs.49.EP1187

receptor inhibitor (RU486), respectively, their effects on EMT and pluripotency

of ES cells were restored to the control levels. Collectively, these results suggest

that E2 and P4 may regulate EMT and pluripotency of human ES cells by

mediating their receptors. The present study might be useful to understand the

roles of sex steroid hormones in cellular biology of human ES cells. (This

research was supported by a grant from the Next-Generation BioGreen 21

Program (no. PJ011355-2015), Rural Development Administration, Republic of

Korea.)

Keywords: sex steroid hormones, human embryonic stem cells, pluripotency,

epithelial-mesenchymal transition

Paediatric Endocrinology

DOI: 10.1530/endoabs.49.EP1189

EP1188

17alpha-hydroxyprogesterone in non-CAH children and adolescents at

different ages

Christian Trummer¹, Nicole Hacker¹, Julia Munzker¹,

Michaela Goschnik^1,2, Kerstin Koschka^1,2 & Barbara Obermayer-Pietsch^1,2

¹Medical University, Graz, Austria;²CBmed, Graz, Austria.

17a-hydroxyprogesterone (17OHP) is currently used as a diagnostic parameter in

children and young adults when a milder form of congenital adrenal hyperplasia

(CAH, late-onset) is suspected. A basal serum level of

17OHP (2 ng/ml;

6.0 nmol/l, respectively) has been discussed as cut-off for suspected late-onset

EP1190

disease. We analysed 17OHP in a cohort of children and adolescents without

Homo-dimerisation of cytochrome P450c17 resolves the conundrum of

CAH and in confirmed CAH patients to define reference ranges for these age

the dual activities of cytochrome P450c17

groups. For the analysis of 17OHP, we used a novel automated immunoassay in

Jessica Holien¹, Michael Parker^1,2, Alan Conley³, C Jo Corbin³,

506 anonymized samples from children and adolescents with a previous exclusion

Raymond Rodgers⁴ & Lisandra Martin⁵

of CAH by conventional hormone measurement. 302 girls and 204 boys in two

¹St. Vincent’s Institute of Medical Research, Australian Cancer Research

age groups from 1-11 and 12-18 years were included. In a subgroup of 49

Foundation Rational Drug Discovery Centre, Fitzroy, VIC 3065, Australia;

probands, follow-up samples within one year were available, as well as in 17 out

²Department of Biochemistry and Molecular Biology, Bio21 Molecular

of initially 38 children with genetically confirmed CAH. In prepubertal children at

Science and Biotechnology Institute, University of Melbourne, Parkville,

the age of 1-11 years, mean 17OHP serum concentrations were 0.99 ng/ml G

VIC 3010, Australia;³School of Veterinary Medicine, University of

0.86

(STD) (reference limits 0.31-4.62) for girls and 0.85G0.59 (reference limits

California Davis, Davis, CA, USA;⁴Discipline of Obstetrics and

0.31-2.60) for boys, which was not statistically different (PZ0.852). There was

Gynaecology, School of Medicine, Robinson Research Institute, University

also no difference in mean 17OHP serum concentrations at the age of 12-18 years

of Adelaide, Adelaide, SA 5005, Australia;⁵School of Chemistry, Monash

between female 1.39G0.70 (reference limits 0.37-3.26) and male adolescents

University, Clayton, VIC 3800, Australia.

1.38G0.67 (reference limits 0.32-2.93) (PZ0.95). Repeated measurements in

follow-up samples showed a mean coefficient of variation (CV) for non-CAH

samples of 14.2 and 20.8% in CAH patient samples. In our study, baseline 17OHP

Reproduction requires the temporal and spacial control of specific and exact

was a useful marker for the exclusion of late-onset CAH in the majority of

signals, delivered by locally regulated hormonal flux. In the case of androgen

samples. Based on the established reference ranges, an overlap with confirmed

biosynthesis, cytochrome P450 17a-hydroxylase, 17,20-lyase (P450c17) is the

CAH patients was very small. In suspicious cases, additional hormonal tests as

key enzyme. However, P450c17 is a multi-functional P450, so, it synthesizes

well as stimulation tests of 17OHP have been defined as the standard of late-onset

cortisol in the zona fascicula of the adrenal cortex and also androgen precursors in

CAH diagnosis and therapy monitoring.

the adrenal zona reticularis and the gonads. The regulation of this dual activity has

been the focus of research studies over many decades and remains unresolved.

DOI: 10.1530/endoabs.49.EP1188

Functionally, it is known that each of these reactions of P450c17 require electrons

transferred by the electron donor cytochrome P450 oxidoreductase (CPR). The

first reaction, the 17a-hydroxylation of its substrate, occurs in all cells where

P450c17 is expressed. Remarkably, a second, subsequent reaction, namely the

17,20-lyase activity, only occurs in the zona reticularis and gonads. The

specificity of the second reaction is due to a non-redox ‘allosteric’ interaction with

the haem-protein cytochrome b5. Surprisingly, cytochrome b5 and cytochrome

P450 oxidoreductase have overlapping binding sites on the surface of the

Steroid Metabolism C Action

P450c17 enzyme. This poses the question as to how cytochrome b5

and

EP1189

cytochrome P450 oxidoreductase interact with P450c17 - structurally, function-

Effects of estrogen and progesterone on the protein expression of

ally and physiologically? This conundrum can be rationalized based on the

EMT- and pluripotency-associated markers in human embryonic

observation that P450c17

can homodimersise. A homodimer would allow

stem cells

cytochrome P450 oxidoreductase to bind to one P450c17

of the P450c17

Soo-Min Kim, So-Ye Jeon & Kyung-Chul Choi

homodimer, whilst cytochrome b5 could bind to the other P450c17 simul-

Laboratory of Biochemistry and Immunology, Veterinary Medical Center

taneously, at the surfaces distal to the dimer interface. We present our molecular

and College of Veterinary Medicine, Chungbuk National University,

modelling data that predicts that the P450c17 homodimer is a stable structure and

Cheongju, Chungbuk, Republic of Korea.

the CPR and cytochrome b5 proteins can assemble on the P450c17 dimer to form

a tetrameric

‘CPR:P450c17:P450c17:cyt b5’ assembly, predicted to be the

functional complex required for androgen biosynthesis. This model is fully

Embryonic stem

(ES) cells are pluripotent stem cells derived from a

consistent with extensive experimental data published over the last two decades.

developmental stage of preimplanted embryos. In this study, we investigated

Predictions derived from this model are currently being tested by a range of

the effect of female sex steroid hormones on the characteristics of human ES cells

in vitro and in vivo experimental approaches.

by using a feeder-free culture protocol. In a feeder-free condition without sex

DOI: 10.1530/endoabs.49.EP1190

hormones, human ES cells assumed the form of tightly packed cells that grow in a

monolayer. The cells also displayed clean and defined edges with no evidence of

differentiation and expressed several markers specific for undifferentiated ES

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1191

SHBG by immunoassay and free hormone fractions were calculated. Surgical

liver biopsies scored using NAFLD activity (NAS) and Steatosis, Activity and

Non-alcoholic fatty liver disease and its relation with sex steroids in men

Fibrosis (SAF) scores.

Frederique Van de Velde¹, Yves Van Nieuwenhove², Marlies Bekaert¹,

Results

Anne Hoorens³, Marleen Praet³, Jean-Marc Kaufman¹ & Bruno Lapauw¹

Obese men showed lower T, free T (FT) and SHBG levels, lower (F)T/(F)E2 ratio

¹Department of Endocrinology, Ghent University Hospital, Ghent, Belgium;

(all P!0.001) and higher FE2 (PZ0.019) compared to controls. Within the GBS

²Department of Gastro-Intestinal Surgery, Ghent University Hospital,

patients, no significant differences were found for sex steroid levels according to

Ghent, Belgium;³Department of Medical and Forensic Pathology, Ghent

NAS-based NAFLD severity. However, with increasing grade of steatosis, trends

University Hospital, Ghent, Belgium.

towards lower T and FT levels, and lower (F)T/(F)E2 ratios were observed

Background

(P!0.059). No associations between sex steroid levels and other NAFLD

Obesity associates with co-morbidities as non-alcoholic fatty liver disease

features were detected. Using SAF, we found that lower (F)T levels correlated

(NAFLD). Obese men often present with low testosterone (T) levels. As sex

with steatohepatitis (PZ0.014). These correlations were independent from age,

steroids undergo hepatic metabolization and their serum levels depend on hepatic

BMI, HOMA-IR and SHBG. Remarkably, no differences in SHBG or (F)E2

sex hormone binding globulin (SHBG) secretion, NAFLD could contribute to this

levels according to NAFLD severity were found.

phenomenon. Previous studies however were contradictory and not based on

Conclusion

state-of-the-art technology as mass spectrometry or biopsy-proven NAFLD.

This study confirmed lower T levels in obese as compared to normal-weight men.

Objective

In these obese men, overall NAS-based NAFLD severity was not associated with

To assess the relation between biopsy-proven NAFLD and sex steroid levels in

these lower T levels although presence of steatohepatitis and increasing grade of

obese men undergoing gastric bypass surgery (GBS).

steatosis was related to lower (F)T levels and FT/FE2 ratios.

Methods

DOI: 10.1530/endoabs.49.EP1191

This cross-sectional study included 56 obese men (mean age 44G11 years; BMI

41.6G4.6 kg/m²) and 56 healthy, age-matched control men (mean age 44G11

years; BMI 23.5G1.8 kg/m). T and estradiol (E2) measured using LC/MS-MS,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Clinical Case Reports - Thyroid/Others

thyroid. Ultrasonography of the neck revealed parathyroid adenoma at the inferior

pole of the right thyroid lobe and bilateral thyroid nodules. The patient was

EP1192

subjected to uncomplicated right inferior parathyroidectomy and synchronous

An adverse outcome in a thyrotoxic lady with propylthiouracil induced

total thyroidectomy. Postoperative histopathological examination confirmed the

necrotising leukocytoclastic vasculitis

diagnosis of parathyroid adenoma with coincidence of papillary thyroid

Emily T Mudenha, Anusha P Panthagani, Jonathan M Batchelor,

carcinoma. After surgery, serum parathormone and calcium returned to their

Rand Hawari, Roger Stanworth & David Hughes

normal values and patient was referred to the department of Nuclear Medicine for

Royal Derby Hospital, Derby, UK.

a radioactive iodine ablation therapy.

Conclusion

Concomitant papillary thyroid carcinoma and primary hyperparathyroidism is

A 37 year old lady with relapsing Graves’ thyrotoxicosis initially managed on a

rare. It still remains controversial whether these two pathologies happen

‘block and replace regime’ with propylthiouracil and levothyroxine for 7 years

coincidental or are caused by specific risk factors or genetic changes.

had her medication changed to carbimazole after a relapse from non-compliance

but developed agranulocytosis. She was then restarted on an increased dose of

DOI: 10.1530/endoabs.49.EP1193

propylthiouracil alone. Two weeks later, she developed tender purpuric lesions

and was admitted after developing painful bullous lesions to her lower limbs. She

had previously noted haemorrhagic lesions on her limbs but these would resolve

within a week. Investigations revealed positive MPOANCA antibodies, skin

biopsy confirmation of necrotising leukocytoclastic vasculitis and no evidence of

systemic involvement on imaging. She had rheumatology and dermatology input

regarding the vasculitic rash. Initial treatment involved stopping propylthiouracil,

starting beta blockers, short course of pulsed high dose methylprednisolone and

wound care. Within a few weeks, her skin lesions were improving, but she was

becoming progressively more thyrotoxic. She was commenced on potassium

iodide therapy in preparation for a total thyroidectomy. Unfortunately, her

temperature increased and she rapidly went into septic shock due to pneumonia

requiring inotropic and respiratory support on the intensive care unit before dying

a few days later.

EP1194

Discussion

Necrotising vasculitis remains a rare complication of propylthiouracil therapy. It

A case with langerhans cell histiocytosis having papillary

is classically, as in our patient, strongly associated with positive MPO-ANCA

microcarcinoma of thyroid: two birds in one nest

antibodies. Clinical presentation is variable. Treatment includes discontinuation

Hatice Ozisik¹, Banu Sarer Yurekli¹, Nilufer Ozdemir Kutbay¹, Ilker Altun¹,

of the drug, immunosuppression and good wound care. The prognosis in the

Yesim Ertan², Ozer Makay³ & Gokhan Ozgen¹

absence of major organ vasculitis as in our patient is usually good, and our patient

¹Division of Endocrinology and Metabolism, Ege University, Izmir, Turkey;

seemed to be making good progress whilst being worked up for thyroidectomy.

²Division of Pathology, Ege University, Izmir, Turkey;³Division of General

However, her low grade tachycardia and raised inflammatory markers masked the

Surgery, Ege University, Izmir, Turkey.

early onset of sepsis. Our case highlights the importance of clinical vigilance for

sepsis in patients with the rare complication of propylthiouracil induced

Introduction

necrotising leukocytoclastic vasculitis.

Langerhans cell histiocytosis

(LHH) is an idiopathic, clonal, pleomorphic,

DOI: 10.1530/endoabs.49.EP1192

neoplastic disorder characterized by the presence of atypical histiocytic cells

which are locally or commonly seen in bone, lung, hypothalamus, liver, lymph

nodes, mucocutaneous tissues with damaging them.

Case

58 year-old male patient applied to our clinic due to fatigue. On his physical

examination, lymphadenopathy and hepatosplenomegaly were absent. In his

history, he had an operation owing to Large-cell neuroendocrine carcinoma in

2014. He took chemotherapy but no radiation. In surveillance, a thyroid nodule

was detected in PET-CT. Thyroid US revealed a nodule 5 cm in diameter in

the right lobe. He underwent bilateral total thyroidectomy. In pathological

examination, left lobe was reported as thyroid papillary microcarcinoma,

follicular variant and langerhans cell histiocytosis, right lobe was reported as

follicular nodular disease. The focus of papillary microcarcinoma in 0.2 and

0.1 cm diameter was seen in the left lobe and langerin positive focus was

observed in the morphology of langerhans cell histiocytosis consisting of

EP1193

langerhans cells and eosinophils. Bone marrow biopsy and abdominal MR

Synchronous papillary thyroid carcinoma and primary

were normal. On his laboratory examination urine dansity was normal. FSH:

hyperparathyroidism: a rare association

5.44 mlU/ml

(1.5-12.4), LH:

4.74 mlU/ml

(1.7-8.6), total testosterone:

Nadia Khessairi, Ibtissem Oueslati, Malika Chihaoui, Meriem Yazidi,

2.35 ng/ml

(2.8-8), prolactin:

5.87 ng/ml

(4.6-21.4), TSH:

0.37 mIU/ml

Ons Rjeb, Fatma Chaker & Hedia Slimane

(0.35-5.50), tyroglobulin!0.9 ng/ml

(1.6-60) were detected. In pituitary

Department of Endocrinology, La Rabta hospital, Tunis, Tunisia.

MRI, nodular focus with different contrast enhancement according to pituitary

gland referred as intermediate lobe was detected in the middle posterior of

pituitary gland

Introduction

Discussion

Although the association between parathyroid and thyroid diseases is not

In LHH and papillary thyroid carcinoma coexistence, papillary microcarcinoma

uncommon, the coexisting of parathyroid adenoma causing primary hyperpar-

was frequently encountered.Gold standard treatment for limited LHH is surgical

athyroidism (PHPT) and papillary thyroid carcinoma (PTC) is rare. Probably this

resection and it has usually good prognosis. Diffuse goitre (59%) or nodules

can be partially explained by different embryologic origin of thyroid and

(25.8%) can be detected in patients with LHH having thyroid gland involvement.

parathyroid cells. Herein, we report a case of PHPT associated with synchronous

Large cell neuroendocrine carcinoma of the lung is rarely seen and has poor

bifocal PTC.

prognosis.

Observation

A 65-year-old woman was referred to our department with incidental

DOI: 10.1530/endoabs.49.EP1194

hypercalcaemia and biochemical PHPT. A Technetium

(99mTc) sestamibi

scintigraphy showed a distinct functioning nodule in the lower right pole of the

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1195

usually followed by a reduction of TRAb levels in variable degrees; the degree of

reduction remains controversial. The median TRAb value half-life has been

Amiodarone and refractory thyrotoxicosis in a patient with complex

estimated at 93.5 days after total thyroidectomy in patients without orbitopathy or

arrhythmia

smoking, such as our patient. This case therefore demonstrates that remnant

Nelson Cunha¹, Leonor Gomes^1,2, Diana Martins^1,2, Diana Oliveira^1,2,

thyroid cells after total thyroidectomy in Graves’ disease can become stimulated

Adriana Lages¹, Mara Ventura¹, Lúcia Fadiga¹, Diana Catarino¹ &

under the mediation of TRAb causing recurrent thyrotoxicosis. Revision surgery

Francisco Carrilho¹

would be challenging and therefore radioactive iodine necessary.

¹Endocrinology, Diabetes and Metabolism Department, University Hospital

of Coimbra, Coimbra, Portugal;²Faculty of Medicine, University of

DOI: 10.1530/endoabs.49.EP1196

Coimbra, Coimbra, Portugal.

Background

Amiodarone is a potent antiarrhythmic drug used to treat tachyarrhythmias.

However, is linked to a number of adverse effects, including thyroid dysfunction.

It is the main cause of drug-induced thyrotoxicosis. Here we report a clinical case

EP1197

of amiodarone-induced thyrotoxicosis (AIT) in a patient with complex ventricular

Where is the thyroxin disappearing?

dysrhythmia.

Ioannis Svilias, Filip Gabalec & Jan Cap

Case report

4th Department of Internal Medicine, Hematology and Endocrinology,

A 23 years-old women with dilated cardiomyopathy, severe depression of

Faculty of Medicine, Charles University Hospital, Hradec Králové, Czech

ejection fraction of left ventricle and complex ventricular dysrhythmia under

Republic.

amiodarone treatment

200 mg id since June of

2013, presented asthenia

and weight loss since march of 2016, with worsening of heart failure. TSH was

!0.008 mUI/ml (0.4-4.0), Free T₄ (FT₄) 3.4 ng/dl (0.8-1.9) and Free T₃ (FT₃)

Introduction

6.1 pg/ml (1.8-4.2). Autoimmunity was negative. Thyroid ultrasound: normal

The most common cause of loss of adequate substitution on a stable dose of

dimensions, without nodularity or increased vascularity at doppler study.

replacement therapy is noncompliance. Impaired absorption and weight gain are

^99mTc-sestamibi thyroid scintigraphy: signal in lower limit of normality. It was

also possible. We present a rare case of renal loss of thyroxin in severe nephritic

started methimazole 30 mg/day and prednisolone 40 mg/day. After 3 months, she

syndrome.

presented undetectable TSH, FT4 2.4 ng/dl and FT₃ 4.0 pg/ml. Methimazole was

Case report

increased to 40 mg/day and prednisolone to 60mg/day and amiodarone was

We present a 46 year old female after total thyroidectomy for Graves-Basedow

suspended. After 2 months, TSH was still undetectable and FT₄ 2.2 ng/dl, with

disease. From 2005 she was euthyroid on a stable dose of L-thyroxin (100 mg/day).

development of steroids side effects. So thyroidectomy was performed, without

On physical examination she had oedemas of the lower extremities. A marked

complications. After surgery, started levothyroxine

75 mg/day, steroids were

hypercholesterolemia (17.49 mmol/l, normal range 0-5.2 mmol/l) and a very high

tapered and amiodarone was restarted. Three months after surgery, normal

TSH value (92.5 mU/l, normal range 0.27 - 4.2 mU/l) were found. Celiac disease

thyroid function and improvement of her clinical condition were observed.

was excluded, abdominal ultrasound was performed with a normal finding.

Conclusion

During examination proteinuria

(6.19 g/day, normal range to

0.14 g/d) and

In this case, a type 2 AIT was diagnosed, resistant to medical therapy and with

thyroxin loss in urine (50 mg/l) were found. Renal biopsy was performed with the

steroids side effects. This uncommon scenario illustrates the difficulty of

finding of membranous glomerulopathy (glomerulonephritis). Treatment will be

controlling thyrotoxicosis in a patient of high risk of sudden death, requiring an

started in nephrology department. After increase of L-thyroxin dose (300 mg/den)

invasive procedure to its resolution. Thereby, when thyrotoxicosis is uncontrol-

normalisation of TSH was established.

lable and patients are at high cardiovascular risk, thyroidectomy should be

Conclusion

considered for the resolution of AIT. This could be lifesaving by controlling the

Nephrotic syndrome increases L-thyroxine requirements because of urinary loss

disease, avoiding iatrogeny and maintaining the possibility of amiodarone

of free and protein-bound thyroid hormones. Physical examination, careful

therapy.

history taking and laboratory findings are the key to the accurate diagnosis. After

DOI: 10.1530/endoabs.49.EP1195

treatment of membranous glomerulopathy reduction of L-thyroxin dose is

expected.

DOI: 10.1530/endoabs.49.EP1197

EP1196

Relapsed Graves’ thyrotoxicosis following total thyroidectomy 20 years

earlier

EP1198

Edouard Mills, Ali Naqvi & Jeannie Todd

Hyalinizing trabecular tumor of the thyroid gland

Imperial Centre for Endocrinolgy, Imperial College NHS Trust, London,

Buket Yilmaz Bulbul¹, Mehmet Celik¹, Semra Ayturk¹, Nuray Can²,

UK.

Ebru Tastekin², Atakan Sezer³, Funda Ustun⁴ & Sibel Guldiken¹

¹Department of Endocrinology and Metabolism, Medical Faculty, Trakya

We report a 55-year-old non-smoker with a history of Graves’ disease diagnosed

University, Edirne, Turkey;²Department of Pathology, Medical Faculty,

in 1990 at age 29 years old. Due to poor compliance to therapy, she underwent a

Trakya University, Edirne, Turkey;³Department of Surgery, Medical

total thyroidectomy within 1 year of diagnosis. She remained well controlled on

Faculty, Trakya University, Edirne, Turkey;⁴Department of Nuclear

thyroid hormone replacement for over 20 years with Levothyroxine 100 mg daily.

Medicine, Medical Faculty, Trakya University, Edirne, Turkey.

However, in the two years before referral to the Endocrine Clinic, she had difficult

to treat hypothyroidism with persistent over-replacement; at the time of referral

Hyalinizing trabecular tumor is an uncommon, controversial lesion of thyroid gland.

she was taking Levothyroxine 25 mg daily. She reported no symptoms of over-

Hyalinizing trabecular neoplasm share similarities with medullary thyroid

replacement. She had no evidence of thyroid associated orbitopathy. Taking

carcinomas (MTC) and exhibit nuclear features resembling papillary thyroid

Levothyroxine 25 mg daily, TSH remained suppressed at !0.01 mIU/l, Free T₄

carcinoma (PTC). However, the clinical behaviour unclear. We aimed to present a

14.5 pmol/l and Free T₃ 4.3 pmol/l. Thyroid autoantibodies were both positive:

rare case of hyalinizing trabecular tumor of thyroid gland and ten-year follow up.

thyroid peroxidase 285 unit/ml and TSH receptor 2.9 unit/ml. Ultrasound of the

A 54-year-old woman who was being followed up because of multinodular goiter

thyroid bed confirmed three hypervascular thyroid nodules measuring 8, 27 and

on examination of neck, the thyroid gland was nodular, measured 20 mm!

16 mm. Thyroid hormone replacement was discontinued. Subsequent NM

10 mm and non-tender. Serum FT3, FT4 and TSH were within normal limits.

Thyroid scan with uptake Technetium demonstrated three toxic nodules and

Ultrasonography showed a hypoechoic nodular lesion of 12 mm!6 mm in the

therefore concordant with the ultrasound. Graves’ disease is an autoimmune

right lobe and 29 mm!11 mm hypoechoic nodular lesion in the left lobe. Fine

condition characterised by the production of autoantibodies against the thyroid-

needle aspiration cytology the diagnosis was suspicious due to cells similar to

stimulating hormone receptor: TSH-receptor antibodies (TRAb). TRAb stimu-

papillary carcinoma cells. She underwent a total thyroidectomy. Histopatholo-

lates target organs with the majority developing hyperthyroidism from

gical examination showed the nuclei were oval, slightly pleomorphic, trabecular

stimulation of follicular cell production of thyroid hormone and about half

growth pattern, intratrabecular hyalinization and nuclei with grooves and

developing thyroid associated orbitopathy. Total thyroidectomy removes target

cytoplasmic pseudoinclusions. Immunohistochemically the tumor was thyroglo-

tissue for TRAb and controls hyperthyroidism. Surgical thyroid resection is

bulin positive, and calcitonin and HBME-1 negative, galectin 3 and TTF-1 focal

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

positive.The pathological diagnosis was hyalinizing trabecular tumor with

Conclusions

lympositic thyroiditis. L-thyroxine 0.1 mg/day therapy was started. The patients

The rare finding of increased thyroid hormones (T3 and T4) with normal or

treated was found to be euthyroid over the ten year follow-up period. Hyalinizing

increased TSH level presents a differential diagnosis between a TSH secreting

trabecular tumor is a unique neoplasm of follicular derivation. Most authors

pituitary adenoma and RTH. Mutational analysis of the TR-b gene enables both

consider this tumor to be benign. The differentiation of hyalinizing trabecular

definitive diagnosis of RTH and family screening. We present a novel mutation of

tumor from other thyroid tumors such as PTC and MTC, based on overlapping

this gene that has not been previously reported. Although, there have been

nuclear features. Cytological diagnosis of hyalinizing trabecular tumor has a

reported mutations affecting another aminoacid substitution at this position

characteristic trabecular growth pattern and hyalinizing stroma. The prognosis of

(L450P) in cases of RTH.

hyalinizing trabecular tumor is favorable.

DOI: 10.1530/endoabs.49.EP1200

DOI: 10.1530/endoabs.49.EP1198

EP1201

EP1199

Tuberculosis of the thyroid gland: a case report

Riedel thyroiditis presenting with pleuro-pericardial involvement

Imen Sakka, Ibtissem Oueslati, Fatma Chaker, Ons Rjeb, Meriem Yazidi,

Asena Gokcay Canpolat & Murat Faik Erdogan

Malika Chihaoui & Hedia Slimane

Department of Endocrinology and Metabolism, Ankara University Faculty

Department of Endocrinology, La Rabta Hospital, Tunis, Tunisia.

of Medicine, Ankara, Turkey.

Introduction

Riedel thyroiditis (RT) is a rare kind of chronic thyroiditis which may be a part

The involvement of the thyroid gland by tuberculosis is extremely uncommon

of a multifocal systemic fibrosis syndrome. When it is generally accepted as a

even in countries in which tuberculosis is endemic. In the majority of the reported

thyroid manifestation of IgG4 related systemic disease. We hereby present a 54

cases, thyroid function was preserved. Herein we report a case of thyroid

year old woman who was suffering from shortness of breath because of a mass

tuberculosis in a patient with a primary hypothyroidism.

lesion originating from thyroid and invading neck and upper mediastinal

Case report

structures, leading to dyspnea and dysphagia, as shown by CT, 15 years ago. After

A 52-year-old woman was referred to our department for a gradually growing

an isthmectomy and decompression surgery she was diagnosed as RT.

goiter without compressive symptoms. She presented with a productive cough.

Corticosteroid therapy was given as the firstline agent and she responded well

Her Past medical history included type 2 diabetes mellitus, goiter and primary

to the therapy, the dose was tapered off in about 6 months. However she was

hypothyroidism in the last fifteen years. On examination, she had a plunged

readmitted with severe dyspnea and chest pain with no large mass lesion at neck.

multinodular goiter. The rest of the clinical examination and laboratory tests were

Investigations revealed an exudative pleural and pericardial effusion and

normal. Chest radiography showed a nodule located in the right lung upper lobe.

mediastinal enlargement. The detailed evaluation of pleuropericardial effusion,

Cervical ultrasonography revealed an enlarged heterogeneous multinodular

did not point out any spesific etiology. Glucocorticoid theraphy was restarted

thyroid gland. Total thyroidectomy and lung nodule biopsy were performed to

along with colchicines and azathioprine. Alleviation of the symptoms were

the patient. Thyroid histopathological examination showed benign multinodular

achieved. She was followed by tamoxifene and colchicines on the long term. She

hyperplasia with epithelioid cell granulomas and giant cells. The histopatholo-

is now symptom-free with loss of the soft tissue mass and effusions for more than

gical examination of the lung biopsy showed foci of granulomatous inflammation

years. This case is interesting because of reporting pleuropericardial

along with caseous necrosis. The diagnosis of tuberculosis involving the lungs

involvement and the success of being in remission for more than 15 years.

and the thyroid gland was established. Then, patient was put on antitubercular

Although the etiology and definite treatment of the IgG4 related thyroid diseases

drugs with a good recovery.

are unclear; expanding knowledge about IgG4 related diseases will further clarify

Conclusion

the optimal approach to RT.

Although thyroid tuberculosis is a rare condition, it should be considered as

DOI: 10.1530/endoabs.49.EP1199

differential diagnosis of thyroid masses especially in an endemic country. In this

case, the use of fine needle aspiration biopsy can help to avoid unnecessary

surgical interventions.

DOI: 10.1530/endoabs.49.EP1201

EP1200

A Novel Thyroid Hormone Receptor Beta Gene Mutation: p.L450F

(c.C1633T) in a family with Resistance to Thyroid Hormone

Lourdes Garcia-Garcia-Doncel, Rosa Marquez-Pardo, Isabel Torres-Barea,

EP1202

Gloria Baena-Nieto, Rosario Lopez-Velasco & Manuel Cayón-Blanco

Follicular variant of papillary thyroid carcinoma with lung, bone, and

Jerez Hospital, Jerez, Spain.

soft tissue metastases

Constantinos Belis¹, Stavroula Gavriilidou¹, Aikaterini Afentoulidi¹,

Kalliopi Xydiari¹, Vasilios Athanasiou¹, Sofia Malaktari- Skarantavou¹,

Introduction

Sofia Saranti² & Christos Savvidis¹

Resistance to thyroid hormone

(RTH) is a rare autosomal dominant (AD)

¹Department of Endocrinology, ‘Hippocratio’ General Hospital of Athens,

condition caused by mutations of the Thyroid Hormone Receptor Beta (TR-b)

Athens, Greece;²Nuclear Medicine Department, ‘Saints Anargyri’ Cancer

gene, resulting in generalized tissue resistance to thyroid hormone. Euthyroidism

Hospital, Athens, Greece.

is usually maintained at the expense of increased levels of thyroid hormones and

with non-supressed TSH.

Case report

We report on a case of a 63-year-old male patient with a history of metastatic

A 61 year-old-woman was evaluated for increased free T4 index: 2.29 ng/dl

DTC, with both lung and bone metastases and an additional paravertebral mass.

(normal, 0.9-2.1) and free T3 index: 4.59 pg/ml (normal, 2.57-4.43) and normal

The patient presented with enlargement of the left thyroid lobe. FNA was positive

TSH levels:3.22 mUI/ml (normal, 0.3-5)). Analysis were repeated and laboratory

for malignancy and subsequent CTs were negative for distant metastases, whereas

error was excluded. The patient was asymptomatic. A physical examination

laboratory tests showed elevated thyroglobulin (TgO500 ng/ml). The patient

detected a moderate diffuse goitre and a normal resting heart rate. Thyroid

underwent total thyroidectomy and the pathology report revealed a multifocal,

antibodies were negative. Sex hormone binding globulin and gonadotrophin

follicular variant of papillary thyroid cancer, with localized extrathyroidal

a-subunit were within the normal range and pituitary magnetic resonance imaging

extention. He was then referred to the Endocrinology Department. After

ruled out a pituitary adenoma. Thyroid ultrasound showed a multinodular goitre

withdrawal of levothyroxine (preablation laboratory results: TSH: 52.6 mIU/ml,

with micronodules (!6 mm size). Thyroid scintigraphy demonstrated a diffuse

Tg: 9900 ng/ml) the patient received 80 mCi of I¹³¹ (RAI uptake: 7,6%).^. A

goitre with increased technetium uptake. A diagnosis of RTH was suspected.

subsequent SPECT/CT scan revealed lung and bone metastases (ribs with

Molecular genetic studies showed a change in exon 10 of the TR-b gene: p.L450F

adjacent soft tissue mass). Thoracic CT showed bilateral, scattered lung

(c.C1633T). Later, our patient’s daughter was also diagnosed of RTH and AD

metastases with lymph node enlargement of the hili as well as a paravertebral

inheritance was demonstrated in family segregation studies.

soft tissue mass 6.2!3.8 cm of diameter which metastasize to the 7th rib and the

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

respective thoracic vertebra. Tc99^m bone scan showed metastases in the ribs (6th,

results

(TSH:

12 U/mL; Free T4:

0.7 ng/dl) and therapy with

100 mg of

7th) as well as the 7th thoracic vertebra. The patient 6 months later received

L-thyroxine was initiated. Two months after therapy, thyroid function was

150 mCi I¹³¹. The post-therapeutic scan revealed radioiodine avid metastases in

normalized (TSH: 1.3

U/ml; Free T4: 1.1 ng/dl). Exophthalmia persisted, even

both lungs without response to the previous therapy as well as uptake in the right

though TSAb title was virtually undetected (0.6 U/l). At the age of 45, there was

maxillary area. The latter blood test (6 months after the 2nd RAI) showed

onset of binocular vertical diplopia and blurred vision. Upon administration of

biochemical improvement (Tg: 403 ng/ml, anti-Tg !42 IU/ml), while the last

500 mg ev Methylprednisolone, symptoms were only transiently relieved and

thoracic CT

months after the

2nd RAI treatment) revealed radiologic

thereafter rapidly worsened. Persistent diplopia and mild exophthalmos were

improvement on the lung metastases and the paravertebral mass (5.6!3 cm), as

confirmed in ophthalmology appointments. The patient was clinically euthyroid,

well as disappearance of the right maxillary area lesion. The case presented is

thyroid function tests were normal under Levothyroxine replacement and TSAbs

about the management of a patient with DTC and distant metastases, without

remained negative. Computed tomographic scan and magnetic resonance imaging

objective benefit showed by the postablation scan, but followed by decreasing Tg

of the orbits showed symmetric bilateral exophthalmia (grade I/III) with inferior

and radiologic improvement revealed by computed tomography.

rectus muscle thickening on the right eye, consistent with Graves’ disease.

DOI: 10.1530/endoabs.49.EP1202

However, the single fiber electromyography revealed a moderate defect in

neuromuscular transmission. Anti-acetylcholine receptor antibodies were

times the reference value, compatible with the diagnosis of Myasthenia Gravis.

Moreover, the patient denied fatigue, movement disorders or other neurological

symptoms. By reporting this case, we would like to draw attention for a possible,

although rare, association of myasthenia gravis and Graves’ ophthalmopathy and

stress the importance of a clinical judgment.

EP1203

DOI: 10.1530/endoabs.49.EP1204

Severe acute hepatitis associated with thyrotoxicosis

Isabel Torres-Barea, Lourdes Garcia-Garcia-Doncel, Manuel Cayón-

Blanco, Gloria Baena-Nieto, Rosario López-Velasco &

Rosa Márquez-Pardo

Hospital De Jerez, Jerez De La Frontera, Spain.

EP1205

Pleiotropic function of vitamin D and goiter

Roman Kołodziejczak¹, Alicja Łuczyn´ ska-Kołoldziejczak1 &

Liver dysfunction related to hyperthyroidism encompasses abnormalities

Anhelli Syrenicz²

associated with the effects of thyroid hormone excess, drug-related hepatic

¹Ragional Hospital, Gorzów Wlkp, Poland;²Pomeranian Medical

injury, and the presence of concomitant liver disease. Mild liver abnormalities

University, Szczecin, Poland.

such as hypoalbuminemia and increased serum level of liver enzymes may be

seen in 45-90% of patients with hyperthyroidism. Nevertheless, there are a few

case reports of thyrotoxicosis associated with severe acute hepatitis. A 37 year old

Objective

woman presented to the Emergency Department with abdominal pain associated

Among women over 40 the prevalence of goiter in Poland is over 40% and the

with diarrhea for 2 weeks and new-onset jaundice for 2-3 days. She had been

prevalence of vitamin D deficiency is over 80%. There have not been any

diagnosed with hyperthyroidism 6 months before and it was prescribed treatment

previous studies that investigate the vitamin D level in women with and without

with methimazole but she decided to stop the treatment one month later. On initial

goiter.

physical examination there was significant jaundice and tachycardia. Blood

Methods

pressure and body temperature were normal. There was no exophthalmos and the

152 women-96 with and 56 without nontoxic goiter were examined in 2014. In US

thyroid gland was diffusely enlarged. There were no findings of heart failure,

examination we calculated the volume of the thyroid gland and volume of

chronic liver disease, lymphadenopathy or hepatosplenomegaly. Laboratory

nodules. Blood samples for 25-(OH) D total were taken. We made statistical

workup showed hyperthyroidism and abnormal liver function tests: FT3 was

analysis of correlation between volume of the thyroid gland, volume of the

21.59 pg/ml

(normal

2.57-4.43), FT4

7.77 ng/dl

(normal

0.9-2.1), TSH

nodules and levels of vitamin D.

0.01 mU/l (normal 0.3-4.2). Total bilirubin 8.47 mg/dl (normal 0.1-1), direct

Results

bilirubin

7.7 mg/dl

(normal

0.05-0.2), ALT

674 IU/l

(normal

0-31), AST

96 women with goiter size from 5.67 ml to 68.85 ml - mean 19.7 ml, median

664 IU/l (normal 0-31), GGT 42 IU/l (normal 5-36), albumin 2.9 g/dl (normal

15.6 ml, the total nodules volume varied from 0.1 to 39 ml mean 4.59 ml, median

3.4-4.8). After excluding other etiologies for her liver injury, she was treated with

0.94 ml and the control group of 50 women with thyroid volume in normal range

antithyroid medications. One week after starting treatment we observed an

from 5.1 to 19.9 mean 11.2, median 11.2 ml. The 25(OH) total levels varied in

important decline in FT3 to normal values, bilirubin and liver enzymes dropped

control group from 5.3 to 31.8 ng/ml, mean - 14.4, median 12.95, and in goiter

to half of maximal values. One month later normalization of thyroid hormones

group from 4.7 to 39.8 ng/ml, mean 15.00, median 13.3 ng/ml. Only 14% in

and near normalization of bilirubin and liver enzymes was documented. In

control and 22% in goiter group had vitamin level over 20 ng/ml. We found no

conclusion, severe acute hepatitis is rarely associated with thyrotoxicosis.

correlation between vitamin D level and volume of thyroid gland in goiter group

Hyperthyroidism should be rule out in patients with acute liver failure of

and no correlation between vitamin D level and summary volume of the thyroid

unknown origin.

nodules. There is negative correlation between vit. D level and thyroid volume

DOI: 10.1530/endoabs.49.EP1203

in healthy subjects.

Discussion

As vitamin D deficiency affects majority of both groups and can result in

osteoporosis, osteomalacia, and increased risk of fragility fractures, our study

demonstrates the importance of screening and educating a broader age group of

women with goiter disease but also in the ‘healthy’ population.

Conclusion

EP1204

There is an unacceptably high level of vitamin D deficiency among women in

both examined groups. The pleiotropic effects of vitamin D seems to be

Isolated ocular Miasthenia Gravis and Graves’ disease - a challenging

insignificant in development of goiter, but may play a role in healthy thyroid.

ophtalmopathy

Raquel Vaz de Castro¹, José Maria Aragués², Florbela Ferreira¹,

DOI: 10.1530/endoabs.49.EP1205

Vânia Gomes¹, Ana Wessling¹, Ana Cláudia Fonseca¹, Isabel Concei

¸ão¹

& Maria João Bugalho¹

¹Santa Maria Hospital, Lisboa, Portugal;²Beatriz Ângelo Hospital, Lisboa,

Portugal.

EP1206

We report the case of a Caucasian woman presenting with a challenging

Amyloid goiter secondary to Crohn’s disease

differential diagnosis of ophtalmopathy. The patient was diagnosed with Graves’

Ana Saavedra^1,2, Elisabete Rodrigues^1,2, Ana Marques⁴ &

disease during postpartum at the age of 28 (TSH!0.001 U/ml; FT3 6.7 ng/dl;

Davide Carvalho^1,2

FT4 2.2 ng/dl; TSAb 15 U/l). Besides 16 pack-year smoking history, no other

¹Department of Endocrinology, Diabetes and Metabolism of Centro

previous disease was known. At examination, exophthalmos grade I/III with

Hospitalar de São João, Porto, Portugal;²Faculty of Medicine, University of

bilateral lid retraction was evident. Persistency of the disease despite optimal use

Porto, Porto, Portugal;³Instituto de Investiga

¸ão e Inovaça˜o em Saúde,

of medical antithyroid therapy led to radioactive iodine ablation (10 mCi) at the

University of Porto, Porto, Portugal;⁴Department of Pathology, Centro

age of 34.Three months afterwards, hypothyroidism was detected on blood tests

Hospitalar de São Joa˜o, Porto, Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction

Conclusion

Amyloidosis results from deposition of insoluble proteins in the extracellular

Although uncommon, extreme cases of thyroid dysfunction can occur in patients

space. It can be both primary or secondary to chronic inflammatory diseases.

on amiodarone therapy, underlining the importance of thyroid function

Although microscopic thyroid involvement is common, cases in which it becomes

monitoring.

clinically evident (amyloid goiter) are rare.

DOI: 10.1530/endoabs.49.EP1207

Case report

Woman, 45 years. In 2009, she was diagnosed with Crohn’s disease after

Bartholin’s gland abscess excision and evaluation for weight loss, anemia and

renal failure. In 2010, during hospitalization in Gastroenterology department, an

euthyroid diffuse goiter was identified (without compressive symptoms, except

easy choking) and she was oriented to endocrinology consultation. Due to chronic

kidney disease, she underwent renal biopsy (Jan/2011), that established the

EP1208

diagnosis of renal amyloidosis. Because she presented hepatic cytolysis a liver

Hashimoto’s thyroiditis in a patient with ectopic thyroid tissue

biopsy was also done, which revealed amyloid deposits in the wall of some portal

Nadia Khessairi, Ibtissem Oueslati, Ons Rjeb, Fatma Chaker,

arteries. She has been followed in Endocrinology since

05/2011, being

Meriem Yazidi, Malika Chihaoui & Hedia Slimane

asymptomatic, with diffuse goiter. Thyroid function tests and calcitonin are

Department of Endocrinology, La Rabta Hospital, Tunis, Tunisia.

normal with negative thyroid antibodies. Thyroid ultrasound has shown an

enlarged gland (LD 16!25!58 mm, LE 18!20!57 mm T!AP!L), with

increased echogenicity and diffuse heterogeneity, but without dimensional

Introduction

progression. Considering the imaging findings and the presence of systemic

Abnormalities in the development and migration of the thyroid gland are known

amyloidosis, she underwent thyroid core biopsy, which confirmed the amyloid

to produce ectopic thyroid tissue, usually in the midline between the tongue base

goiter diagnosis.

and the diaphragm. Hashimoto’s thyroiditis involving ectopic thyroid tissue is

Discussion

particularly unusual. Herein we report a case of Hashimoto’s thyroiditis

In the majority of cases of amyloid goiter there is a rapid thyroid growth (in weeks

developing in a midline thyroid cervical mass.

to months), although in the case described there was no progression. Despite the

Observation

widespread involvement of the thyroid by the disease, patients are usually

A 55-year-old man was referred for hypothyroidism. His physical and

euthyroid. Since amyloid deposits can also be found in association with medullary

psychomotor development was completely normal. His thyroid gland was not

thyroid carcinoma, this possibility must always be excluded. In conclusion, the

palpable in its normal pretracheal position. Elevated thyroid-stimulating hormone

diagnosis of amyloid goiter should be considered in patients with systemic

levels

(TSHZ19.8 mIU/ml, range 0.35-4.5) with low free serum thyroxine

amyloidosis or chronic inflammatory disease who present with bilateral and

(0.64 ng/ml) value were found. In addition, high titers of antiperoxydase

rapidly progressive enlargement of the thyroid, even in the presence of normal

antibodies (295.8 IU/ml) were detected. The neck ultrasound revealed a left

thyroid function.

lobar hypoplasia and a midline cervical mass representing aberrant thyroid tissue

DOI: 10.1530/endoabs.49.EP1206

due to migration defects. A Tc-99 m pertechnetate marked isotope showed

accumulation at the left thyroid lobe and at the midline cervical mass with no

uptake at the right thyroid lobe.

Conclusion

Ectopic thyroid tissue itself is not known to demonstrate a predilection for

Hashimoto’s thyroiditis. Despite its rarity, the presence of ectopic thyroid should

be considered in the differential diagnosis of all tongue, neck and trachea masses.

The ectopic tissue may be functional and affected by the same pathological

processes as the thyroid gland.

DOI: 10.1530/endoabs.49.EP1208

EP1207

Two case reports of amiodarone induced thyroid dysfunction:

thyrotoxic and myxedematous crisis

Francisco Sousa Santos, Cátia Ferrinho, Ricardo Capitão, Catarina Roque,

Carlos Bello, Clotilde Limbert & Carlos Vasconcelos

Servic¸o de Endocrinologia, Centro Hospitalar Lisboa Ocidental, Lisbon,

Portugal.

EP1209

Autoimmune thyroid disease occurring as a possible late complication

Introduction

after a non-occupational HIV Postexposure Prophylaxis

Amiodarone is a well-established antiarrhythmic drug frequently used in

Iulia Crumpei^1,2, Voichita Mogos^1,2, Maria-Christina Ungureanu^1,2,

tachyarrhythmias. Side effects include hypothyroidism and hyperthyroidism.

Anamaria Bursuc^1,2, Ioana Armasu^1,2, Mirela Tirnoveanu^1,2,

Extreme cases such as myxedematous and thyrotoxic crisis are very uncommon.

Valentina Adomnicai², Georgiana Constantinescu^1,2 & Carmen Vulpoi^1,2

Here we report one case of each of these presentations.

¹University of Medicine and Pharmacy, Iasi, Romania;²Department of

Case Report no.1

Endocrinology, Iasi, Romania.

A 73-year-old woman with history of atrial fibrillation under treatment with

amiodarone presented to the emergency department with headache, nausea and

Introduction

chest pain. On admission, she was tachycardic - atrial fibrillation with heart rate of

Nonoccupational postexposure prophylaxis (nPEP) is a three-drug antiretroviral

127 bpm. Her free T4 (fT4) and TSH were 31.5 rmol/l and !0.01 mU/l,

regimen used to decrease the risk for HIV infection after less than 72 h from

respectively and her antithyroid antibodies were all negative. Thyroid ultrasound

nonoccupational exposure to body fluids that might contain HIV. The most

demonstrated a micronodular gland with increased Doppler sign. Amiodarone

frequent side effects concern the gastro-intestinal intolerance, renal and hepatic

was discontinued and she was started on propylthiouracil, propranolol,

toxicity, with no hormonal imbalance to have been yet reported.

hydrocortisone, cholestyramine and Lugol’s iodine, without laboratorial or

Case report

clinical improvement

- sustained tachycardia and coma. As such she was

24 years old male patient, consulted for palpitations, hoarseness, shortness of

thyroidectomized. Her thyroid function tests and heart rate improved, however

breath, laryngeal tightness, weight loss

(4 kg /3 months), fatigue, insomnia,

she died due to sepsis secondary to MRSA on the 18th post-operative day.

recurrent panic attacks and anxiety-symptoms progressively installed since 3

Case Report no.2

months. Patient’s previous history contains a nonoccupational exposure to body

A 90-year-old woman with history of atrial fibrillation under treatment with

fluids containing HIV 8 months previously, treated with nPEP (Lamivudine,

amiodarone presented to the emergency department with a 12-h history of

Zidovudine and Kaletra- Lopinavir/Ritonavir), with a negative serology at the

diminished consciousness level. On admission, she was myxedematous,

check-ups. He presented high blood pressure and tachycardia, tremor,

hypothermic, bradycardic and with bradypnea. Laboratory studies revealed

hyperhidrosis and excessive preoccupation concerning his illness. Thyroid tests

respiratory acidemia, increased creatinine, toxic benzodiazepine levels, TSH

found an autoimmune thyroiditis with subclinical thyrotoxicosis: ATPOZ

80.2 mU/l and fT4 4.47 rmol/l (antithyroid antibodies were negative). She was

57.5 IU/ml (N: 0-35), TSHZ0.09 mIU/ml (N: 0.4-4), FT4Z1.35 ng/ml (N: 0.89-

started on IV fluids, non-invasive ventilation and antibiotherapy due to suspected

1.76), TRAb- negative, normal thyroid at the ultrasound. Cardiac evaluation was

pneumonia. Amiodarone was discontinued and IV L-thyroxine (250 mg) and

normal so the patient was advised to start betablocker and anxiolitic treatment,

hydrocortisone (200 mg) were administered and continued orally on the following

along with psychological counselling. At the one month follow-up, the blood test

days. She showed dramatical clinical improvement and was discharged after

has shown persistence of the thyroid autoimmunity with normalisation of the

10 days on oral L-thyroxine 75 mg/day.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

function: TSHZ0.602 mIU/ml, FT₄Z1.38 ng/dl, without any other abnormal-

hemodynamic stability. He was discharged after radiofrequency ablation of an

ities.

abnormal signal pathway with EKC in sinus rhythm and amiodarone was

Conclusions

suspended. Thyroid ultrasound showed thyroid goiter (24.5 ml) with hetero-

The occurrence of the autoimmune thyroid disease after a 6 month period post

geneous structure. There was a lack of 99 mTc uptake in scintigraphy (0.5%).

nPEP has not yet been cited. It may be a result of either the autoimmune system

Normalization of hormones was reached after eight months of onset of the

rebound after the antiretroviral therapy or an inflammatory imbalance induced by

disease, with tiamazol 70 mg/day and prednisolone 20 mg/day.

the treatment with consecutive immune reconstitution syndrome.

Conclusions

DOI: 10.1530/endoabs.49.EP1209

Amiodarone-induced thyrotoxicosis occurs in 5-10% of patients and may cause

significant morbidity, especially in patients with significant cardiac disease and

when it cannot be discontinued. Differential diagnosis between type 1 and type 2

is not always easy and sometimes mixed forms occur, adding more challenges and

difficulty to the treatment, particularly when antithyroid drugs and corticosteroids

are ineffective.

DOI: 10.1530/endoabs.49.EP1211

EP1210

Recurrent Thyroiditis in an Amiodarone treated patient:

An Illustrative Case Demonstrating the Spectrum of Abnormalities

Mohit Kumar & David James Tymms

WWL Foundation Trust, G. Manchester, UK.

EP1212

A 65 yo gentleman was referred to the endocrinology department with

Atrial flutter with 1:1 atrioventricular conduction: An uncommon

thyrotoxicosis. He had a history of IHD and recurrent VT necessitating

cardiac manifestation of hyperthyroidism

amiodarone for 8 years. Routine TFTs had shown TSH undetectable, fT₄ 34.1,

Amal Rached, Mariem Yazidi, Imen Sakka, Ons Rejeb, Nedia Khessairi,

fT₃ 8.7. There were no symptoms or signs of thyrotoxicosis or cardiovascular

Malika Chihaoui & Hedia Slimane

compromise. He had been treated with carbimazole by his GP for the previous 3

La Rabta, Tunis, Tunisia.

weeks, this was discontinued at the initial evaluation due to recurrent vomiting.

TPO antibodies were negative, a thyroid uptake scan showed normal uptake

(2.86% at 20 mins) with a hot nodule in the isthmus. The thyroid function

Introduction

normalised over a period of 2 months with no medication. It was felt unsafe to

Atrial flutter (AFL) is a rapid, regular atrial tachyarrhythmia that occurs most

discontinue the amiodarone. Sixteen months later there was a further episode of

commonly in patients with underlying structural heart disease. Patients with

thyrotoxicosis, again asymptomatic with no CV compromise. A repeat thyroid

tachyarrythmias as a result of thyroid storm have been typically treated with beta-

uptake scan showed a cold thyroid. This episode too was managed conservatively.

blockers to decrease the heart rate and alleviate beta-receptor mediated

This was followed by a further two self-resolving episodes (2 and 3 years later);

symptoms. We report an unusual case of AFL with 1:1 atrioventricular (AV)

subsequently the patient developed permanent hypothyroidism treated with

conduction.

levothyroxine 100 mg. Amiodarone induced thyrotoxicosis (AIT) comes in two

Case report

forms: type 1 (iodine-induced excess thyroid hormone production) and type 2

Patient H, M 45 years old was admitted to our hospital with Graves Disease. He

(thyroiditis), though in some patients an overlap is thought to exist.

presented with typical symptoms which included tiredness, shaking, palpitations

Differentiation of these types can be difficult. Our case seems to demonstrate

and opthalmopathy. He had lost 36 pounds over 3 months. He had a heart rate of

both forms; initially type 1, then three episodes of type 2. Recurrent thyroiditis

280/min, blood pressure of 130/80 mmHg, a moderate sized goitre without signs

has been reported with suppurative thyroiditis and postpartum thyroiditis. Whilst

of right heart failure. An electrocardiogram revealed atrial flutter with 1:1 (AV)

there are reports of recurrence of thyroiditis with ongoing treatment with

conduction. The echocardiogram showed a preserved internal dimension and

amiodarone, to our knowledge this is the first case to show four episodes of AIT

overall normal systolic function. The diagnosis of hyperthyroidism was

with ongoing administration of this drug. The continuation of amiodarone is

confirmed: Thyroid stimulating hormone:

0.002 mIU/l, Free T₄:

3.52 ng/dl

sometimes clinically necessary, but can lead to a longer time to cure if treated

(0.7-1.5). He was treated with propranolol 60 mg/day and thiamazole 40 mg/day.

with steroids. Thyroidectomy and perhaps radioiodine are options in troublesome

He was placed on anticoagulation with warfarin for a target INR of 2-3. We

cases.

performed a linear radiofrequency ablation and he reverted to sinus rhythm. His

DOI: 10.1530/endoabs.49.EP1210

symptoms improved and he was discharged 1 week later.

Conclusion

This case report shows that AFL with 1:1 AV conduction may be observed in

patients with hyperthyroidism and rapid supraventricular tachycardia.

DOI: 10.1530/endoabs.49.EP1212

EP1211

Thyroid storm subsequent to amiodarone-induced thyrotoxicosis

Catarina Machado, Patrícia Tavares, Sara Monteiro, Gustavo Rocha

& Maria João Oliveira

Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE, Vila Nova de Gaia,

EP1213

Portugal.

Pharyngeal Irritation, Incidental Neck Masses; A difficult journey

Bonnie Grant¹, Raj Tanday¹, Augustine William¹, Antony Pittathankal²,

Edel Casey¹ & Khash Nikookam

Introduction

¹Diabetes and Endocrinology Department, Barking Havering and Redbridge

Thyroid storm is a rare medical emergency with high mortality, which usually

University Trust, Greater London, UK;²Surgery Department, Barking

results from acute exacerbation of hyperthyroidism. Amiodarone is a highly used

Havering and Redbridge University Trust, Greater London, UK.

class III antiarrhythmic drug and amiodarone-induced thyrotoxicosis is an

infrequent effect of this medication, whose treatment may be difficult.

Case study

This is a case of a 48-year-old lady initially referred to respiratory clinic with

A 20-year old male with congenital cardiomyopathy (Fallot tetralogy and Ebstein

symptoms of breathlessness. She had a high-resolution CT thorax where an

anomaly), chronically medicated with amiodarone 200 mg/day since age 2, was

incidental finding of a right para-oesophageal 2.4-cm soft tissue density at the

admitted to the emergency room with palpitations, diaphoresis, nausea, vomiting

level of the thyroid gland identified. A CT neck was performed for further

and diarrhea. EKG showed atrial fibrillation with rapid ventricular response (HR

evaluation again showed the soft tissue mass (26 mm!37 mm) situated to the

160 bpm). Blood analysis showed hyperthyroidism - TSH !0.005 mUI/ml;

right of the oesophagus and another mass

(16 mm!26 mm) left of the

FT₃ 7.83 pg/ml (2.57-4.43) and FT₄ 5.50 ng/dl (0.93-1.70). Burch-Wartofsky’s

oesophagus. Discussion at the Lung MDT felt they may represent thyroid

score was 55. He started tiamazol 30 mg/day and prednisolone 40 mg/day, but

nodules but given location and relative normality of the rest of the thyroid

because of his cardiac disease, amiodarone could not be withdrawn. Despite

parenchyma, parathyroid adenomas were possibilities hence she was referred to

adequate treatment, there was no clinical response and patient remained

the endocrine surgeon. She then described symptoms of irritation in her throat on

hypotensive, taquicardic and at risk of cardiogenic shock. Potassium perchlorate

swallowing over the previous 6 weeks but no subsequent breathing problems. On

was initiated at 400 mg 8/8 h with subsequent normalization of heart rate and

neck examination, the thyroid lobes were just palpable, with no cervical

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

lymphadenopathy. She was clinically and biochemically euthyroid with a normal

multinodular thyroid disease. The thyroid function was normal, antithyroid

calcium and parathyroid hormone level. Ultrasound thyroid reported hypoechoic

antibodies were negative and calcitonin (Ct) serum levels were moderately

heterogenous solid masses posterior to the thyroid; 3 cm on the right and 2 cm on

elevated (28.9 pg/ml). The thyroid ultrasound will detect bilateral hypoechoic

the left. These masses appeared separate from the thyroid with minimal internal

areas the largest to the right of 2.4 cm with hypoechoic halo and peri- and

vascularity, likely representing parathyroid adenomas. MRI soft tissue neck could

intranodular vascularization. Total body CT scan showed splenomegaly almost

not differentiate between parathyroid and thyroid origin. Following Endocrine

breaking and so was made of splenectomy. The histology showed splenic

multi-disciplinary team discussion, the patient had a thyroid technetium scan and

localization of lymphoma diffuse large B cell. The PET/CT scan with F18 FDG

technetium MIBI scan with findings concordant that it was probably thyroid in

was positive of upper- and subdiaphragmatic lymph nodes and a right thyroid

origin rather than parathyroid adenomas. Endoscopic fine needle biopsies found

nodule. Immunochemotherapy was initiated according to the R-COMP protocol

small foci of follicular tissue with immunochemistry showing strong nuclear

and at the end a new PET/CT F18FDG detects activities only to the lower right

positive staining with positive thyroglobulin antibodies, suggesting thyroid tissue,

thyroid pole. A control of Ct showed an increase to 45.1 pg/ml and the calcium

not parathyroid.

gluconate infusion test was suggestive of MTC (peak Ct O2.000 pg/ml). Total

Conclusion

thyroidectomy and lymph node draining was performed. Histology showed a

This case highlights the difficulty differentiating between thyroid and parathyroid

MTC bifocal, 2.5-1.5 cm to the right and left respectively, with all node-negative.

masses found incidentally. Dedicated imaging and biopsies may be the only way

Screening for MEN 2 was negative. Seven months after surgery Ct levels are

to confirm the nature of these masses.

!1.0 pg/ml; molecular analysis of the RET gene showed no pathogenetic

DOI: 10.1530/endoabs.49.EP1213

variants. In conclusion, the two neoplasms appear to be independent and not

correlated to a multiple cancer syndrome; moreover also in the NHL detect on

palpation of the neck and then the morphological examinations a thyroid nodule

suggest the dosage of Ct.

DOI: 10.1530/endoabs.49.EP1215

EP1214

Papillary thyroid microcarcinoma in struma ovarii tissue: a case report

Cem Onur Kirac, Suleyman Baldane, Suleyman Ipekci & Levent Kebapcilar

Division of Endocrinology and Metabolism, Selcuk University Faculty of

Medicine, Konya, Turkey.

Introduction

Struma ovarii is an uncommon ovarian neoplasm that more than half of itself is

EP1216

made up of thyroid tissue. In clinical trials about the disease, malign

miRNAs microarray differential profile in papillary thyroid carcinoma

transformation has been detected at the rate of 0.5-5%. Because of the disease’s

Sorina Schipor^1,2, Ana-Maria Niculescu³, Anca Botezatu⁴,

rareness, there is no absolute agreement about diagnosis and treatment of the

Dumitru Ioachim¹, Dana Manda¹, Andra Caragheorgheopol¹,

disease.

Catalina Picu¹, Oana Popa¹, Ioana Nedelcu¹ & Corin Badiu^1,2

Case report

¹National Institute of Endocrinology ‘C. I. Parhon’, Bucharest, Romania;

A 33-year-old woman admitted to gynecology department with abdominal pain.

²‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania;

Her pelvic MR revealed 147!99 mm multiseptated cyst in right over which may

³Agilrom Scientific, Bucharest, Romania;⁴‘Stefan S. Nicolau’ Institute of

compatible with teratoma. On laboratory evaluation, her CA-125 level was

Virology, Bucharest, Romania.

43.8 U/ml (normal range: 0-35). The cyst was excised and frozen section analysis

was performed. The frozen section showed stuma ovarii so no additional surgical

procedure was performed. Diameter of 300 micron papillary thyroid carcinoma

Introduction

was determined at the histopathological examination. At postoperative

The deregulation in miRNA expression has been described in thyroid tumors, and

evaluation, there was no metastasis on thoracic and abdominal imaging. There

is considered an important factor in thyroid carcinogenesis. mRNA expression

was no nodule on thyroid USG. In the second operation, omentectomy, excision

profiling in cancer allows identifications of signatures associated with diagnosis,

of paraovarian palpable lymph nodes and right oophorectomy were performed.

staging, prognosis, and response to treatment.

Pathologic examination revealed no over invasion or lymph node metastasis.

Objective

Preoperative and postoperative thyroid function tests were measured in normal

We aimed to detect miRNAs species differentially expressed between tumor and

range; on the other hand postoperative thyroglobulin level was 0.071 ng/ml

peritumoral tissue in papillary thyroid carcinoma.

(normal range: 1.4-78) and anti-thyroglobulin value was 427 IU/ml (normal

Materials and methods

range:

0-115). Postoperative CA-125 level of the patient was found to be

After informed consent and study approval by ethics committee, 24 patients were

regressed to

12.9 U/ml. Because of the diameter of the tumor tissue,

included in the study: seven patients with classic papillary thyroid carcinoma

thyroidectomy or adjuvant radioactive iodine therapy treatment was not

(cPTC), 14 patients with follicular variant of papillary thyroid carcinomas

performed. There has been no recurrence in 1 year follow-up.

(fvPTC) and three patients with insular and sclerosing variant of PTC, using intra-

Conclusion

operatively obtained tumor and peritumoral normal tissue. RNA was isolated

There is still no consensus on the diagnosis and treatment of malignant SO. The

from thyroid tissue using Trizol

(Invitrogen, Life Technologies). miRNA

general approach is that low-risk cases can be followed without adjuvant

microarray analysis was performed using miRNA Microarray System with

radioactive iodine therapy such as primary thyroid papillary carcinoma. However,

miRNA Complete Labeling and Hyb Kit and SurePrint G3 Human miRNA r21

further studies are needed to determine the effect of this approach on recurrence

Array Kit

(Agilent Technologies). SureScan Microarray Scanner Agilent

and mortality rates.

(G2600D) with Feature Extraction v11.0 and Agilent GeneSpring GX v14.5

DOI: 10.1530/endoabs.49.EP1214

were used for data extraction and analysis.

Results

Our analysis showed that 2570 miRNA species differ between normal and tumor

tissues. From all these, a fold change (FC)O1.1 identified 2516 species, with 276

having a FCO2. Applying an asymptotic P value below 0.05 and Benjamini-

Hochberg correction for false-discovery rate we found eight miRNAs

significantly different between normal and tumor thyroid tissues, namely hsa-

EP1215

miR-181c-5p, hsa-miR-181d-5p, hsa-miR-221-3p, hsa-miR-34a-5p, hsa-miR-

Simultaneous occurrence of RET-negative Medullary Thyroid

34b-5p, hsa-miR-5703, hsa-miR-630

and hsa-miR-744-5p,

of them up-

Carcinoma (MTC) and extrathyroidal B large cell Non-Hodgkin

regulated and two of them downregulated in tumor vs normal tissue.

Lymphoma (NHL)

Conclusion

Serafino Lio

miRNA microarrays expression profile using a specific platform allowed a very

Department Medicine-Endocrine Unit-ULSS2, Oderzo-TV, Italy.

good differentiation between tumor and normal thyroid tissue, providing an

important tool for the individualized, specific variant-based management of

thyroid cancer.

The simultaneous occurrence of MTC and extrathyroidal B large cell NHL are

Acknowledgement

very rare. MTC may be sporadic or part of a MEN and NHL is not reported in

UEFISCDI grant PN-II-PT-PCCA-2011-3.2-1337.

association with MEN. A woman of 76 year old with a history of cholelithiasis

and hepatitis B, is admitted for left abdominal pain. On examination it is detected

DOI: 10.1530/endoabs.49.EP1216

inguinal, axillary and clavicular lymphadenopathy, splenomegaly and also a

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1217

(35/349). The highest false negative rates (15%) were in nodules !2 cm. There

was no significant difference in the false negative rates for nodules O4 cm (8%)

Simultaneous papillary and medullary thyroid carcinoma in siblings

or !4 cm (10%) respectively.

with RET 611 mutation. More than a coincidence?

Conclusions

Miguel Paja, Alba Zabalegui, Maddalen Dublang, Eider Etxeberría,

After adjusting for patient age and gender, nodules that measured O4 cm had a

Natalia C Iglesias, Laura A Calles, Cristina Arrizabalaga, Aitzol Lizarraga,

greater malignancy risk. The false negative rates were not higher for nodules

M Teresa Gutiérrez & Aitziber Ugalde

O4 cm. Thyroidectomy should not be recommended based solely on nodule size.

Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain.

DOI: 10.1530/endoabs.49.EP1218

Germinal mutations of the oncogene RET originate the development of medullary

thyroid carcinoma (MTC) in carriers with phenotypic expression depending on

the mutated codon and other unknown factors. Simultaneous detection of

differentiated thyroid carcinomas is considered a casual phenomenon (collision

tumours). We communicate two brothers with double heterozygous mutation of

maternal inheritance at codon 611 of RET, TGC to TTT, changing to encode

EP1219

phenylalanine (C611F), with a simultaneous papillary thyroid carcinoma (PTC).

Struma ovarii - A report of thirteen cases

Case 1

Sara Donato, Hélder Simo˜es & Valeriano Leite

A 42-year-old male who underwent through total thyroidectomy and bilateral

Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon,

central dissection (TTCBCD) after genetic diagnosis in 2006. Basal preoperative

Portugal.

calcitonin was 6.0 pg/ml and stimulated, 34 pg/ml. Histology showed a bifocal

MTC, the bigger of 3 mm, and a classic infiltrative PTC of 3 mm with intense

desmoplastic stromal reaction and four metastatic lymph nodes out of five in

Introduction

central compartment, two with extranodal extension. BRAFV600E mutation was

Struma ovarii (SO) is a rare ovarian teratoma characterized by the presence of

positive. He received 100 mCi of I¹³¹ with stimulated thyroglobulin of 1.9 ng/ml.

thyroid tissue in O50% of the tumour. Malignant transformation is rare and

Ten years later, he has undetectable calcitonin and excellent therapeutic response.

defined by the same histological criteria as for thyroid cancer. There is few data

Case 2

on the literature and treatment is controversial. The objective of this study was to

A 48-year-old male received TTCBCD after genetic diagnosis in 2016, with

describe the clinical, pathologic and treatment characteristics of women

basal calcitonin of 25.2 pg/ml and stimulated of 124.5 pg/ml. Histology showed a

diagnosed with SO in our centre.

bifocal MTC,

6 and 5 mm, and two foci (5C2 mm) of well limited not

Methods

encapsulated follicular variant of PTC, BRAFV600E negative. There was no

Retrospective analysis of the SO followed in our Institution between 2000 and

involvement by any of the two tumours in six resected nodes. After 3 months,

2015.

basal calcitonin is 0.8 pg/ml, and basal thyroglobulin, without radioiodo, reaches

Results

0.31 ng/dl. We are remarking simultaneous occurrence of MTC and PTC,

A total of 13 patients were identified with a median age at diagnosis of 46 years

originated from different thyroid cell types, in siblings bearing the same RET

(range 19-85). No patient had previous history of thyroid disease. In nine cases

mutation. This coincidence raises the possibility of an underlying common

the diagnosis was made by routine imaging exams and in three cases by associated

genetic drive in both PTC, although with different mutational events added that

symptoms (mostly pelvic pain). CA 125 and HE4 serum levels were normal in

explain distinct differentiation, among them BRAF V600E mutation.

every patient tested

(four and three patients respectively). Seven patients

DOI: 10.1530/endoabs.49.EP1217

underwent bilateral oophorectomy plus hysterectomy

(with or without

omentectomy or external iliac lymphadenectomy) and in six the surgical

procedure was a unilateral oophorectomy. Three cases were diagnosed as

malignant SO. In these cases thyroidectomy followed by radioactive iodine was

performed and papillary thyroid cancer (PTC) was diagnosed in two.131I-WBS

performed after surgery, showed no uptake in the pelvis in any patient. In one

benign SO case, thyroid imaging and fine-needle biopsy disclosed PTC as well.

During a median follow-up of 14 months (range 1-78), nine patients remained

EP1218

with no evidence of disease, one died with a non-related cause and one was lost to

Thyroid nodule size at ultrasound as a predictor of malignancy

follow-up. Two of the malignant SO patients were found to have biochemical

Gema López Gallardo¹, Julia Sastre², Abel González³, Sandra Arranz⁴,

evidence of disease.

Julia Silva⁵, Miguel Angel Valero⁶ & Jaime Aranda⁷

Conclusions

¹Hospital Santa Bárbara, Puertollano/Ciudad Real, Spain;²Hospital Virgen

SO was frequently asymptomatic. Patients with malignant SO had often

de la Salud, Toledo, Spain;³Hospital General, Ciudad Real, Spain;

persistence of disease, although they had a good overall survival rate. An

⁴Hospital General, Albacete, Spain;⁵Hospital Mancha Centro,

important proportion of these patients developed thyroid cancer.

Alcázar/Ciudad Real, Spain;⁶Hospital General, Talavera, Spain;

DOI: 10.1530/endoabs.49.EP1219

⁷Hospital General, Cuenca, Spain.

Introduction

Most thyroid nodules are benign. Some studies have shown largest nodule size,

specially O4 cm, can predict malignancy and reduce fine needle aspiration

(FNA) accuracy. Recent studies, however, have shown conflicting results as to

whether nodule size may be used to distinguish at risk-lesions. We attempt to

EP1220

determine whether nodule size predicts thyroid malignancy and to examine

Diagnosis of medullary thyroid carcinoma at early stage

accuracy of fine needle aspiration (FNA) by size.

Cristina Stancu¹, Cristina Corneci¹, Andra Caragheorgheopol¹,

Material and methods

Bogdan Stanescu^2,3, Mirela Diana Ilie¹ & Corin Badiu^1,2

A multicenter, retrospective analytical study was performed on a total of 882

¹‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;

patients with thyroid solitary nodules and put underwent partial or total

²‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania;

thyroidectomy between 2010 and 2013. We compared nodules by size cutoffs

³Life Memorial Hospital, Bucharest, Romania.

using Chi-squared and Fisher exact test where appropriate. Binary logistic

regression analysis was used to identify the independent factors associated with

thyroid malignancy. All data were analyzed using SPSS software for Windows

(version 18.0).

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor derived

Results

from the thyroid C cells producing calcitonin, ac-counts for 0.6% of all

Of the 882 nodules, 664 (73%) were benign and 238 (27%) malignant. Nodules

thyroid cancers. It occurs either sporadically or in a hereditary form (RET

!2 cm had the highest malignancy rate (49.2%). Decreasing malignancy rates

mutation). MTC can be cured only by complete resection of the thyroid

(23.1, 16.8, 4.6, and 6.3%) were observed with increasing size (2-3 cm, 3-4 cm,

tumor and any loco-regional metastases. Calcitonin (CT) measurement is

4-5 cm, O5 cm). Thyroid nodule size O 4 cm was associated to less risk of

crucial to the early diagnosis and the follow-up of MTC. If the evaluation of

malignancy (OR O.589 (0.421-0.824)). After adjusting for patient age and

stimulated CT levels is required, a provocative test can be performed. We

gender, nodules that measured O4 cm had a greater malignancy risk compared to

report the case of a 52-year-old woman presenting with multinodular goiter,

those measuring !4 cm (OR 2.031 (P:0.001)). In nodules with a benign FNA

positive TPO antibody and basal CT in repeated samples 42.92, 38.15,

diagnosis (Bethesda II), the overall malignancy rate (false negative rate) was 10%

and

33.99 pg/ml respectively. The patient was euthyroid. Plasmatic

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

metanephrines and PTH were in normal ranges. The thyroid ultrasound

elusive. In a previous work, we described that the injection of several hTRa

showed an isoechoic nodule 6 mm in size with a punctate calcification in the

variants in zebrafish eggs caused a marked reduction of circulating

left lobe and two hypoechoic nodes on the right lobe 19 and 9 mm in size,

erythrocytes at later stages of the erythropoiesis. To characterise the

with central and peripheral vascular signal. After a provocative test with

involvement of TRa during erythrocyte development, we analysed by qRT-

high dose Ca was performed, stimulated CT level was 96.6, 98.10 and

PCR and in situ hybridization

(ISH) the expression of different

82.10 pg/ml at 2, 5 and 10 min respectively. The patient underwent total

haematopoietic markers. We microinjected the zebrafish eggs at 1-2 cells

thyroidectomy. The histology showed multifocal medullary microcarci-

stage with 80pg/embryos of the purified mRNAs of several hTRa variants,

noma (max 5/5 mm in the left lobe), pTN: pT1a(m) Nx and positive

and from the 6-hpf, the injected embryos were treated with the control

immunohistochemistry for calcitonin. Postoperatively calcitonin level

vehicle, or with 20 mM-T3, added in the harvested water. By qRT-PCR, the

!0.2 pg/ml and CEA was negative. The mutations of RET protooncogene

expression of genes involved in the specification of lateral mesoderm (cdx4,

was tested, too.

bmp2b, smad5, chd), induction and proliferation of haematopoietic stem

Conclusion

cells (HSC) (tal1, lmo2, gata1, gata2) and proliferation of erythrocytes (zin,

We have to pay attention for patients with bCT O10 pg/ml and, a high-dose Ca

grx5, cia, cha) appeared significantly reduced in all hTRa-injected embryos.

test is reliable for the identification of MTC.

Consistent with previous results, the treatment with high T3 doses can

DOI: 10.1530/endoabs.49.EP1220

rescue the DN-activity of the missense variants D211G and A263V, whereas

the truncated receptors A382PfsX7, E403X and F397fs406X are unaffected

by TH treatment. Furthermore, we analysed the specification of HSC in

embryos at 8-somite stage, by ISH. The vast majority of the hTRa-injected

embryos showed a reduced or undetectable expression of early erythropoi-

esis markers, such as c-myb, pu.1, tal1 and gata1 in anterior or posterior

lateral mesoderm. At 36-hpf, we also observed a dramatic reduction of gata1

in the intermediated cell mass of hTRa-injected embryos. Therefore, our

EP1221

results highlight a relevant role for TRa during the early phases of the

primitive haematopoiesis, when the HSC start to proliferate and

Clinicopathological characteristics and outcomes of differentiated

differentiate.

thyroid carcinoma in children and adolescents

Research founding

Andrei Liviu Goldstein¹, Iulia Andreea Chiriac¹, Adina

Mariana Ghemigian^1,2, Camelia Procopiuc¹, Mircea Vasile Ghemigian¹,

IAI-Ricerca Corrente RF-2011 05C102.

Daniel Brasoveanu¹, Daniela Goldstein¹, Mariana Purice¹, Florin Alexiu¹,

DOI: 10.1530/endoabs.49.EP1222

Gabriela Voicu¹, Dumitru Ioachim¹ & Iuliana Gherlan^1,2

¹‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;

²‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania.

Introduction

Differentiated thyroid carcinoma is a rare entity in pediatric population, with

particularities in diagnosis, management and outcomes.

Paediatric Endocrinology

Methods, aim

EP1223

Retrospective noninterventional study describing clinical presentation and

An interesting etiology in childhood choreoathetosis; autoimmune

outcomes of children with DTC.

hyperthyroiditis

Results

Ayca Torel Ergur¹, Sevinc Odabasi Gunes¹, Cihat Sanli² &

Between 2011 and 2017 54 children and adolescents aged 7.8-18 years (mean age

Rabia Gundogan²

at diagnoses 14.4 years) with DTC were diagnosed/followed up in our Institution.

¹Kirikkale University Faculty of Medicine, Department of Pediatric

The female to male ratio was 3.5:1. In 70% cases unilateral thyroid nodule was the

Endocrinology, Kirikkale, Turkey;²Kirikkale University Faculty of

first manifestation of the disease, in 25.9% cases the DTC was diagnosed during

Medicine, Department of Pediatric Cardiology, Kirikkale, Turkey.

the follow-up for chronic thyroid pathology, whereas in 3.7% cases cervical

lymph node enlargement was the first clinical sign. 29.6% patients had cervical

node involvement at diagnosis, 9.3% had pulmonary metastases. The initial

Introduction

tumour size (over 4 cm diameter), the diffuse sclerosing form of papillary cancer

Neurologic symptoms due to autoimmune encephalopathy related to autoimmune

were independent risk factors for initial metastasis. A total thyroidectomy was

hyperthyroidism (AEAH) cases are very rare in childhood. The reason why

performed in 58.5% cases, a total thyroidectomy with central neck dissection in

hyperthyroidism causes this situation is still unknown. In this case we discussed

41.5% cases. 57.4% patients were classifies as low risk, 18.6% as high risk

the diagnosis, treatment and follow-up of a case with choreoathetosis in the

patients. The follow-up period was between 1 and 98 month, with an average of

review of literature.

30.4 months. At the last visit 36.3% patients had a good response to therapy,

Case

28.5% were in complete remission of the disease and 9.5% had stable persistent

15 years old female admitted to hospital with the complaint of nervousness,

disease.

discomfort for last 3 weeks. There was not any particular feature in personal and

Conclusion

family history. In physical examination, heart rate was

110/min, goiter,

DTC in children and adolescents has good prognosis even in loco-regionaly

exophthalmos, dysarthria, involuntary hand-foot movements, and decrement of

advanced forms of the disease.

fine motor skills was observed. Laboratory results were sT3:

12.59 ng/dl,

DOI: 10.1530/endoabs.49.EP1221

sT4:3.6 ng/dl, TSH:0.007 mU/ml anti-TPO 591.4 595 IU/ml, ani-Tg:357.9 IU/ml,

TRAb: positive. In thyroid ultrasonography volume OC2S.D., and parenchymal

heterogeneity were observed. History of beta streptococcus infection was

negative, mitral valve prolapse and non-rheumatologic mitral regurgitation was

seen on echocardiography so Sydenham’s chorea was not considered. Lupus

antibodies were negative; C3, C4, cranial MR and MR spectrogram were normal.

Anti-thyroid and beta-blocker treatment were started. On the 14th day of the

treatment major recovery in patient’s walking and talking were observed.

Nuclear Receptors and Signal Transduction

Recovery of the fine motor skills was evaluated comparatively with weekly video

records. On the first month of the treatment fine motor skills were definitely

EP1222

normal.

The human TRa variants affect the specification of haematopoietic stem

Discussion

cells during zebrafish haematopoiesis

Cranial hypoperfusion due to cerebral vasculitis, autoimmunity specific to

Federica Marelli¹, Giuditta Rurale², Silvia Carra¹ & Luca Persani^1,2

cerebral tissues and primary demyelination secondary to neuronal dysfunction

¹IRCCS Istituto Auxologico Italiano, Milan, Italy;²University of Milan,

were blamed in pathogenesis of AEAH. Plasmapheresis and corticosteroids are

Milan, Italy.

used in addition to anti-thyroid drugs in the treatment. The best aspect of is our

patient responded anti-thyroid drugs well. Our case is very challenging since it

reminds us the autoimmune thyroiditis in the etiology of major neurologic

Anaemia in RTHa patients correlates with documented abnormal

symptoms in children and adolescents.

erythropoiesis and reduced haematocrit in TRa-null or mutant mice, but

DOI: 10.1530/endoabs.49.EP1223

the underlying mechanisms and characterization of the defect remain

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1224

plasma T₃ and GH concentrations at 1st, 3rd, 6th, 7th, 10th-15th and 18th

Thyroid pathology and breasts diseases in adolescent girls

and 19th year. The plasma T₃ levels were positively correlated with plasma

Olga Gumeniuk & Yuriy Chernenkov

GH concentrations during infancy, pre-puberty, early and mid-puberty. The

Saratov State Midical University, Saratov, Russia.

concentrations of T₃ and LGV were positively correlated at 1st, 3rd, 4th, 7-

15th and 18-20th year. The plasma concentrations of T₃ were positively

correlated with LGV at infancy, pre-puberty, early and mid-puberty. In

conclusion, the present study shows negative correlations between T₄ and

Several studies have noted that there is a connection between thyroid

GH and LGV and positive correlations between T₃ and GH and LGV at

pathology and breast diseases.

infancy and mid-puberty.

Purpose

DOI: 10.1530/endoabs.49.EP1225

The study was undertaken to estimate the frequency of the breasts diseases in

adolescent girls with thyroid pathology.

Patients and methods

The study included 2371 girls

(aged

10-18 years). Thyroid diseases were

diagnosed on the basis of hormonal analysis and typical picture of examination

and thyroid ultrasound. Breast diseases were diagnosed on the basis of signs and

typical picture of breast ultrasound. We have identified the two groups: girls

EP1226

(nZ618) with thyroid pathology (group I) and girls (nZ30) without thyroid

pathology

(control group). Statistical analysis was performed using Mann-

Pediatric case of Autoimmune Polyglandular Syndrome type IIIC:

Whitney Test, P value of!0.05 were considered statistically significant. This

autoimmune thyroid disease and severe autoimmune thrombocytopenia

study has been carried out in accordance with the Helsinki Declaration.

Joanna Prokop¹, Elzbieta Leszczynska³, Maryna Krawczuk-Rybak³ &

Results

Artur Bossowski²

The endemic goiter was diagnosed in every forth girls. Autoimmune thyroiditis

¹Endocrinology Department, Centro Hospitalar Lisboa Central, Lisbon,

was found in 30 girls, nodul goiter in 4 and congenital hypothyroidism (later

Portugal;²Department of Pediatrics, Endocrinology, Diabetology with

form) in 2 adolescent girls. The investigation shows that every adolescent girl

Cardiology Divisions, University Children’s Clinical Hospital of Bialystok,

with thyroid diseases had breast disorders. Breast cysts (cystic dysplasia) was

Bialystok, Poland;³Department of Pediatric Oncology and Hematology,

diagnosed in 42% cases, fibrous mastopathy (dysplasia) - in 35%, adenosis

University Children’s Clinical Hospital of Bialystok, Bialystok, Poland.

mastopathy - in 18%, breast secretion - in 5% and fibroadenoma in 4 patients. All

girls with breast dysplasia and fibroadenoma complained of mastalgia. The

Introduction

average level on the visual analog pain scale in cases of mastalgia amounted

Association between autoimmune thyroid disease (AITD) and other autoimmune

6.9G2.1 points (in group I). The investigation shows that only 2 girls without

disorders is common and known as autoimmune polyglandular syndrome (APS).

thyroid pathology had breast diseases (predmenstrual mastalgia) (!0.001). The

It may involve hypoparathyoridism with Addison disease (AD) and mucocuta-

average level on the visual analog pain scale in control group was 3.8G1.4 points

neous candidiasis - APS type I, AD with Diabetes mellitus type 1 (DM1) or

(PZ0.02).

AITD- APS type II, AITD associated with other autoimmune diseases (excluding

Conclusions

AD): DM1- type IIIa, pernicious anemia- IIIb, or alopecia and/or vitiligo and/or

This study has shown a high frequency of the breast diseases among the

other autoimmune disorder- IIIc, any other combination being classified as APS

adolescent girls with thyroid pathology. Thyroid diseases are risk factor for breast

type IV. We report a case of a 15-year old patient diagnosed simultaneously with

disorders and show the necessity of for observation and examination of breast.

Graves disease (GD) and severe autoimmune thrombocytopenia (AIT).

DOI: 10.1530/endoabs.49.EP1224

Clinical case

A 15-year-old female patient was admitted to hospital with palpitations, weight

loss, petechiae on lower limbs, during menstruation. Physical examination

revealed tachycardia, goiter, thyroid bruit, fine distal tremor, petechiae of trunk,

upper and lower limbs. Abnormalities in laboratory studies: thrombocytopenia-

platelet count: 4.0!10³/ul, clinical hyperthyroidism with positive TSH receptor

antibody. Myelogram: normal. Thyroid ultrasonography: enlarged thyroid gland,

colour Doppler: increased blood flow. She was treated with intravenous

EP1225

immunoglobulin (IVIG), platelets concentrate and started methimazole. During

Age and development stage dependent association between thyroid

follow-up she had 4 more episodes of severe thrombocytopenia, with good

hormones and growth hormone and linear growth velocity in boys

however temporary response to therapy with IVIG or intravenous corticosteroids.

between the age of 1 and 20 years

Meanwhile vitamin B12 deficiency was detected and vitamin B12 replacement

Afzaal Ahmed Naseem¹, Mazhar Qayyum¹, Maleeha Akram¹,

therapy started. After normalization of thyroid function, maintaining low dose of

Zubaria Iqbal¹, Faheem Tahir², Sarwat Jahan³, Kiran Afshan³ &

methimazole, thrombocytopenia persisted (platelet countO20!10³/ul). Anty-

Syed Shakeel Raza Rizvi¹

glutamic acid decarboxylase(GAD) antibodies were tested: positive, without

¹Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University

hyperglycemia.

Rawalpindi, Rawalpindi/Punjab, Pakistan;²Reproductive Physiology,

Comments

Public Health Laboratories Division, National Institute of Health,

Although some autoimmune diseases may coexist, combination of AIT and GD is

Islamabad, Pakistan;³Department of Animal Sciences, Quaid-e-Azam

rarely reported. Moreover it was unusual because of juvenile onset, severity of

University, Islamabad, Pakistan.

thrombocytopenia, simultaneous diagnosis of GD, concomitant presence of GAD

antibodies and vitamin B12 deficiency. The patient needs to be monitored closely

for early detection of other autoimmune disorders or glandular failure and initiate

hormone replacement therapy if it is established.

During the time of puberty, thyroid hormones (THs), thyroxin (T₄) and

DOI: 10.1530/endoabs.49.EP1226

triiodothyronine (T₃), influence growth and developmental processes by

working in association with growth hormone (GH), insulin like growth

factor-I (IGF-1), glucocorticoids, insulin and gonadal steroids. THs have a

direct effect on GH secretion, which stimulates IGF system. It has been

suggested that THs control increase in bone length through synergy with

GH. This investigation determined age and developmental stage dependent

EP1227

association between circulating concentrations of T₄, T₃, GH and linear

Pediatric thyroid nodule: cytologic and histopathologic correlation

growth velocity (LGV). Blood samples were collected from 540 normal

Ana Miranda¹, Sofia Pires², Maria José Noruegas², Cláudia Piedade²,

healthy boys (27 boys/age group) between 1 to 20 years of age and plasma

Manuel Ramos², Joana Caetano², Rita Cardoso², Isabel Dinis² &

concentrations of T₄, T₃ and GH were determined using specific ELISA;

Alice Mirante²

LGV was measured by calculating changes in height in cm/year. Data were

¹Hospital Prof. Doutor Fernando Fonseca E.P.E., Amadora, Portugal;

analyzed using Student’s t test, ANOVA and Pearson correlation r. The

²Hospital Pediátrico do Centro Hospitalar e Universitário de Coimbra,

concentrations of T₄ and GH were positively correlated at 3rd, 7-9th, 14-

Coimbra, Portugal.

16th and 18th and 19th year. T₄ and GH concentrations were positively

correlated at pre-puberty and early and late puberty. The concentrations of

T₄ and LGV were positively correlated at 3rd, 4th, 7th, 14-16th and 18-20th

Background

year. There were positive correlations between plasma T₄ levels and LGV at

Thyroid nodule in the pediatric age group is rare, but the rate of malignancy is

pre-puberty and late puberty. There were positive correlations between

much higher than adult population. Fine needle aspiration biopsy (FNAB) is an

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

accurate test commonly used to determine whether thyroid nodules are malignant

EP1229

in adults. However, less is known about its diagnostic accuracy for this purpose in

Thyroid disorders and type 1 diabetes

children.

Ach Taieb, Hasni Yosra, Maaroufi Amel, Kacem Maha, Chaieb Molka &

Aim

Ach Koussay

To characterize the outcomes of FNAB of nodular thyroid disease at a pediatric

CHU Farhat Hached Sousse, Sousse, Tunisia.

tertiary-care institution and to correlate cytopathology with histopathology.

Materials and methods

Retrospective analysis to identify children who underwent FNAB of the thyroid

Introduction

between 2000 and 2016. Epidemiological, clinical, radiological, cytologic and

Type 1 Diabetes is an auto-immune disease caused by a disturbance of the

histopathologic data were analysed. The smears were categorized according to

immune system, damaging the Beta-cells. The association with other auto-

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) into six

immune diseases was frequently described, and dysthyroidism represents an

categories - Nondiagnostic, benign, atypia of undetermined significance/follicular

important part of these associations. In type 1 diabetes, the hormonal profile can

lesion of undetermined significance

(AUS/FLUS), suspicious for follicular

be disturbed regardless of auto-immunity. The goal of our study the thyroid

neoplasm (SFN), suspicious for malignancy (SM), and malignancy.

hormonal profile in type 1 diabetes, as well as the prevalence of auto-immune

Results

dysthyroidism associated with it.

Out of 32 cases, 87.5% were females. Patients ranged in age from 6.8 to 17.9

Material and methods

years (meanGS.D., 14.8G2.6 years). Seven individuals underwent more than one

This is a retrospective cross-sectional study based on the observation of patients

FNAB. Histological follow-up was available in

50%cases. The diagnosis

admitted for diabetes with insulin deficiency. The positivity of anti-pancreas

according to TBSRTC included 3 (9.4%) nondiagnostic, 22 (68.8%) benign,

antibodies testified to the auto-immune characteristic; anti glutamic acid

(3.1%) AUS/FLUS, 0SFN, 2 (6.3%) SM, and 4 (12.5%) malignancy cases. On

decarboxylase GAD and/or anti tyrosine phosphatase IA2. The goal is to

histological follow-up (nZ16), the rate of malignancy was 50%.There was no

determine the type 1 diabetic patients’ thyroid hormonal profile, and the auto-

difference in the ecografic size of the nodule of benign versus malignant lesions

immune dysthyroidism profile.

(PZ0.27) or diagnostic versus non-diagnostic lesions (PZ0.61). No difference

Results

was found in benign versus malignant lesions (PZ0.97) or diagnostic versus non-

Our series was conducted with 359 patients: 209 men and 150 women, aged

diagnostic lesions (PZ0.60), concerning mean age. Diagnoses at cytopathology

between 10 and 69 years with an average of 28.75 years. The clinical picture was

and surgical pathology were concordant in

9/14

(64%) nodules. Overall

ketotic in the majority of cases: 336 (93.6%), with inaugural ketosis in 313 cases

sensitivity of FNAB was 66.7% and specificity was 75%.

(87.2%). Insulin deficiency varied between one week an 36 months, with an

Conclusion

average of 3.75 months and a standard deviation of 6.8 months, exceeding 6

Due to the limited sample size our FNAB sensitivity and specificity are lower than

months achieving a slow form and a previous oral treatment in 24% of cases.

the previous reported on literature (90.6-100% and 76.2-100%, respectively). In

Regarding weight, the average BMI was 22 (extremes: 15 and 39), over 30 in 22

patients whose cytology was reported as inadequate or benign, is important to

patients. Upon admission, average blood sugar levels were 16.40 mmol/l with an

maintain follow-ups.

average glycosylated hemoglobin HbA1C of 12.32%. Average TSH levels were

DOI: 10.1530/endoabs.49.EP1227

of 3.23 mUI/l and the average T4 levelsZ12.43 pg/l in 242 patients who had

thyroid function tests. Auto-immune thyropathies were frequent: 54 patients (71%

of cases). Hashimoto’s disease dominated the etiologic profile and was confirmed

by the presence of anti-TPO antibodies found in 37 patients (48.6% of cases).

Basedow’s disease was found in 17 other patients (22.3% of cases) with positive

anti-TSH receptor antibodies.

Conclusion

Type 1 Diabetes is common in adults and children, and the association with auto-

immune diseases is frequent, hence the necessity of looking for these diseases

when patients are diagnosed with diabetes.

DOI: 10.1530/endoabs.49.EP1229

Thyroid (non-cancer)

EP1228

Thyroid autoimmunity in beta thalassemia minor

Sati Sena Yildiz¹ & Ali Ramazan Benli²

¹Department of Health and Social Services, Kayisdagi Darulaceze Ministry,

Istanbul Metropolitan Municipality, Istanbul, Turkey;²Department of

Family Medicine, Medikal Fakulty, Karabuk University, İstanbul, Turkey.

EP1230

Keep calm and put on the emergency list: total thyroidectomy for

refractory thyrotoxicosis

Background-aim

Ahmed Al-Sharefi¹, Suhel Ashraff¹, Wael Elasaify² & Rasha Mukhtar¹

Tendency to autoimmune diseases has been reported to be increased in beta

¹Department of Diabetes and Endocrinology, The James Cook University

thalassemia minor (BTM). Our aim was to examine the prevalence of thyroid

Hospital, Middelsbrough, UK;²Department of Surgery, The James Cook

autoimmunity in BTM.

University Hospital, Middelsbrough, UK.

Method

Eighty six adults with BTM and 93 age and gender matched controls were

included in the study. The two groups were compared cross-sectionally in terms

The standard management for Grave’s thyrotoxicosis includes the use anti-

of anti-thyroid antibodies (anti-TG and anti-TPO) and thyroid hormones. Patients

thyroid drugs, surgery and radioactive iodine treatment. In certain

with known autoimmune disorders other than autoimmune thyroid disease were

situations,alternative methods including bile acid sequestrants and therapeutic

not included in the study.

plasma exchange (TPE) have proven effective especially when other treatment

Results

modalities fail. We describe a case where conventional and alternative non-

In the BTM group, serum TSH, FT4, FT3 levels were statistically indifferent from

invasive measures failed to restore an euthyroid state and resorted to emergency

the control group. Serum anti-TG and anti-TPO antibody levels were found to be

thyroidectomy. A 49 years old female was referred signs and symptoms consistent

similar in the two groups. BTM and control groups were similar in terms of anti-

with Grave’s thyrotoxicosis. She was already started on pulse IV methylpredni-

thyroid antibody positivity prevalence. In the BTM group, anti-TG was 11.6%

solone for active thyroid eye disease. Her thyroid functions tests showed a

and anti-TPO was 14% positive, while these were respectively 14% and 12.9%

suppressed TSH of !0.05 mIU/l (0.27-4.2),free T4 of 52.7 pmol/l (10.0-21.0)

positive in the control group

(PZ0.806 and PZ0.989, respectively). The

and free T3 of 18 pmol/l (3.5-6.5). Her Thyroid receptor antibodies were high of

proportion of anti-TG and/or anti-TPO antibody positive subjects was found to be

O100 IU/l (1.0-1.8). She was started on anti-thyroid drugs which were stopped

20.9% in the BTM group, and 20.4% in the control group (PZ0.919). Ratios of

due to side effects. She had active thyroid eye disease so radioiodine was not

subjects with euthyroidism, hypertiroidism and hypothyroidism were similar in

appropriate and surgery considered the best option. She failed to block on

both group.

Potassium iodide, and surgery was cancelled due to hyperthyroidism. She was

Conclusion

started on Steroids and Cholestyramine but failed to respond with worsening

Because thyroid autoimmunity prevalence in the BTM group is not increased

symptoms and biochemistry. As a last resort, therapeutic plasma exchange was

compared to the control group, we consider that there is no necessity for routine

initiated with improvement in her thyroid biochemistry but no resolution despite

anti-thyroid andibodies and thyroid hormone testing in subjects with BTM.

seven sessions. An emergency total thyroidectomy was rearranged as the final

DOI: 10.1530/endoabs.49.EP1228

resort with steroid and B-blocker cover. Fortunately, the surgery was uneventful

and she made an uneventful recovery with subsequent improvement in her thyroid

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

functions and clinical symptoms. This case demonstrates how Graves’s

EP1233

thyrotoxicosis can pose a clinical challenge when it is refractory to all medical

Risk factors associated with the severity of Graves’ ophthalmopathy

therapies including plasma exchange. Total thyroidectomy remains the best and

Rym Belaid, Ibtissem Oueslati, Wafa Mimita, Karima Khiari,

only option, a comprehensive multidisciplinary approach involving an

Nadia Mchirgui & Néjib Ben Abdallah

endocrinologist, a surgeon and an anaesthetist is crucial to optimize the outcome

Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.

and reduce the risk of thyroid storm.

DOI: 10.1530/endoabs.49.EP1230

Introduction

Graves’ ophthalmopathy (GO) is an autoimmune disorder affecting the retro-

orbital tissues. It represents the main extra- thyroidal expression of Graves’

disease (GD). Its onset and progression are influenced by several factors that

are potentially modifiable. The aim of this study was to identify risk factors for

severe GO.

Methods

EP1231

Patients with GD were enrolled into a retrospective study. We compared possible

Screening with TSH and anti-TPO antibodies of patients with vitiligo

risk factors and various clinical findings between patients with mild to moderate

Anca E Chiriac¹, Anca Chiriac² & Doina Azoicai¹

GO and those with a severe form.

¹University of Medicine and Pharmacy ‘Grigore T Popa’, Iasi, Romania;

Results

²Nicolina Medical Center, Iasi, Romania.

Of 90 participants with GD, 59 patients (65.8%) presented with GO. Their mean

age was 35.15G12.25 years and their M/F ratio was 31/28. GO was the

Aim

circumstance of discovery of GD in 11% of cases. Its clinical manifestations range

The aim of the study was to evaluate the relation of vitiligo with thyroid

from mild findings such as tearing (25.6%), conjunctival injection (16.7%), gritty

autoimmunity.

eyes (10%) and photophobia (8, 9%) to more significant findings including

Materials and methods

exophthalmos (65.6%), eyelids retraction (41.1%), palpebral edema (18.9%),

A cross sectional study was done on 75 patients clinically diagnosed (old and

Oculo-palpebral asynergy (17.8%), exposure keratopathy (7.8%), diplopia (6.7%),

new) with different types of vitiligo. Patients with known thyroid disease were

reduced visual acuity (5.6%) and strabismus (2.2%). GO was mild in 64.4%,

excluded from the study. Serum TSH and anti-TPO antibodies were measured in

moderate in 16.9% and severe in 18.6% of cases. On multiple logistic regression

all patients.

analysis, smoking status (PZ0.005) and male gender (P!0.001) were predictive

Results

factors associated with the severity of GO. Other factors such as age, initial free T4

The prevalence of anti-TPO antibody positivity was found in 23 of 75 patients

level, TSH-receptor antibodies and a history of diabetes were studied but were not

(30.6%).

predictive of severe GO.

Conclusion

Although none of vitiligo patients enrolled in the study had symptoms or signs of

Although various factors may influence the severity of GO, our study showed that

thyroid disease at the time of clinical examination anti-TPO antibodies proved to

smoking and male gender were the major and the more significant risk factors for

be positive and with high values in almost one third of the patients.

developing severe GO. Therefore it is important for patients with GD to stop

smoking.

Multidisciplinary approach for patients diagnosed with vitiligo and screening

with anti-TPO antibodies are strongly recommended.

DOI: 10.1530/endoabs.49.EP1233

DOI: 10.1530/endoabs.49.EP1231

EP1234

Determination of plasma cortisol levels in women with dysthyroidism

EP1232

Samira Akdader-Oudahmane, Zohra Hamouli-Said &

Clinical aspects of cardiothyreosis in patients with Graves’ disease

Fatma Hadj-Bekkouche

Rym Belaid, Ibtissem Oueslati, Wafa Mimita, Nadia Mchirgui,

University of Algiers, Algiers, Algeria.

Karima Khiari & Néjib Ben Abdallah

Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.

Activation of the corticotropic axis seems to affect the thyroid axis at the central

level and/or by a direct effect on the thyroid gland. The aim of this study is to

Introduction

investigate a possible disruption of the adrenal cortical function that would cause

Cardiothyreosis

(CT) is the most frequent and dangerous complication of

dysthyroidism in a population of women by assaying plasma cortisol. The study

hyperthyroidism (HT). It is defined as an association of HT with severe heart

was carried out in a human population divided into three subpopulations

abnormalities such as: rhythmic troubles, heart and/or coronary insufficiency. The

according to plasma levels in TSH, FT4 and FT3: the subpopulation with

aim of our study was to describe the frequency and the clinical characteristics of

euthyroidism (control), the subpopulation with hyperthyroidism (Hyper) And the

CT in Graves’ disease (GD).

subpopulation with hypothyroidism (Hypo). Hormone levels were determined by

Methods

radioimmunoassays (FT3, FT4 and cortisol) and radioimmunometric (TSH).

Patients with GD were enrolled into a retrospective study. The prevalence and the

Variations in plasma cortisol content in subpopulations with dysthyroids have

clinical characteristics of CT were described.

been observed and are in favor of an interrelation between the two glands. These

Results

results could be explained by the fact that factors responsible for the activation of

Out of 90 participants with GD, 12.2% patients presented with cardiothyreosis.

the corticotropic axis are capable of causing structural and functional changes in

Their sex ratio (M/F) was 9/2 and their mean age was 46.72G15.11 years. CT was

the thyroid as a function of the nature of the stimulus, Its intensity and its duration.

the circumstance of discovery of GD in 2.2% of cases. Its clinical manifestations

Keywords: Glucocorticoids, thyroid, hyperthyroidism, hypothyroidism, cortisol.

were palpitation in 75.5%; dyspnea in 24.4% and anginal pain in 5.6%. Different

DOI: 10.1530/endoabs.49.EP1234

modes of presentation of CT were found: ten cases of atrial fibrillation (ACFA)

(90.9%); five cases of Heart failure

(45.45%) and three cases of coronary

insufficiency

(27.27%). Systolic blood pressure was on average

128G

11.6 mmHg and mean diastolic blood pressure was 76G19 mmHg. Mean heart

frequency was measured at 106G20 beats/min. Underlying mitral valvulopathy

was found in two cases. Six out of 11 patients presented anemia (54.5%) and

EP1235

90.9% had severe hyperthyroidism. Arrhythmia was reduced in 72.7% of the

Therapeutic plasma exchange in the treatment of hyperthyroidism

cases, after treating with betablocker.

Hamide Piskinpasa¹, Meral Mert¹, Ahmet Cem Dural², Pinar Karakaya¹,

Conclusion

Firuze Midi Kursat³, Yildiz Okuturlar³ & Bahar Ozdemir³

CT, although rare, remains a serious life-threatening complication of GD. The

¹Department of Endocrinology and Metabolism, Bakirkoy Dr Sadi Konuk

ACFA is its most common clinical form and underlying cardiac disease is often

Education and Research Hospital, Istanbul, Turkey;²Department of General

present.

Surgery, Bakirkoy Dr Sadi Konuk Education and Research Hospital,

DOI: 10.1530/endoabs.49.EP1232

Istanbul, Turkey;³Department of Internal Medicine, Bakirkoy Dr Sadi

Konuk Education and Research Hospital, Istanbul, Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Preoperative preparation of the hyperthyroid patient for thyroidectomy is

EP1237

imperative to avoid perioperative complications due to severe thyrotoxicosis.

Asymptomatic riedel thyroiditis presented in a patient with thyroid

24-years old woman was admitted at our clinic for uncontrolled Graves’ disease.

storm and polyglandular autoimmune disease

In our case, agranulocytosis introduced by propylthiouracil. Therefore, surgery

María Laura García¹, Yamila Martinez Artola¹, Marta Endelman¹,

was the only chance of an effective therapy. In cases when the patient is

Sabrina Mayoni¹, Daniel Santiago García¹ & Noelia Rella^1,2

unresponsive to medical therapy or when such therapy is contraindicated,

¹Hospital Méndez, Buenos Aires, Argentina;²Hospital Británico, Buenos

therapeutic plasma exchange (TPE) could be useful for preparing patients for

Aires, Argentina.

surgery. After 13th TPE, our patient both FT4 and FT3 levels remained above the

normal limits but the sign and symptoms of thyrotoxicosis improved In the

literature, number of plasmapheresis sessions done were usually less than 13

Riedel Thyroiditis is a rare form of infiltrative and fibrotic disease of the thyroid

except a case of Jod Basedow with 17 sessions We observed a moderate decrease

that is characterized by compressive symptoms resulting from a rapidly enlarging

in FT3

and at least decrease in FT4

levels after thirteen session. Total

goiter. The association with Graves Thyroiditis and autoimmune diseases is very

thyroidectomy was performed successfully. In cases when the patient is

rare. The aim of this presentation is to report a patient with asymptomatic Riedel

unresponsive to medical therapy or when such therapy is contraindicated, TPE

Thyroiditis associated with Thyroid Storm and Polyglandular Autoimmune

could be useful for preparing patients with thyrotoxicosis for surgery. It is still

Disease. A 54-year-old female patient with recent diagnosis of Grave’s Disease

unclear why some patients achieve the maximum benefit from TPE, regardless of

was admitted to our hospital with congestive heart failure, abdominal pain,

their etiology. Our patient both FT4 and FT3 levels remained above the normal

vomiting and diarrhea. Her medical history was remarkable for dilated

limits but the sign and symptoms of thyrotoxicosis improved and maybe reduced

myocardiopathy, cholecystectomy and precocious ovarian failure. At physical

the risk of thyroid storm in the perioperative period. We continued to use the

examination ascites, bilateral pleural effusion and a 50 g goiter with a 19 mm

b-blocker and systemic steroid therapy in order to avoid thyroid storm during the

nodule were present. Thyroid Storm was diagnosed according to Burch-Wartofsky

operation and a few days after surgery. These findings suggested that TPE

Score. A 10 miCu I131 dose was administrated given the impossibility to prescribe

ameliorates the clinical symptoms of thyrotoxicosis rather than thyroid hormone

antithyroid drugs because of severe liver disease associated. Due to persistent

status. It is unclear which elements are responsible for determining patient

hyperthyroidism a second dose of

12 miCu I131 was administrated. After

response to TPE.

achieving euthyrodism on L-thyroxine treatment a hepatic biopsy was indicated

due to chronic intrahepatic cholestasis with negative antibodies and confirmed a

DOI: 10.1530/endoabs.49.EP1235

stage 2 Primary Biliary Cirrhosis. Later on the patient presented impaired fasting

glycaemia. A pancreatic, adrenal and ovary autoimmune panel was asked and only

GADA resulted positive. Histocompatibility study showed HLA DQ9 and DQ4.

Three fine needle aspirations (FNA) were performed during follow up due to

changes in the vascular flow of the nodule. After a negative first result the second

FNA leads to III Bethesda diagnosis. Given the insufficient material obtained

during the third a total thyroidectomy was indicated. Histopathological

examination revealed a

1.5 cm Follicular Adenoma surrounded by Riedel

Thyroiditis. To our knowledge asymptomatic Riedel Thyroiditis associated with

Thyroid Storm and Polyglandular Autoimmune Disease has not been described.

DOI: 10.1530/endoabs.49.EP1237

EP1236

Adult outcome of congenital hypothyroidism

Najoua Lassoued, Selmane Ouannes, Hbib Soua, Hachmi Ben Hammouda

& Mohamed Taher Sfar

Pediatric Department, Taher Sfar University Hospital, Mahdia, Tunisia.

EP1238

Congenital hypothyroidism in children with down syndrome

Najoua Lassoued, Salmane Ouannes, Sobhi Ghanmi, Hachmi

Introduction

Ben Hammouda, Hbib Soua & Mohamed Taher Sfar

It is because of the heavy somatic and especially intellectual impact of congenital

Pediatric Departement, Taher Sfar Unversity Hospital, Mahdia, Tunisia.

hypothyroidism that its systematic screening from birth has been proved to be

essential. Numerous publications have already reported the considerable

improvement in the prognosis of this condition but still few relate to adults.

Introduction

This preliminary work proposes to report the adult outcome in a cohort of 12

Congenital hypothyroidism is 30 times more frequent in newborns with Down

patients followed for congenital hypothyroidism.

syndrome (DS) than in the population of healthy children. Mild isolated TSH

Patients and methods

elevation with normal thyroxine (T4) levels is the most commonly seen pattern of

Descriptive study of 12 patients, seven girls and five boys, followed for congenital

thyroid dysfunction in these children.

hypothyroidism in the pediatric department of Mahdia and who reached an age of

Patients and methods

18 years.

A retrospective study was carried out on eleven patients with DS in the pediatric

Results

department of Mahdia who were followed for congenital hypothyroidism.

The mean age at diagnosis was 4.5 months. The average term was 38 SA. The

Results

mean birth size was 49.5 cm. The mean birth weight was 3700 g. Regarding

The average age of diagnosis of hypothyroidism was 3 months. Trisomy 21 was

statural development: the average final size was

153.5 cm (128-174). The

free in 10 patients and secondary to a translocation (46, XY, t rob (14;21),C21) in

difference between final size and target size was -0.7 DS. The last average BMI

a single patient. Four patients had interventricular communication, 3 patients had

was 21.35 kg/m² (16-27). Regarding pubertal development: In girls, the onset of

atrial septal defects, 2 patients had arteriovenous communication and only one

breast development (S2) appeared at the average age of 9 and a half years, the

patient had cleft palate. Renal ultrasound was normal in all patients except one

average age of menarche was 12 years. In boys, the onset of increased testicular

patient who had a moderate left pyelocalicial dilatation. Thyroid hormone tests

volume (G2) appeared at the average age of 13 years, the onset of pubic hair (P2)

were done after the discovery of an umbilical hernia in one patient and a neonatal

12 years. For the school curriculum: in primary school, all children were

jaundice in 3 patients; the thyroid assessment was then requested before the

admitted to the normal age of 6 years. Only one patient redoubled in primary.

genetic confirmation of trisomy 21 by the karyotype. For the remaining 7 patients,

Four patients redoubled in secondary, only nine patients reached the baccalauréat

hypothyroidism was discovered during a biological assessment requested as part

and three left the high school.

of the systematic follow-up of these patients. The mean TSH value was

Discussion

13.72 mU/ml. Hypothyroidism was subclinical in 4 patients (with normal T4

An improvement in the results is still possible by acting on the different

value). Cervical ultrasound showed a thyroid gland in place in all patients. No

prognostic factors: age at onset of treatment, higher dose of thyroxine in the

patients developed goiter. The initial mean dose of L-thyroxine was 7.25 mg/kg/d.

neonatal period, psychological monitoring with appropriate aids if necessary and

After 3.25 years of follow-up, hypothyroidism proved to be transient in one

above all compliance in adolescence.

patient while it was permanent in the others.

Conclusion

It is impossible to draw definitive conclusions from this study, given the small

Newborns with DS have often subclinical hypothyroidism at birth. Systematic

number of patients studied. This is a preliminary study of work to be continued in

screening at birth and subsequent repeat screening is necessary because L-

the adult sector. For this these patients were oriented in the service of adult

thyroxine administration will improve growth, hypotonia and psychomotor

endocrinology.

functions in these patients.

DOI: 10.1530/endoabs.49.EP1236

DOI: 10.1530/endoabs.49.EP1238

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1239

Conclusion

In non-diabetic patients, IR and thyroid dysfunction have strong correlations with

Retrospective audit: To investigate the long-term outcome of fixed

NAFLD. The role of thyroid autoimmunity in this relationship needs further

dose 300 MBq of radioiodine (131-I) treatment for Autonomous

assessment.

Toxic Thyroid Nodule

Vikram Lal & Richard Quinton

DOI: 10.1530/endoabs.49.EP1240

Royal Victoria Infirmary, Newcastle, UK.

Introduction

Radioiodine (131-I) treatment for benign thyroid disease has a 70 year history.

Among the radioactive isotopes, (131-I) can be used successfully. The intention

of radioiodine treatment is primarily to induce a euthyroid or hypothyroid state,

EP1241

but in the case of large multinodular goitres, shrinkage represents a secondary aim

of therapy. The optimal method for determining iodine-131 treatment doses for

Two pseudomalabsorbtion cases successfully treated with parenteral

Toxic Thyroid nodule is unknown, and techniques have varied from a fixed dose

levothyroxine

Seher C¸ etinkaya Altunta¸, Mehtap Evran, Murat Sert & Tamer Tetiker

to more elaborate calculations based upon gland size, iodine uptake, and iodine

Cukurova University Medical Faculty, Department of Internal Medicine,

turnover. Historically, UK prescribing has varied widely according to local

Division of Endocrinology, Adana, Turkey.

custom and practice. The range of activities currently prescribed varies between

200-800 mega Becquerel (MBq), with the majority of patients receiving 400-

600 MBq. Toxic adenoma, usually mild hyperthyroidism required 500 MBq of

Hypothyroidism is a common endocrine disorder which is easily treatable by an

131-I radioiodine.

appropriate thyroid hormone replacement therapy in the majority of patients. In

Data/Method

some patients, hypothyroidism is refractory to oral levothyroxine substitution.

We collected data from nuclear medicine department and hospital electronic and

Common causes of lack of response to levothyroxine replacement comprise non-

paper patient records. In this retrospective audit we had total 10 patients (8-female

compliance and impaired absorption. We report a case of pseudomalabsorption of

and 2 male) who received a single fixed dose radioiodine (131-I) for autonomous

levothyroxine. Here, we report two female patients with hypothyroidism who had

toxic thyroid nodule in the 10-year period from 2007-2016. Patients’ age were

multinoduler goiter and thyroid papillary carcinoma with total thyroidectomy,

between 20 to 75 years. All patients had suppressed TSH at!0.05 nmol/l, with

despite the use of levothyroxine sodium at very high doses (800 mcg/day to

mildly raised thyroid hormones, and thyroid antibodies (TPO and TR) were

1100 mcg/day). Desired blood TSH and fT4 levels were reached soon after the

negative which tended to excluded thyroid immune disorders.

days of administration of levothyroxine by parenteral routes(intramusculer-

Results

intravenosus) to the patient who had malabsorption but no detectable etiology. By

We checked their Thyroid function tests at 3, 6, 12 and 24 -month periods. There

investigation during hospitalization in the endocrinology department. Symptoms

were significant improvements in thyroid function tests, with

4/10 patients

of the patients have declined. Clinical and laboratory improvement in pollinic

achieving results within the euthyroid range and

patients becoming

follow-ups continued in these two patients. With these findings, these two patients

hypothyroid. All nodules shrank down to become non-palpable and no patient

were diagnosed as pseudomalabsorbtion.

required a repeated dose of 131-I.

DOI: 10.1530/endoabs.49.EP1241

Recommendations

Though,

500MBq of 131-I radioiodine is recommended for toxic thyroid

adenoma in the UK, our data showed that a smaller fixed dose is 100% effective

and probably associated with lower rate of hypothyroidism (60%) at 2 years. Ref;

Radioiodine in the management of benign thyroid disease Clinical guidelines,

Royal College of Physicians, UK.

DOI: 10.1530/endoabs.49.EP1239

EP1242

Follow-up observations on nodular goiter in Japanese - Progression and

related factors

Takao Kunori, Noriko Nemoto, Nanako Fujikawa, Satoru Shiraso,

Hiroshi Yoshida, Akihiko Hashimoto, Shinya Kawaguchi & Fumiaki Shinya

EP1240

Iwaki-kyoritsu Hospital, Iwaki-shi, Fukushima-ken, Japan.

Assessment of thyroid functions, thyroid autoimmunity and insulin

resistance in non-diabetic patients with non-alcoholic fatty liver disease

Nodular goiter (ND) is increasingly found by image analysis. The long-term

Maha Assem¹, May Fawzi¹, Alhosaeyn Ibrahim² & Aasem Saif¹

course of ND, however, is not necessarily clear and may differ in locality. The

¹Faculty of Medicine, Cairo University, Cairo, Egypt;²Ahmed Maher

present study analyzed the changes of ND in Japanese, taking iodine-rich foods,

Hospital, Cairo, Egypt.

during follow-up periods.

Patients and methods

Patients (nZ4,229) were followed up to 28 years (3.4G5.8 years). Volume of

Introduction

nodules (VOL) by ultrasonography (US) and laboratory data, including thyroid

Non-alcoholic fatty liver disease (NAFLD) is a common cause of impaired liver

hormones (TH), thyroglobulin (Tg), autoantibodies (Ab) and thyroid stimulating

functions. It is associated with hepatic and adipose tissue insulin resistance (IR) as

hormone (TSH), were examined. Increase rates of VOL (VIR, start from 100%)

well as decreased whole-body insulin sensitivity. Thyroid hormones are important

and Tg were compared in 5 periodic intervals; B-period (!2 years), C (2- yrs),

for the intrahepatic metabolism of lipids. Thyroid disorders have been associated

D (3- yrs), E (5- yrs) and F (10- yrs).

with IR due to various mechanisms such as altered insulin secretion and lipid

Results

levels.

1) VIR in 5 periods: In 6 scales (K50% to 400%-), NOD (%) of VIR!150%,

Aim

clinically ‘unchanged’, decreased in A (81%) to F (43%), while NOD (%) of

The aim of our study was to assess thyroid functions, thyroid autoimmunity and

VIRO200%, ‘visible enlargement’ increased; A (11%) to F (46%). 2) Analysis in

IR in non-diabetic patients with NAFLD.

solitary nodules (nZ1,314): a) VIR increased; B (119G82%) to F (176G140)

Material and methods

(P!0.05). b) Serum Tg showed mild increase; B (105G82%) to F (134G131). c)

The study was conducted on 90 non-diabetic subjects (60 patients with NAFLD

US detected fluids, ‘cystic’, more in F (78%) than in B (32%). 3) Pathology: VIR

and

subjects with normal liver). Both groups were sex matched.

of adenomatous goiter (AG) was 15% higher than that of non-AG (P!0.05).

Ultrasonography was used to categorize the study subjects into NAFLD and

4) Factors related to VIR: Initial VOL, Abs and length of follow-up periods were

normal liver groups. Thyroid functions and thyroid peroxidase antibody (TPO-

significantly related to VIR. Use of ethanol or TH-drugs also influenced VIR.

Ab) were assessed in all subjects. Homeostatic model assessment (HOMA-IR)

5) Late surgery (after 2 years): VIR of surgical cases (nZ24, 159G133%) was

was used to assess IR in the study population.

higher than that of non-surgical cases (nZ572, 129G96%, PZ0.14).

Results

Conclusions

Our study showed a highly-significant positive correlation between NAFLD and

NOD remained unchanged (VIR!150%) in 40% of patients over 10 years.

IR (P!0.001). It also showed a significant positive correlation between NAFLD

Progression of NOD seemed to be associated with pathology, TSH and Abs. Late

and thyroid functions with higher prevalence of subclinical thyroid dysfunction in

surgery tended to be performed in patients with higher VIR.

NAFLD patients (PZ0.02). Thyroid functions didn’t show any statistically

significant correlations with IR, but TPO-Ab showed significant positive

DOI: 10.1530/endoabs.49.EP1242

correlation with IR (PZ0.02) within the total study population.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

9,0

EP1243

8,5

Aggravation of thyroid dysfunction in a case of thyroid hormone

8,0

resistance after near total thyroidectomy for multinodular goiter

7,5

7,0

Ilkay Kartal & Gonca Tamer

6,5

Medeniyet University Goztepe Training and Research Hospital, Istanbul,

6,0

Turkey.

5,5

5,0

4,5

4,0

Introduction

3,5

Resistance to thyroid hormone

(RTH), a syndrome reduced end-organ

3,0

responsiveness to thyroid hormone.

2,5

Case report

2,0

1,5

A 42 year old woman underwent near total thyroidectomy due to her enlarged

1,0

thyroid with multiple nodules. At that time she had sligthly elevated values of

0,5

MedianA

plasma FT4, FT3 and normal TSH values and had no sign and symptoms of

0,0

25%-75%

-0,5

Min-Max

thyrotoxicosis or hypothyroidism. After thyroidectomy she recieved L-T4

TSH PRE TSH 3M TSH 6M TSH 12M TSH 24M

treatment but her TSH levels remains elevated although FT4 was high. She

Figure 1

was reffered endocrinology polyclinic when she began to have symptoms of

hypothyroidism like fatique, fibromyalgia. The results were FT4: 1.93 ng/dl (n:

0.61-1.12), FT3: 2.2 pg/ml (n: 2.5-3.9) TSHO100 uIU/ml (n: 0.27-4.2) under

Limitations

150 mcg L-T4 treatment. There were no detectable anti-thyroid autoantibodies.

This study is a retrospective review and did not employ controls, blinding, or

Alpha subunit of TSH level was 0.8 IU/l (n: 0-0.8) normal. No pituitary adenoma

randomization. Additionally, the thyroid antibodies did not evaluate.

was determined in pituitary MRI. She has no family history of thyroid disease.

Conclusion

Genetic test is not available in our hospital. We performed TRH stimulation test

Weight loss after the gastric bypass improved and normalized thyroid hormone

after taken off levothyroxine for 14 days and TSH diluted up to 20 times during

levels. More studies are required to clarify the reason of decrease in serum TSH.

test. After intravenous bolus injection of TRH

(200 mcg) serum TSH

concentration increased from

269 uIU/ml

(basal value) to a peak of

DOI: 10.1530/endoabs.49.EP1244

1330 uIU/ml at 30 min. As a result RTH was considered and LT4 initiated

again. After L-T4 titrated up to 175 mcg a day L-T3 added 12.5 mcg two times a

day. Six weeks after this treatment FT4:

2.58 ng/dl

(n:

0.61-1.12), FT3:

3.99 pg/dL (n: 2.5-3.9), TSH: 14 uIU/ml sn: 0.27-4.2). Her complaints were

reduced. Blood pressure was 120/80 mmHg, pulse 74/min. She was clinicaly

better.

EP1245

Conclusion

Correlation between serum nitrite (NO2) levels, TQ7 and GHQ12

Treatment with L-T3 would be more appropriate for reducing goitre size than

questionnaire scores in treatment-naïve hypothyroid patients

attempting thyroidectomy in that patient. In patients with RTH thyroid gland

Zoran Gluvić¹, Vladimir Samardzi

´¹, Jelena Tica Jevti

´¹, Marina Vujovi

´¹,

ablation tends to aggravate thyroid dysfunction and multinodularity. Large glands

Milena Lačković¹, Vesna Popović-Radinović¹, Saša Radenkovi

´²,

have been successfully treated by administration of a single high dose of L-T3

Violeta Mladenovi

´³, Emina Sudar-Milovanovi

´⁴, Milan Obradovi

´⁴ &

given every other day. Symptoms of thyrotoxicosis usually respond to the

Esma R Isenović⁴

administration of the beta bloker, atenolol.

¹Division of Internal medicine, Department of Endocrinology, Zemun

DOI: 10.1530/endoabs.49.EP1243

Clinical Hospital, School of Medicine, University of Belgrade, Belgrade,

Serbia;²Clinic for Endocrinology and Diabetes, Nis Clinical Centre, School

of Medicine, University of Nis, Nis, Serbia;³Center for Endocrinology and

Diabetes, Clinical Centre Kragujevac, Faculty of Medical Sciences,

University of Kragujevac, Kragujevac, Serbia;⁴Lab for Molecular

Endocrinology and Radiobiology, Institute for Nuclear Sciences ‘Vin

ˇa’,

University of Belgrade, Belgrade, Serbia.

EP1244

Thyroid function and weight loss after Roux-en-Y gastric bypass:

Introduction

observational study

Primary hypothyroidism, as a clinical syndrome caused by insufficiency or

Gisah Amaral de Carvalho, Cleo Mesa Junior, Rodrigo Strobel &

inefficacy of thyroid hormones, significantly influences on patients’ quality of life

Paula Carolina Dambros Granzotto

(QoL). Accelerated atherosclerosis induces increased cardiovascular morbidity

Clinical Hospital of The Federal University of Parana, Curitiba, Brazil.

and mortality rates in hypothyroid patients. Serum NO2 levels, the stable NO

metabolites, are among well-known markers for endothelial dysfunction and

atherosclerosis in hypothyroidism. We examined the correlation between serum

Background

NO2 levels and QoL questionnaires scores (TQ7 and GHQ12) in treatment-naïve

TSH seems to be positively related to the degree of obesity and weight loss seems

hypothyroid females.

to induce a reduction in the TSH levels and T3Total. TSH is the first regulatory

Material and methods

mechanism of total energy expenditure and T3 regulates energy metabolism and

Cross-sectional study involved 82 females, divided into three groups according to

thermogenesis (1)

TSH and fT4 levels: latent (22) and overt (22) hypothyroid, and euthyroid (38)

Objective

group, respectively. Initially, after informed consent was signed, serum NO2

The aim of this study was to investigate the association between thyroid function

levels were measured and TQ7

and GHQ12 questionnaires were fulfilled.

and body mass index (BMI) in obese population. And evaluate the influence of

Obtained data were analysed with appropriate statistical methods. Statistical

weight reduction after gastric by-pass on thyroid hormone levels.

significance was 0.05.

Design

Results

Retrospective observational study

Overall mean of NO2 level was 11.2 mmol/l (0.9-79.0 mmol/l) and didn’t differ

Setting

between groups. Mean overall TQ7 and GHQ12 scores were 14 (5-40) and 12 (1-

A single center study in Curitiba, Brazil.

32) respectively, and statistically differ between groups (P!0.01). Correlation

Methods

between serum NO2 levels and TQ7 and GHQ12 scores didn’t significantly differ

We studied 215 obese patients (BMI 35-58.5 kg/m²), age between 18-65 years,

(rNO2/TQ7ZK0.241, rNO2/GHQ12ZK0.141; PO0.05).

baseline,

12,

24 months after laparoscopic Roux-en-Y gastric bypass

Conclusions

(RYGBP). Participants with thyroid disorders were excluded.

Decreased serum NO2 levels in hypothyroid groups pointed out to lowered NO

Results

bioavailability and therefore endothelial dysfunction. Otherwise, thyroid disease

Baseline TSH concentration was not associated with baseline BMI

(Pear-

specific questionnaire score determined hypothyroid patients in moderately

sonZ0.003; PZ0.971). There were a significantly decrease in serum TSH after

stressed cluster. A simultaneous use of NO2 levels and QoL scores can alleviate

RYGBP until 24 months (PZ!0.001) (Figure 1), but did not correlate with

decision to introduce the l-thyroxin management in hypothyroid patients,

weight loss (PearsonZ0.08; PZ0.303). Subclinical hypothyroidism prevalence

presumably in latent ones.

was 9.3% (nZ20) before RYGBP. At 12 months, 8.7% (nZ17) of this patients

had TSH!4.5 (PZ0.003).

DOI: 10.1530/endoabs.49.EP1245

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1246

especially NAC, in orbital fibroblasts. Some of the actions are exclusive to

Vitamin D levels in Graves’ disease (GD) are lower than in general

GO fibroblasts. These observation have important clinical implication, in

population but do not correlate with laboratory and clinical parameters

that some of these antioxidants could be tested in patients with GO.

in GD or SNPs associated with GD

DOI: 10.1530/endoabs.49.EP1247

Tereza Planck^1,2, Bushra Shahida¹, Johan Malm^1,3 & Jonas Manjer^1,4

¹Lund University, Department of Clinical Sciences, Malmo, Sweden;

²Department of Endocrinology, Skåne University Hospital, Malmo,

Sweden;³Department of Clinical Chemistry, Skåne University Hospital,

Malmo, Sweden;⁴Department of Surgery, Skåne University Hospital,

Malmo, Sweden.

EP1248

Introduction

Intrathyroidal and peripheral venous blood lymphocyte subset patterns

The role of vitamin D in GD is poorly understood. The aim was to compare

in patients with Graves disease

vitamin D levels in newly diagnosed patients with GD with the general population

Margarita Dudina^1,2, Dogadin Sergey^1,2, Savchenko Andrey³,

and to correlate vitamin D levels at diagnosis with laboratory and clinical

Mankovsky Vladimir² & Borisov Alexander³

parameters in GD. Moreover, we examined genetic variation in genes involved in

¹Krasnoyarsk state Medical University named after prof. V.F. Voyno-

the vitamin D metabolism and their association with GD.

Yasenetsky, Krasnoyarsk, Russia;²Krasnoyarsk region clinical hospital,

Material and methods

Krasnoyarsk, Russia;³Institute for Medical problems of the North, Russian

Levels of vitamin D were compared in 292 patients with newly diagnosed GD and

Academy of Medical Science, Siberian division, Krasnoyarsk, Russia.

2305 controls. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor

(VDR), vitamin D binding protein (DBP) and 1-alpha-hydroxylase (CYP27B1)

Graves’ disease (GD) is an autoimmune disease with genetic predisposition. The

were examined for association with GD and/or Graves’ ophthalmopathy (GO) in

link with the major histocompatibility complex determines the complexity of

708 patients and 1178 controls.

the excess thyroid hormones molecular action on immune system that may cause

Results

the divergence of autoimmune process in GD, functioning not only in peripheral

Patients with GD had significantly lower levels of vitamin D compared to general

immune cells, but also in the thyroid. Objective: to study the phenotypic

population (55.0G23.2 vs 87.2G27.6 nmol/l, P!0.001). In patients with GD

composition of T- and B-lymphocyte subset patterns in peripheral blood and

(nZ219), there was no association between the levels of vitamin D and the levels

thyroid tissue in patients with GD. Materials and methods. The study included 43

of free thyroxine

(fT4), free triiodothyronine

(fT4), thyrotropin receptor

women with GD, mean age 39.95G14.38, who were performed the epifascial

antibodies (TRAb), GO at diagnosis, or relapse after terminating treatment with

thyroidectomy. Phenotypic composition of T

- and B-lymphocytes was

anti-thyroid drugs. Two SNPs in VDR were associated with GD, rs10735810 (OR

investigated by flow cytometry. Analysis of stained cells was performed on a

1.36, 95% CI 1.02-1.36, PZ0.02) and rs1544410 (OR 1.47, 95% CI 1.03-1.47,

flow cytometer FC-500 (Beckman Coulter, USA). Each sample was analyzed at

PZ0.02). However, there was no difference in mean vitamin D levels between

least

50,000 lymphocytes. Results. The median level of thyroid stimulating

genotypes in either rs10735810

(AA 55.9 nmol/l, AG

56.1 nmol/l, GG

hormone

(TSH), free thyroxine and autoantibodies to TSH receptor was

54.1 nmol/l, PZn.s.) or rs1544410

(AA 56.6 nmol/l, AG 57.5 nmol/l, GG

respectively

1,9

(0,9;

2,9) umol/ml,

16,8

(13,2;

19,0) and

15,8 (9,4;

24,2)

54.8 nmol/l, PZn.s.).

IU/ml. In peripheral blood of GD patients compared with healthy controls

Conclusion

identified the increased in 9.2% the relative number of total T lymphocytes

Patients with GD have lower vitamin D levels compared with general population;

(CD3C, P!0.001) and in 5.8% relative level of T-helper cells (CD3CCD4C,

however, the levels of vitamin D do not affect the laboratory or clinical

PZ0.019), but decreased content of T-regulatory cells

(CD3CCD4C

parameters of the disease. SNPs in the VDR influence the risk of GD through

CD127LowCD25High, PZ0.048) and total activated T cells

(P!0.001),

mechanisms other than reducing the vitamin D levels.

T-helper cells (CD3CCD4CCD25C, PZ0.045) and cytotoxic T-lymphocytes

DOI: 10.1530/endoabs.49.EP1246

(CD3CCD8CCD25C, PZ0.041). It is revealed that in the blood of GD patients

increased in 35.9% the relative number of B2-lymphocytes (CD19CCD5C,

PZ0.003), while reducing the amount of activated total B cells (CD19CCD23C,

P!0.001), B2 cells (CD19CCD5K, P!0.001), B2K simplet (CD19CCD5-

CD27K, P!0.001) and B2-memory (CD19CCD5KCD27C, P!0.001) cells.

In a comparative analysis of the phenotypic composition of T

- and

B-lymphocytes in peripheral blood and thyroid tissue revealed that in the tissues

EP1247

is 2.3 times higher relative content of total activated T cells (CD3CCD25C,

PZ0.037), in 5.1 times more of activated cytotoxic T-lymphocytes (PZ0.023),

Action of several bioavailable antioxidants in orbital fibroblasts from

1.7

times increased the percentage of B2-memory (CD19CCD5KCD27C,

patients with Graves’ Orbitopathy (GO): a new frontier in GO

treatment?

PZ0.028) cells. Conclusions. The reduction of activated T - and B-lymphocytes

Giovanna Rotondo Dottore¹, Giamberto Casini², Stefano

content in peripheral venous blood of patients with GD is determined by the

Sellari Franceschini³, Marco Nardi², Paolo Vitti¹, Claudio Marcocci¹ &

migration of immune cells in thyroid tissue.

Michele Marinò¹

DOI: 10.1530/endoabs.49.EP1248

¹Department of Clinical and Experimental Medicine, Endocrinology Units,

University of Pisa and University Hospital of Pisa, Pisa, Italy;²Department

of Surgical, Medical and Molecular Pathology, Ophthalmopathy Unit I,

University of Pisa and University Hospital of Pisa, Pisa, Italy;³Department

of Surgical, Medical and Molecular Pathology, ENT Unit I, University of

Pisa and University Hospital of Pisa, Pisa, Italy.

EP1249

Oxidative stress plays a crucial role in the pathogenesis of Graves’

No impact of subclinical hypothyroidism on cognitive functions among

Orbitopathy

(GO), supporting the use of antioxidants in GO patients.

the elderly

Selenium has a beneficial effect, but other antioxidants have not been

Harleen Kaur^1,2, Nitin Malhotra² & Jubbin Jacob^1,2

investigated. Here we evaluated several antioxidants in primary cultures of

¹Endocrine & Diabetes Unit, Christian Medical College and Hospital,

orbital fibroblasts from GO patients and control subjects. The following

Ludhiana, Punjab, India;²Department of Medicine, Christian Medical

substances were tested: Vitamin C (Vit-C), N-Acetyl-l-Cysteine (NAC),

College and Hospital, Ludhiana, Punjab, India.

melatonin (Mel), retinol (Ret), beta-carotene (bCar), Vitamin E (Vit-E).

Cells were treated with H₂O₂, which induced oxidative stress (increased

Background

glutathione disulfide). Pre-incubation with non cytotoxic concentrations of

Most recent cross sectional and longitudinal studies have failed to find an

all substances in GO, and with Vit-C, NAC and Mel in control fibroblasts,

association between cognitive dysfunction and subclinical hypothyroidism. A

prevented oxidative stress. H₂O₂ caused increased proliferation, which was

recent paper from our country however suggested a significant association.

reduced by Vit-C, NAC and bCar in GO, but not in control fibroblasts. H₂O₂

Objectives

did not affect HA release, which was however reduced by NAC and

This study was undertaken to determine the prevelance of cognitive impairement

melatonin in GO, and by all substances except for Vit-E in control

among educated, elderly Indian patients (O60 years) with and without subclinical

fibroblasts. Our findings show an antioxidant actions of several compounds,

hypothyroidism.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Materials and methods

¹Sanatorio Méndez, Buenos Aires, Argentina;²Hospital Británico, Buenos

This study was conducted on educated, elderly patients admitted to the in-patient

Aires, Argentina;³CEBBAD, Universidad Maimonides, Buenos Aires,

department of Christian Medical College, Ludhiana. One hundred patients with

Argentina.

subclinical hypothyroidism an equal number of controls with normal thyroid

functions were interviewed after taking informed consent. Subclinical hypothyr-

oidism was defined as serum TSH level more than 4.0 mIU/L with serum fT3 and

fT4

in the normal reference range. Cognitive function was assessed by

Thyroid storm (TS) is a rare and life threatening condition that requires a

Hindi/English Mini mental status examination (MMSE) and clock drawing test

prompt recognition and treatment. The clinical features may overlap with

(CDT).

other acute medical conditions. Currently both Akamizu Criteria (JTA) and

Results

Burch and Wartofsky Scale (BW) are helpful diagnostics tools.

Objective

The cases (nZ100) had a mean age of 68.2 years, were 59% males and had a

To evaluate TS patients according to currently available criteria and to identify

mean body mass index of 25.5 kg/m² compared to controls (nZ100) who had a

the clinical features and outcomes.

mean age of 69.9 years (P-0.09), were 64% male (P-0.5) and had a mean BMI of

Methods

25.3 kg/m².All other baseline variables including co-morbidities, family history

A single center retrospective study covering a 6 year period was performed.

of dementia, head injury, smoking, alcohol use, fruit and vegetable intake, daily

Results

newspaper reading, education and exercise regularity were comparable in both

Fifteen cases were identified, resulting in four cases of TS per 10 000 admitted.

groups. The cases had mean MMSE of 26.1 and controls of 25.9 (P-0.68)

Mean age 49.8G17.3 years (range:

31-86). Male/Female:

3/12. Etiology:

respectively The cases had mean CDT of 2.19 and controls 2.18 (P-0.95).

autoimmune (nZ8), factitious (nZ3), amiodarone-induced (nZ3), undetermined

Conclusions

(nZ1). Manifestations at admission: cardiovascular

(nZ8), fever

(nZ3),

There is no difference in cognitive function in elderly with subclinical

delirium (nZ2), diabetic ketoacidosis (nZ1) and hypokalemic paralysis (nZ1).

hypothyroidism in comparison with elderly population having normal thyroid

Eleven had previous history of thyroid disease. Precipitating factors were found in

function.

cases. Thyroid hormone levels did not correlate with the severity of

Keywords: Subclinical, Hypothyroidism, Biochemical, Cognitive functions,

thyrotoxicosis. Mortality rate was 6.6%: 1 patient died from sepsis. Late hospital

Elderly

discharge was found in

4 patients

(PZ0.01): 3 required antithyroid drugs

DOI: 10.1530/endoabs.49.EP1249

withdrawal and the other received a heart transplant. The table resumes patients

according to BW and JTA. JTA fails to detect 4 patients with impending TS (st0),

one of which later on developed st1 (p8).

Conclusions

Ours results shows discrepancies between the two diagnostic systems. BW

appears to select a higher percentage of patients for aggressive therapy than JTA.

This presentation provides useful information for the management of TS, a rare

EP1250

and acute disease that requires high clinical suspicion in order to improve patient

Prolonged iodine excess due to hysterosalpingography in a pregnant

survival.

woman

Abbas Ali Tam, Sevgul Faki, Didem Ozdemir, Cevdet Aydin, Reyhan Ersoy

& Bekir C¸ akir

p10

p11

p12

p13

p14

p15

Yildirim Beyazit University School of Medicine, Endocrinology and

Metabolism Diseases, Ankara, Turkey.

JTA st0

st0

st2

st1

st2

st1

st0

st1

st2

st1

st0

Introduction

Hysterosalphingography (HSG) is the radiographic examination of uterine cavity

and fallopian tubes. It is generally used during evaluation of infertility and

DOI: 10.1530/endoabs.49.EP1251

radioopaque contrast is injected through cervical duct during the procedure.

Lipiodol which is the most commonly used contrast media in HSG is a fatsoluble

iodinated contrast media. This iodine is progressively cleared from the body in a

period ranging from a few weeks to a few months. Here, we present a 6 week

pregnant woman who underwent HSG 9 months ago and has very high urinary

iodine excretion.

Case

EP1252

A 31 years old woman at the 6th week of pregnancy was consultated for high

blood glucose. She was evaluated for infertility for 2 years, and HSG was

The role of FNDC5 gene expression in irisin level changes

performed

9 months before conception. There was no history of drug or

accompanying thyroid pathologies

nutritional supplement use that has high iodine content and that might affect

Ariadna Zybek-Kocik¹, Nadia Sawicka-Gutaj¹, Miroslaw Andrusiewicz²,

iodine status. Iodine excretion was 10087 mcg/L (100-700 mcg/L) in random

Joanna Waligórska-Stachura¹, Piotr Bialas², Jerzy Skrobisz³ &

urine sample and O450 ug/L in 24 hour urine. Her serum TSH was 2.19 uIU/ml,

Marek Ruchala¹

fT4

was 1.32 ng/dl and fT3

was 1.32 pg/ml. Thyroid autoantibodies were

¹Department of Endocrinology, Metabolism and Internal Medicine, Poznan

negative and thyroid ultrasonography was normal.

University of Medical Sciences, Poznan, Poland;²Department of Cell

Conclusion

Biology, Poznan University of Medical Sciences, Poznan, Poland;

The optimal time for normalization of body iodine stores after exposure of

³Department of General Surgery and Multiple Trauma, with Division of

iodinated contrast media is not known exactly. Thyroid dysfunctions in the form

Gastroenterological and Endocrine Surgery, Provincial Hospital, Poznan,

of both hypothyroidism or thyrotoxicosis can develop in euthyroid subjects after

Poland.

use of iodinated contrast media during HSG. In our case, thyroid functions were

normal but urinary iodine was very high even several months after HSG. This

suggests that females at reproductive age who underwent HSG might have excess

Irisin is a recently reported, widely discussed new adipo-myokin secreted

iodine concentration for a prolonged time and should be carefully evaluated for

mainly by muscle tissue. It is a cleaved and secreted part of fibronectin type

development of thyroid dysfunctions.

III domain containing

5, encoded by the FNDC5 gene. Some of the

DOI: 10.1530/endoabs.49.EP1250

previously published studies claim that alterations of irisin levels in patients

affected by thyroid diseases may be connected mainly with accompanying

myopathy. However, to date it has not been evaluated, whether the changes

in expression of FNDC5 may play a role in irisin level alterations. The aim

of the presented study is to assess the expression of FNDC5 gene in thyroid

EP1251

tissue of subjects with Graves’ disease, multinodular benign goiter, toxic

goiter and papillary thyroid cancer. The group of 80 patients with above

The challenge of diagnosing thyroid storm: a comparison of the

mentioned thyroid pathologies were involved. All included subjects

Japanese Thyroid Association Criteria to de Burch Wartofsky

underwent total thyroidectomy for reasons unrelated to the study.

Point Scale

Quantitative RT-PCR was used to analyze the FNDC5 gene expression.

María Laura García¹, Gabriela Szuman¹, María Florencia Scoscia¹,

As a result, the expression of FNDC5 was noted in all analyzed samples. No

Susana Bacigaluppi¹, María Victoria Panebianco³ & Noelia Rella^1,2

statistical difference between FNDC5 expression in benign and malignant

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

changes, as well as conditions associated with hyperthyroidism and

needed 1200 mg/day of Propylthiouracil. She delayed surgery for 2 weeks,

euthyroid state were found. Statistically significant overexpression of

then the dosage required for euthyroidism was 1800 mg/day for three weeks.

FNDC5 in patients with toxic goiter in comparison with tissues affected by

The goitre had 1.2 kg, from mandible angle to the supraclavicular region;

Graves’ disease, papillary thyroid cancer (tumor staged pT1 or pT2) and

she did not develop hypoparathyroidism or palsy of recurent laringeal nerve.

controls was observed. In conclusion, toxic goiter may be associated with

Second patient, 47 years old,with Graves’s disease, Addison disease, came

FNDC5 overexpression in thyroid tissue, in comparison with Graves’

with class III heart failure and severe asthma, She required 1800 mg of PTU

disease, papillary thyroid cancer staged pT1 or pT2 and controls. The

before surgery and had persistent hypoparathroidism. Third patient, 60 years

FNDC5 overexpression, on the other hand, is not directly associated with

old had severe cardiomyopathy at the beginning, left ventricle ejection

hyperthyroid state, as well as thyroid malignancy development. Hence, the

fraction 15%, atrial fibrillation that nedeed Cordarone both intravenously

changes in FNDC5 expression probably do not play the role in irisin

and orally. The dosage was progressivly increased from 60 to 180 mg/day

concentration changes associated with thyroid pathologies.

Thyrozol until safely opperated. Patient did not tolerate Propylthiouracil due

DOI: 10.1530/endoabs.49.EP1252

rash. Ejection fraction became 30% postopperatively and no complications

occurred.

DOI: 10.1530/endoabs.49.EP1254

EP1253

Long term effects of the less than total thyroidectomy: The experience of

a tertiary care center

EP1255

Georgios Boutzios¹, Zoe Garoufalia², Krystallenia Alexandraki¹,

Postpartum thyrotoxicosis - a diagnosis, sometimes, postponed

Gregory Kaltsas¹, Grigorios Kouraklis² & Gerasimos Tsourouflis²

Alexandra Novais Araújo, José Marçalo, Cristiana Costa, Ana Wessling &

¹Endocrine Unit, Department of Pathophysiology, Laiko University

Maria Joa˜o Bugalho

Hospital, Medical School, University of Athens, Athens, Greece;

Centro Hospitalar Lisboa Norte, Lisboa, Portugal.

²Second Department of Propedeutic Surgery, Laiko University Hospital,

Medical School, University of Athens, Athens, Greece.

Postpartum thyroid dysfunction occurs in 5-10% of women in the general

Background and aims

population within one year of delivery. The prevalence of postpartum

Less than total thyroidectomy (lobectomy, partial or subtotal thyroidectomy) is

Graves’ disease is estimated at 0.54%. Postpartum thyroiditis is much more

used mainly to treat thyroid nodules, and/or hyperthyroidism. The aim of the

common. Differential diagnosis is essential for an adequate treatment.

study was to investigate the long term effects of less extensive surgical

Radioactive iodine uptake can be useful to establish the etiologic diagnosis,

procedures. such as re-appearance of nodules and the need of thyroxin

but is contraindicated during lactation. Elevated titers of antithyrotropin

supplementation, or re-operation.

receptor antibodies (TRAbs) are suggestive of Graves’s disease but may be

Material and methods

measurable in approximately 10% of patients with painless thyroiditis and

Retrospective study in a tertiary Academic medical center. The study population

their titers can be low in the early phase of Graves’ disease. Therefore,

comprised initially 76 patients. Of whom 67 patients (ageGS.D.: 64.1G13.3, 58

the evolution of thyroid function and TRAbs’ titers may be needed to

(86.5%) females) who underwent lobectomy, partial thyroidectomy or subtotal

distinguish both pathologies. We present the case of a

25-year-old

thyroidectomy with benign histology and a follow-up equal or longer to 5 years

Caucasian woman who presented to the Emergency Department, 4 months

were included (9 excluded). None the patients appeared post-surgery permanent

after giving birth and still breastfeeding, complaining of palpitations,

iatrogenic hypoparathyroidism or recurrent laryngeal nerve injury.

anxiety, fatigue and insomnia with 1 week of duration and referring a 15 kg

Results

weight loss postpartum. She mentioned that her mother had Graves’ disease.

Mean follow up was 22.1G10.8 years. Patients who underwent lobectomy, partial

There was no ophthalmopathy; her heart rate was

140 bpm and the

thyroidectomy and subtotal thyroidectomy were 24 (35.8%), 9 (13.5%) and 34

electrocardiogram confirmed sinus tachycardia. Thyroid examination

(50.7%), respectively. Patients received thyroxin replacement were 62 (92.5%).

showed a painless tender and slightly enlarged gland. Blood tests - TSH

Relapse as defined by re-appearance of nodules or recurrence of hyperthyroidism

0.011 uU/nl (0.3-4.2), FT3O20 pg/ml (2.3-4.2) and FT4 5.33 ng/dl (0.93-

in total population was in 39 (58.2%) patients: 70.8% (17/24) in lobectomy group;

1.7). She was referred to the Endocrinology Department under treatment

77.8%

(7/9) in partial thyroidectomy, and

44.1%

(15/34) in subtotal

with methimazole and propranolol. Further testing revealed positive anti-

thyroidectomy group, respectively. Re-operation underwent 7 patients (10.4%)

thyroid peroxidase and thyroglobulin antibodies and TRAbs within ‘grey

of total or 17.9% of the recurrence cases. Univariate analysis showed that the type

zone’. Thyroid function was monitored with slowly tapering of methimazole

of operation and the length of follow up were predictors for relapse (OR: 1.81,

dosage. Eight months postpartum, despite low methimazole dosage (2.5 mg

95%CI: 1.03-3.19, PZ0.038 and OR: 0.92, 95%CI: 0.87-0.97, PZ0.002,

id) she presented with asymptomatic hypothyroidism (TSHO100 uU/ml).

respectively). Multivariate analysis showed that the length of follow up was

Anti-thyroid antibodies remained positive but TRAbs were negative.

superior independent factor predicting relapse (OR: 0.92, 95%CI: 0.87-0.98,

Methimazole was suspended and levothyroxine 25 mcg id initiated. At

PZ0.006).

last follow-up, the patient remains asymptomatic and in euthyroidism.

Conclusions

Diagnosis of postpartum thyroiditis was assumed. Monitoring thyroid

The majority of patients received thyroxin replacement. The length of follow-up

function and TRAbs levels for several months might be necessary to allow

and the type of operation have an impact on relapse, but mostly the length of

the differential diagnosis.

follow up. Treatment with total thyroidectomy could eventually avoid a relapse

DOI: 10.1530/endoabs.49.EP1255

and a possible need for re-operation.

DOI: 10.1530/endoabs.49.EP1253

EP1256

EP1254

Clinical characteristics of painless thyroiditis

Severe hyperthyroidism imposes large amounts of antithyroid

Yonghyun Kim, Jeonga Choi & Donghyun Shin

compounds

Daejin Medical Center, Seongnam, Republic of Korea.

Adina Mazilu¹, Cristina Spiroiu¹ & A E Ranetti^1,2

¹Central Military Emergency Hospital, Romania, Romania;

Background

²National Institute of Endocrinology, Romania, Romania.

There are a lot of painless thyroiditis cases without symptoms diagnosed on health

check up or thyroid hormone screening, but there is a few data about it compared

to much data about painful subacute thyroiditis. So, we collected data about

We present three cases of females with low body weight that needed large

diagnostic routes, laboratory and clinical characteristics of painless thyroiditis.

amounts of anti-thyroid drugs - 4-5 mg/kg Thiamazole and 50 mg/kg of

Method

Propylthiouracil. First patient, aged 32, weight 45 kg, had Graves’s disease

Painless thyroiditis patients diagnosed between 2010 and 2016 were reviewed.

evolving for more than five years. She has been proposed surgery and

We defined painless thyroiditis as disease with typical clinical courses of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

thyrotoxicosis and sequential hypothyroid phase and decreased uptake on thyroid

Introduction

scan.

Brittle hypertyroidism is a term used for the clinical situation characterized by

Result

hypo-hyperthyroidism with antithyroid drugs, despite good compliance and

Total 191 patients (139 female, 52 male) were involved. The diagnostic routes

follow-up. Here, we presented five patients suggested to have Brittle Graves.

were classified under four entry. First, health check up: 47 patients, 24.6%.

Case-1

Second, patients evaluated with thyroid function test because of nonspecific other

Thyrotoxicosis was observed in a 57-year-old female patient and Graves was

symptoms or routine check up of inpatient: 68 patients, 35.6%. Third, patients

diagnosed after laboratory and imaging examinations 25 months after initiation of

evaluated with thyroid function test because of thyrotoxic symptoms or signs

propylthiouracil 50 mg/day, she developed hypothyroidism and the drug was

(fatigue, palpitation, tremor, goiter etc): 59 patients, 30.9%. Fourth, patients

discontinued. Thyrotoxicosis recurred in 3 months and the patient underwent

associated with postpartum: 17 patients, 8.9%. Permanent hypothyroidism was

thyroidectomy. The histopathological diagnosis was lymphocytic thyroiditis.

not uncommon (7/191; 3.7%). Higher peak TSH level (P value below 0.001) was

Case-2

related with permanent hypothyroidism. 11.5% (22/191) experienced recurrence.

Graves was diagnosed in a 22-year-old female patient with Down syndrome.

Lower peak TSH (P value 0.018) and short duration of thyrotoxicosis phase

After 15 days of propylthiouracil treatment, serum TSH was 100 IU/ml and

(P value 0.001) was associated with recurrence.

hyper-hypothyroid periods recurred despite appropriate treatment and thyroid-

Discussion

ectomy was offered.

More than 50% of painless thyroiditis was diagnosed on health check up or

Case-3

accidental thyroid function test without typical thyrotoxic symptoms. Many

Thyrotoxicosis was observed in a 48-year-old female patient with a history of

patients with heterogenous parenchymal echogenecity on sonography finding

levothyroxine use for 10 years. She had positive TSH receptor antibody and

without history of thyroid disease could be go for that cases. Higher peak TSH

ophthalmopathy. Methimazole was started because thyrotoxic state persisted

was related with permanent hypothyroidism. In contrast, lower peak TSH was

despite discontinuation of levothyroxine, but hypothyroidism developed in a short

associated with recurrence and short duration of thyrotoxicosis phase was also

time and thyroidectomy was offered.

related with recurrence.

Case-4

DOI: 10.1530/endoabs.49.EP1256

A 67-year-old male patient with a diagnosis of Graves disease has used

methimazol for 14 months and the drug was discontinued due to hypothyroidism.

Recurrent periods of hyper-hypothyroidism developed in follow-up and BTT

(bilateral total thyroidectomy) was performed.

Conclusion

Hyper-hypothyroid fluctuations can be observed in patients with Graves disease.

This clinical manifestation overlap with hashitoxicosis. “Brittle Graves” seems to

be a better definition for such cases.

EP1257

DOI: 10.1530/endoabs.49.EP1258

The effectiveness of parathyroidectomy in children with primary

hyperparathyroidism

Nazira Rikhsieva

Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan.

Objective

To Evaluate the effectiveness of parathyroidectomy in children with primary

hyperparathyroidism.

Materials and methods

Under our observation in the period 2014-2015, were 46 patients with primary

EP1259

hyperparathyroidism at the age of 11-16 years. To assess the effectiveness of

parathyroidectomy a questionnaire was used and table PAS (Parathyreoidectomy

The role of an ultra-sensitive fourth-generation TSH assay in the

Assessment of symptoms- table of symptoms in primary hyperparathyroidism to

management of subclinical hyperthyroidism

assess the effectiveness of parathyroidectomy).

Emily Austin¹, Steve Peacey² & Andrew Bates¹

The results of the study

¹Heart of England NHS Foundation Trust, Birmingham, UK;

Evaluation of the effectiveness of parathyroidectomy with regard to the

²Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.

elimination of most symptoms in primary hyperparathyroidism table PAS

revealed a statistically significant reduction of symptoms and complaints. The

amount of symptoms in the preoperative period was 445, a month after surgery

The management of endogenous subclinical hyperthyroidism is largely guided by

decreased to 350, 3 months later 200, with certainty P!0.01. Indicators of the

perceived risk, including the presence of cardiovascular disease, atrial fibrillation

sum of symptoms after 1 year was 155, which represents a dramatic difference

or osteoporosis. We have utilised a fourth-generation TSH assay, providing a

compared to the preoperative period. While decrypting the received data of the

10-fold increase in sensitivity compared to third-generation assays, to determine

questionnaires, it became evident a significant reduction of complaints and

whether patients with subclinical hyperthyroidism can be differentiated from

symptoms of primary hyperparathyroidism which undoubtedly attests to the

those with overt hyperthyroidism, based on their now measurable TSH levels.

effectiveness of the operation.

Two groups of patients were identified using thyroid function tests measured with

Conclusions

a traditional third-generation assay (Roche). The first (Group 1) had normal free

Parathyroidectomy is undoubtedly the most effective treatment of primary

thyroid hormone levels and the second (Group 2) had elevated free thyroid

hyperparathyroidism in children today. We recommend you to use the

hormone levels. Both had a suppressed TSH (!0.02). The samples were then

questionnaire on the table as PAS in the outpatient setting and in hospitals.

re-analysed using a fourth-generation assay (Olympus AU3000i) and the values

This way complaints will allow you to suspect primary hyperparathyroidism in

compared. All results are given as median and interquartile range. Group 1

patients. Early detection of pathology of the parathyroid gland, and operative

(nZ23, M:F 4:19), free T4 17.5 pmol/l (15.8-19.9), free T3 6.1 pmol/l (5.5-6.3);

intervention are essential to early recovery of patients and their wellbeing.

Group 2 (nZ54, M:F 14:40) free T4 32.3 pmol/l (25.7-54.9), free T3 pmol/l 10.7

DOI: 10.1530/endoabs.49.EP1257

(7.9-13.0). Group 1 fourth-generation TSH 0.009 mU/l (0.007-0.014); Group 2

0.004 mU/l (0.003-0.008) (P!0.001, Mann-Whitney U). Whilst group 1 has a

significantly greater fourth-generation TSH than group 2, comparison of the

interquartile ranges confirms significant overlap. In group 1 12/23 patients had

fourth-generation TSH values above the upper limit of the interquartile range of

those with overt hyperthyroidism (group 2). Thus, the measured fourth-generation

TSH may be of value in determining the need for treatment. Those in group 1 with

EP1258

TSH values falling within a comparable range to those with overt hyperthyroid-

Fluctuating thyroid hormones in Graves disease: a case series of

ism should be considered for treatment, whilst those with greater TSH values

brittle Graves

could be monitored for progression. Our data suggest that a fourth-generation

Muhammet Cuneyt Bilginer, Sevgul Faki, Cevdet Aydin, Didem Ozdemir,

TSH assay is of value in assessing which patients with subclinical

Abbas Ali Tam, Reyhan Ersoy & Bekir Cakir

hyperthyroidism should be treated and those who should be monitored.

Ankara Yildirim Beyazit University School of Medicine, Department of

DOI: 10.1530/endoabs.49.EP1259

Endocrinology and Metabolism, Ankara, Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1260

still suppressed

(fT4

13.7 pmol/l; fT3

4.71 pmol/l; TSH

0.01 mIU/l). We

concluded that severe thyrotoxicosis in our patient was due to malabsorption of

Non-thyroidal illness syndrome in chronic renal failure and oxidative

thyrosupressive drugs caused by Crohn’s disease and thyrotoxicosis itself. In such

stress: preliminary data on triiodothyronine relationships with

cases alternative therapy options should be considered.

extracellular superoxide-dismutase

Antonio Mancini¹, Nicola Panocchia², Giuseppe Martino¹, Carmine Bruno¹,

DOI: 10.1530/endoabs.49.EP1261

Sonia Silvestri³, Patrick Orlando³, Fabio Marcheggiani³, Luigi Tazza²,

Luca Tiano³, Giovanni Gambaro² & Alfredo Pontecorvi¹

¹Catholic University of the Sacred Heart, Operative Unit of Endocrinology,

Rome, Italy;²Fondazione Policlinico Gemelli, Nephrology Division, Rome,

Italy;³Polytechnic University of Marche, Department of Life and

Environmental Sciences, Ancona, Italy.

EP1262

Congenital disorders in children of the mothers with thyroid

malfunctioning at pregnancy

Non-thyroidal-illness syndrome (NTIS) is present in chronic renal failure and

Saba Akbar¹, Rubina Mansoor² & Muhammad Irfan¹

considered an adaptive mechanism. However oxidative stress is linked to NTIS in

¹Department of Zoology, Pir Mehr Ali Shah, Arid Agriculture University,

a vicious circle, due to deiodinases alteration and negative effect on antioxidant

Rawalpindi, Pakistan;²Chemical Pathology, Rawalpindi Medical College,

levels or activity. One key antioxidant, protective toward ROS-mediated tissue

Rawalpindi, Pakistan.

damage, is extracellular superoxide-dismutase (ec-SOD), present in extracellular

matrix and with a role in mediating nitric oxide-induced signaling. ec-SOD is

specifically released from endothelium by heparin injection, allowing the

In the present study we hypothesized that maternal thyroid disorders may be

determination of ec-SOD activity in vivo without affecting Cu,Zn-SOD or

associated with maternal and foetal morbidity and mortality. The present study

Mn-SOD. No data are reported on ec-SOD in renal failure and its relationship

included 136 pregnant women selected randomly in first trimester and observed

with thyroid function. Therefore we have studied 12 hemodialysis patients (9

throughout the pregnancy till birth. The assessment of thyroid hormones showed a

males and 3 females, mean age 67 ys), evaluating thyroid hormones and ec-SOD

total of 33.08% (nZ45) pregnant ladies were having thyroid disorders; 17.65%

activity after enoxaparin administration. Blood samples were obtained at the

(nZ24) with hypothyroidism and 15.44% (nZ21) with hyperthyroidism. The

starting of hemodialytic session, 5 and 10 min after 1000-4000 U enoxaparin and

mothers with hypothyroidism were significantly (P!0.05) heavier than normal

at the end of the session. SOD activity was measured by a modified nitrite method.

mothers while the mother with hyperthyroidism were significantly (P!0.05)

Superoxide generated by hypoxanthine and xanthine oxidase was changed by

lighter than normal and those with hypothyroidism. The hyperthyroidism

hydroxylamine to nitrite ion which was measured spectrophotometrically at

increased the odds (OR: 6.80; 95% CI: 1.65-28.09) of miscarriages significantly

550 nm by the use of a chromogen. The amount of SOD required to inhibit 50%

(P!0.05). Maternal hypothyroidism increased the gestational period signi-

nitrite ion generation was defined as 1 U SOD activity. Six patients exhibited low

ficantly

(P!0.05) and hyperthyroidism decreased the gestational age signi-

fT3 values (1.8G0.1 pg/ml); the others had normal fT3 (2.5G0.2 pg/ml); fT4 and

ficantly (P!0.05). Maternal hypothyroidism may lead to significantly (P!0.05)

TSH values were normal. Basal eC-SOD did not differ between the two groups,

increased birth weight and maternal hyperthyroidism may decreased the birth

but the percentual increase after heparin was significantly correlated with T3

levels

(rZ0.24, P!0.05). These preliminary data suggest that low T3 can

weight significantly (P!0.05). The maternal hypothyroidism may lead to a

negatively influence endothelial antioxidant defenses. The relationships of this

statistically significant (P!0.05) decrease in the size of skull and brain weight in

datum with cardiovascular complications and prognostic usefulness remain to be

neonates. Furthermore, the hypothyroidism and hyperthyroidism increased the

established.

odds of webbed neck neonates (OR: 5.87; 95% CI: 1.22-28.30 & OR: 11.73 95%

CI: 2.64-52.06, respectively. The data exhibited that the maternal hyperthyroid-

DOI: 10.1530/endoabs.49.EP1260

ism increased the odds (OR: 10.47; 95% CI: 1.78-61.78) of eyes defects in

neonates. The maternal hypothyroidism increased the risk (OR: 18.00; 95% CI:

1.91-169.10) of neonatal congenital heart defects.

DOI: 10.1530/endoabs.49.EP1262

EP1261

Therapeutic options in severe thyrotoxicosis with malabsorption

Mirjana Stojkovic^1,2, Slavica Savic¹, Biljana Nedeljkovic-Beleslin^1,2,

EP1263

Jasmina Ciric^1,2, Tanja Nisic¹ & Milos Zarkovic^1,2

Psychometric evaluation of the newly developed hypoparathyroidism

¹Clinic of Endocrinology, Diabetes and Metabolic diseases, Clinical Center

symptom diary

of Serbia, Belgrade, Serbia;²School of Medicine, University of Belgrade,

Theresa Coles¹, Kristina Chen², Lauren Nelson¹, Nimanee I Harris¹,

Belgrade, Serbia.

Montserrat Vera-Llonch² & Susan Martin¹

¹RTI Health Solutions, Research Triangle Park, NC, USA;²Shire Human

Abstract

Genetic Therapies, Inc., Lexington, MA, USA.

A 55-year-old woman was admitted to our hospital due to severe hyperthyreosis.

She started to feel symptoms of hyper-metabolism four months prior to

Objective

hospitalization. At that time she was admitted in regional hospital and had

The purpose of this study was to evaluate the psychometric properties of a novel,

gastroenterological examination because of diarrhea. Crohn’s disease was

patient-reported outcome

(PRO) measure, the Hypoparathyroidism

(HPT)

diagnosed and therapy started. At the same time, thyrosupressive therapy started.

Symptom Diary (HPT-SD), using data collected during a cross-sectional,

She had a history of hyperthyreosis thirteen years ago, duodenal hemorrhage

noninterventional, observational study. The HPT-SD, developed according to

ulcer, hypertension, cerebral vascular insult and myopericarditis. Despite

the US Food and Drug Administration PRO guidance, addresses the severity of

maximal dose of thiamazole, on admission she was highly hyper-metabolic.

key symptoms (muscle cramping, tingling and muscle spasms/twitching, fatigue,

Hormonal analysis revealed severe thyrotoxicosis (fT4 O100.0 pmol/l; T4O

cognition, emotions) and impacts on sleep, ability to exercise, ability to work, and

320.0 nmol/l; TSH!0.005 mIU/l) with increased TRAb (13.9 IU/l), and negative

family relationships.

TPOAb (!28.0 U/ml) and TgAb (!15.0 IU/ml). Stool analysis was positive for

Methods

muscle fibers, fat and carbohydrates indicating maldigestion and malabsorption.

Individuals who self-reported HPT were recruited to participate in a paper-based

Because of multiple comorbidities, we decided to prepare a patient for radioactive

survey collecting demographic and HPT-related clinical and treatment

iodine treatment (RAI). We concluded that at this hyper-metabolic state, it could

information, patient global impression of severity (PGIS), the HPT-SD, and

lead her in thyroid storm and that her thyroid hormones should be decreased at

three supporting measures: Functional Assessment in Cancer Therapy-Cognitive

safer levels prior to RAI. After admission, we started with intrathyroidal

Function

(FACT-Cog), Functional Assessment of Chronic Illness Therapy-

dexamethasone injections with initial decreasing of thyroid hormones. The

Fatigue Scale (FACIT-Fatigue), and the Hospital Anxiety and Depression Scale

procedure wasn’t continued because of gastric pain she started to feel (history of

(HADS). Item- and scale-level internal consistency reliability, discriminating and

ulcer). We replaced thiamazole for PTU, and started with therapeutic plasma

construct validity were evaluated. A scoring algorithm was developed based on

exchange

(TPE). After TPE, we observed a significant decrease in fT4

psychometric and qualitative results.

(54.5 pmol/l), T4 (139.0 nmol/l) fT3 (8.5 pmol/l) T3 (2.27 nmol/l) levels. Clinical

Results

improvement was achieved. Patient underwent RAI treatment safely, and after

Participants rated their HPT as moderate (34.6%) or severe (32.7%). Participants

two months, her thyroid hormones were in the normal referent range with TSH

did not endorse the most severe response choices (e.g., ‘Very severe’) for 4

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

muscle-related symptom items. Inter-item correlations revealed a pattern of

Background

moderate to strong relationships among symptom (rZ0.3-0.8) and impact items

Optimal management of hypothyroidism prior to and after conception is

(rZ0.5-0.7), providing evidence for two HPT-SD subscales: symptoms and

associated with improved pregnancy outcomes. Compliance with existing

impacts. Construct validity correlations supported a priori convergent validity

management guidelines in Australia and New Zealand is unknown.

hypotheses (jrj O0.5) between HPT-SD subscales and the FACT-Cog, FACIT-

Methods

Fatigue, and HADS. The HPT-SD demonstrated discriminating ability between

A validated electronic survey was distributed to endocrinologists, obstetricians

patients who reported mild versus severe HPT on the PGIS (P!0.05 for 12 out of

and general practitioners via their specialty professional bodies and results were

13 items).

analysed.

Conclusions

Results

The HPT-SD is an appropriate measure of HPT-related symptoms and impacts.

There were 394 survey respondents: 80.5% (317) from Australia and 19.5% (77)

Severe muscle-related symptoms were reported during qualitative development;

from New Zealand. They comprised 263 Obstetrics and Gynaecology doctors

all HPT-SD response choices were retained to capture severe symptoms. Future

(OG), 69 Endocrinology doctors (E) and 58 General Practitioners (GP). Four

studies should assess the HPT-SD measurement properties using longitudinal

respondents were excluded as they did not meet inclusion criteria. Over half of

study designs.

respondents (57.4%) had more than 10 years of specialty experience. 95.2% of

DOI: 10.1530/endoabs.49.EP1263

respondents (375/394) completed the clinical questions as the remainder were not

involved in managing hypothyroidism in pregnancy or in women of reproductive

age. On confirmation of pregnancy, 68.3% of respondents (nZ233) reported

checking thyroid function tests (TFTs) before adjusting thyroxine dose. 27.7% of

respondents reported increasing thyroxine dose by 30-50% or by 2 tablets per

week as soon as pregnancy is confirmed as recommended by guidelines. 85.2% of

respondents reported adjusting thyroxine dose during pregnancy to recommended

EP1264

TSH targets of TSH ! 2.5 mIU/l in the 1st trimester and ! 3 mIU/l in the 2nd

Early diagnosis of primary biliary cirrhosis during follow-up for

and 3rd trimesters (46.7%Z155/332) or to TSH and free T4 trimester specific

Graves’ disease

ranges for their laboratory

(38.5%Z128/332). 75.9% of respondents would

Sevgul Faki¹, Muhammet Cuneyt Bilginer¹, Cevdet Aydin¹,

appropriately treat pregnant women with thyroxine if TSH was O 2.5 mIU/l

Didem Ozdemir¹, Husniye Baser², Osman Ersoy³, Reyhan Ersoy¹ &

(36.0%Z112/311) or above trimester specific ranges for their laboratory

Bekir Cakir¹

(39.9%Z124/311).

¹Department of Endocrinology and Metabolism, Yildirim Beyazit

Conclusions

University, School of Medicine, Ankara, Turkey;²Department of

Reported practice in management of hypothyroidism prior to and during

Endocrinology and Metabolism, Ataturk Education and Research Hospital

pregnancy in Australia and New Zealand varies significantly from recommended

Education and Research Hospital, School of Medicine, Ankara, Turkey;

guidelines. These findings have significant implications for pregnancy outcomes.

³Department of Gastroenterology, Yildirim Beyazit University, School of

Further education is needed for all medical practitioners involved in treating

Medicine, Ankara, Turkey.

women of reproductive age.

DOI: 10.1530/endoabs.49.EP1265

Introduction

Hepatic dysfunction in hyperthyroidism may occur due to high thyroid hormones,

medications or associated autoimmune liver disease. Autoimmune hepatitis or

primary biliary cirrhosis (PBC) has rarely been reported in Graves’ disease. We

report a patient presenting with pruritus and diagnosed as accompanying PBC and

Graves’ disease.

Case

A 50 years old female patient applied with progressive pruritus for at least 4

months. Laboratory investigations showed normal alanine aminotransferase and

aspartate aminotransferase. Serum alkaline phosphatase

(ALP) was 125 IU/l

EP1266

(%105 IU/l), gamma glutamyl transferase (GGT) was 132 IU/l (%42), and total

Analysis of cardiovascular changes in Graves disease and their dynamic

serum bilirubin and conjugated bilirubin were within normal ranges. She had low

during the treatment

TSH (!0.005 U/l) and high serum free T4 (4.6 ng/dl) and free T3 (14.71 pg/ml).

Arina Frolova, Tatiana Rodionova, Marina Orlova & Marina Chuvashova

Thyroid peroxidase antibody and thyroid stimulating hormone receptor antibody

Saratov State Medical University, Saratov, Russia.

were also positive. She was afebrile and had regular pulse rate of 110/min and

normal blood pressure. There was no exophthalmus, goiter, hepatomegaly or

splenomegaly in physical examination. Ultrasonographically, the thyroid gland

Objectives

was enlarged with increased vascularity. Technetium-99m scintigraphy showed

Estimate the prevalence of of cardiovascular symptoms, to identify the main

increased activity throughout the gland with cold nodules in an enlarged thyroid

changes in echocardiography at Graves disease (GD) and their dynamic during

gland. She was started on methimazole and propranolol. After a week of

treatment.

treatment, her ALP and GGT levels raised to 160 and 151, respectively that we

Methods

discontinued methimazol. Serology tests for viral hepatitis, human immuno-

Investigated 86 patients with GD. The functional class (FC) chronic heart failure

deficiency virus and cytomegalovirus were negative; laboratory tests excluded

(CHF) was determined according to the New York Heart Association (NYHA).

copper, iron-related metabolic disorders and autoimmune liver diseases. Anti-

All patients underwent echocardiography before treatment and after 3 months of

mitochondrial antibody was found positive and PBC was diagnosed with clinical

euthyroid state.

and laboratory findings. She was started on ursodeoxycholic acid and underwent

Results

bilateral total thyroidectomy.

At baseline 32.6% patients had no symptoms of CHF, I FC had 19.7%, II FC -

Conclusion

34.9% and III FC - 12.8%. Tachycardia was presented in 87.2% patients,

PBC is often associated with other autoimmune diseases. When a cholestatic

shortness of breath - 67.4%, arrithmias - 58.1%, pain in the chest - 26, 7%.

pattern of liver enzymes is observed during follow-up for Graves’ disease, PBC

Patients without CHF and with 1 FC showed no significant differences in the

should be considered in the differential diagnosis.

echocardiological parameters compared with the control. Patients with 2 FC

observed a higher left ventricular ejection (LVE) (P%0.05), left ventricular

DOI: 10.1530/endoabs.49.EP1264

posterior wall thickness

(LVPWT) (P%0.05) and interventricular septum

thickness (IVST) (P%0.05). Patients with 3 FC characterized by an increase of

size of the left (P%0.05) and right atrials (P%0.05), end-diastolic dimension of

left ventricle

(EDD LV) (P%0.05), EDD of left (r%0.05) and right atrial

(P%0.05). Clinically 3 months after reaching the euthyroid state at 48.8% were

EP1265

maintained complaints of palpitations, at 20.9%- shortness of breath. In patients

Survey on the management of hypothyroidism during pregnancy by

with FC 2 maintained high LVE, LWPWT, IVST. Among patients with FC 3 also

general practitioners, endocrinologists and obstetricians in Australia

were signs oh heart cavities diliatation.

and New Zealand

Conclusions

Danijela Dravec³, Bernard Champion^1,2, Jack Wall¹ & Emily Hibbert^1,4

Cardiovascular symptoms frequently encountered in GD, and some may be stored

¹University of Sydney - Sydney Medical School Nepean, Sydney, Australia;

on reaching euthyrosis. For patients with CHF FC 2 is characterized by left

²Macquarie University, Sydney, Australia;³Specialists on Derby, Kings-

ventricular hypertrophy and myocardial hyperfunction that persist over time

wood, Australia;⁴Nepean Hospital, Kingswood, Australia.

during treatment. At 3 FC showed signs of heart cavities diliatatation combined

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

systolic dysfunction, which are only partially reversible with normalization of

EP1269

thyroid function.

Effectiveness of radioiodine treatment for autonomous toxic node

DOI: 10.1530/endoabs.49.EP1266

Ana Sofia Osório¹, Ana Filipa Martins¹, Vânia Gomes¹, Raquel Vaz de

Castro¹, Ema Nobre¹, Mickael Antoine Ferreira³, Guilhermina Cantinho²

& Maria João Bugalho¹

Serviço de Endocrinologia, Diabetes e Metabolismo, Hospital de Santa

Maria, Centro Hospitalar de Lisboa Norte, Lisboa, Portugal;²Instituto de

Medicina Nuclear da Faculdade de Medicina de Lisboa, Lisboa, Portugal;

Statistical Independent, Lisboa, Portugal.

EP1267

Prevalence of the thyroiditis in childbearing age women

Objective

Mohammed El Amine Amani¹ & Farida Chentli²

The aim of this study was to evaluate the treatment outcomes in patients with

¹1st November 1954 University Hospital, Oran, Algeria;²Bab-el-oued

autonomous toxic nodule (ATN) that received a radioiodine treatment (RAIT)

University Hospital, Algiers, Algeria.

and to determine the influence of age, gender, nodule size and iodine activity.

Methods

Background and aims

We performed a retrospective study of all RAIT done for hyperthyroidism

It has been demonstrated that the thyroid autoimmunity, during pregnancy,

(nZ149) in our hospital during 2014 and 2015. Patients with ATN submitted to

adversely affects the course of the pregnancy. The anomalies may be prior to the

RAIT were selected to analysis. We studied 58 patients (mean age 59.6G13.98

conception, hence the interest of studying the women during the genital activity

years), a total of 59 treatments, corresponding to 39.6% of all RAIT. Treatment

period. Our objective was to determine the prevalence of the thyroiditis in

success was analysed according to demographic (age and gender) and clinical

childbearing age women.

data (thyroid function tests 1 year after RAIT, iodine activity administered and

Materials and methods

nodule size). Activities of 5 or 10 mCi were the most used. Treatment success was

Prospective study, on 270 childbearing age women. Study protocol: clinical

defined as achieving euthyroidism or hypothyroidism 1 year after the last RAIT.

examination, thyroid stimulating hormone

(TSH), free thyroxine

(FT4) and

For statistical data analyses was used a 95% confidence interval (sig!0.05).

thyroid antibodies. Statistics tests: collection of data on EPI INFO 5.1.

Results

The cure rate was 84.6%. Hypothyroidism was observed in 25.6% (10 patients).

Data expressed as mean (270 women), age: 30.3G0.4 years, weight: 65.9G

Only 6 patients remained in hyperthyroidism. Age and nodule size did not

0.9 kg, body mass index: 24.7G0.3 kg/m², TSH: 2.4G0.2 mIU/l and FT4: 14.8G

influence the outcome. Additionally, no correlation was found between gender

0.2 pmol/l. The positivity of the antithyroperoxidase antibodies

(TPO-ab)

and iodine activity in therapeutic effectiveness. Although not statistically

concerned 38/270 women (14.1%), the antithyroglobulin antibodies (Tg-ab)

significant, the cure rate was higher with

10 mCi (92.6%) comparing with

42/270 women (15.6%) and one of the two antibodies (TPO-ab and / or Tg-ab)

5 mCi (72.7%).

54/270 women (20.0%). The mean TSH of the women with thyroiditis was 4.39G

Conclusion

4.93 mIU/l vs 1.89G1.06 mIU/l for those without it (P!0.0001). The mean FT4

There is a trend for a higher effectiveness with 10 mCi than with 5 mCi. The cure

of the women with thyroid autoimmunity was 14.38G1.08 pmol/l vs 14.87G

rate with 10 mCi is similar to those described in the literature for 15 and 20 mCi,

with a lower rate of hypothyroidism.

2.05 pmol/l for those with negative antithyroid antibodies, NS. Of the 54 women

with thyroiditis, 35/54 were in euthyroidism (64.81%) and 19/54 of them were in

DOI: 10.1530/endoabs.49.EP1269

hypothyroidism (35.19%), 9/54 in subclinical hypothyroidism (16.67%) and

10/54 in overt hypothyroidism (18.52%).

Conclusion

In our study, 20.0% of the women had thyroiditis and their mean TSH was

significantly higher vs those with negative antithyroid antibodies. In the subgroup

of women with thyroiditis, 64.81% were in euthyroidism.

EP1270

DOI: 10.1530/endoabs.49.EP1267

Endemic goiter in Xinjiang, Northwestern China

Yoichi Izumi¹, Yuji Kasamaki¹, Yukio Ozawa² & Hirosi Kawamura²

Department of Medicine, Himi Municipal Hospital, Kanazawa Medical

University, Himi, Toyama, Japan;²Blood Pressure Center,

MJG Cardiovascular Institute, Saitama, Japan.

EP1268

Background

Prevalence and etiology of the hypothyroidy in childbearing age women

Endemic goiter occurs frequently in iodine deficient areas. Our past medical

Mohammed El Amine Amani¹ & Farida Chentli²

survey revealed that goiter was endemic in Xinjiang, Northwestern China,

¹1st November 1954 University Hospital, Oran, Algeria;²Bab-el-oued

because, several elderly Uygur subjects had goiter. In the present study, several

University Hospital, Algiers, Algeria.

medical parameters were compared between subjects with and those without

goiter.

Methods

Background and aims

Elderly Uygur (age, 65-70 years nZ99) and very old Uygur subjects (age, O90

The hypothyroidism may be prior to the conception, hence the interest of studying

years nZ111) were hospitalized, requested to provide blood and urine samples,

women during the genital activity period. Our objective was to determine the

and underwent 24 h-ambulatoly blood pressure monitoring. Goiter was not

prevalence and the etiologies of the hypothyroidism in childbearing age women.

identified in Hun and Kazakh participants.

Materials and methods

Results

Prospective study, on 270 childbearing age women. Study protocol: clinical

No subjects had any symptoms attributable to abnormal thyroid function. The

examination, urinary iodine, thyroid stimulating hormone (TSH), free thyroxine

goiters identified ranged in size from that of the walnuts to the fist. Body mass

(FT4) and thyroid antibodies. Statistics tests: collection of data on EPI INFO 5.1.

index of the subjects with goiter (GOC) was slightly but significantly lower than

Results

Data expressed as mean (270 women), age: 30.3G0.4 years, weight: 65.9G

that of the subjects without goiter (GOK). There were no significant differences

0.9 kg, body mass index: 24.7G0.3 kg/m², urinary iodine: 225.6G5.8 mg/l, TSH:

in blood pressure, heart rate, urinary catecholamine levels, insulin sensitivity, and

2.4G0.2 mIU/l and FT₄: 14.8G0.2 pmol/l. The iodine deficiency was found in

serum levels of free thyroxin, thyroid stimulating hormone, triglycerides, or low-

19/270 women (7%). The hypothyroidism involved 31/270 women (11.5%),

density lipoprotein and high-density lipoprotein cholesterol, between GOC and

the subclinical form in 19/270 (7.1%) and the overt form in 12/270 (4.4%). Of the

GOK participants. The prevalence of goiter in women was 6 times that of men.

31 hypothyroid women, the etiology of the hypothyroidism was related to the

The iodine content in the salt extracted from the study area was 0 parts per million

autoimmune thyroid disease in 19/31 women (61.3%) and to the iodine deficiency

(ppm) while in that obtained from the market was 29.1 ppm.

in only one case (3.23%).

Conclusion

The results suggest that prevalence of goiter in Uygur might have been caused by

In our study, 11.5% of women of childbearing age were in hypothyroidism (overt

intake of iodine-free salt. Individuals with goiter would live safely and come

and subclinical forms). The etiology of the hypothyroidism was dominated by the

today. The higher prevalence of goiter among women suggests that hormones

thyroiditis.

might play a role in the development of thyroid disease.

DOI: 10.1530/endoabs.49.EP1268

DOI: 10.1530/endoabs.49.EP1270

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1271

EP1273

How does overt and subclinical hypothyroidism due to thyroiditis of

Evaluation of circulating irisin levels in patients with never treated

Hashimoto affect lipid parameters

overt hyperthyrodisim

Gergana Tosheva¹, Mira Siderova¹, Kiril Hristozov¹, Yana Bocheva² &

Asena Gokcay Canpolat, Mustafa Sahin, Demet Corapcioglu, Rıfat Emral &

Mila Kostova¹

Ali Rıza Uysal

¹University Hospital ‘St Marina’ Clinic of Endocrinology, Varna, Bulgaria;

Ankara University Faculty of Medicine, Ankara, Turkey.

²University Hospital ‘St Marina’ Central Clinical Laboratory, Varna,

Bulgaria.

Aims

Because of an increased metabolic activity and thermogenesis in hyperthyroid-

Aim

ism, we aimed to evaluate the association of serum irisin with thyroid hormones.

The aim of this retrospective study is to assess the lipid disturbances in patients

Methods

with autoimmune thyroiditis.

A total of 25 hyperthyroid patients and 24 age- and gender-matched healthy

Methods

controls were enrolled. Serum irisin levels, thyroid hormones and body

1380

patients with autoimmune thyroiditis, hospitalized in Endocrinology

compositions were analyzed.

department of ‘St. Marina’ Hospital, Varna for the period of 2004-2015 year,

Results

participated in the study. After excluding conditions influencing lipid profile, 771

Serum irisin levels were significantly higher in hyperthyroid group (P!0.001).

patients remained for analysis (36 men and 735 women, mean age 49.81G13.98

Distribution of fat free mass and muscle mass was similar between study groups.

years). They are divided in three groups according to TSH values - group A (0.4-

Serum irisin level has a negative correlation with TSH level (P!0.001), %fat

4 mU/l), group B (4.01-10 mU/l), group C (TSH R10.01 mU/l). Group B is

mass (PZ0.021) and positive correlation with TSH receptor antibody (TRAB)

divided into two subgroups - B1 - patients with negative thyroperoxidase

level (PZ0.002).

antibodies (TPO Ab) and B2 - patients with positive TPO Ab. We evaluated

Conclusion

thyroid ultrasound data, laboratory tests of TSH, free T3 (FT₃), free T4 (FT₄),

Our results showed that increased serum irisin levels in hyperthyroid patients

TPO-Ab, total cholesterol (TC), triglycerides (TG), LDL - and HDL-cholesterol

might be associated with the effects of TSH.

levels.

Keywords: Hypertyroidism; irisin; TSH receptor antibody

Results

DOI: 10.1530/endoabs.49.EP1273

With the increase of TSH value, we observe elevation in serum triglycerides

(group A-TG 1.34 mmol/l, group B-1, 44 mmol/l, group C-1, 69 mmol/l); as well

as in LDL-c values (group A-3, 41 mmol/l; group B- 3, 53 mmol/l; group C-4,

19 mmol/l). The comparison of the two subgroups B1 and B2 find out increasing

levels of TC, TG, LDL-c and a decreasing of HDL-c. A significant difference in

EP1274

TG between patients in group A and C is observed (P 0.001). Statistical

significance in LDL-c level is achieved in group A and C (P 0.000), group B and

Is there a correlation between serum selenium level and the severity of

C (P 0.000), in group B2 and C (P 0.001). 16.9% of the patients from group B and

Graves’ orbitopathy?

17.1% from group C had already coronary heart disease and/or cerebrovascular

Iwona Palyga¹, Danuta Gasior-Perczak¹, Klaudia Gadawska-Juszczyk¹,

disease.

Estera Mikina¹, Monika Piwowar¹, Monika Szymonek¹, Tomasz Trybek¹,

Conclusions

Agnieszka Walczyk¹, Ryszard Mezyk¹, Urszula Majewska² &

Autoimmune thyroiditis as one of the main reasons for hypothyroidism is

Aldona Kowalska^1,2

associated with lipid abnormalities and increased cardiovascular risk, which are

¹Holycross Cancer Centre, Kielce, Poland;²The Faculty of Health Sciences,

more pronounced in overt than in subclinical hypothyroidism.

Jan Kochanowski University, Kielce, Poland.

DOI: 10.1530/endoabs.49.EP1271

Introduction

Selenium (Se) deficiency is a known risk factor for autoimmune thyroid diseases

including Graves’ orbitopathy (GO).

Objective

EP1272

To determine the concentration of Se in serum and to determine the dependency

of Se concentration on known markers of disease severity: the TRAB levels and

Primary hypothyreosis in cobalt intoxication

the CAS (clinical activity score) in patients with GO.

Dagmar Langova

Material

IK IPVZ, KNTB as, Zlín, Czech Republic.

64 patients (50 women, 14 men; average age- 54.5 years) with active, moderate to

severe GO who have not received prior selenium supplementation and were

Most common causes of primary hypothyreosis are destruction of thyroidal

qualified to i.v. metylprednisolone treatment according to the EUGOGO scheme,

parenchyma by the autoimmune antibodies, interventions on the gland (surgery,

at a single site in the years 2014-2016.

radioiodine treatment) and external actinotherapy

(hematologic and ENT

Method

malignancies). Drug induced thyroidal impairment is well-known too (amio-

Set average and median concentrations of Se, TRAB and CAS in the group of

darone, lithium, interferon). Our case demostrates the primary hypothyreosis

patients and determined the correlation coefficients between serum Se and TRAB

caused by cobalt. The source was Co-Cr hip prostehis after its rupture (PHACT).

and CAS.

A 55 old man was reffered to endocrinologist in 2011 with enlargement of thyroid

Results

gland (volume 84 ml) and signs of primary hypothyreoidism (TSH 76 mU/l). No

Selenium deficiency was found in 15 patients, in 27 the concentration was normal,

elevation of antibodies levels was present, family history of thyroid disease

in 22- the Se level was above the upper limit of normal. There was no correlation

negativ. Thyroxin substitution treatment resulted in both normalisation of thyroid

between Se and CAS or TRAB revealed.

function and thyroid gland volume (TSH 1.3 mU/l, 18 ml).

Conclusions

Personal history

1) The severity of OG expressed by well known indicators: CAS and TRAB were

Hyperlipoproteinema, smoking. The man also underwent implantation of right

not dependent on the concentration of Se.

2) It seems that it should be

hip prosthesis after an injury in 2002. The course was complicated by deep venous

recommended to measure the concentration of selenium before starting the

thrombosis of the right leg and massive pulmonary embolism requiring

supplementation of Se because of low frequency of Se deficiency in this group of

thrombolysis treatment. The prosthesis was damaged in 2010 because of necrosis

patients.

and replaced with the Co-Cr type. Since 2010 the patient was examined by

DOI: 10.1530/endoabs.49.EP1274

multidisciplinary specialists because of polymorhpic atypical complaints

(arrhytmias - considered cardiomyopathy, atypical neuropathy, hypacusis). In

2014 patient was admitted to hospital with atypical back and pelvis pains.

Following RDG imaging of the right trochanter and acetabulum a diagnosis was

finally obtaned showing pathology - local osteal reaction. The puncture of the

affected spot revealed dark fluid with high levels of cobalt and chromium. The

EP1275

defficient prosthesis was then removed. PHACT id.e prosthetic hip-associates

Nicotinamide phosphoribosyltransferase expression in thyroid glands of

cobalt toxicity. The symptoms are atypical - arrhytmias, different neurological

patients with Graves’ disease

symptoms, changes of thyroid gland functions, deafnes, eye disorders.

Nadia Sawicka-Gutaj¹, Miroslaw Andrusiewicz², Agata Czarnywojtek^1,3,

Joanna Waligorska-Stachura¹, Maciej Biczysko⁴, Jerzy Skrobisz⁴,

DOI: 10.1530/endoabs.49.EP1272

Jerzy Sowinski¹ & Marek Ruchala¹

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Poznan University of Medical Sciences, Department of Endocrinology,

EP1277

Metabolism and Internal Medicine, Poznan, Poland;²Poznan University of

Hypothyroidism - once a week treatment option in young- and

Medical Sciences, Department of Cell Biology, Poznan, Poland;³Poznan

middle-aged adults

University of Medical Sciences, Department of Pharmacology, Poznan,

Satish Chander Wasoori¹, Manoj Naik², Deepak G Pande¹ &

Poland;⁴Department of General Surgery and Multiple Trauma, with

Chetan Bhardwaj¹

Division of Gastroenterological and Endocrine Surgery, Provincial Hospital,

¹Park Hospital, Gurgaon, Haryana, India;²Sunjeevan Hospital, Thane,

Poznan, Poland.

Maharashtra, India.

Abstract

Objective

Nicotinamide phosphoribosyltransferase (NAMPT) overexpression was reported

To evaluate the effectiveness and compliance to L-thyroxine in the treatment of

in many autoimmune diseases. We have also found NAMPT overexpression in

Hypothyroidism in a weekly dose of 7 times of normal dose as an alternative to

leukocytes of patients with Graves’ orbitopathy. Therefore, we aimed to analyze

daily dosing in young and middle aged adults.

NAMPT expression level in thyroid gland of patients with Graves’ disease with

Methods

orbitopathy and without orbitopathy, and in healthy thyroid gland. We have

A randomized prospective observational study on 180 patients (female:male)

analyzed 80 thyroid tissue samples of patients who underwent thyroidectomy.

ratio of 5:1 aged between 18 and 55 years with an established diagnosis of

Among these, there were 41 patients with Graves’ disease (20 patients with

Hypothyroidism were assigned a weekly dose of seven times of normal dose. The

orbitopathy and 21 patients without orbitopathy), and 39 samples of healthy

patients were randomized in 3 groups G1, G2 and G3. Group 1 (G1): 60 patients

thyroid tissue. NAMPT overexpression was found in thyroid glands of patients

with established diagnosis of Hypothyroidism with TSH value of 4.2 or less,

with Graves’ orbitopathy (P!0.000001). NAMPT expression in patients with

currently on daily dose. The subjects were assigned weekly dose of L-thyroxine

Graves’ disease without orbitopathy was similar to healthy controls. Our results

which was 7-fold of normal dose. Group 2 (G2): 60 patients with established

suggested that NAMPT might be involved in the inflammatory cascade in Graves’

diagnoses of Hypothyroidism with TSH value of more than 4.2. The subjects were

orbitopathy.

assigned weekly dose of L-thyroxine which was 7-fold of normal dose, the dose in

DOI: 10.1530/endoabs.49.EP1275

this group was individualized as per the body weight and TSH value. Group 3

(G3): 60 patients newly established diagnoses of Hypothyroidism with TSH value

of more than 4.2. The group was started with a weekly dose which was

individualized as per the body weight and TSH value. All subjects in all the

groups were screened for malabsorption and were not receiving any drugs which

interfere with the absorption of L-thyroxine. The minimum to maximum dose

used in this study was 175-1050 mcg.

Results or case presentation

We achieved complete restoration of euthyroidism in all 59 subjects in the group

(G1) at 12 weeks and it continued to 24 weeks. We had to withdraw it in a

EP1276

55-year male patient because of hyperthyroid symptoms. In group 2 (G2), we

Associations between thyroid and kidney functions

achieved complete euthyroidism in 52 subjects at 12 weeks and it increased to

Lina Zabuliene^1,2, Modesta Petraviciute³, Birute Pauliukiene⁴ &

55 subjects with some dose adjustment at 24 weeks. We could not achieve

Jurgita Urboniene⁵

euthyroidism in 5 subjects at 24 weeks. This may be attributed to other metabolic

¹Clinics of Rheumatology, Traumatology - Orthopaedics and Reconstruc-

disorders like diabetes and obesity. In (G3) we achieved complete euthyroidism in

tive Surgery, Faculty of Medicine, Vilnius University, Vilnius, Lithuania;

54 subjects at 12 weeks and it increased to 59 subjects with some dose adjustment

²Karoliniskiu Outpatient Clinic, Vilnius, Lithuania;³Faculty of Medicine,

at 24 weeks. 1 subject shifted to another city and so did not complete the study.

Vilnius University, Vilnius, Lithuania;⁴Antakalnio Outpatient Clinic,

Conclusion

Vilnius, Lithuania;⁵Centre of Infectious Diseases, Vilnius University

Once weekly dose of L-thyroxine as an alternative to daily dosing regimen was

Hospital Santariskiu Klinikos, Vilnius, Lithuania.

shown to be efficacious and safe for the treatment of hypothyroidism to treat non-

compliant hypothyroid young- and middle-aged adults. The results show that it

can be started in newly diagnosed hypothyroid patients. For patients who find it

difficult to adhere to a rigorous treatment regime it is a valid therapeutic option

Two-way interactions between thyroid and kidney functions are known. Chronic

and can also be considered as a first line therapy in young and middle aged

kidney disease

(CKD) is accompanied by changes in synthesis, secretion,

working adults facing impaired absorption due to early breakfast (no need to wait

metabolism, and elimination of thyroid hormones, increased risk of hypothyroid-

30-45 min for breakfast).

ism, rarely subclinical hyperthyroidism, whereas thyroid dysfunction affects

physiology of the kidney, renal blood flow, glomerular filtration rate (GFR),

DOI: 10.1530/endoabs.49.EP1277

tubular function, metabolism of water and electrolytes, and kidney structure. The

aim of the study was to examine associations between thyroid stimulating

hormone (TSH) level and kidney function.

Methods

We analysed retrospective data of

781 adult patients, referred for routine

EP1278

simultaneous testing of TSH and serum creatinine in 2015 in Vilnius Antakalnio

Effect of subclinical hypothyroidism and autoimmunity on adverse

outpatient clinic. GFR was estimated by the simplified Modification of Diet in

pregnancy and neonatal outcome in our population

Renal Disease equation. Linear regression was used to evaluate the association

Cristina López-Tinoco, Begon˜a Sánchez-Lechuga, Almudena Lara,

between TSH and estimated GFR.

Julia Barcala, Laura Larrán, Daniel Medina & Manuel Aguilar-Diosdado

Results

Endocrinology Department, Cádiz, Spain.

Mean TSH concentration was 2.58G4.19 mIU/l, mean serum creatinine 72.72G

22.32 mmol/l and mean estimated GFR 83.12G24.91 ml/min/1.73 m². 45.3% of

patients had stage 2 CKD, 16.0% - stage 3 CKD, 1% - stage 4 or end stage CKD.

Patients with CKD of any stage were older than those with normal kidney

The effect of subclinical hypothyroidism (SH) and thyroid autoimmunity on

function (mean age 66.98G11.20 vs 50.96G15.42 years, P!0.0001) and their

adverse pregnancy and neonatal outcome, are still subject of interest and

TSH was higher (2.86G5.07 vs 2.12G1.93 mIU/l, PZ0.004). 12.9% of patients

controversy. Nowadays, guidelines recommend establishing reference

had thyroid dysfunction:

7.9% had subclinical hypothyroidism

(TSH 4.69-

values of local thyroid hormones that allow definition of the SH in a

10 mIU/l), 1.3% overt clinical hypothyroidism (TSH O10 mIU/l) and 3.7%

specific population. The objective of this study was to assess the effect of SH

subclinical hyperthyroidism

(TSH !0.465 mIU/l).

12.8% of patients with

and autoimmunity in early pregnancy on adverse pregnancy and neonatal

estimated GFR !60 ml/min/1.73 m² had subclinical hypothyroidism, 1.5% -

outcome in our population. The reference range of thyrotropin (TSH) was

overt clinical hypothyroidism. Lower estimated GFR was associated with higher

3,86 mUI/ml, in our Cádiz-San Fernando area, in Spain. 438 pregnant

TSH level (BZK0.72 (95% CI K1.13 - K0.30), PZ0.001).

women with HS (defined according to our reference values) in the first

Conclusions

trimester of gestation were recruited. Women were classified into two

Thyroid dysfunction is relatively common among persons with CKD: 14.3% of

groups according to thyroid function and anti-TPO results. The mean age

patients with moderate, severe and established kidney failure have hypothyroid-

was 31,32G5,5 years, BMI was 24.5G5.3 kg/m². Twenty-four percent of

ism. Reduction in estimated GFR is independently associated with increased TSH

the patients had a family history of Thyroid disease and 23% of miscarriage.

levels.

The mean of levels of TSH at diagnosis were 5,1G1,3 mUI/l with a final

DOI: 10.1530/endoabs.49.EP1276

mean dose of levothyroxine 64.9 mcg/day and levels of TSH 2.5G1.2 mIU/l

at the end of pregnancy. Sixteen percent of the deliveries were by cesarean

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

section, and 20% had complications (premature rupture of membranes,

Aim and objective

preeclampsia, preterm delivery, small for gestational age). Thirteen percent

The aims of this study were to determine the incidence of breast cancer molecular

had anti-TPO positive. Comparing anti-TPO positive/negative groups with

subgroups, to investigate the relationship between autoimmune thyroid disease

obstetrics and perinatal outcomes, no statistically significant differences

and prognostic and predictive factors in patients who were diagnosed with breast

were found. We concluded that in our area, patients with HS, defined

cancer.

according to our local reference values, have a low rate of adverse

Materials and methods

pregnancy and neonatal outcome. Also, if we consider the presence of anti-

One hundred one patients who were followed up with the diagnosis of breast

TPO positive, there are no differences. Further studies will be needed to

cancer at our Endocrinology and Medical Oncology Departments were included.

determine the relationships between HS and autoimmunity and adverse

Patients are divided into subgroups based on the molecular classification. Patients

pregnancy and neonatal outcome.

with high serum levels of thyroid peroxidase antibody

(anti-TPO) were

DOI: 10.1530/endoabs.49.EP1278

considered as autoimmune thyroid disease. Prognostic and predictive parameters

such as tumor size, axillary involvement, histological grade, lymphovascular

invasion, hormone receptor status, HER2 overexpression were collected. The

relationships between autoimmune thyroid disease and tumor’s prognostic and

predictive factors were studied.

Results

The prevalence of thyroid autoimmunity was 23.8% (nZ24) among with our

study group. Patients with autoimmune thyroid disease had a significant lower

rate of axillary involvement (37.5% vs 61% [PZ0.043], respectively). Other

parameters did not differ between patients with and without autoimmune thyroid

disease.

EP1279

Conclusions

We found a favorable association between autoimmune thyroid disease and

Metastatic differentiated thyroid carcinoma: cumulative doses of

axillary involvement which is crucial and strongly prognostic parameter of breast

adjunct 131i-iodide therapy

cancer prognoses. This supports the idea of thyroid autoimmunity being a

Patrícia Gouveia¹, Teresa Pereira², Ana Amado², Ricardo Teixeira¹,

favorable prognostic parameter in breast cancer. Further studies are necessary to

Antonio Costa³, André Carvalho², Cláudia Freitas² & Fátima Borges²

investigate the reasons of protective or predictive effect of high anti thyroid

¹Department of Nuclear Medicine, Centro Hospitalar do Porto, Porto,

peroxidase levels in breast cancer patients.

Portugal;²Department of Endocrinology, Centro Hospitalar do Porto, Porto,

Portugal;³Department of Surgery 2, Centro Hospitalar do Porto, Porto,

DOI: 10.1530/endoabs.49.EP1280

Portugal.

Introduction

131I-iodide therapy (RIT) is an important treatment modality for patients with

differentiated thyroid carcinoma (DTC). However, despite the overall excellent

outcome, some DTC patients with poor prognosis may require multiple doses of

radioactive iodine.

Aim

The purpose of our study was to evaluate the efficacy of cumulative doses (CDs)

of RIT in metastatic DTC patients.

EP1281

Material and methods

Subacute Thyroiditis with an atypical clinical course and thyroid

A retrospective study was conducted on a cohort of 84 metastatic DTC patients

^99mTc uptake

(mean age 46.6G17.4 years) who received a CDs R300 mCi of RIT, between

Deniz Sema, Maktav Celikmen & Ali Ozdemir

January 1956 and December 2016. A disease-free status was established as:

Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey.

undetectable TSH-suppressed Thyroglobulin levels, whole body imaging scan

without local-regional uptake or distant metastases and negative cervical

ultrasound or thoracic CT scan.

Background

Results

Subacute thyroiditis (SAT) is a transient inflammatory, probably viral disease of

Eighty-four patients, 58 females and 26 males, who completed more than one RIT

the thyroid gland. It is clinically characterized by pain, fever, increased

with a CD R300 mCi, were followed up for 15.0G8.8 years. At the time of

erythyrocyte sedimentation rate

(ESR) or other markers of inflammation,

diagnosis 62 (73.8%) patients had local cervical metastases and 22 (26.2%) had

transient thyrotoxicosis, and has a tendency to recur. In most cases, in addition

distant metastases. Papillary carcinoma sub-type was present in 75 (89.3%) of

to the clinical features, scintigraphy and ultrasound may support the diagnosis of

patients. Seventeen out of 84 patients (20.2%) achieved a disease-free status. No

SAT. However, in the present case, SAT with an atypical thyroid^99mTc uptake

patient with CDs higher of 450mCi has reached a disease-free status. Patients with

and a nodule formation in ultrasound lead to diagnosis difficulties.

evidence of brain or bone metastases (7 out of 94) did not achieve the disease-free

Case presentation

status, regardless of the CDs received.

A 31-year-old woman with the clinical suspicion of SAT was observed.

Conclusion

Thyrotoxicosis was present and the tests for anti-thyroid peroxidase, anti-

Twenty percent of patients who received a CDs R300 mCi of RIT achieved a

thyroglobulin and TSH receptor antibodies were negative. Thyroid scintigraphy

disease-free status. Quality of life and the disease progression rate are important

with^99mTc demonstrated decreased uptake in the right but a normal uptake in the

aspects that were not addressed in our study. The decision of further treatment

left lobe. Four weeks after clinical and laboratory remission she developed a

with RIT should be carefully evaluated and made on a case-by-case basis.

painful palpable nodule of the left thyroid lobe. Increased erythyrocyte

Furthermore, this study seems to indicate that brain or bone metastases may not

sedimentation rate above 100 mm/h and elevated C reactive protein were present.

respond to higher CDs.

Ultrasonographic examination showed an enlarged left lobe and area of low

DOI: 10.1530/endoabs.49.EP1279

echogenicity with shaded margins and microcalcifications. The lesion showed a

contrast uptake in contrast-enhanced magnetic resonance imaging (MRI). The

second scintigraphy demonstrated a bilateral, heterogeneous uptake with a

suspected hipoactive nodular image of the left thyroid lobe. Fine-needle

aspiration biopsy from the nodule revealed multinuclear giant cells consistent

with SAT.

EP1280

Conclusion

Autoimmune thyroid disease may affect prognosis of breast cancer

In most cases, the diagnosis of SAT can be made based on the physical and

Selim Yalcin¹, Ramazan Cosar², Aydin Cifci², Askin Gungunes³ &

laboratory findings of the patient and the clinical course of the disease. Findings

Senay Arikan Durmaz³

of thyroid scintigraphy and ultrasound that are not consistent with subacute

¹Department of Oncology, School of Medicine, Kirikkale, Turkey;

thyroiditis do not exclude the diagnosis of SAT. For definitive diagnosis of an

²Department of Internal Medicine, School of Medicine, Kirikkale, Turkey;

atypical SAT and exclusion of thyroid malignancies, fine-needle aspiration

³Department of Endocrinology and Metabolism, School of Medicine,

biopsy may be required.

Kirikkale, Turkey.

DOI: 10.1530/endoabs.49.EP1281

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1282

EP1284

Weak numeracy is common problem in patients with thyroid diseases

Percutaneous ablation of benign thyroid nodules: specific simulators for

Ewa Wawak¹, Pawel Basinski¹, Malgorzata Gasiorek¹ &

practicing enolization and laser procedures

Krzysztof Marczewski^1,2

Teresa Jiménez, Pablo Vidal-Ríos, Antonio Rodríguez, Laura Villas &

¹Department of Nephrology and Endocrinology Pope John Paul II Regional

Sebastian Vidal-Ríos

Hospital, Zamosc, Poland;²Faculty of Health Sciences University of

Coruna Endocrinology Center, La Coruna, Spain.

Economy and Innovations, Lublin, Poland.

Introduction

Ethanol and laser ablation of benign thyroid nodules is bursting rapidly in

In modern medicine, we expect from patients numeracy skills. Starting with the

clinical practice because of its efficacy, safety and economy. However, these

correct dosage of drugs up to understand the principles of risk assessment of

techniques require some manual operator training. In order to facilitate this

alternative treatments. These skills, however, are probably rarely checked. Just as

hands-on training, we propose two homemade, cheap and specific simulators

the skills of reading, where we entrust signature ‘read and understood’. That is

to practice these clinical procedures.

why we want to introduce our observation.

Material and methods

Method

Two models were optimized: Gel-Phantom Coruna VR16 (gelatine and

Subsequent patient, outpatient endocrinological clinic, we have proposed making

plantago-ovata with inlays of different objects simulating pure and mixed

two tests to assess numeracy: Schwartz test (max. 3 points) and Berlin Numeracy

cysts) and Proteon-Phantom Coruna VR17 (pork loin with inlays of different

Test (max. 4 points).

objects simulating solid nodules (homogeneous, heterogeneous and with

Results

microcalcifications). For enolization, pure ethanol and a 2-way device (Device

We investigated 112 patients (101 women) in age 17 to 85 years (average 55G15).

Coruna VR15, poster 94, 58th Congress Malaga, Spain, SEEN 2016) were

No one person became maximal possible results, and 11 (10%) had not answered

used for sequential ethanol-NSS instillation (to reduce irritation of the capsule

any question. The results of other patients indicate significant problems with

upon withdrawal of the needle). For laser ablation, a 1064 nm Nd-YAG

simple counting. 2 person rejected Schwartz test, and 1 person rejected BNT test.

laser through a thin optic fiber of

300um obtained from an EchoLaser

From others 36 person became 0 points in Schwartz test, 43 patients 1 point, 23

generator (Elesta, Florencia-Italy) was used. Monitoring was performed with

patients 2 points and only 8 maximally possible 3 points. Similar or even worse are

the Acusson

2000

Hellix ultrasound platform

(Siemens, Forchheim-

the results in BNT 29 person became 0 points, 56 1 point, 22 2 points, only 3 3

Germany). The assessment was performed among different operators

point and no one maximal possible

4 points. We did not find significant

(nZ12), especially those attending the Coruna Workshop on Laser Ablation.

correlations between the results of the tests, and the sex, age and TSH.

Results

Conclusion

For cystic nodules simulation and practicing ethanol sclerosis, the most

Weak numeracy is a common problem in patients with thyroid diseases.

valued simulators were: fluid on a knotted glove (pure cyst), grapes or

DOI: 10.1530/endoabs.49.EP1282

dwarfish tomatoes (mixed cyst), piece of wet sponge wrapped in knotted

kitchen plastic (‘sponge’ cyst) and anchovy stuffed olive (hyperechoic nodule

with hypoechoic center). For solid-state nodules simulation and practicing

laser ablation, the most valued were: beef liver wrapped in knotted plastic

(solid isoechoic nodule), cooked yolk wrapped in knotted plastic (hyperechoic

solid nodule), raisins and water wrapped in knotted plastic (heterogeneous

nodule), and raisins, water and eggshells

(heterogeneous nodule with

‘microcalcifications’).

Conclusion

In summary Gel-Phantom Coruna VR16 and Proteon-Phantom Coruna VR17

EP1283

simulators were surprisingly useful for practicing percutaneous ethanol and laser

A case of levothyroxine tablet malabsorption associated with gastric

ablation procedures. In addition, we highlight their low cost and easy preparation.

neuroendocrine tumour corrected with gel capsule formulation

DOI: 10.1530/endoabs.49.EP1284

Olivera Boskovic¹, Ranko Lazovic^1,2, Brigita Smolovic^1,2 &

Mirha Hasanbegovic^2,3

¹Clinical Center of Montenegro, Podgorica, Montenegro;²Medical Faculty,

University of Montenegro, Podgorica, Montenegro;³General Hospital

Pljevlja, Pljevlja, Montenegro.

EP1285

Improved diagnostics with increased treatment of hypothyroidism

Multiple dose adjustments can sometimes be inefficient in reaching

during pregnancy - a 10 year study of Finnish pregnant women

eumetabolic state in patients with hypothyroidism treated by levothyroxine

Suvi Turunen^1,2, Tuija Männisto^3,5, Anna-Liisa Hartikainen³, Mika Gissler⁴,

sodium tablets. We report a case of 44-year-old female who has been on

Anna-Maria Lahesmaa-Korpinen⁴, Marja Vääräsmäki^1,3 & Eila Suvanto^1,3

levothyroxine sodium tablet replacement therapy since 2004 without ever

¹Oulu University Hospital, Obstetrics and Gynecology, Oulu, Finland;

reaching eumetabolic state, presented as outpatient one year ago. As sellar

²Medical Research Center Oulu (MRC Oulu), Oulu, Finland;³University of

MRI ruled out pituitary adenoma, investigation targeting malabsorption was

Oulu, Oulu, Finland;⁴Institute of Health and Welfare, Helsinki, Finland;

initiated. Antibodies to gliadin and transglutaminase were in normal range.

⁵Nordlab, Oulu, Finland.

Absorption test with

300 mcg levothyroxine was positive in aspect of

presence of selective levothyroxine malabsorption. Initial endoscopies

revealed chronic atrophic gastritis without excluding possibility for tumor

presence. Serum CgA level was 521 mcg/l. The final third endoscopy was

Thyroid diseases affect up to 4% of all pregnancies. Several evidence-based

successful in detecting the gastric submucosal change, confirmed by

recommendations have been created to observe and treat thyroid diseases in

endoscopic ultrasound as submucosal lesion no larger than 12 mm located in

pregnant women. We studied whether the diagnostics and treatment of

the upper part of anterior gastric wall. Histological analysis of biopsy

hypothyroidism among pregnant women have improved in the course of

specimen confirmed lesion to be neuroendocrine tumor grade 1. Further

time. Data consisted of all singleton pregnancies (NZ571785) during 2004-

imaging excluded its metastatic spreading, so the indication for surgical

2013 in Finland, collected from the Finnish Medical Birth Register (MBR).

removal was established. Patient could not undergo surgery with TSH levels

Data on maternal thyroid diseases were obtained from the MBR and the

exceeding 100 mmU/l and free T4 lower than 5 pmol/l despite being on

Hospital Discharge Register, and combined with the Special Refund

300mcg of levothyroxine daily substitution regimen. Changing to a gel

Entitlement Register and the Register on Reimbursed Drug Purchases

capsule formulation taken once a day at dose of 100 mcg lead to a rapid TSH

consisting data on medication purchases during the index pregnancy.

decreasement and thyroid hormones normalization, so the patient was

Women with thyroid diseases other than hypothyroidism were excluded

surgically treated as eumetabolic. On reviews thereafter she remained

(NZ4561), rendering a final study population of

567 224

singleton

euthyroid, without complaints of previously reported fatigue and loss of

pregnancies. Pregnancies were divided into four categories: mothers with

appetite. This case suggests that gastric chronic inflammatory processes and

diagnosed hypothyroidism treated with levothyroxine (NZ8893), mothers

neuroendocrine tumors as well may affect levothyroxine absorption where

treated with levothyroxine without a recorded hypothyroidism diagnosis

gelatine capsules appear to be effective treatment option.

(NZ6788) (mostly treated in the primary care), mothers with diagnosed

DOI: 10.1530/endoabs.49.EP1283

hypothyroidism but without levothyroxine treatment (NZ683) and mothers

without thyroid diseases or thyroid medication

(NZ550 860). In 2004

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

approximately 1% of pregnant women had diagnosed hypothyroidism and

mild swelling of extraocular muscles. She was diagnosed with Graves’

were treated with levothyroxine. By 2013 this prevalence had more than

ophthalmopathy too. After that, it was decided thyroidectomy. In addition,

doubled up to 2.4%. The prevalence of women receiving levothyroxine

oligoamenorrhea appeared and ultrasound and magnetic resonance of the

treatment without recorded hypothyroidism diagnosis was 0.2% in 2004 but

abdomen and pelvis detected an

11!11!9 cm solid-cystic mass in right

12-fold higher (2.5%) in 2013. The increase in prevalence of diagnosed

ovarian. The patient underwent right salpingo-oophorectomy. Histology revealed

hypothyroidism and levothyroxine treatment has been steady over time.

a benign SO. Immediately, ocular disease and hyperthyroidism improved.

Surprisingly, the prevalence of pregnant women with hypothyroidism and

Subsequently, total thyroidectomy was performed, which showed GD and benign

no recorded levothyroxine treatment has been constant between 0.1 and

thyroid nodules.

0.2%. Our study shows that the diagnoses of hypothyroidism and use of

Conclusions

levothyroxine treatment among pregnant women have increased markedly

The diagnosis of functioning SO in presence of GD may be a challenge and it may

during the past 10 years. This suggests that clinical recommendations have

be difficult to determine the precise cause of hyperthyroidism. When a patient has

improved the awareness on the risks of hypothyroidism on pregnancy and

increased thyroid uptake of technetium in the scan, an ectopic hormone

the threshold to treat hypothyroidism during pregnancy seems declining.

production is not suspected. When SO is surgically removed and subsequently

DOI: 10.1530/endoabs.49.EP1285

the hyperthyroidism and ocular disease improve considerably, the diagnosis of

functioning SO is quite likely.

DOI: 10.1530/endoabs.49.EP1287

EP1286

EP1288

Radiofrequency ablation for benign thyroid nodules: 450 patients -

three years follow-up

Clinical characteristics and outcomes of patients with myxedema coma:

Viacheslav Solovov, Aleksandr Makhonin, Mikhail Vozdvizhenskiy &

a 15-years experience of a tertiary care center in Thailand

Andrew Orlov

Suwanna Pitchaiprasert¹, Patinut Buranasupkajorn¹,

Samara Oncology Center, Samara, Russia.

Sompongse Suwanwalaikorn^1,2, Sarat Sunthornyothin^1,2,

Weerapan Khovidhunkit^1,2 & Thiti Snabboon^1,2

¹Department of Medicine, Faculty of Medicine, Chulalongkorn University,

Purpose

Bangkok, Thailand;²Excellence Center for Diabetes, Hormone and

The objective of this study was to evaluate the efficacy and safety of ultrasound

Metabolism, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

(US)-guided radiofrequency ablation

(RFA) for treating of benign thyroid

nodules.

Material and methods

Background

The retrospective analysis included the results of treatment of 450 patients with

Myxedema coma is an uncommon but life-threatening condition of severe and

benign tumors of the thyroid gland in the Samara Oncology Center. 91 (20.2%)

decompensated hypothyroidism requiring early recognition and prompt treat-

patients had autonomously functioning thyroid nodules and 359 (79.8%) had

ment. The aim of this study is to describe the clinical features and identify factors

symptomatic ones. The mean volume of nodule was 33.5 (4.1-179.5).

associated with mortality of our patients diagnosed myxedema coma over the past

Results

15 years.

RFA reduced nodular volume by 70% after 6 months, 84% after 36 months and it

Materials and methods

was an effective method for treating nodule-related clinical problems and hot

Retrospective chart review of patients diagnosed and treated at King

nodules. 47 (10.4%) patients with big nodule volume underwent 2-6 sessions of

Chulalongkorn Memorial Hospital for myxedema coma during 2002-2016 was

RFA. Cosmetic results were excellent in 96% of patients in the RFA group. No

performed. Their demographic data, clinical features, precipitating factors and

serious complications such as thyroiditis, voice change, and hematomas were

treatment outcomes were analyzed. We also compared different scoring systems

observed in RFA patients.

including Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health

Conclusion

Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA)

RFA was effective and safe for treating benign thyroid nodules. RFA might be

score and Wartofsky myxedema coma score to predict the outcomes.

recommended for treating benign thyroid nodules as the first-line treatment.

Results

A total of 13 cases, 9 females and median age of 79 years ranged between 60-94

DOI: 10.1530/endoabs.49.EP1286

years, were recruited. All of them had primary hypothyroidism. Seven patients

(54%) were newly diagnosed hypothyroidism at the time of presentation of

myxedema coma. Six patients (46%) died and sepsis was the major cause of

death. Lower FT₄ level was only parameter significantly different between the

patients who survived and those who died (PZ0.04). On analyzing the various

scoring systems, they did not demonstrate a significant difference between

EP1287

survivors and non-survivors; however, a Wartofsky myxedema score below 90

Coexistence of Graves’ disease and unilateral benign struma ovarii:

was associated with a better outcome.

A case report

Conclusions

Rosa Marquez-Pardo, Lourdes Garcia-Garcia-Doncel, Mgloria

Myxedema coma still carries a high mortality rate even with the appropriate

Baena-Nieto, Manuel Cayon-Blanco, Rosario Lopez-Velasco &

diagnosis and treatment. With a high proportion of undiagnosed hypothyroid

Isabel Torres-Barea

patients in our study, it should be alert clinicians to beware of this preventable

Jerez Hospital, Jerez de la Frontera, Cadiz, Spain.

condition in an appropriate clinical context. Thyroid hormone levels and

Wartofsky myxedema score may be applied as clinical prognostic parameters.

DOI: 10.1530/endoabs.49.EP1288

Introduction

Struma ovarii (SO) is a rare ovarian teratoma composed predominantly (more

than 50%) or entirely of thyroid tissue. It constitutes 2% to 4% of ovarian

teratomas. This tumor is often asymptomatic and discovered incidentally. Only

8% of patients present clinical hyperthyroidism.

Case report

EP1289

A 42-year-old woman presented palpitations, anxiety, sweating, emotional

Evaluation of interrelationships between thyroid function,

lability and weight loss for several months. Physical examination revealed goitre,

autoimmunity, insulin resistance and lipid profile in Graves’ disease

tachycardia and slight tremor. Laboratory tests confirmed hyperthyroidism:

António Carujo¹, Celestino Neves², Joa˜o Sérgio Neves2, Sofia Castro

thyrotropin (TSH) 0.01 mcU/ml (0.3-5), serum-free thyroxine 5.21 ng/dL (FT4)

Oliveira², Oksana Sokhatska³, César Esteves², Miguel Pereira²,

(0.9-2.1), serum-free triiodothyronine

(FT3)

22.5 pg/ml

(2.57-4.43) and

José Luís Medina¹, Luís Delgado³ & Davide Carvalho^1,4

thyrotropin receptor antibody

(TRAb)

21.78 U/l

(positive O2). Thyroid

¹Faculty of Medicine, University of Porto, Porto, Portugal;²Endocrinology

ultrasound identified a multinodular goitre with a dominant nodule of 14 mm in

Service, São João Hospital, Faculty of Medicine, University of Porto, Porto,

left lobe. Technetium thyroid scan showed diffuse uptake. She was diagnosed as

Portugal;³Immunology Department, São João Hospital, Faculty of

having Graves’ disease (GD) and started on thiamazole and propranolol. Several

Medicine, University of Porto, Porto, Portugal;⁴Instituto de Investigação e

months later, she remained hyperthyroid and appeared proptosis, lid retraction

Inovação em Saúde, Faculty of Medicine, University of Porto, Porto,

and ocular chemosis. Magnetic resonance of the orbits demonstrated bilateral

Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

EP1291

Thyroid hormones modulate the lipoprotein and glucose metabolisms. In

Trans-axillary endoscopic thyroidectomy - technique

hyperthyroidism, insulin resistance is a frequent finding.

Jaime Vilaça, Susana Graça & Paula Mendes

Aim

Tiroide Center, Porto, Portugal.

To assess interrelationships between thyroid function, autoimmunity, lipid

profile, glucose metabolism and other cardiovascular risk factors in patients

with Graves’ disease.

Introduction

Methods

Trans-axillary surgery is an emerging technique for cervical approach with

We recorded free T3 (FT3), free T4 (FT4), TSH, TSH receptor antibodies

fantastic cosmetic result. With more than 50 cases treated by our group, we

(TRAB), parameters of the lipid profile, glucose metabolism [including insulin

developed our technique with specific safe methodologies.

resistance marker Homeostasis Model Assessment for Insulin Resistance

Aims

(HOMA-IR)], C reactive protein (CRP) and homocysteine in 126 patients with

To present step-by-step technique of trans-axillary endoscopic thyroidectomy.

Graves’ disease in the first cycle of treatment with methimazole (93% females,

Material and methods

mean age 44.8G15.2 years). Patients were divided in subgroups according to:

This is a video surgery that uses three trocars and a harmonic scalpel for

TRAB (positive (nZ57) or negative (nZ69)) and thyroid function (normal

dissection and ligation. Incisions are made in the armpit and areolar border.

(nZ74), subclinical (nZ29) or clinical hyperthyroidism (nZ22)). Spearman

Results

correlations, T-tests and Mann-Whitney tests were performed for statistical

Technique is described in 10 steps: (i) trocars and patient position; (ii) dissection;

analysis.

(iii) landmarks (sternal notch, ECM anterior border, thyroid cartilage); (iv) omo-

Results

hyoid muscle dissection; (v) split strap muscles; (vi) upper pole dissection and

Comparing TRAB- and TRABC groups, significantly lower apolipoprotein B

ligation; (vii) ligation of the middle thyroid vein and recurrent laryngeal nerve

(80.3(73.2-87.4) vs 89.7(83.5-95.8)mg/dl, PZ0.047) and TSH (0.180(0.002-

(RLN) visualization; (viii) inferior pole ligation; (ix) lobectomy; (x) specimen

1.080) vs 1.020(0.235-2.055]mUI/ml, P!0.001) were found in the TRABC

removal and haemostasis; Three auxiliary techniques are used to increase safe and

group. Comparing with the normal thyroid function group, patients in the

to reduce complications:

clinical hyperthyroid group presented significantly lower apolipoprotein B

1. Intra-operative ultrasound

(70.9(57.2-84.6) vs

89.7(83.7-95.8)mg/dl, PZ0.007) and higher fasting

2. Neuromonitoring of the RLN

glucose

(96.0(83.0-109.0) vs

86.4(83.8-89.0)mg/dl, PZ0.019), insulin

3. Indocyanine green (ICG) fluorescence for parathyroid vascular assessment

(10.4(6.2-15.8) vs

7.5(4.8-9.7)mUI/ml, PZ0.021), HOMA-IR

(2.09(1.29-

Conclusions

4.53) vs 1.55(0.95-2.13), PZ0.023) and CRP (0.57(0.20-0.93) vs 0.20(0.07-

Cervical scar-less surgery is very appealing for the patient. For the surgeon with

0.38)mg/l, PZ0.005). No significant differences were found between the

advanced laparoscopic skills this is a feasible and reproducible technique, with

subclinical hyperthyroid group and the remaining groups. There was a negative

excellent results. Security techniques can have great value in more demanding

correlation between TSH and TRAB (rZK0.386, P!0.001). Apolipoprotein B

cases.

was positively correlated with TSH (rZ0.236, PZ0.016), and negatively with

DOI: 10.1530/endoabs.49.EP1291

TRAB (rZK0.211, PZ0.030). Both FT3 and FT4 were positively correlated

with fasting insulin (rZ0.268, PZ0.008 and rZ0.226, PZ0.025, respectively)

and HOMA-IR (rZ0.258, PZ0.010 and rZ0.259, PZ0.010, respectively).

FT4 was also positively correlated with fasting glucose (rZ0.269, PZ0.008).

Conclusion

In patients with Graves’ disease, the interrelationships between thyroid function,

autoimmunity, insulin resistance and lipid profile may contribute to the increased

cardiovascular risk.

EP1292

DOI: 10.1530/endoabs.49.EP1289

Trans-axillary endoscopic thyroidectomy - scarless surgery of the neck:

our experience

Jaime Vilaça, Susana Graça & Paula Mendes

Tiroide Center, Porto, Portugal.

Introduction

Endoscopic techniques are uprising in the cervical field mainly because of the

exceptional cosmetic results. These surgeries are frequent in the far east Asia but

still rare in Europe. We started these approach on November 2014. This paper is a

review of our experience.

EP1290

Aims

Successful radioiodine treatment of Graves disease for a patient with a

To present a series of trans-axillary endoscopic thyroidectomy.

history of «iodide allergy»

Material and methods

Nesrine Cheikhrouhou, Intidhar Elbez, Kaouthar Limem, Aida Mhiri,

This is a cohort study of

50 consecutive patients treated by trans-axillary

Bechir Ltaeif & Faouzi Ben Slimene

endoscopic thyroidectomy. Patients are selected using the following indications:

Department of Nuclear Medicine, Salah Azaiez Institute, Tunis, Tunisia.

benign or suspicious nodules until 35 mm, micro papillary cancer, lobes until

65 mm. Interventions are video recorded and time, recurrent laryngeal nerve

Introduction

identification and parathyroid identification are registered. Laryngoscopy is

Graves’s disease is the most common cause of hyperthyroidism. There are three

performed at the end of the procedure. Morbidity data are collected during

current therapeutic options: anti-thyroid medication, surgery, and radioactive

surgery, on the day after, 2 weeks, 2 months and one year after the operation. All

iodine (I 131). There are few data in the literature regarding the effects of

the pathological reports are reviewed.

radioiodine therapy.

Results

Case report

Among the series, 78% were women with an average of 48 year old. All patients

We describe a 47-year-old patient who had Grave’s disease resistant to anti

had normal thyroid function at the time of the operation and 95% were low-risk

thyroid medication. Radioactive iodine was indicated. The patient was reluctant

anaesthetic candidates (ASA1 or 2). Half complained of goitre. All but 2 were

because she had a history of anaphylactic reaction to computed tomography (CT)

submitted to lobectomy. There was no conversion to open surgery. No dead was

contrast agent. We explicated to the patient that the implication of iodine has

registered. There were 5 cases of morbidity: 2 seromas, 2 skin burn and 1 transient

never been demonstrated during allergic hypersensitivity reactions due to

recurrent laryngeal nerve palsy. All cases of lobectomy were discharged home on

iodinated drugs. She successfully underwent treatment with 12 mCi (444 MBq)

post-operative day 1.

radioactive iodine.

Conclusions

Conclusion

Endoscopic cervical approach is difficult to implement among surgeons without

Asking a patient if he/she is ‘allergic to iodine’ is a question that should be

advanced laparoscopic skills.The technique revealed to be safe and reproducible

avoided because its significance is null. A diagnosis of drug allergy, essentially

with potential to enlarge indications. The use of neuromonitoring, ICG

relying on clinical symptoms, biological tests and cutaneous tests, is required to

fluorescence and intra-operative ultrasound are tools already tested by the

take adequate preventive measures.

group with a benefit in safety.

DOI: 10.1530/endoabs.49.EP1290

DOI: 10.1530/endoabs.49.EP1292

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1293

EP1295

TSH oscillations in young patients with type 1 diabetes may be due to

Treatment of toxic multinodular goiter with 131 radioactive iodine -

glycemic variability

effects in volume reduction, thyroid function and autoimmunity

Giuseppe Bellastella¹, Ofelia Casciano¹, Lorenzo Scappaticcio¹,

Catarina Roque¹, Francisco Sousa Santos¹, Tania Pilli² & Furio Pacini²

Dario Giugliano¹, Maria Ida Maiorino¹ & Katherine Esposito²

¹Endocrine Unit, Hospital de Egas Moniz, C.H.L.O. E.P.E., Lisbon,

¹Endocrinology and Metabolic Diseases Unit, Department of Medical,

Portugal;²Endocrine Unit, University of Siena, Siena, Italy.

Surgical, Neurological, Metabolic Sciences and Aging, University of

Campania, L. Vanvitelli, Naples, Campania, Italy;²Diabetes Unit,

Abstract

Department of Medical, Surgical, Neurological, Metabolic Sciences and

Radioiodine is a definite treatment option for toxic goiter. We have evaluated

Aging, University of Campania, L. Vanvitelli, Naples, Campania, Italy.

volume reduction, function and autoimmunity outcomes with a 15 mCi fixed

regimen. Patients with at least one US evaluation before and after Iodine-131

therapy and with at least one year of follow-up were included. TSH, free-T4,

A link between thyroid dysfunction and diabetes mellitus exist. Uncertainties on

antibodies and goiter volume before and yearly after Iodine-131 treatment were

the role of glycemic variability on thyroid hormones and TSH concentrations still

analysed for the length of the entire follow-up. The total 151 patients, 72.6%

persist. We want to evaluate the influence of glycemic variability on thyroid

females, had a mean follow-up of 6.2 (1-12) years. At the time of treatment, the

hormones and TSH concentrations in patients with type 1 diabetes (T1DM). 77

mean age was 68.8 years and the initial goiter volume 48.9 (8-255.7) ml, with no

patients with T1DM on insulin therapy without thyroid dysfunction and 100

statistical difference between sexes. Increased volume was observed in 96.5%

healthy controls were evaluated for basal glucose concentrations, HbA1c, thyroid

females and 91.7% males and there were 10.6% in hyperthyroidism and 89.4% in

hormones and TSH levels. Glucose variability was investigated through the

subclinical hyperthyroidism. The mean percentage volume reduction in the first

standard deviation of blood glucose (BGSD) readings and through the mean

year was 29.8% which represents 14.7 ml with a Pearson coefficient of correlation

amplitude of glycemic excursions (MAGE) and continuous overlapping net

with initial volume of 0.058. During the following years mean reductions of 19.7,

glycemic action (CONGA), the low (LBGI) and high (HBGI) blood glucose

15.8,

9.7,

5.8

and 1.4% were observed. Absolute volume reductions were

indices. The links between TSH, thyroid hormones, glycemia and HbA1c were

maximal at the 3rd and 4th years representing mean reductions of 50 and 52%.

studied in patients and in controls, whereas those between TSH, thyroid hormones

Initial volume, TSH and age could not produce an explicative model for the

and indices of glucose variability only in patients. All subjects had TSH, thyroid

percentage of reduced volume. Euthyroidism was achieved in 60.9% patients,

hormones and thyroid antibodies in the normal range. No correlations were found

subclinical hyperthyroidism in 8.6% and hypothyroidism in 26.5% of which

in T1DM patients between free thyroid hormones and glycemic values, HbA1c

23.8% were subclinical. Hypothyroidism was related significantly with initial

and indices of glucose variability, while an inverse correlation was observed

volume (P!0.001) and maximal percentage of reduction (PZ0.012). The

between TSH levels and glycemic values (rZK0.4; PZ0.02), CONGA index

development of new detectable anti-thyroid antibodies was identified in 5 patients

(rZK0.3; PZ0.04) and HBGI (rZK0.3; PZ0.05) but not with HbA1c

(6.9%), the result being above cut-off in none of them. New anti-TSH-receptor

(rZK0.1; PZ0.47). No significant correlations of TSH and thyroid hormones

antibodies developed in 4 (5.5%) patients 1-3 years post-treatment. With 15 mCi,

with glycemia and HbA1c were observed in controls. In T1DM patients was

all patients experienced volume reduction in the first years after treatment,

found an inverse correlation between TSH and glycemic variability with direct

achieving means above 50% at the 3rd year, most were rendered euthyroid and

action of glycemic excursions on TSH secretion disengaged from variations

developed no auto-immunity.

of thyroid hormone concentrations. The study of thyroid function

(TSH

DOI: 10.1530/endoabs.49.EP1295

concentrations) in these patients should be made by multiple samples on patients

in euglycemic state to avoid underestimation or overestimation of thyroid

dysfunction due to a misdiagnosis of euthyroidism or dysthyroidism with

consequent inappropriate therapy.

DOI: 10.1530/endoabs.49.EP1293

EP1296

Four out of five patients with acute kidney injury have thyroid

dysfunction

Manpreet Choulia¹, Jasmine Das², Maria Ghosh³ & Jubbin Jacob

Endocrine and Diabetes Unit, Department of Medicine, Christian Medical

College and Hospital, Ludhiana, Punjab, India;²Department of Nephrology,

Christian Medical College and Hospital, Ludhiana, Punjab, India;

EP1294

³Department of Biochemistry, Ludhiana, Punjab, India.

May erythrovirus (parvovirus) B19 trigger autoimmune thyroid

diseases?

Objectives

Serdar Ucgun¹, Kevser Onbasi¹ & Nilgun Kasifoglu²

This study was undertaken to ascertain the prevalence of thyroid dysfunction(TD)

¹Dumlupinar University, Kutahya, Turkey;²Eskisehir Osmangazi

in patients with Acute Kidney Injury(AKI) and assess the prognostic implications

University, Eskisehir, Turkey.

of TD in AKI patients.

Materials and methods

Consecutive adult patients (O18 years) admitted with AKI to the departments of

Erythrovirus (EVB19) can recognize auto-antigens by using molecular mimicry

Nephrology & Medicine were recruited if they met AKIN classification criteria

mechanisms. EVB 19 is accused in the pathogenesis of many autoimmune

for AKI after

48 h of admission

(1). Patients were screened for thyroid

diseases. Especially EVB19 is very important in the pathogenesis of autoimmune

dysfunction with serum sampling of Thyroid stimulating hormone, Free T3 and

thyroid diseases. Thus in some case presentations; it was shown that EVB19

Free T4 after taking informed consent. Prognosis of TD in AKI patients was

might be related with Hashimoto’s thyroiditis. Although etiopathogenesis of

assessed in terms of: 1) Duration of hospital stay, 2) Need for Renal Replacement

Graves’ disease and Hashimoto’s thyroiditis is not known exactly; they are

Therapy (RRT), 3) In-hospital mortality.

thought to occur as a result of interaction of genetic and environmental factors.

Results

Infections are one of the environmental factors, which were alleged to be involved

147 patients with AKI (93M:54F) with a mean age of 57.8 years were recruited

in the pathogenesis, but this was not proved. Parvovirus B19 (EVB19) is an

and TD was noted in 114 patients(77.5%). Of these, 74(64.91%) patients had

unproven viral agent, which was thought to play a role in pathogenesis. In this

Non-thyroidal illness (NTI), 10(8.77%) had primary hypothyroidism, 17(14.91%)

study; the prevalence of EVB19 was studied in autoimmune thyroid patients. This

had subclinical hypothyroidism,

4(3.51%) had primary hyperthyroidism,

study was conducted on patients who were followed-up in the Endocrinology and

7(6.14%) had subclinical hyperthyroidism and 2(1.75%) had central hyperthyr-

Internal Medicine Polyclinics and who agreed to participate in the study. Total 90

oidism. A trend to longer duration of hospitalisation for AKI patients (O7 days)

individuals were counted in this study including 30 patients with Hashimoto’s

was seen in 65(75.58%) patients with TD compared to 17(62.96%) patients

thyroiditis, 30 patients with Graves’ disease and 30 control individuals who were

without TD (PZ0.09). RRT requirements (56.36 vs 59.38%) (PZ0.84) and

compatible in terms of age. EVB19 IgG-IgM was studied manually using

in-hospital mortality

(31.58 vs 33.33%) (PZ0.84)of AKI patients with and

immunological ELISA method and values were read in spectrophotometer.

without TD were similar. However, a trend of increasing mortality was seen in

According to results of this study; there was no significant difference for

AKI patients with NTI (PZ0.059).

Parvovirus B19 IgG-M levels between patients with autoimmune thyroid disease

Conclusions

and the control group.

Four out of five patients with AKI had some form of thyroid dysfunction, of which

DOI: 10.1530/endoabs.49.EP1294

majority of them had NTI. However, presence of TD did not significantly affect

prognosis of these patients.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Reference

physician to visually differentiate between necrotic or destroyed tissue (which

(1) Lopes JA, Jorge S. The RIFLE and AKIN classification for acute kidney

shows absent or very low uptake of the radiopharmaceutical) from hypermeta-

injury: a critical and comprehensive review. Clin Kidney J 2013 6 8-14.

bolic cells (with increased uptake).

DOI: 10.1530/endoabs.49.EP1296

Case report

A 72-year-old male with atrial fibrillation treated with amiodarone for 10 years

was sent to our Endocrinology outpatient clinic for new-onset asymptomatic

subclinical hyperthyroidism (FT3 2.56 pg/ml (2.00 4.40); TT3 85 ng/dl (80-200);

FT4 1.59 ng/dl (0.93-1.70); TT4 10.0 (5.1-14.1); TSH 0.03 mU/l (0.27-4.20)).

He had a history of euthyroid benign nodular disease. We admitted AIT type 2,

but considering the mild thyroid dysfunction, we chose to pursue further

EP1297

evaluation with

99mTc sestamibi scintigraphy, in order to initiate targeted

The assessment of influence vitamin D deficiency on the Hashimoto’s

therapy. Scintigraphic images showed initial uptake by the thyroid gland with

thyroiditis activity

rapid washout, a pattern described in literature as corresponding to AIT type 3.

Katarzyna Lizis-Kolus¹, Alicja Hubalewska-Dydejczyk², Anna

The patient’s thyroid hormones normalized before starting any medication and he

Sowa-Staszczak², Anna Skalniak², Aldona Kowalska^1,3 & Pawel Lizis⁴

is currently on follow-up.

¹Department of Endocrinology, Holycross Cancer Center, Kielce, Poland;

Conclusion

²Department of Endocrinology, Jagiellonian University Medical College,

This case report is illustrative of the possible role of

99mTc sestamibi

Krakow, Poland;³The Faculty of Health Sciences of the Jan Kochanowski

scintigraphy in diagnosis and management of thyroid disfunction induced by

University, Kielce, Poland;⁴Holycross College, Department of Education

amiodarone. However, more expertise is further needed.

and Health Protection, Kielce, Poland.

DOI: 10.1530/endoabs.49.EP1298

The observed increase in the incidence of Hashimoto’s thyroiditis (HT) requires

research on factors that may affect its development. One of them may be vitamin

D deficiency which is an epidemiological problem all over the world.

Aim

The assessment of influence vitamin D deficiency on the HT activity.

EP1299

Material and methods

Effect of vitamin D supplementation on patients with Graves disease

310 people were enrolled in the study: 155 patients with HT (a-TPO and/or a-TG

Maram Maher, Nermin Sheriba, Abeer Elewa, Ahmed Mohamed

positivity)-144 women (93%), 11 men (7%) and 155 healthy volunteers-139

Bahaa Eldin, Nesma Ali Ibrahim & Dina Marawan

(90%) women and 16 men (10%); mean age: 49G18, 58G17, 49G17 and 56G

Ain Shams University, Cairo, Egypt.

16 years respectively. For analysis purposes the HT group was divided into two

subgroups: without (E) and with l-thyroxine treated hypothyroidism (H): 45

patients aged

50G14 and 110 patients aged

50G17 respectively. Serum

Multiple factors contribute to the etiology of Graves disease(GD), including

25OHD3, TSH, a-TPO, a-TG, 25OHD3 levels were measured in all subjects.

genetic and environmental factors.vitamin D is well known in calcium

Vitamin D deficiency was defined as 25OHD3! 30 ng/ml.

metabolism and has also been shown to be a modulator in innate and adaptive

Results

immunity. There is a well-established link between vitamin D deficiency and

In HT patients 25OHD3 level was lower than in the control group: 23.2 ng/ml

various autoimmune diseases. The prevalence of vitamin D deficiency was

(Q₁-Q₃: 18.6-29.0) vs 25.6 ng/ml (Q₁-Q₃: 21.0-31.4; PZ0.006). There is no

reported to be common in patients with GD. Whether vitamin D deficiency has a

difference between 25OHD3 concentration in subgroup E and control group (28.7

causal relationship with GD remains controversial.Aim:to evaluate the effect of

vs 25.6 ng/ml; PZ0.4) but 25OHD3 level was significantly lower in subgroup H

vitamin D supplementation in patients with GD with and without opthalmopathy

than in subgroup E (21.5 ng/ml; Q₁-Q₃: 17.8-27.3 vs 28.7 ng/ml; Q₁-Q₃: 21.4-

methods: A randomized prospective study was conducted on 60 adult patients

33.2; P! 0.001). The study showed higher 25OHD3 level in a-TPO negative than

with GD.

in a-TPO positive patients (32 ng/ml; Q₁-Q₃: 25.6-37.7 vs 22.1 ng/ml; Q₁-Q₃:

Group 1

18.1-28.4; P!0.001); the same was observed in a-TG negative and a-TG positive

20 patients with GD receiving 30 mg of methimazole daily.

subjects

(28.7 ng/ml; Q₁-Q₃:

23.2-32.7

20.2 ng/ml; Q₁-Q₃:

15.4-23.6;

Group 2

P!0.001). In subgroup E 25OHD3 level was similar independently of a-TPO

patients with GD receiving same dose of methimazole and vit. D3

or a-TG positivity.

200 000 IU/month. Patients were followed up for 3 months.

Conclusions

Results

Evidence of a link between increased level of antithyroid antibodies in

40% of patients in group 1 and 72.5% in Group 2 were vit. D deficient,Vit. D was

hypothyroid patients with HT and 25OHD3 deficiency may suggest that this

significantly correlated with thyroid volume and degree of exophthalmos. Gp 2

group is particularly prone to the vitamin D deficiency and can benefit from its

had significant lower thyroid volume and better effect on degree of exopthalomos.

alignment.

Conclusion

DOI: 10.1530/endoabs.49.EP1297

Vit. D suuplementation for GD has a favourable effect on thyroid volume and

degree of exophthalmos.

DOI: 10.1530/endoabs.49.EP1299

EP1298

The role of 99mTc-sestamibi in amiodarone-induced

thyrotoxicosis - Case report

EP1300

Margarida Victor, Ana Gonçalves Ferreira, Susana Carmona, Henrique

Primary hyperparathyroidism coexisting with Graves’ disease in a

Vara Luiz, Maria Carlos Cordeiro, Jorge Portugal & Ana Isabel Santos

patient with vitamin D deficiency

Hospital Garcia de Orta, Almada, Portugal.

Panagiotis Athanassiou¹, Ifigenia Kostoglou-Athanassiou² & Eleni Pantazi³

¹Department of Rheumatology, St Paul’s Hospital, Thessaloniki, Greece;

²Department of Endocrinology, Red Cross Hospital, Athens, Greece;

Introduction

³Department of Endocrinology, Alexandra Hospital, Athens, Greece.

Amiodarone is an antiarrhythmic iodine-rich drug, known to induce thyroid

dysfunction both due to its high iodine content and through amiodarone-induced

thyrotoxicosis (AIT), being this latter process classified into three different types.

Primary hyperparathyroidism is known to coexist with thyroid cancer and breast

Type 1 is associated with increased thyroid hormone synthesis; type 2 is a

cancer. However, primary hyperparathyroidism coexisting with Graves’ disease

destructive process with thyroid hormone release and type 3 is thought to be a

is extremely rare. The aim was to describe the case of a patient with Graves’

mixture of the former two. Since treatment options are different, there has been

disease causing severe hyperthyroidism who in the course of the disease

a growing need for a diagnostic method that could accurately distinguish these

developed vitamin D deficiency and primary hyperparathyroidism. A patient,

types and therefore allow targeted therapy. 99mTc-sestamibi scintigraphy has

female, aged

years, presented with severe hyperthyroidism causing

been gaining a specific role in this matter: with recognized increased uptake by

tachycardia, palpitations and weight loss. TSH receptor antibodies were positive

epithelial cells that show high mitochondrial concentration, it allows the

in the context of Graves’ disease. She was treated with methimazole and

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

propranolol and the disease went into remission. A year later treatment with

Introduction

methimazole was discontinued and 4 months later the patient had a relapse of

The incidence of depressive type psychoaffective disorders is significantly

hyperthyroidism. Laboratory tests revealed hyperthyroidism along with vitamin

increased in patients with chronic autoimmune thyroiditis.

D deficiency and elevated PTH levels. Vitamin D was administered along with

Objectives

methimazole and propranolol. During follow up, despite normal vitamin D levels,

The study of thyroid autoimmunity correlated with serum levels of TSH, FT4 and

PTH levels remained extremely elevated and blood calcium levels in the upper

depression degree.

normal range. Ultrasound of the thyroid and parathyroid glands revealed a

Methods

parathyroid adenoma adjacent to the left thyroid lobe. The adenoma was visible in

The study comprised 70 patients (64 women and 6 men), aged between 18 and 66

a scan with ^99mTc-sestamibi. The patient is being followed up and prepared for

years, divided in 4 groups. All study groups were analyzed according to the

surgical treatment of both hyperthyroidism and primary hyperparathyroidism.

degree of depression and serum TSH, FT4, thyroid peroxidase antibody(TPOAb)

The extremely rare case of a patient with concurrent Graves’ disease causing

,thyroglobulin antibody(TGAb). There were calculated the average values,

severe hyperthyroidism and primary hyperparathyroidism along with vitamin D

standard deviation, incidence and statistical significance of p value !0.01. Beck

deficiency is presented. This case further illustrates that primary hyperparathyr-

depression test was used to determine the level and severity of depression.

oidism may be diagnosed in the context of severe vitamin D deficiency, being

Results

aggravated by vitamin D administration and that primary hyperparathyroidism

Absence of depression was associated with elevated TSH (6.49G3) and low

may coexist with thyroid disorders.

FT4(10G6); TPOAb values (199G12) and TGAb values (358G8). Minimum

DOI: 10.1530/endoabs.49.EP1300

depression was correlated with elevated TSH (6.6G3) and normal FT4 (14.8G

9.8); TPOAb values

(247G18) and TGAb values

(385G22). Moderate

depression has been associated with normal TSH (4.2G2) and normal FT4

(18.5G15); TPOAb values (253G26) and TGAb values (422G16). Severe

depression was accompanied by slightly elevated TSH (4.3G3) and normal

FT4(15.5G8.7); TPOAb values (336G18) and TGAb (425G22).

Conclusions

It was revealed a high incidence of depressive disorders among the pacients with

EP1301

chronic autoimmune thyroiditis with a distribution of medium and severe forms of

Primary underdosed hypothyroidism - parodontal implications

depression predominantly in women without any evidence of thyroid hormonal

in adults

level involvement.The study shows a heterogeneity of thyroid autoimmunity

Razvan Circo, Seila Ibadula & Eduard Circo

regarding the effect of antithyroid antibodies in generating psycho-emotional

Clinical Endocrinology Department, SCJU ‘Sf. Apostol Andrei’, Constanta,

processes commonly found in these patients.

Romania.

DOI: 10.1530/endoabs.49.EP1302

Introduction

Dento-maxillary system changes associated to thyroid disorders are constantly

present. Differentiated impairment, depending on the period of evolution of the

disease, explains the high percentage of over 60% of cases with parodonthopathy.

Aim of the study

Evaluating the oro-maxillo-facial changes in patients with underdose treated

EP1303

hypothyroidism.

Frequency and prognostic factors of non-diagnostic cytology in

Methods

ultrasound guided thyroid fine needle aspiration biopsy: a 2-year single

The study group comprised 154 patients with hypothyroidism, 132 women and 22

centre experience

men. The examination included the assessment of oral cavity under parodontal

Vasileios Chambidis, Athanasios Siolos, Zoe Efstathiadou, Albana Sykja,

status, the quality of dentition, changes of dento-maxillary dynamics.

Thomas Georgiou, Eleni Chambidou, Athanasios Panagiotou,

Results

Fotini Adamidou & Marina Kita

Facial and lip changes were present in 28.4% of cases; macroglossia 13%; mucoid

‘Hippokration’ General Hospital of Thessaloniki, Thessaloniki, Greece.

infiltration of lingual mucosa and oral submucosa K76%; gingivitis and chronic

marginal periodontitis K98%; pathological tooth mobility - grade 1(73%) and

grade 2 (15%); 12 patients (9.16%) required periodontal abscess drainage - 2

Aim

cases of upper premolars (14%) - 10 cases of lower molars (36,5%). Modification

Ultrasound-guided Fine Needle Aspiration Biopsy (USg-FNAB) is the most

of occlusion by changing maximum pressure points - 72 patients (52%). A total

accurate modality for distinguishing malignant or possibly malignant from benign

of 61 patients (46.5%) presented vestibular pockets - 23 periodontal (17.5%), 25

thyroid nodules. However, a certain amount of specimens turn out to be non-

palatal

(19%) and 13 with lingual localization (10%). The average time of

diagnostic or inadequate. Several factors contribute to this outcome such as the

evolution of hypothyroidism with subdosed treatment was 4.3G1.2 months.

examiner’s experience, characteristics of the nodule and patient’s compliance.

Dental cavities were present in 77% of patients; partial edentation - in 89.3%;

Understanding these factors could contribute to reduction of non-diagnostic

total edentation - 9.16%.

results.

Atrophied prosthetic field

Methods

Four cases (3%); 8 cases (6%): osteophitic hyperostosis. The average time of

All nodules examined by USg-FNAB between Jan 2014 and Nov 2015 at the

evolution of hyperthyroidism: 7.4G1.5 months. The specific dento-parodontal

thyroid clinic of our department were reviewed (nZ682 patients with 987

and prosthetic treatment previously assumes the control of the thyroid hormone

nodules). Patient demographic characteristics

(sex and age), nodule charac-

deficiency.

teristics (size, location, previous FNAB) and the experience of the examiner were

Conclusions

recorded.

Periodontal changes are almost constantly found in hypothyroidism. The extent of

Results

the disease without a normal substitution is directly proportional to the severity

The only factor that exhibited a significant positive association with non-

and a high incidence of complications.

diagnostic cytology on USg-FNA was the age of the patient (P ! 0.01). Nodule

DOI: 10.1530/endoabs.49.EP1301

size was marginally negatively associated (PZ0.054). No other factor emerged as

a predictor of non-diagnostic cytology.

Conclusions

The present study indicates that patient age is a prognostic factor for non-

diagnostic cytology on USg-FNA. This might be attributed to the fact that older

patients usually present with nodules baring morphologic characteristics such as

cystic composition and peripheral calcifications that are associated with non-

diagnostic cytology. On the other hand, the marginally negative association with

EP1302

nodule size, seems justified by the fact that small nodules are technically more

Assessment of the degree of depression in patients with chronic

difficult to biopsy. It is of note that the examiner’s experience has not emerged as

autoimmune thyroiditis depending on the serum autoantibodies and

a prognostic factor, possibly due to the fact that nodules which are not easily

thyroid hormone levels

accessible are usually biopsied by more experienced staff.

Seila Ibadula, Olesea Scinic & Eduard Circo

DOI: 10.1530/endoabs.49.EP1303

Spitalul Judetean de Urgenta ‘Sf.Apostol Andrei’, Constanta, Romania.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1304

EP1306

Juvenile hypothyroidism-particularities in the development of the

Audit of utility of radio-isotope scan in the investigation of

dento-maxilary system

thyrotoxicosis or subclinical hyperthyroidism and timing of

Razvan Circo, Seila Ibadula & Eduard Circo

anti-thyroid medication

Spitalul Judetean de Urgenta ‘Sf. Apostol Andrei’, Constanta, Romania.

Satish Artham, Heather MacFarlane, Nishwa Ali & Andy James

Royal Victoria Infirmary, Newcastle, UK.

Introduction

Juvenile hypothyiroidism shows various complications depending on the

Thyrotoxicosis is one of the most common clinical problems in patients referred

correctitude of substitutive treatment.

to endocrine clinic. TRAb is specific for graves disease (GD) and radioisotope

Aims of the study

scan (RIS) is useful diagnostic test in the investigation of thyrotoxicosis. RIS is

To identify the massive facial changes with occlusive disorders, dental

commonly used when TRAb is borderline or negative to exclude thyroiditis.

malpositions, altered chronology of dental eruption, periodontal changes in

Aims and methods

terms of absence of thyroid replacement therapy or drug sub-dosing.

To look at the use of RIS in the investigation of thyrotoxicosis and sub-clinical

Methods

hyperthyroidism (SCH), and use of anti-thyroid medication (ATM) in these

The study group comprised 24 children, 15 girls and 8 boys; 4 cases of congenital

conditions. Retrospective audit, data collected from electronic pathology and

myxedema;19 cases of earned hypothyroidism and the mean age was 9G2.4

radiology system, and clinic letters over 11months (Jan 15 to Nov 15).

years- that presented in their evolution periods of underdosed substitutive

Results

thyroxine treatment.

nZ66, of which 63 (95.5%) were sub-clinical hyperthyroidism or thyrotoxicosis.

Results

FemaleZ52(82.5%). Mean age: 54.07 years. 60 (95%) patients had TRAb

Facial changes: infiltrated facial skin and lips; widened transverse diameter of the

checked and 3 (5%) patients not. (nZ1 SCH, planned for radio iodine, nZ1 on

skull; microretrognathia - 12 cases (52%). pale and infiltrated lingual and jugal

carbimazole and planned for radioiodine, nZ1

TRAb requested but not

mucosa, 14 children (60.8%) - lingual fungal detritus; 8 children (34.7%) -

processed). All patient with TRAb Kve and 5 patients with TRAb Cve had

‘geographic’ tongue. Occlusive disorders: frontal malocclusion in the sagittal

RIS. 23 (36.5%) were diagnosed with graves disease. 3 patients with negative

plane - 19 children (80%); front reverse occlusion - 8 cases (34.7%); open bite -

TRAb who were later diagnosed with GD on RIS were commenced on

4 cases (17.4%); lower proalveolodentition with interdental spacing - 17 children

carbimazole before diagnosis. 17 (27%) were diagnosed with thyroiditis, of which

(68%). Dental malpositions:reverse overlap - 11 cases (47.8%), eruption of

(23.5%) were commenced on carbimazole before diagnosis.

central upper incisors in vestibular position - 1 case (4.3%); bilateral ectopic

Conclusion

canine - 1 case (4.3%); dentoalveolar incongruence - 1 case

(4.3%). The

This audit shows appropriate use of RIS in all patients in the investigation of

chronology of dental eruption: late eruption - 19 patients (78.2%); prolonged

thyrotoxicosis and SCH. 5 patients with positive TRAb had RIS as TRAb was

mixed dentition - 14 patients (60.8%); taurodontism - upper molars-1 case

borderline and history was not typical of graves disease.

7 patients were

(4.3%); accelerating the teeth eruption when introducing thyroxine therapy

commenced on ATM before diagnosis of GD. All these patients had mild to

between 6 and 8 months. Periodontal changes: pathological dental mobility,

moderate thyrotoxicosis. These patients could have been started on b-blockers

pathological diastemas, gingival recession, real periodontal pockets - 8 cases

rather than ATM as they are associated with side effects of agranulocytosis which

(34.7%).

can risk life threatening infections.

Conclusions

DOI: 10.1530/endoabs.49.EP1306

In hypothyroid child prevail the disorders of occlusion and chronology of

eruption. Early diagnosis and a well conducted thyroxine treatment requires the

prophylaxy of dento-maxillary complications in children.

DOI: 10.1530/endoabs.49.EP1304

EP1307

Thyroid autoimmunity and frequency of malignant or suspicious for

malignancy thyroid nodule cytology

Athanasios Siolos, Vasileios Chambidis, Zoe Efstathiadou,

Thomas Georgiou, Athanasios Panagiotou, Fotini Adamidou & Marina Kita

‘Hippokration’ General Hospital of Thessaloniki, Thessaloniki, Greece.

EP1305

Introduction

Thyrotoxic periodic paralysis

Thyroid autoimmunity has been associated with the diagnosis of differentiated

Ahmet Kaya & Mustafa Kulaksizoglu

thyroid (DTC) cancer in surgical series. However, this finding has not been

Division of Endocrinology and Metabolism, Meram Medical Faculty,

consistent in Fine Needle Aspiration Biopsy (FNAB) cytology series.

Necmettin Erbakan University, Konya, Turkey.

Aim

We aimed to investigate the association between thyroid autoimmunity and DTC

in patients who underwent ultrasound-guided FNAB.

Thyrotoxic periodic paralysis (TPP) is due to a fall in potassium levels and threat

Methods

life if it effects respiratory muscles. Men are more effected than women, and

A retrospective analysis of patients who had undergone ultrasound-guided FNAB

lower extremeties are more prone to involvement. Serum potassium in

between Jan 2014 and Nov 2015 was performed. Patients were classified into two

hyperthroidism is usually normal, but Na^C/K^C ATP’ase sensitivity is increased

groups, according to the presence of thyroid auto-antibodies

(ATA): ATA

and extracellular potassium rapidly passes to the intracellular space. Beta

negative (ATA K) and ATA positive (ATAC) patients. In ATAC patients,

blockers, small dose potassium replacement and hyperthyroidism treatment

either one or both antibody types

(anti-thyroid peroxidase abs or anti-

blocks this shift and TPP can be treated. Achieving euthyroidism is essential for

thyroglobulin abs) were positive. Patient demographic characteristics, the

the cure of TPP. Although hyperthyroidism effects mainly females, TPP is seen

presence of risk factors for thyroid cancer and nodule size were recorded.

more in males especially in the second and fourth decades. Periodic paralysis is

Cytology reports were classified, according to the Royal College of Pathologists

seen only in 2% of thyrotoxic patients which is characterized by hypokalemia,

guidance, as negative for malignancy

(Thy2), possible neoplasm

(Thy3),

proximal muscle weakness and acute onset. We present four cases of male

suspicious for malignancy

(Thy4) and malignant

(Thy5). Non-diagnostic

patients aged between 28 and 36 years old. Their complaints were, fatique,

cytology reports (Thy1) were excluded. The frequency of possible neoplasm,

weakness and difficuilty in walking. Two patients had known Graves’ disease and

suspicious or malignant (Thy3, Thy4, Thy5) was estimated in the two patient

two patients were diagnosed as new onset Graves’ disease. They did not have

groups (ATAK, ATAC).

predisposing factors such as alcohol intake, using diuretics or laxatives. On

Results

phsical examination, they all had proximal muscle weakness and diminished

During the study period 673 nodules of 466 patients were biopsied. Thyroid

lower extremity deep tendon reflexes. Their potassium levels were 2.7-2.3-2.1-

autoimmunity was present in 41.8% of patients. The frequency of suspicious or

1.9 mEq/l respectively. Their thyroid antibodies were positive, TSH levels were

malignant (Thy3, Thy4, Thy5) cytology reports was comparable in the two patient

supressed and free thyroid hormones were elevated. Patients were treated with

groups (5.8% in ATAC patients vs. 4% in ATAK patients; PZ0.303).

potassium replacement and antithyroid drugs and lower extremity weakness and

Conclusion

paralysis were disappeared. HPP is a genetic disorder but rarely it can be due to

In the present study, no association between the presence of thyroid autoimmunity

thyrotoxicosis. Although TTP is more commonly seen in Graves disease, it is free

and suspicious or malignant findings in thyroid nodule cytology was found.

of disease duration and severity.

DOI: 10.1530/endoabs.49.EP1307

DOI: 10.1530/endoabs.49.EP1305

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1308

EP1310

Clinical experience with glucocorticoid therapy in patients with

Relapsing Graves’ hyperthyroidism in a male patient with central

endocrine ophthalmopathy

hypothyroidism after surgery of craniopharyngioma: case report

Irina Bourko¹, Halina Korolenko², Olga Bourko³, Oksana Dudich¹ &

Anisoara Bumbu, Yawa Abouleka, Louis Potier, Ronan Roussel &

Viktoria Krasilnikova¹

Michel Marre

¹Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus;

Universitary Hospital Bichat Claude-Bernard, Paris, France.

²10th Clinical Hospital, Minsk, Belarus;³Republican Scientific and

Practical Center of Cardiologz, Minsk, Belarus.

Introduction

Graves’ disease is an autoimmune thyroiditis, less common in men but with

Objective

relapse of hyperthyroidism significantly more frequent in men than in women

To evaluate the efficacy, safety and to determine the criteria for the glucocorticoid

after anti-thyroid medications’ withdrawal. Craniopharyngioma is a rare brain

therapy scheme: intravenous pulse therapy followed by tablet form in prolonged

tumor which arises in the pituitary stalk and project into the hypothalamus. The

regime in the treatment of active phase of endocrine ophthalmopathy (EOP).

distribution by age is bimodal with a slight male predominance and a poor

Materials and methods

survival rate for older than 65 years. The association of these pathologies is

28 patients of both sexes (52 eyes) with endocrine ophthalmopathy in the active

extremely rare.

phase were included in the study. The average age - 43.4G10.6 years. The

Observation

duration of the disease ranged from 3 to 12 months. The activity of disease was

We report the case of a 67 years-old patient who presented a severe thyrotoxicosis

evaluated according to a scale of clinical activity of EOP - Clinical Activity Score

due to a relapse of a Graves’ disease in remission since 2009. At the moment of

(CAS), and thickening of the extraocular muscles based on MSCT of the orbits.

presentation the patient was in treatment with levothyroxine for a central

Results

hypothyroidism secondary of a craniopharingyoma surgery. Clinically he

One month after the start of pulse therapy there was a significant reduction of EOP

presented tachycardia, weight loss, confusion, anorexia and biologically he had

activity and severity in all patients, which was confirmed by an increase in vision,

low TSH value and very high FT4 (100 pmol/l) and FT3 (50 pmol/l) values which

a decrease in the level of intraocular pressure, reduction in the amount

were increasing 5 days after stopping the levothyroxine. TSH receptor antibodies

exophthalmus at 0.8G0.02 mm (P !0.05) and the frequency of diplopia. 3

were positives (2.8 U/l) and the I-123 scintigraphy found an intense and uniform

months after the start of glucocorticoid therapy in 100% of cases a transition to the

fixation confirming the relapse of Graves’ disease. A treatment with carbimazole

inactive phase of the disease was determined. Reoccurrence of the disease after 12

60 mg per day was started with a strictly surveillance of hepatic enzymes. There

months was diagnosed in 3 patients (10.7%).

was a decrease of thyroid hormones and hepatic enzymes and also symptoms in 2

Conclusions:

weeks. A thyroidectomy is to discuss, because of the relapse and the severity of

i) Intravenous pulse therapy with high doses of methylprednisolon followed by

the symptoms, after achieving the euthyroid status.

oral administration in prolonged regime is effective and safe; it contributes to the

Conclusion

rapid achievement of clinical effect and stable remission of the disease. ii) A

We described here, for the first time, an association of a relapsing Graves’ disease

thickening of the extraocular muscles is the criteria for the start of glucocorticoid

in patient with hormonal supplementation for central hypothyroidism after

therapy.

surgery of craniopharyngioma, with a favorable evolution after treatment with

DOI: 10.1530/endoabs.49.EP1308

anti-thyroid medications.

DOI: 10.1530/endoabs.49.EP1310

EP1309

Thyroid storm presenting in the context of recent influenza vaccination

and untreated Graves disease

Neil Kelly, Dushyant Sharma & Reza Zaidi

EP1311

Royal Liverpool University Hospital, Liverpool, UK.

TSH normalization and negative anti-TSH receptor

antibodies - Predictive value for remission in Graves’ disease

Catarina Roque, Francisco Sousa Santos, Ricardo Capita˜o, Carlos Bello,

Introduction

Catia Ferrinho & Carlos Vasconcelos

Thyroid Storm is a life-threatening but rare (incidence 0.2 per 100 000) disease

Endocrine Clinic, Hospital de Egas Moniz C.H.L.O. E.P.E., Lisbon,

state which presents as an extreme form of thyrotoxicosis. A hyper-metabolic

Portugal.

state resulting from excessive thyroid hormone release which can be precipitated

by both thyroidal and non-thyroidal illness.

Case

Graves’ disease is the most common cause of hyperthyroidism in non-endemic

In this case we discuss a 72 year old female with previously treated Graves

areas and antithyroid drugs are the preferred first-line therapy in many centers.

disease who presented in thyroid storm one week after annual flu vaccination. On

The aim of this retrospective investigation was to verify the association of

initial presentation, she was in overt heart failure with bilateral pleural effusions

remission with the achievement of normal TSH and free-T4 during the first 18

and a community acquired pneumonia, atrial fibrillation at a rate of 170 beats per

months of treatment and to compare it with negative anti-TSH-receptor antibodies

minute and acute confusion with significant agitation. The decision to treat

at 18 months, a marker with known prognostic value. All patients diagnosed with

initially with beta blockers was complicated by her being in heart failure with

Graves’ disease from 2008 to 2015 were selected. Those with more than 2 years of

significant pulmonary oedema and a rapid ventricular rate precipitating a peri-

follow-up and with synchronous determination of TSH, free-T4 (fT4), free-T3

arrest state. The guidance of the cardiologists to give amiodarone to chemically

and anti-TSH-receptor antibodies (TRAb) performed at our clinic were included.

cardiovert conflicted with her thyrotoxic state. Relevant Data includes a Thyroid

We compared TRAb titer, TRAb positivity, TSH and fT4, between the group that

stimulating hormone of !0.05 mIU/l and a T4 of 96.5 pmol/l. A biochemically

achieved remission and the one that did not, for the length of treatment and follow

euthyroid state was eventually achieved using propathyaurocil, intravenous

up. We obtained 71 patients with mean age of 47 years of which 76% were

hydrocortisone, Lugols Iodine and Bile salts. Beta blockers and amiodarone were

females. The mean follow-up after remission was 2 years. Remission was

used with caution in the context of heart failure/suspected thyrotoxic

achieved in 28% patients after 18 months of treatment. There were no significant

cardiomyopathy and a thyrotoxic state respectively. Further investigation showed

differences in sex or age among the 2 groups. No association was found between

the patient had previously been treated for Graves and this was a late presentation

the development of hypothyroidism during therapy and remission. Negative

recurrence seven years after completing block and replace therapy.

TRAbs at 18 months associated with remission significantly (P!0.001) with a

Discussion

strength of association of 0.86. A non-supressed TSH accompanied by normal fT4

We present this case because it highlights a rare case of thyroid storm presenting

levels achieved during therapy was associated significantly with remission (P !

seven years following initial block and replace therapy had discontinued. The

0.001) with a strength of association of

0.74. Logistic regression with this

temporal relationship between presentation and the administration of the flu

parameter could explain 59.8% of remissions after initial therapy with P!0.001.

vaccination mean this must be considered as a potential non-thyroidal precipitant.

This profile of thyroid function was associated with negative TRAbs significantly

The presentation in fast atrial fibrillation is also significant as the treatment of

(P!0.001). Achieving a non-suppressed TSH in the presence of normal fT4,

choice was amiodarone and this could have potentially exacerbated her

during the first 18 months of therapy, associates with TRAb negativization and

underlying thyrotoxicosis.

could predict remission in approximately 60% of patients.

DOI: 10.1530/endoabs.49.EP1309

DOI: 10.1530/endoabs.49.EP1311

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1312

months).

44% would recommend routine neck US, and

19.3% would

recommend routine DEXA. In a case of thyrotoxicosis due to 3 cm toxic nodule

Treatment choice and patient satisfaction in thyrotoxicosis

tirads 4a most endocrinologists (70%) would refer to RAI ablation, 46.4% without

Helen Conaglen, Jade Tamatea, Mark Swarbrick, John Conaglen &

FNA and 23.7% with FNA. No significant difference was found in correlation

Marianne Elston

with gender, years of board certificate, or work environment.

Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand.

DOI: 10.1530/endoabs.49.EP1313

Background

Thyrotoxicosis may be associated with considerable patient morbidity. Graves’

disease (GD) and toxic multinodular goitre (TMNG) are the most common causes

of thyrotoxicosis. Therapeutic options include anti-thyroid medication or

definitive treatment by radioiodine or surgery. Efficacy, quality of life and cost-

effectiveness are among the outcomes that have been compared between these

EP1314

two therapies. However, there is still no clear consensus as to which treatment

option offers a better outcome.

Case report: identification and characterization of interference by

IgM anti-streptavidin antibody in a patient with spurious thyroid

Aims

function tests

The aim of this study was to assess quality of life amongst patients who received

Leo Lam³, Warwick Bagg^1,2, Julie Lim⁴, Martin Middleditch⁵ &

anti-thyroid medication, radioiodine or surgery and to assess patient satisfaction

Campbell Kyle^3,6

with the treatment modality selected.

¹Department of Endocrinology, Auckland District Health Board, Auckland,

Method

New Zealand;²Medical Programme Directorate, Faculty of Medical and

Participants in a prospective study with new onset thyrotoxicosis were invited to

Health Sciences, The University of Auckland, Auckland, New Zealand;

participate. Those who agreed to be involved completed a questionnaire detailing

³Department of Chemical Pathology, LabPlus, Auckland City Hospital,

factors involved in treatment choice, quality of life (ThyPRO) and satisfaction

Auckland, New Zealand;⁴Department of Physiology, School of Medical

with their treatment.

Sciences, New Zealand National Eye Centre, The University of Auckland,

Results

Auckland, New Zealand;⁵Auckland Science Analytical Services,

Of those eligible for the study

146 patients completed the questionnaires,

University of Auckland, Auckland, New Zealand;⁶Department of

representing a return rate of 73%. GD was the cause of the thyrotoxicosis in 84%

Biochemistry, Labtests, Auckland, New Zealand.

and TMNG in 16%. Fifty-eight percent of patients had received anti-thyroid

medication, 19% radioiodine, and 22% thyroid surgery, the latter two groups

usually following a period of medical therapy. The impact of treatment on

Introduction

recovery time, activities of daily living, possibility of depression or anxiety, and

Falsely high FT4 and FT3 with concurrent falsely low TSH have been reported in

doctor’s recommendations were identified as the most important factors in

patients taking biotin and in a few case reports of patients with IgG anti-

choosing a treatment. Satisfaction levels were high across all three treatment

streptavidin antibody. However, other isotypes and effects on other immunoas-

types. There was no difference in quality of life between the treatment types apart

says have not been reported.

from a higher score for cosmetic concerns in the surgical group.

Case

Conclusions

A 77 year female presented with worsening fatigue with a background of

These results indicate that overall patient satisfaction with treatment and quality

hyperthyroidism on carbimazole. Clinically she appeared hypothyroid. Her

of life are comparable across all three treatment options. Therefore, factors such

results on Roche Cobas platform were: TSH 0.75 mIU/l (R.I. 0.27-4.2), FT4

as patient preference and resource availability may be more important than

12 pmol/l (12-22) and FT3 8.1 pmol/l (3.9-6.8). However, tests repeated on

treatment type.

Siemens Centaur platform were: TSH 37 mIU/l (0.3-4.0), FT4 7 pmol/l (10-20)

DOI: 10.1530/endoabs.49.EP1312

and FT3 3.0 pmol/l (3.0-6.5), suggesting Cobas results were falsely low for TSH

and falsely high for FT4 and FT3. To identify the cause of interference a second

sample from the patient was preincubated with streptavidin microparticles. After

incubation TSH on Cobas platform increased from 0.2 to 0.7 mIU/l, while FT4

reduced from 28 to 16 pmol/l, and FT3 from 9.0 to 4.7 pmol/l. Siemens results

were unchanged. Elution of streptavidin microparticles with 0.1M citric acid

identified a 75 kDa band on reducing SDS-PAGE. Purification and sequencing of

peptide fragments by LC-MSMS of this band identified this protein as IgM heavy

EP1313

chain. This demonstrates IgM anti-streptavidin antibody as the cause of

Management of relapsing Graves: a clinical survey among

interference. The patient’s hypothyroid symptoms resolved when carbizamole

endocrinologists in Israel

was stopped. The effect of preincubation with streptavidin microparticles was also

Shlomit Koren¹, Miriam Shteinshnaider^1,4, Karen Or^1,4, Dror Cantrell^1,3,

tested on Roche Cobas immunoassays for FSH, LH, oestradiol and testosterone in

Carlos A Benbassat^1,4 & Ronit Koren¹

this patient’s serum. Sandwich immunoassays were falsely low and competitive

¹Endocrine Institute, Assaf Harofeh Medical Center, Zerifin, Israel;

immunoassays were falsely high. Oestradiol exhibited the largest difference,

²Department of Internal Medicine A, Assaf Harofeh Medical Center,

at 240 pmol/l initially but becoming undetectable following incubation.

Zerifin, Israel;³Department of Internal Medicine C, Zerifin, Israel;

Conclusions

⁴Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

This is the first case describing IgM anti-streptavidin antibody as the cause of

interference on thyroid function tests and also shows its effects on other

immunoassays.

Background

DOI: 10.1530/endoabs.49.EP1314

The management of relapsing Graves’ disease is controversial. Previous surveys

from different regions in the world demonstrated variations in the clinical

practices of patients with Graves’ disease relapse.

Methods

To determine management pattern among endocrinologists in Israel an electronic

questionnaire was e-mailed to all members of the Israeli Endocrine Society.

Questionnaires included demographic data and clinical scenarios with questions

regarding the treatment and follow up of patients with relapsing Graves’ disease.

Results

EP1315

We received 98 responses from Israeli endocrinologists. 42 (43%) males and 56

Severe Grave’s dermopathy and acropachy discording with moderate

(57%) females. 41.8% had board certificate for more than 10 years. 72.4%

ophtalmopathy: (a case report)

responders work in hospital environment and 26.5% work in community clinics.

Dhiyaeddine Bellarbi, Hafsa Si Youcef & Noura Soumeya Fedala

61.2% see more than 10 thyroid patients in clinic per week. When managing

Endocrine and Metabolic Diseases Department, Bab El Oued Hospital,

Graves’ relapse following ATD treatment in a young male, 68% would restart

Algiers, Algeria.

ATD (98% mercaptizol) and 32% would refer to RAI treatment. Interestingly,

endocrinologist who treat more thyroid patients (more than 10/week) tend to

choose ATD over RAI (PZ0.04). In case of recurrent Graves’ and ophtalmopaty

Introduction

50% would continue ATD, 22.4% would recommend RAI treatment and 27.6%

Pretibial Myxedema(PM) and acropachy(AP) are rare extrathyroidal mani-

surgery. Most endocrinologists (56%) would continue ATD for 12-24 months.

festations of Graves’ disease observed only in

0.5-4% of all cases. These

75% would monitor CBC and liver function (39% for the first month and 36% for

extrathyroidal manifestations are generally associated to severe ophtalmopathy.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Only few cases of severe thyroid dermopathy and achropachy occurring with

Aim

moderate ophtalmopathy were reported.

There are studies showing that Hashimoto’s thyroiditis (HT) progresses more

Observation

rapidly, thyroid echogenicity is lower and thyroid autoantibodies are higher titer

We present a 60years old female patient who developed grave’s disease on a pre-

positive in immunoglobulin G4 (IGg4) positive patients.But a small number of

existing goiter associated to extrathyroidal manifestations. Physical examination

studies that do not support this data have also been published.We planned this

revealed; some signs of hyperthyroidism, moderate exophthalmos measured by

study to evaluate the findings of IgG4 (C) Hashimoto’s thyroiditis cases.

hertel’s exophtalmometer at 20 for right eye and 19 for Left eye, bilateral severe

Materials and methods

PM manifested by elephantiasis, severe AP manifested by clubbing and finger

New diagnosis without treatment of thyroid 92 patients with HT and 60 healthy

deformations, compressive goiter with 3 palpated nodules (a 5 and 4 cm nodules

volunteers were included fort he study between October 2015 and October 2016.

occupying the totality of the right and left lobe respectively, and a 2 cm left lobo-

After 8 hours of fasting, basal thyroid function tests and serum IgG4 level were

isthmic nodule) which were confirmed by ultrasound of the neck that showed

analyzed in the whole of the individual and thyroid ultrasonography was

hypervascularization of the normal parenchyma. Thyroid function tests before

performed all of them.HT patients were divided into subgroups with IGG4 (group

treatment showed FT3 predominating hyperthyroidism: TSHus!0.005, FT4Z

1) and without IgG4 (group 2).

4.11 ng/dl (N:0.7-1.4), FT3O30 pmol/l (N:3.0-8.3 pmol/l). Anti-thyroid per-

Findings

oxidase antibodies were positive 149.6 UI/ml (N:!12 UI/ml). Total thyroid-

Mean IgG4 levels were similar between patient group and healthy volun-

ectomy was performed after normalization of thyroid function under 60 mg of

teers.There were 22 patients in group 1 and 70 patients in group 2. Mean age

neomercazol, and this goiter was benignant on pathology. PM was stabilized after

values of two groups were similar.Statistically men patients were more in group 1

surgery and management of hypothyroidime by levothyroxine.

(PZ0.009). There was no statistically significant difference was detected between

Conclusion

two groups in terms of mean thyroid stimulant hormone (TSH), free T4, free T3,

PM and AP are very rare. They reflect the severity of autoimmunity and long

anti-TPO and anti-Tg antibodies, thyroid volume, thyroid nodule quantity and

duration of hyperthyroidism. These signs are often observed in severe

thyroid parenchyma echogenicity.

hyperthyroidism and are constantly associated to ophtalmopathy which is

Results

generally severe. Infiltration corresponds to the accumulation of GAG in the 3

There are publications in the literature that, IgG4 positive HT is more often

conditions. Moderate ophtalmopathy occurring with severe PM(elephantiasis)

detected in younger age and men patients, it is related lower echogenity

and AP(clubbing and deformations) is not habitually reported.

ultrasonographically and higher titre thyroid autoantibodies. However in our

DOI: 10.1530/endoabs.49.EP1315

study, among IgG4 positive HT patients, statistically meaning difference was not

detected in terms of parameters examined, except more men numbers. We have

thought that, these results arised because of the premise of working and IgG4

positive case number scarcity.

DOI: 10.1530/endoabs.49.EP1317

EP1316

The importance of the study of several immunoregulatory cytokines in

the manifest hypothyroidism

Marina Orlova, Arina Frolova, Tatiana Rodionova, Irina Badak &

Tatiana Baitman

Saratov State Medical University named V.I. Razumovsky, Saratov, Russia.

The research goal was to study serum concentration of immunoregulatory

EP1318

cytokines

(IL-1ß, IL-6ß, IL-8ß, IL-10ß) in

patients with manifest

TRAB positive thyroid dysfunction associated with Alemtuzumab

hypothyroidism at the age of

21-50.

patients suffering from chronic

treatment for MS: A case series

autoimmune hypothyroidism and 32 patients with postoperative hypothyroidism

Aoife Garrahy, Sulaiman Ali, Siobhan McQuaid & Maria M Byrne

were examined. It was revealed that autoimmune hypothyroidism effects balance

Department of Endocrinology, Mater Misericordiae Hospital, Dublin,

disturbance of cytokine-producing activity Th1 and Th2 types, this plays an

Ireland.

important role in development of autoimmune state, chronization and disease

progress. The research goal was to study kidneys’ function in conditions of

thyroid hormone deficit. Estimation of kidneys’ function included study of daily

Alemtuzumab is a monoclonal antibody directed against CD52 licenced for the

microalbuminuria; serum concentration of creatinine and rate calculation of

treatment of relapsing remitting multiple sclerosis (MS). Thyroid dysfunction

glomerular filtration with MDRD formula; examination of urea level; potassium

occurs in one third of patients, likely secondary to lymphocyte reconstitution.

and natrium in blood serum; urinary excretion of chemokines: monocyte

Case 1

chemoattractant protein-1 (MCP-1) and Regulated on Activation, Normal T-cell

A 36 year old female, treated with alemtuzumab 15 months prior, presented to

Expressed and Secreted. In both groups of patients with hypothyroidism is

antenatal clinic at 12 weeks gestation with symptoms of thyrotoxicosis. fT4 was

established a significant decrease of glomerular filtration rate, tubular

83.7 pmol/l (RR 12-22), TSH suppressed, TRAB positive. She was treated with

reabsorption, and increase sodium excretion in the urine, indicating a violation

carbimazole and remains on antithyroid medication at 30 weeks gestation; TRAB

of tubular functions in form of decrease sodium reabsorption in the proximal

titer has risen to O40 IU/l (RR 0-1.5).

tubule, and was accompanied by a decrease in median serum sodium levels below

Case 2

the normal range. Level of proinflammatory cytokines IL-1ß, IL-6ß, IL-8ß and

A 36 year old male, treated with alemtuzumab 18 months prior, was admitted for

anti-inflammatory cytokine IL-10ß; vascular endothelial growth factor in blood

investigation of weight loss and functional decline. fT4 was 37.9 pmol/l, TSH was

serum of 80 patients with clinical hypothyroidism and 50 healthy persons were

suppressed and he had a large smooth goiter. TRAB was 18.9 IU/l. He was treated

studied. Our data are the evidence of increase in patients with autoimmune

with carbimazole and is undergoing rehabilitation.

hypothyroidism of IL-6 level of blood serum and urea excretion level of anti-

Case 3

inflammatory cytokine MCP-1, decrease of IL-10 production in patients with

A 39 year old female, treated with alemtuzumab 2 months prior, was referred to

clinical hypothyroidism in their second age period. Healthy persons aged over 35

the endocrine clinic with fT4 of 60.2, suppressed TSH and TRAB 24 IU/l. She

demonstrate increase of level of anti-inflammatory cytokine IL-10

on a

was asymptomatic and became hypothyroid four weeks later (fT4 !5.2 pmol/l,

background of gently cut cue of proinflammatory cytokines IL-1ß, IL-8ß.

TSH 58 mU/l). Twelve months on, she is euthryoid on L-thyroxine 100 mg daily.

DOI: 10.1530/endoabs.49.EP1316

In this case series we demonstrate three cases of alemtuzumab induced thyroid

disease, occurring 2-18 months post treatment, all of which are TRAB positive.

Case 1 highlights that women of child-bearing age treated with alemtuzumab

should be counseled regarding the risk of thyroid dysfunction in future pregnancy.

TRAB should be monitored in each trimester and close monitoring for foetal

thyrotoxicosis is required. Case 3 highlights that TRAB positivity is not specific

EP1317

for Graves disease and in this case is associated with overt hypothyroidism. This

The position of immunoglobuline G4 positive in Hashimoto’s thyroiditis

case series illustrate the unpredictable clinical course of thyroid dysfunction in

Zeynep Cetin¹, Bulent Can¹, Merve Catak¹, Ozden Ozdemir Baser¹,

patients treated with alemtuzumab; long-term monitoring of thyroid function is

Dilek Berker¹ & Serdar Guler²

recommended.

¹Numune Training and Research Hospital, Ankara, Turkey;²Liv Hospital,

DOI: 10.1530/endoabs.49.EP1318

Ankara, Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1319

controls (PZ0.04). However, fT3 levels were similar statistically between groups

(PZ0.347), free T4 was significantly lower in the patient group (PZ0.01). Mean

Serum levels of insulin-like growth factor 1 in patients with

native thiol and total thiol levels were significantly higher in the patient group

hyperthyroidism or euthyroidism

compared to the control group (PZ0.04 and PZ0.036, respectively). There were

Fen-Yu Tseng¹, Yen-Ting Chen², Yu-Chao Chi², Pei-Lung Chen^1,3 &

not any statistically significant differences between groups regarding calculated

Wei-Shiung Yang^1,2

disulphide/native thiol (-S-S-/-SH), disulphide /total thiol (-S-S-/-SHC-S-S-),

¹Department of Internal Medicine, National Taiwan University Hospital,

native thiol/total thiol (-SH/-SHC-S-S-) ratios. The association between acute

Taipei, Taiwan;²Graduate Institute of Clinical Medicine, National Taiwan

phase reactants and thiol-disulphide parameters were evaluated and no significant

University, Taipei, Taiwan;³Department of Medical Genetics, National

correlation was found. Similarly, there was no significant correlation between

Taiwan University Hospital, Taipei, Taiwan.

antibody positivity and thiol-disulphide parameters.

Conclusion

Background

To our knowledge, our study is the first one that evaluated the association between

Insulin-like growth factor 1 (IGF1) has molecular structure similar to insulin. As

HT and thiol-disulphide status according to Erel and Neselioglu method. In

an important mediator of growth hormone, IGF-1 plays roles in growth of

conclusion native and total thiol levels were detected to be increased in euthyroid

children and anabolic effects of adults. We evaluate serum levels of IGF-1 in

HT patients, these results were not consisted with the literature data using

patients with hyperthyroidism or euthyroidism.

different methods.

Subjects and methods

DOI: 10.1530/endoabs.49.EP1320

In this study, 30 patients with hyperthyroidism (HY group) and 30 euthyroid

individuals (EU group) were recruited. The patients of HY group were treated

with anti-thyroid regimens as clinically indicated, whereas no medication was

given to EU group. The demographic characteristics, anthropometric and

laboratory data of both groups at baseline and at the 6th month were compared.

Associations between levels of IGF1 and free thyroxine (fT4), TSH, or log

transformation of TSH (logTSH) were analyzed.

Results

At baseline, the HY group had significantly higher serum IGF1 levels than the EU

group (median (Q1, Q3): 305.4 (257.4, 368.1) vs 236.7 (184.6, 318.8) ng/ml,

EP1321

P!0.01). The serum IGF-1 levels of the HY group decreased after anti-thyroid

Hashimoto Encephalopathy with polymorphic neuropsychiatric signs:

regimens, but still were higher than that of the EU group at the 6th month (299.5

a case report

(249.9, 397.9) vs 222.1 (190.2, 305.4) ng/ml, P!0.01). At the baseline, the serum

Diana Simoniene^1,2, Raimonda Klimaite^1,2, Greta Mikelaityte² &

levels of IGF1 in all patients were positively associated with fT4 (bZ29.02,

Evalda Danyte^1,3

P!0.01) and negatively associated with TSH (bZK31.46, PZ0.04). The

¹Hospital of Lithuanian University of Health Sciences, Kauno Klinikos,

associations between serum levels of IGF1 with fT4 or TSH became insignificant

Kaunas, Lithuania;²Lithuanian University of Health Sciences, Kaunas,

at the 6th month. However, the serum IGF1 levels were persistently negatively

Lithuania;³Institute of Endocrinology, Lithuanian University of Health

associated with logTSH both at baseline (bZK29.04, P!0.01) and at the 6th

Sciences, Kaunas, Lithuania.

month (bZK26.65, PZ0.02).

Conclusions

In comparison to EU group, patients with hyperthyroidism had higher serum IGF1

Hashimoto encephalopathy (HE) is a rare and steroid responsive encephalopathy

levels, which decreased after anti-thyroid regimens. The serum IGF1

associated with autoimmune thyroiditis (1). Patients with Hashimoto encephalo-

concentrations were negatively associated with logTSH in patients with

pathy may present with a variety of neuropsychiatric signs (2). 68-year old

hyperthyroidism or euthyroidism.

woman was admitted to the Neurology Department, of Hospital of Lithuanian

University of Health Sciences, Kauno klinikos (HLUHS KK), due to disorder of

DOI: 10.1530/endoabs.49.EP1319

consciousness of uncertain aetiology in August

2016. The signs of motor

dysfunction, generalized rigidity, and disorientation, with several episodes of loss

of and recurrent episodes of psychosis with hallucinations were observed since

2011. She had hospitalisations in neurology units of several hospitals and was

discharged with different diagnoses and modes of treatment. She developed

cerebral oedema with abundant myoclonic seizures in extremities in August 2016.

The possibility of ischemic, neurodegenerative or neuro-inflammatory disease

was ruled out in LUHS KC. Irregular activity of slow range waves was observed

in EEG. Brain CT showed no signs of ischemia. High protein concentration was

EP1320

found in lumbar aspirate. Brain MRI SI T2W revealed changes characteristic of

HE. Laboratory tests: FT4 6.7 pmol/l (normal 9-21), TSH 17.71 mU/l (0.4-3.6),

Evaluation of oxidative stres by means of thiol-disulphide homeostasis

antiTPO 270 kU/l (0-2), and signs of chronic thyroiditis in thyroid ultrasound

in patients with euthyroid Hashimoto’s thyroiditis

made possible to diagnose autoimmune thyroiditis with hypothyroidism and HE.

Merve Dirikoc¹, Oya Topaloglu², Cevdet Aydin², Ahmet Dirikoc²,

The treatment with L-thyroxine

50 mg/d, and

3-day bolus therapy of

Sefika Burcak Polat², Ozcan Erel³, Reyhan Ersoy² & Bekir Cakir²

Methylprednisolone

1 g/d was started with rapid regression of clinical

¹Department of Internal Medicine, Ataturk Education and Research

neurological signs. Prednisolone per os followed, with gradually reduced dose.

Hospital, Ankara, Turkey;²Department of Endocrinology and Metabolism,

The patient’s condition improved significantly and she was discharged. During

Yildirim Beyazit University School of Medicine, Ankara, Turkey;

follow-up appointment after 3 months, her neurological state and psychiatric

³Department of Biochemistry, Yildirim Beyazit University School of

condition were deemed stable, thyroid hormones in normal range on L-thyroxine

Medicine, Ankara, Turkey.

50 mg/d. MRI HE changes have regressed. Patients with unexplained

encephalopathy, progressive cognitive impairment, polymorphic neuropsychia-

Aim

tric should be considered to rule out HE, MRI and test of antiTPO levels should be

In this study we aimed to evaluate the oxidative stress via evaluating changes in

performed.

dynamic thiol-disulphide status in euthyroid patients with Hashimoto’s thyroiditis

DOI: 10.1530/endoabs.49.EP1321

(HT).

Methods

Fifty euthyroid patients with HT and 50 healthy individuals were enrolled in this

study. Thyroid function tests (free triiodothyronine (fT3), free thyroxine (fT4),

thyrotropin

(TSH)), acute phase reactants

(C-reactive protein

(CRP), high

sensitive CRP (hs-CRP)) and thiol-disulphide parameters were evaluated. Native

thiol

(-SH), total thiol

(-SHC-S-S-), disulphide

(-S-S-) levels, calculated

disulphide/native thiol (-S-S-/-SH), disulphide /total thiol (-S-S-/-SHC-S-S-),

native thiol/total thiol (-SH/-SHC-S-S-) ratios were compared between groups.

EP1322

Results

Cardiothyreosis: prevalence and risk factors

Mean age was 38.3G10.4 years in the patient group and 37.2G10.1 years in the

Meriem Yazidi^1,2, Mélika Chihaoui^1,2, Hiba Oueslati¹, Ons Rejeb^1,2,

control group. There were 43 (86%) females and 7 (14%) males in the patient

Sana Ouali^1,2, Salsabil Rejaibi¹, Fatma Chaker^1,2 & Hédia Slimane^1,2

group while there were 39 (78%) females and 11(22%) males in the control group.

¹Faculté de médecine de Tunis, Université de Tunis El Manar, Tunis,

Median TSH level was significantly higher in the patient group compared to

Tunisia;²Hôpital La Rabta, Tunis, Tunisia.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Background

¹Faculté de médecine de Tunis, Université de Tunis El Manar, Tunis,

Cardiothyreosis (CT) or thyrotoxic heart is associated with higher morbidity and

Tunisia;²Hôpital La Rabta, Tunis, Tunisia.

mortality than the other forms of hyperthyroidism. Its risk factors have been

investigated in a limited number of studies. The aim of our study was to identify

Subclinical hypothyroidism (SCH) is a common disorder and indications of

risk factors of CT in patients with hyperthyroidism.

treatment are still being debated. The aim of our study was to describe the

Methods

therapeutic and evolutionary characteristics of SCH.

We identified 538 patients with a hospital discharge diagnosis of hyperthyroidism

Methods

from January 2000 to December 2015. Thirty five patients were diagnosed with

We undertook a longitudinal retrospective study in 110 patients with SCH

CT. Their demographic, clinical and biological characteristics were retro-

biologically defined by increased serum thyroid-stimulating hormone (TSH)

spectively studied and compared with those of 72 controls randomly selected,

levels (O4 mIU/l) and normal FT4. Pregnancy, age less than 18 years, personal

using univariate and multivariate analysis.

history of partial thyroidectomy or radioactive iodine therapy were exclusion

Results

criteria.

The prevalence of CT in patients hospitalized for hyperthyroidism was 6.5%. The

Results

cardiac complications were atrial fibrillation (AF) in 33 cases (6.1%) and cardiac

Sixty-one (55.5%) patients were put under L-thyroxine therapy. The TSH level of

heart failure (CHF) in 11 cases (2%). The risk factors of CT were age greater than

treated subjects was significantly higher than that of untreated subjects (8.1 mIU/l

50 years (ORZ13.1 (95% CI, 4.9-34.4)), low socioeconomic status (ORZ2.8

vs 5.9 mIU/l, P!0.001). Thyroid peroxidase antibodies were more frequently

(95% CI, 1.2-6.7)), low educational level (ORZ3.1 (95% CI, 1.2-8.3)), history

positive in treated subjects (93% vs 7%, P!0.001). The dose of L-thyroxine

of hypertension (ORZ3.5 (95% CI, 1.1-11.2)) and a multinodular toxic goiter as

which allowed the normalization of the TSH level was on average 63.9 mgG

the etiology of hyperthyroidism (ORZ4.6 (95% CI, 1.6-13.9)). After multi-

39.4 mg/day. There was no significant difference between the results of the

variate analysis, age greater than 50 years was the only independent risk factor of

metabolic parameters (weight, blood pressure, fasting glucose, total cholesterol,

CT (adjusted ORZ11.6 (95% CI, 2.7-49.5)). Severe biological hyperthyroidism

triglycerides and HDL cholesterol) before and after normalization of TSH level.

(FT4O 3 times normal) was associated with a lower risk of CT (adjusted ORZ

In untreated patients, spontaneous TSH normalization occurred in 27% of cases

0.2

(95% CI, 0.1-0.9)).

after an average time of 3.5G3.1 months.

Conclusions

Conclusion

The prevalence of CT in patients with hyperthyroidism was 6.5%. The two types

L-thyroxine replacement in patients with SCH concerned almost half of our

of cardiac disease observed were CHF and AF with a clear predominance of the

patients. Higher TSH level and positive thyroid peroxidase antibodies were more

latter. Advanced age was the only independent risk factor of CT.

frequently associated with L-thyroxine requirement. Spontaneous TSH normal-

DOI: 10.1530/endoabs.49.EP1322

ization was relatively frequent (one quarter of untreated patients); hence repeating

measurement of FT4 and TSH is necessary before starting L-thyroxine therapy.

DOI: 10.1530/endoabs.49.EP1324

EP1323

Takotsubo cardiomyopathy associated with thyrotoxicosis

Helena Vitorino, Joana Costa, Filipa Moleiro, Cláudia Jesus, Ana Afonso,

Nadine Monteiro, Sofia Santos, Eduarda Comenda & Helena Cantante

EP1325

Hospital Lusíadas Lisboa, Lisboa, Portugal.

The manner of performing the thyroid ultrasound examination and the

reliability of assessment of the thyroid size in school-aged children

Background

Arkadiusz Zygmunt¹, Zbigniew Adamczewski¹, Malgorzata

Takotsubo cardiomyopathy is a rare, acute, nonischemic cardiomyopathy causing

Karbownik-Lewinska² & Andrzej Lewinski¹

transient systolic disfunction of the apical and/or mid segments of left ventricle

¹Department of Endocrinology and Metabolic Diseases, Medical University

and is commonly associated with emotional and physical stress. Thyrotoxicosis is

of Lodz, Lodz, Poland;²Department of Oncological Endocrinology, Lodz,

a rare cause of this condition, resulting from direct and indirect action of thyroid

Poland.

hormones on the cardiovascular system.

Case presentation

A 43-year-old woman presented at emergency room with chest pain, shortness of

Goitre incidence in school-aged children evaluated by the use of ultrasonography

breath, palpitations, nausea, anxiety, slurred speech and myalgia. Two months

(US), apart from reflecting urine iodine concentration and percentage of

earlier she had been admitted in another hospital with chest pain and a diagnosed

households consuming iodized salt, is an essential indicator for assessing iodine

Takotsubo cardiomyopathy, based on normal cardiac catheterization and

intake in a given area. The position in which the US examination is being

compatible echocardiographic changes. At admission, diagnosis of recurrent

performed can also be an important problem in terms of its result interpretation.

Takotsubo cardiomyopathy in the context of thyrotoxicosis was assumed (TSH !

The aim of the study was to examine what is the difference between the thyroid

0.05 mm/l, fT4

65 mg/dl). Further evaluation confirmed Graves’ disease.

volume measured in the supine and sitting position and to determine the

Recomended treatment was started and follow-up at

weeks revealed

coefficients of variation between measurements performed by the same observer

improvement of cardiac function and near normalization of thyroid hormone

(intra-observer variation), between two (2) observers (inter-observer variation)

and between two different positions

(inter-position variation). The survey

levels.

included 87 children (56 girls and 31 boys, aged 7-13 years). The US tests

Conclusions

were carried out by two (2) examiners (AZ and ZA). Thyroid volume measured in

Takotsubo cardiomyopathy could be the presenting manifestation of thyroid

a sitting position was significantly lower than in the supine position. The intra-

storm. Awareness of this possible association is important in establishing the

observer variations equalled 9.7% (CI - 8.1-11.13) for ZA and 9.56% (CI - 7.66-

diagnosis and institution proper management.

11.45) for AZ. The inter-observer variations amounted to 34.53% (CI - 31.9-

DOI: 10.1530/endoabs.49.EP1323

37.1) and 35.7% (CI - 32.5-38.9) for measurements performed in the supine and

the sitting position, respectively. We have concluded that the size of the thyroid

gland depends on the position in which it is examined. The manner the US

evaluation is being performed is important for the analysis of the results. It is

crucial to aim at the smallest value of inter-observer variation, which can be

achieved by strictly defining the methods of measurement of the thyroid and

comparing one’s measuring techniques with the reference technique. Con-

EP1324

clusions: The use of standards in US evaluation performed in the supine position,

Therapeutic and evolutionary characteristics of subclinical

as well as those without a strict determination of the study method, including body

hypothyroidism

position during examination, can lead to erroneous conclusions.

Meriem Yazidi^1,2, Imed Mezghani¹, Fatma Chaker^1,2, Ons Rejeb^1,2,

DOI: 10.1530/endoabs.49.EP1325

Mélika Chihaoui^1,2 & Hédia Slimane^1,2

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1326

processed with the chi-square test. Pearson and spearman correlation analysis

were performed for normally and non-normally distributed data, respectively.

Which cytologic or architectural characteristics are associated with

Results

malignancy in AUS/FLUS cytologies according to subgroups?

There was an inverse correlation between baseline serum vitamin D levels and

Oya Topaloglu¹, Aysegul Altinboga², Fatma Neslihan Cuhaci¹,

thyroid volume, TRAb, fT3 and PTH levels (PZ0.02, rZK0.31; PZ0.005,

Cevdet Aydin¹, Husniye Baser³, Omer Yazicioglu⁴, Afra Alkan⁵,

rZK0.36; PZ0.04, rZK0.26; PZ0.02, rZK0.32; respectively). Thyroid

Reyhan Ersoy¹ & Bekir Cakir¹

volume was also correlated with serum fT4, fT3, TRAb and TPOAb (PZ0.001,

¹Department of Endocrinology and Metabolism, Yildirim Beyazit

rZ0.426; PZ0.001, rZ0.50; PZ0.04, rZ0.26; PZ0.001, rZ0.42; respect-

University Faculty of Medicine, Ankara, Turkey;²Department of Pathology,

ively). Low vitamin D and high TgAb levels were independently associated with

Ataturk Education of Research Hospital, Ankara, Turkey;³Department of

thyroid volume in logistic regression analysis (PZ0.03, OR:18.7, CI 95% 1.34-

Endocrinology and Metabolism, Ataturk Education of Research Hospital,

260.91 and PZ0.04, OR: 16.6, CI 95% 1.07-255.64; respectively).

Ankara, Turkey;⁴Department of General Surgery, Ataturk Education and

Conclusion

Research Hospital, Ankara, Turkey;⁵Department of Biostatistics, Yildirim

Baseline serum vitamin D levels are inversely related with thyroid volumes, fT3

Beyazit University Faculty of Medicine, Ankara, Turkey.

and TRAb levels in new-onset Graves disease. In addition to several advantages,

optimization of vitamin D levels would also be beneficial in the surveillance of

Aim

these patients. However larger scale studies are required in order to make further

Atypia/follicular lesion of undetermined significance(AUS/FLUS) is a category

suggestions.

of thyroid cytology with features that are neither definitely benign or malignant.

DOI: 10.1530/endoabs.49.EP1327

We aimed to determine whether specific cytologic or architectural features are

associated with malignancy in AUS/FLUS category of Bethesda system

according to subgroups.

Methods

The specimens of patients who underwent surgery with preoperative thyroid fine

neeedle aspiration (FNA) biopsies of Bethesda Category III (AUS/FLUS) were

reanalyzed. An experienced cytopathologist who blinded to original cytology and

EP1328

final histopathology was reevaluated the specimens and numerated the cytology

A novel mutation in thyroid hormone receptor-beta gene causing

from 1 to 7 according to Bethesda system as follows; Group 1: cells producing

resitance to thyroid hormone in a tunisian female

microfollicles, Group 2: containing predominantly Hurthle cells with rare cells

Ons Rejeb, Melika Chihaoui, Meriem Yazidi, Ibtissem Oueslati,

and colloid, Group 3: difficulty in evaluation of atypia due to smear artifacts,

Fatma Chaker & Hedia Slimane

Group 4: cellular smears containing benign Hurthle cells, Group 5: focal cells

University of Tunis El Manar, Faculty of Medicine of Tunis, La Rabta

with nuclear changes like papillary carcinoma but generally benign appearance,

Hospital, Department of Endocrinology, Tunis, Tunisia.

Group 6: cells with atypic features but generally benign appearance, Group 7: rare

follicular cells with nuclear enlargement and frequently apparent nucleoli.

Results

Introduction

Specimens of one hundred and ninety five patients (153 females, 42 males) with a

The syndrome of resistance to thyroid hormone is a rare inherited disorder

mean age of 47.87G12.18 years were included to the study. Of these 195 patients,

characterized by elevated circulating thyroid hormones, failure to suppress

148 had AUS and 47 had FLUS cytology. Nuclear groove formations are found as

pituitary thyroid stimulating hormone

(TSH) and variable tissue target

higher in malignant group in overall study population and in also AUS subgroup

hyposensitivity to thyroid hormone action. We reported the case of a RTH

(PZ0.005 and PZ0.023, respectively), but not in FLUS subgroup (PZ0.164).

syndrome with a novel mutation.

Nuclear enlargement, overlapping, elongation, inclusions, and papilleroid

Case report

features were similar between malignant and benign groups in all patients,

A 15-year-old girl was investigated for visual hallucinations and behavior

AUS and FLUS subgroups. Furthermore cytologic groups distributions are

disorders. Her medical history was unremarkable except for a learning disability

similar between benign and malignant groups in all patients, and in AUS and

and a hyperactivity disorder in childhood. There was no family history of thyroid

FLUS subgroups (PO0.05, for all).

diseases and she was not taking any regular medication. She was found to have

Conclusion

abnormal thyroid function tests with increased plasma free T₃, free T₄

Patients in Bethesda Category III particularly in AUS subgroup with cytologic

2.51 ng/dl

(reference range:

0.71-1.85 ng/dl) with non-suppressed TSH of

interpretation of nuclear grooves are at higher risk of malignancy and should

7.7 mUI/ml (referance range: 0.12-3.4 mUI/ml). On examination, weight was

undergo surgery.

48 kg, height was 141 cm, blood pressure was normal and pulse rate was 92

DOI: 10.1530/endoabs.49.EP1326

beats/min. She had clinical symptoms of thyroid hormone excess: moist skin,

insomnia and agitation. She had no goiter or dysthyroid eye disease. Repeated

thyroid function tests confirmed previous findings. Thyroid antibodies (anti-

peroxydase and anti-TSH receptor) were negative. The level of TSH a-subunit

was normal 0.54 mUI/ml (range: 0.05-0.9) and the ratio TSH a-subunit/TSH was

less than 1. TSH-secreting tumor was ruled out by normal pituitary magnetic

resonance imaging (MRI). Genetic analysis yielded a novel mutation in the THRb

gene, c.1369 GOA in exon 10, due to a base pair substitution of glutamic acid by

lysine in position 457.

EP1327

Discussion

Relationship between thyroid volume and baseline vitamin D levels in

We reported a novel mutation in the THRb gene that has not been previously

new-onset graves disease

described and discussed the clinical presentation of the thyroid hormone

Gulsah Y Yalin¹, Fuat Cenik², Huseyin Celik¹ & Abdulbaki Kumbasar²

resistance syndrome according to the different mutations.

¹Department of Internal Medicine, Division of Endocrinology and

DOI: 10.1530/endoabs.49.EP1328

Metabolic Diseases, Kanuni Sultan Suleyman Research and Training

Hospital, Istanbul, Turkey;²Kanuni Sultan Suleyman Research and

Training Hospital Department of Internal Medicine, Istanbul, Turkey.

Introduction

Serum 25(OH) vitamin D levels are shown to be significantly lower and

associated with lower remission rates in Graves disease. In this study we aimed to

EP1329

investigate the impact of baseline vitamin D levels on thyroid volume in patients

Succesfull treatment of hyperthyroidism with plasmapheresis

with new-onset Graves disease.

Ozden Ozdemir Baser¹, Derya Koseoglu², Merve Catak¹, Zeynep Cetin¹ &

Materials and methods

Dilek Berker¹

This is a monocenter cross sectional study with a total of 61 new-onset Graves

¹Ankara Numune Education and Research Hospital, Ankara, Turkey;

disease patients (n:61, F: 40, M:21) who were divided into two groups according

²Hitit University Hospital, Corum, Turkey.

to baseline serum vitamin D levels, as Group-1 (D vit !20; n:42) and Group-2 (D

vit R20; n:19). Plasma fT4, fT3, TRAb, TPOAb and PTH levels were analysed

and thyroid volume (ml), isthmus thickness (mm) were measured by the same

Introduction

physician with thyroid ultrasonography at the time of diagnosis for each patient.

Hyperthyroidism is the condition that occurs due to excessive release of thyroid

The results were compared between the two groups. Categorical variables were

hormone by the thyroid gland. Anti-thyroid drugs are usually the first choice of

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

the treatment but surgery and radioactive iodine can also be used in treatment of

method is more reliable for ATG detection and how a result of ‘ATG positive’

hyperthyroidism. Plasmapheresis is a rapid and effective treatment option in cases

actually influences the Tg measurement.

where immediate euthyroidism is needed to be obtained due to complications of

thyrotoxicosis and major side effects of antithyroid drugs.

DOI: 10.1530/endoabs.49.EP1330

Material and method

Between January 2012 and December 2016, we evaluated patients who received

plasmapheresis to provide immediate euthyroidism due to severe hyperthyroid-

ism or side effects of anti-thyroid drugs or urgent non-thyroid surgery were

included to the study.

Results

Eighteen patients were included the study, of whom 11 were female and seven

EP1331

were male. The mean age was 52.44 years. Seven patients had TDG (%38.9), two

patients had TDMNG (%11.1), two patients had TA (%11.1), four patients had

Reference range determination of TSH during the first trimester of

TMNG (%22.2) and one patient had amiodarona induced thyrotoxikosis (%5.6).

pregnancy and the impact of its future implantation in the South

Additionally, plasmapheresis was performed to achieve euthyrodism before non-

area of Seville

Guillermo Martínez de Pinillos Gordillo, Carmen Carretero Marín, José

thyroid surgery in two patients (11.1%). The mean plasmapheresis sessions was

Álvaro Romero Porcel, María del Mar Viloria, María Dolores Hidalgo,

5.22. The mean sessions was 3.62 for patients with TDG and TDMNG, whereas it

Rufina Carrasco, Joaquín Bobillo, Mariana Tomé Fernández-Ladreda &

was 6.43 for patients with TA and TMNG (P:0.029). The decrease of mean fT₄

María Victoria Cózar León

and fT₃ were 48% and 65%, respectively (P!0.0001). Anaphylaxis was seen

Hospital de Valme, Sevilla, Spain.

only in one patient due to fresh frozen plasma. So treatment was changed to

albumin.

Conclusions

Objectives

Although plasmapheresis is not commonly used for the treatment of the

Different scientific societies recommend performing screening for clinical

hypertyroidism, it is a reliable and effective treatment option for patients who can

primary hypothyroidism during the first trimester of pregnancy using local

not use antithyroid drugs or hyperthyroidism can not resolve with these drugs

normality ranges of TSH and just in the lack of these, should the American

before total thyroidectomy, RAI or non thyroid emergency surgery.

population reference levels be used. Our objective is to determinate the reference

DOI: 10.1530/endoabs.49.EP1329

range of TSH during the 1^st trimester of pregnancy in our healthcare area and the

impact of its implantation.

Material and methods

Prospective study where women selected had no history of thyroid pathology nor

where taking any drugs that may disrupt thyroid function. TSH, FT4 and anti-

thyroid antibodies (TPOab, TGab, TRab) were determined between week 9 and

11. TSH O5 mU/ml, positive thyroid autoimmunity or any condition that may

EP1330

interfere were excluded

(final nZ282). Reference levels were defined by

Measurement of anti-thyroglobulin antibodies, a matter of equipment?

calculating the confidence interval between p2.5 and p97.5 of the distribution.

Ricardo Capita˜o1, Susana Prazeres2, Ana Font2, Conceição Godinho3,

Tests for hypothyroidism screening in the last two years were reviewed and

Isaura Rodrigues³, Frederico Cerveira⁴, Grac¸a Belo1, João Viana1 &

variations on the diagnosis of hypothyroidism depending on the TSH reference

Deolinda Madureira⁵

level used was analysed.

¹Hospital Egas MonizCentro Hospitalar Lisboa Ocidental, Lisboa, Portugal;

Results

²Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa,

New local reference level for the 1^st trimester: TSH 0.17-4.39 mU/ml; T4L 0.97-

Portugal;³Centro Hospitalar Lisboa Central, Lisboa, Portugal;⁴Centro

1.88 ng/dl. Screening tests in the last 2 years (1/12/2014 to 30/11/2016) nZ6032.

Hospitalar do Baixo Vouga, Aveiro, Portugal;⁵Sociedade Portuguesa de

Diagnosis of hypothyroidism using American standard reference levels (TSHO

Endocrinologia Diabetes e Metabolismo, Lisboa, Portugal.

2.5 mU/ml):

35.8% (2181

women). Diagnosis of hypothyroidism with our

reference levels (TSH O4.39 mU/ml): 8,6% (524 women). Total number of TSH

R 10 mU/ml: 0.6% (37 women).

Introduction

Conclusions

The presence of anti-thyroglobulin antibodies (ATG) can induce falsely lower

Reference levels for TSH in our study are similar to others in different Spanish

thyroglobulin

(Tg) values. The methods characteristics used for ATG

areas and differ significantly from the American reference range, those standard

measurement vary according to the equipment/reagent used. ATG at our centre

ranges imply an unacceptable rate of diagnosis of hypothyroidism (one out of

is measured by Unicap.

three women), even more if a universal screening strategy is carried out.

Objective

Determination and implementation of locally assessed reference levels would

To assess if patients with negative ATG by Unicap^w have different results with

avoid overdiagnosis, unnecessary treatment and follow-up.

other equipment.

Methods

DOI: 10.1530/endoabs.49.EP1331

A cross-sectional retrospective study was conducted in February-March of 2016,

in which blood samples from patients followed at our Centre, with negative ATG,

were selected and separated into three groups: 1) differentiated thyroid carcinoma

(DTC), total thyroidectomy, Tg!0.2 ng/ml; 2) without DTC and positive TPO;

3) without DTC and negative TPO. ATGs were measured by Immulite^w, Cobas^w,

Architect^w and Advia^w. ATG’s classification was based on the cut-off of each

manufacturer. Q-Chrocan test was used to calculate the p-values (P!0.05 were

considered statistically significant).

EP1332

Results

Iodine content of iodized salt in Spain

A total of 141 samples were analysed. The results are described in the table

Vanessa Arosa¹, Maider Sánchez Goitia¹, Mercedes Espada^2,9,

below: high significant differences were found between the various methods in all

Luis Irigoyen¹, Gonzalo Maldonado¹, Juan José Arrizabalaga^1,9,

groups. The Architect and the Immulite had the highest and lowest rate of ATG

Piedad Santiago^3,9, María Orosia^4,9, Edelmiro Menéndez^5,9, Lluís Vila^6,9,

positives, respectively, compared to Unicap.

Silvia Wengrowicz^7,9 & Sergio Donnay^8,9

Discussion

¹Endocrinology and Nutrition Department, Hospital Universitario Araba,

ATG results depend on the equipment used. This can influence the follow-up

Vitoria-Gasteiz, Spain;²Unidad de Química Clínica, Laboratorio Normativo

strategy of patients with DTC. These results also raise the question of which

de Salud Pública, Departamento de Sanidad y Consumo del Gobierno

Vasco, Derio, Spain;³Endocrinology and Nutrition Department, Complejo

Hospitalario de Jaén, Jaén, Spain;⁴Endocrinology and Nutrition Depart-

Table 1

ment, Hospital Royo Villanova, Zaragoza, Spain;⁵Endocrinology and

Positive ATG

Q test

Nutrition Department, Hospital Central de Asturias, Oviedo, Spain;

⁶Endocrinology and Nutrition Department, Hospital de Sant Joan Despí

Group

N Unicap Immulite Cobas Architect

Advia

c²

Moisès Broggi, Sant Joan Despí, Spain;⁷Instituto Catalán de Endocrino-

(A) DTCC/Tg!0.2

(1%)

(3%)

(26%)

(7%)

70.0

!0.001

logía, Barcelona, Spain;⁸Endocrinology and Nutrition Department,

(B) DTCK/TPOC

(7%)

(29%)

(93%)

(39%)

67.2

!0.001

Fundación Hospital Alcorcón, Alcorcón, Spain;⁹Área de Conocimiento del

(4%)

(24%)

(8%)

17.7

0.001

Tiroides de la Sociedad Espan˜ola de Endocrinología y Nutrición, Madrid,

Total

141

(2%)

(9%)

(39%)

(14%)

152.7

!0.001

Spain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction

Optimization of iodine intake aims to prevent the irreversible damage that iodine

deficiency (ID) can cause in the central nervous system during its development,

as well as thyroid disorders that can be induced by both ID and excessive

micronutrient intake. The Spanish legal regulation stipulates that iodized salt (IS)

must contain 60 mg of iodine per kg of salt (60 ppm), allowing a tolerance of

G15%. The aim of this study is to address the iodine content of different

commercially available IS in Spain.

Methods

Reference

162 different IS lots from 51 different product presentations were collected from

1) van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJ, Brouwer E,

Spanish food stores in Andalusia, Aragon, Asturias, Balearic Islands, Catalonia,

Codreanu C, Combe B, et al. EULAR definition of arthralgia suspicious for

Madrid and Basque Country between 2014 and 2016. Iodine concentration in

progression to rheumatoid arthritis. Annals of the Rheumatic Diseases. 2016

these samples was assessed by HDL-chromatography (HPLC).

October 6.

Results

2) Radu L, Groppa L, Vudu L. Musculoskeletal impairement in primary

The mean (S.D.) and median (P25-P75) iodine concentration for these 162

hypothyroidism. Rev Med Chir Soc Med Nat Iasi. 2016 April-June; 120 244-251.

samples was 61.2

(19.7) and

(50-70) mg I/g salt, respectively. Iodine

3) Jorge Cárdenas Roldán, Jenny Amaya-Amaya, Juan Castellanos-de la Hoz,

concentration dispersion was mainly attributable to iodide-fortified IS (nZ67).

et al., Autoimmune thyroid disease in rheumatoid arthritis: a global perspective,

The analysis of these fortified IS revealed that 67.2% of them had iodine levels

Arthritis, 2012. doi:10.1155/2012/864907

out of the legal threshold (51-69 mg I/g salt), whereas only 43.2% of the iodate-

4) Amr H Sawalha, Susan Kovats. Dehydroepiandrosterone in systemic lupus

fortified IS (nZ95) were outside this limit (P!0.05).

erythematosus. Current Rheumatology Reports. 2008 August 10 286-291.

Conclusions

5) Ernestam S1, Hafstrom I, Werner S, Carlstrom K, Tengstrand B. Increased

IS, having an average 60 mg I/g salt, is an important alimentary source of iodine in

DHEAS levels in patients with rheumatoid arthritis after treatment with tumor

Spain. The use of iodate instead of iodide for the fortification of the salt allows a

necrosis factor antagonists: evidence for improved adrenal function. Journal of

greater proportion of IS with iodine concentration within the legal limits. Public

Rheumatology. 2007 July; 34 1451-1458.

Health and Consumer Affairs authorities should closely monitor IS production

processes and eventually check IS sale points in order to homogenize the iodine

content of commercially available IS packages and thereby optimize their intake

DOI: 10.1530/endoabs.49.EP1333

by the population.

DOI: 10.1530/endoabs.49.EP1332

EP1334

A thyroid storm in a context of diabetic ketoacidosis: case report

Ghizlane El Mghari, Loubna Oukit & Nawal El Ansari

Endocrinology Department, CHU Mohammed VI, Marrakesh, Morocco.

EP1333

Low DHEAS levels predict rheumatism in primary hypothyroidism:

preliminary data from tertiary hospital

Introduction

Ravindra Shukla, Praveen Sharma, Vikram Singh & Gopal Vohra

The association of a thyroid storm and diabetes ketoacidosis is relatively rare.

AIIMS, Jodhpur, Jodhpur, India.

We report two cases.

Observations

The first one is a 20 years old woman, with no history of diabetes, who came with

Introduction

ketoacidosis, a history of non medicated thyrotoxicosis, and she was complaining

DHEAS is weak androgen with specific role in human physiology illdefined.

about fever, a thyrotoxicosis syndrome, a vascular goiter, and exophtalmos. Her

Various studies have implicated role of DHEAS in autoimmune arthritis

general condition had improved significantly after the treatment in emergency and

including SLE and RA. Recently EULAR consensus statement has approved

under maintenance therapy. The second one is a 54 years old female, with a case

CSA (clinically significant arthralgia) for incipient RA.

of diabetes mellitus, who presented a ketoacidosis. But despite the control of this

Methods and material

situation, the patient’s consciousness level became disturbed and she presented

34 follow up patients of primary hypothyroidism rated their symptom score on

hyperthermia. The thyroid function tests revealed hyperthyroidism. Thus, thyroid

CSA (clinically suspect arthralgia) as given by EULAR(1) Their DHEAS levels

storm was evocated and managed. The patient finally passed away despite the

were divided into quartiles while CSA was graded from 100 sensitivity (when one

prompt medical care.

component is positive) to 100 specificity (when all seven component are positive).

Discussion

Kendal tau test of correlation was run using SPSS 21. ROC curve for DHEAS to

In these two cases, a thyroid storm, associated with Graves’ disease covered by

predict at least one symptom of CSA was run. SPSS version 20 used for analysis.

diabetic ketoacidosis was the final diagnostic. Thereby, for patients having

Results

diabetic ketoacidosis one should seek an eventual thyroid storm, and vice versa:

Anti TPO Ab were available for 19 subjects, out of which 16 were Anti TPO AbC.

in fact, there are some symptoms in common. But there are scores to help

25(OH) vitamin D levels were available for only seven patients hence excluded

systematize the diagnosis. The management is controlled, acutely based on

from analysis. Kendal’s tau correlation test yieldedstrong negative correlation

antithyroid drugs in high doses, betablockers and corticosteroids. We should not

between DHEAS levels at the time of presentation and CSA score.{P!0.01;

disregard the search for and treatment of precipitating factors: ketoacidosis in our

r K0.512}.

cases. And identify the thyroid underlying disease: most commonly Graves’

Discussion

disease.

This the first study evaluating role of DHEAS in rheumatism of primary

DOI: 10.1530/endoabs.49.EP1334

hypothyroidism. Musculoskeletal abnormalities arecommon in primary auto-

immune thyroid disease (AITD); 2) AITD is also associated with rheumatoid

arthritis

(RA); 3) There has been recent acknowledgement of role of local

androgen in molecular pathogenesis of autoimmune arthritis; 4) We found inverse

correlation between serum DHEAS and rheumatism. The serum DHEAS levels

seemed to predict grade of rheumatism in these patients. The finding and strength

of association is significant and opens further avenues for research regarding role

EP1335

of DHEAS in musculoskeletal manifestations of AITD. DHEAS supplementation

Hyalinizing trabecular adenoma of the thyroid

has been evaluated in SLE (4) but not in hypothyroidism. Although association

Ozen Oz Gul¹, Soner Cander¹, Pinar Sisman² & Canan Ersoy¹

between Rheumatoid arthritis (RA) and DHEAS is not well defined, improvement

¹Uludag University Medical School, Department of Endocrinology and

in RA is associated with increase in DHEAS levels

(5) Does DHEAS

Metabolism, Bursa, Turkey;²Kars State Hospital, Department of

supplementation early in RA or pre -RA alters its natural history, in background

Endocrinology and Metabolism, Kars, Turkey.

of hypothyroidism? Well designed studies are needed.

Conclusion

Introduction

Rheumatism as evaluated by CSA criteria bears strong inverse correlation with

Hyalinizing trabecular adenomas (HTA) of the thyroid gland is a rare neoplasm of

DHEAS. Further trials examining role of DHEAS in such group of patients can be

follicular cell origin. HTA can be present as a thyroid nodule or incidental finding

explored.

in a thyroidectomy specimen. HTA is generally accepted to be a benign tumor,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

but their cytological features can be similar to those of papillary thyroid

autoimmune mechanism leading to absolute insulin deficiency. In patients

carcinoma (PTC).

with an autoimmune endocrine disease, there is a high risk of development of

Case report

another autoimmune endocrine disorder. The purpose of our work is to assess the

A 59 year old woman, who had cholangiocellular carcinoma, admitted to our

prevalence of thyroid autoimmunity among our LADA patients.

institution with a solitary thyroid nodule and cervical lymphadenopathy. Fine

Patients and methods

needle aspiration biopsy of the cervical lymphadenopathy revealed suspicious for

Our study has included 17 patients followed for LADA. Thyroid status and

carcinoma metastasis. Her serum free thyroxine (fT₄), free triiodothyronine (fT₃)

thyroid autoimmunity were ordered in all patients.

and TSH levels are 1.42 ng/dl, 2.82 pg/ml, and 0.486 mIU/ml. Ultrasonography

Results

of the thyroid gland showed a 1.4 cm sized, regularly marginated, hypoechoic,

The mean age of patients was 46.7 years and the mean age of discovery was 40.5

calcified thyroid nodule. Fine needle aspiration biopsy of the thyroid nodule

years. The sex ratio was 1.4 with a female predominance. The average BMI was

revealed suspicious for PTC. Total thyroidectomy were perfomed. The final

24.5 kg/m². The TPO antibodies were positive in five of our patients (29.4% of

pathology was 1.0-cm sized hyalinizing trabecular adenoma. Histologically, the

cases), including four women. The rate of anti-GAD antibodies was higher in the

tumor showed tumor cells arranged in trabeculae and a prominent hyaline stroma.

LADA group with positive anti TPO antibody compared to the group with

The neoplastic cells were focally immunoreactive for thyroglobulin and negative

negative anti TPO (345.6 mUI/l vs. 250.4 mUI/l).

for calcitonin and chromogranin. After surgery L-thyroxine replacement therapy

Discussion

was started. Cervical metastasis was thought to be associated with cholangio-

The prevalence of thyroid antibodies in patients with LADA varies between 20

cellular carcinoma. The patient referred to the Oncology department for the

and 30%. The association has been explained by the sharing of a common genetic

treatment of metastatic cholangiocellular carcinoma.

material, but also by a deficit in the immune regulation or a poor ability to develop

Conclusion

tolerance to auto antigens.

Ultrasonografic features of HTA similar to malign thyroid lesions and frequently

Conclusion

misdiagnosed as papillary carcinoma on fine-niddle aspiration cytology. The most

Thyroid autoimmunity is frequently observed in LADA diabetes, identifying a

recent and controversial debate surrounding HTA concerns its potentially

particular phenotype of patients with higher titer of anti GAD antibodies, and

malignant behavior and the possible relationship to PTC. Although cases of

eventually, a poor glycemic control where the interest of its systematic screening.

malignant HTA have been recorded, HTA should be considered a benign

DOI: 10.1530/endoabs.49.EP1337

neoplasm or, at most, a neoplasm of extremely low malignant potential. In this

report we present and discuss an unusual case of a patient who had a hyalinizing

trabecular adenoma and cholangiocellular carcinoma.

DOI: 10.1530/endoabs.49.EP1335

EP1336

Amiodaron induced hyperthyreosis and recurrent ventricular

tachycardia

Roman Kołodziejczak¹, Alicja Łuczyn´ska-Kołodziejczak1 &

Anhelli Syrenicz²

EP1338

¹Ragional Hospital, Gorzow Wlkp., Poland;²Pomeranian Medical

Thyroid and metabolic disorders in patient with kidney injury

University, Szczecin, Poland.

undergoing renal biopsy

Joanna Sztembis, Aneta Kołodziej-Kł

˛k, Agnieszka Gala-Bł

˛dzin´ska &

Grzegorz S´ wider

52 years old man medicated with amiodaron

12 months, with laboratory

Department of Internal Medicine, Nephrology and Endocrinology,

confirmed hyperthyroidism, in us-examination 45 ml Basedow goiter, TRAb

St. Queen Jadwiga Clinical Hospital No. 2, Rzeszow, Poland, Rzeszow,

positive; ventricular tachycardia 180/min intermittent with sinusal tachycardia

Poland.

120/min, thiamasol 120 mg i.v./daily, hydrocortisone 400 i.v. daily, crystalloids,

beta blockers, diazepam, albumin. J131

scintigraphy

- no iodine uptake.

natriumperchlorate 1500 mg daily initially, continued next month 900 mg coused

There are a several known interactions between kidney functions, thyroid and

iodine uptake 17%. Finally -radioiodine 20 mCi, followed with thiamazole and

metabolic balance. Hypothyroidism is associated with reduced GFR and

steroids. After

weeks

- euthyroid.

years old woman after many

hyperthyroidism results in increased GFR and increased RAA activation. Chronic

hospitalizations because of ventricular tachycardia. Clinical, ultrasound and

kidney disease is characterized by low T3

syndrome, increased primary

laboratory parameters of Basedow disease. Medication: thiamasole, cortisone and

hypothyroidism and subclinical hypothyroidism. The hyperthyroidism increases

Irenat prepared to the radioiodine therapy. After three times of 20 mCi I131

CKD progression while hypothyroid state lowers it. Proteinuria, especially in

hypothyroid, 100 mg thyroxin. 48 years old man with hypertrophic cardiomio-

nephrotic syndrome, often results in urinary loss of thyroid hormones bound to the

pathy, after over 6 months use of amiodaron lack of effect and recidive of

various binding proteins which results in reduction in the serum total thyroid

ventricular tachycardia. Lab. - thyreotoxicosis, in ultrasound left lobe tumor 27

hormone levels. Isolated cases of hyperthyroidism have been associated with

ml, biopsy benign. Initially cured with thiamazole 60 mg, followed with irenat

tubulointerstitial nephritis. Thyroid dysfunction is also associated with

900 mg daily and after iodine uptake recurrence

-20mCi radioiodine

131,

glomerulonephritis by a common autoimmune etiology. There are known several

euthyreosis after 3 months.

mechanisms like the presence of circulating immune complex among patients

Cases demonstrate problematic situation of amiodaron cured patients, thyroid

with thyroid disease, the association of Hashimoto’s thyroiditis and membranous

dysfunction may occur during amiodaron therapy and in some patients is

nephropathy with immune complex deposition in the glomerular as well as

dangerous. Hyperthyroidism is difficult to cure if caused by amiodaron but in this

thyroid epithelial basement membrane. There is also common occurrence of

patients should be radical, it is necessary to have available perchlorat for this

thyroid and renal disease in association with other autoimmune diseases such as

cases and rodioiodine therapy.

type 1 diabetes mellitus. We retrospectively analyzed the data (thyroid function,

DOI: 10.1530/endoabs.49.EP1336

metabolic syndrome occurrence, type of diabetes) of 126 patient hospitalized in

our clinic from 2013 to 2016 who underwent renal biopsy (52 women, 62 men and

6 children). The most common indications for renal biopsy were nephrotic

syndrome in 47 patients

(37.3%), non-nephrotic proteinuria in

31 patients

(24.6%), worsening renal function in

22 patients

(17.5%), coexistence of

proteinuria with hematuria in 16 patients (12.7%), nephritic syndrome in 9

EP1337

patients (7.1%) as well as an isolated hematuria in 1 patient (0.8%). Membranous

Autoimmune thyroiditis in patients with latent autoimmune diabetes of

glomerulonephritis was the most common histological diagnosis observed in

adults (LADA)

biopsies, and was diagnosed in 19 patients (15.1%). Our analysis proved higher

El Ansari Nawal, Fatima Zahra Zaher & Ghizlane Elmghari

occurrence of hypothyroidism

(8.7%), hyperthyroidism

(2.38%) and goiter

Department of Endocrinology, Diabetes, Metabolic Diseases and Nutrition,

(3.17%) in comparison to general population. Interestingly there was no higher

Mohammed VI University Hospital, Marrakesh, Morocco.

occurrence of obesity and overweight (40.4%) and type 1 and 2 diabetes, but

many patient had steroid-induced diabetes (16%). It is important to monitor every

Introduction

patient with renal dysfunction due to higher prevalence of thyroid pathology.

Latent autoimmune diabetes in adults

(LADA) is an endocrine disorder

DOI: 10.1530/endoabs.49.EP1338

characterized by a progressive destruction of pancreatic beta cells by an

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1339

relative contribution of each nosological entity. Nevertheless, the clinical

presentation, the EMG and the prompt response to levothyroxine, favor

Reversible thyrotoxic pulmonary hypertension with heart failure:

hypothyroidism as the main cause.

2 cases

Aftab Khattak¹, Eleanor Wong¹, George Mak¹ & James A O’Hare^1,2

DOI: 10.1530/endoabs.49.EP1340

¹University Hospital Limerick, Limerick, Ireland;²University of Limerick,

Limerick, Ireland.

Introduction

Heart failure is a complication of thyrotoxicosis. We present 2 unusual cases

presenting with pulmonary hypertension with isolated right heart failure that

reversed after treatment.

Case description

EP1341

Case 1: A 55-year-old man presented with weight loss, dyspnoea and leg

Is Levothyroxine requirement the same for tablet and soft gel

swelling. HR: atrial fibrillation

51/min. He had a raised JVP, tricuspid

formulation in postsurgical hypothyroidism?

regurgitation and severe pitting oedema. Pro-BNP:

4995 pg/ml, TSH:

Vincenzo Di Donna¹, Rosa Maria Paragliola¹, Chiara De Waure²,

0.06 mU/l, FT4:

54.1 pmol/l, FT3:10.5 pmol/l. TSH receptor antibodies

Annapina De Rosa¹, Giampaolo Papi¹, Alfredo Pontecorvi¹ &

(TRAb) were positive. CTPA: no pulmonary embolism. Echo: PAP 45 mmHg,

Salvatore Maria Corsello¹

LVEF preserved. Carbimazole, diuretics, ACE inhibitors and Apixaban were

¹Endocrinology, Università Cattolica del Sacro Cuore, Rome, Italy;

commenced. Right heart catheterization showed non-obstructive coronary artery

²Institute of Public Health, Università Cattolica del Sacro Cuore, Rome,

disease and pulmonary hypertension. Repeat ECHO 7 months later revealed

Italy.

normal right heart pressure and size when euthyroid. Tricuspid regurgitation and

Pulmonary Hypertension were resolved.

Background

Case 2: A 34-year-old male presented with oedema, elevated JVP, tricuspid

In a previous publication we identified the major predictive factors of

regurgitation and atrial fibrillation. Pro-BNP: 2064 pg/ml TSH: 0.05 mU/l, Free

levothyroxine (LT₄) requirement and proposed an efficient nomogram to calculate

T4: 72.6 pmol/l, TRAb positive. CTPA negative for PE. ECHO: PAP 60 mmHg.

LT₄ substitutive starting dose after total thyroidectomy for benign disease. The

Right cardiac catheterisation when euthyroid demonstrated a RVSP of 32 mm Hg,

aim of this study was to assess whether the LT₄ requirement differs between the

pulmonary artery systolic pressure of

27 mmHg and a wedge pressure of

tablet and the soft gel capsules formulations.

14 mmHg indicating a resolution of his RHF.

Methods

Learning point

One hundred and three consecutive patients submitted to total thyroidectomy for

Selective right heart failure may occur in thyrotoxicosis perhaps due to altered

benign disease and were receiving substitutive therapy with LT₄ were enrolled.

metabolism of pulmonary vasodilators resulting in raised pulmonary vascular

All patients received the LT₄ tablet formulation. The specific substitutive starting

resistance.

dose was calculated using the previously described nomogram and was aimed at

DOI: 10.1530/endoabs.49.EP1339

achieving normal TSH levels

(0.4-2.5 mU/L). Exclusion criteria were:

malignancy at histological examination, symptoms or signs of malabsorption,

assumption of drugs or habits interfering with LT₄ absorption, impaired renal

function, pregnancy, poor compliance with drug administration. TSH, FT₄, and

FT₃ were assessed three months after the switch from tablet to soft gel capsule

formulation at the same dose of LT_4. Mean and standard deviation (SD) were used

for quantitative variables. The paired t-test was applied in order to compare the

thyroid function tests with different formulations of LT₄.

Results

Serum TSH was significantly lower during treatment with soft gel capsules

EP1340

[1.3 mU/L (SD 0.9) and 1.8 mU/L (SD 1.2) respectively, PZ0.02]. There were no

Peripheral neuropathy in hypothyroidism - about a clinical case

statistically significant differences for FT₃ and FT₄.

José Marçalo, Alexandra Araújo, Carolina Faria, Ana Wessling,

Conclusions

Maria Raquel Carvalho, Ema Nobre & Maria João Bugalho

Levothyroxine substitutive dose is not significantly different between soft gel

Hospital de Santa Maria, Lisbon, Portugal.

capsules and tablets in patients without malabsorption but TSH is significantly

lower with the first one. This datum must be considered in clinical practice,

particularly for patients with TSH at limits of the therapeutic range or if a strict

Introduction

Hypothyroidism can affect the nervous system, commonly causing mono and

therapeutic goal is needed.

polyneuropathies which show a variable frequency and pattern. Its mechanisms

DOI: 10.1530/endoabs.49.EP1341

are not fully understood. Symptoms usually correlate better with the duration of

the dysfunction rather than with its severity and typically improve significantly

after medical therapy.

Case report

A 58-year-old woman was admitted at our hospital with a one-year history of

progressive weakness of both lower extremities, more evident on her left limb.

The patient reported a

20-year history of hypothyroidism medicated with

levothyroxine 25mcg id and type 2 diabetes medicated with metformin 1000mg

EP1342

bid, without proper follow-up. She denied other relevant long-term medication or

addictions. Fifteen days prior to admission, she was paraparetic and had lost her

Immune reaction to food antigens in Graves’disease (GD) patients:

ability to walk. No other relevant personal or familial medical history was found.

role of gliadin and other food antigens

Neurological examination showed painless sensorimotor polyneuropathy and

Danila Covelli¹, Giuseppe Colucci¹, Mario Salvi¹, Ulrike Kaiser²,

lower muscular strength on both legs. Laboratory results revealed hypothyroid-

Anja Eckstein², Maria Cristina Burlacu³, Chantal Daumerie³, Gez Richell⁴,

Petros Perros⁴, Mohd Shazli Draman⁵, Marian Ludgate⁵, Giulia Masetti⁶ &

ism: TSH 37.1mU/L and FT4 0.5ng/dl. Serologic studies were negative and

Filippo Biscarini⁶

B12-deficiency was excluded, as well as other common causes of peripheral

¹Graves’ Orbitopathy Centre, Endocrinology, Fondazione IRCCS Cà

neuropathy. Lumbar MRI did not show spinal cord compression and

Granda, and University of Milan, Milan, Italy;²Center for Ophthalmology

cerebrospinal fluid analysis was inconclusive. Bilateral carpal tunnel syndrome

University Clinic, Essen, Germany;³Médecin spécialiste hospitalier Service

and sensorimotor polyneuropathy, without criteria of Guillain-Barré syndrome,

d’Endocrinologie, Diabétologie et Nutrition Cliniques universitaires St-Luc

were found on electromyography

(EMG). Furthermore, myopathic aspects

(UCL), Bruxelles, Belgium;⁴Diabetes & Endocrine Royal Victoria

compatible with muscular necrosis were detected, despite normal creatine kinase

Infirmary, Newcastle Upon Tyne, UK;⁵Division of Infection and Immunity

levels. Few weeks after progressively increasing levothyroxine dose, laboratory

School of Medicine, Cardiff University, Cardiff, UK;⁶PTP Science Park,

studies showed: TSH 10.2mU/L, FT4 1.27ng/dl, Anti-TPO 66U/mL. Unsatisfac-

Lodi, Italy.

torily controlled hyperglycemia persisted (HbA1c 10.2%). Paraparesis signi-

ficantly improved and sensorimotor dysfunction subsided.

Conclusion

As known, an imbalance of the gut microbiota is associated with a higher risk for

In general, sensorimotor peripheral neuropathy is common in diabetes and

autoimmune diseases. Moreover the increased rates of autoimmunity reported in

occasional in hypothyroidism. In the described case, it is difficult to ascertain the

urban residential areas worldwide suggest a possible influence of diet. We report

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

on the antibody response to food antigens in GD patients. Since 10% of celiac

Methods

patients develop an autoimmune thyreopathy we focused on gliadin (DGP),

The primary method used for the analysis of QoL was the own orginal combined

transglutaminases

(tTG) and

other food antigens

(FA). Commercially

questionnaire. Statistical methods from Excel

2010

were used in results

available ELISA assays were performed according to the manufacturer’s

evaluation.

instructions. 105 and 108 sera from 5 European endocrine centres have been

Results

tested for IgG and IgA to tTG and DGP. Results have been compared to

There were 214 patients in the examined group: 34 patients with hyperthyreosis

epidemiological data. 71 sera have also been tested for IgG to FA and compared

(10 men, 24 women) - group A, and 180 patients with hyperthyreosis (25 men,

to 25 healthy controls. 6 out of 105 sera (5.7%) showed positive tTG; 16 and 7

155 women) - group B. QoL was evaluated on numeric scales from 0 - the worst

out of 108 (15 and 6.5%) positive DGP-IgA and IgG, respectively; a higher

to 10 - the best. Present level of QoL was 6.4 vs 7.25, when in the time of

prevalence compared to the worldwide prevalence of celiac disease (1%) (chi-

diagnosis it was 4.6 vs 6.0, in the time without disease - 7.6 vs 8.3 and in the time

squared test; p-value ! 0.001). Prevalence of smokers and ocular involvement

excellent health - 8.0 vs 9.2. The average duration of disease was 6.5 vs 11.30

was not higher in patients with positive sera compared to negative. 23 out of 71

years and the duration of symptoms before diagnosis was 0.74 vs 0.99 years.

(32.3%) GD sera showed sensitivity against a food antigens, compared to 25% (6

Patients were very satisfied with the level of information about their disease: 4.6

out of 24) positive results among healthy controls (chi-squared test; P-valueZ

vs 4.3, with medical care - 4.8 vs 4.7 and with nursing care4.8 vs 4.7 (1- the worst,

0.4). Interestingly, some antigens (cow’s milk, egg white, wheat, yeast) are more

5- the best). Disability of work was 0.8 vs 4.9 days in employed patients (19 in

frequently positive than others. The distribution of antibodies against TSH

group a and 79 in group B) per year. Patients visited endocrinologic outpatients

receptor

(TRAb) values was not different in positive or negative sera. In

department 5.1 vs 2.2 times per year. Willingness to pay was 55 vs 48 V

conclusion, the prevalence of positive tTG antibodies is higher in GD patients

per month.

than worldwide. Even though autoantibodies to DGP and tTG were equally

Conclusions

distributed between all 5 centres we observed the highest percentage of positive

Hyperthyreosis and hypothyreosis had a significant impact on patients’s QoL

responses to other food antigens in Cardiff, suggesting that diet may contribute to

mostly hyperthyreosis. There are a significant differences in duration of disease

the increased sensitivity. More studies are needed to confirm these data.

and symptoms, disability of work and professional visits - hyperthyreosis had

DOI: 10.1530/endoabs.49.EP1342

greater impact. Information about the disease, evaluation of medical and nursing

care and willingness to pay had no statistical differences.

DOI: 10.1530/endoabs.49.EP1344

EP1343

Neutrophil/lymphocyte (N/L) ratio should not be used as an indicator of

inflammation in hyperthyroid patients

Murat Dagdeviren¹, Tolga Akkan², Dilek Celiker², Serdar Karakaya²,

Derun Taner Ertugrul¹ & Mustafa Altay¹

¹Kecioren Education and Research Hospital, Endocrinology and Metab-

olism, Ankara, Turkey;²Kecioren Education and Research Hospital,

EP1345

Internal Medicine, Ankara, Turkey.

Broken heart by thyroid? A rare case of Graves’ disease associated to

Takotsubo cardiomiopathy

Introduction

Georgiana Constantinescu^1,2, Carmen Plesoianu^1,3, Cezara Raileanu^1,3,

Neutrophil/lymphocyte

(N/L) ratio is considered as a sign of systemic

Iuliana Ardeleanu^1,3, Mihaela Negru², George Zmau^1,2,

inflammation in recent years. In our study, we aimed to investigate N/L ratio in

Catalina Arsenescu-Georgescu^1,3 & Carmen Vulpoi^1,2

hyperthyroid patients and healthy control group.

¹Gr. T Popa University, Iasi, Romania;²Saint Spiridon Clinical Hospital,

Material & methods

Iasi, Romania;³Prof. Dr. George Georgescu Institute for Cardiovascular

A total of 121 hyperthyroid patients (71 patients with Graves’ disease and 50

Disease, Iasi, Romania.

patients with other causes of hyperthyroidism) and 40 healthy volunteers were

enrolled. Complete blood count was obtained from both group and thyroid

Introduction

function tests were obtained from hyperthyroid patients.

Takotsubo disease is a non-ischemic, reversible form of cardiomyopathy,

Results

triggered by intense emotional or physical stress. Characterized by normal

There was no significant difference between hyperthyroid patients and control

coronaries and a particular ventricular contraction, it is also known as ‘apical

group in terms of gender, leukocyte and lymphocyte count. There was a

ballooning syndrome’. Thyrotoxicosis, especially Graves’ disease, has been

statistically significant difference between groups in terms of neutrophil count and

associated with Takotsubo cardiomyopathy.

N/L ratio (PZ0.003 and P!0.001). Surprisingly, neutrophil count and N/L ratio

Case report

were significantly lower in Graves’ patients. We also find a significant negative

We report the coexistence of Takotsubo cardiomyopathy in a 37 year old female

correlation between serum free T3 levels and neutrophil count

(rZK0.28,

patient presenting with thyroid storm secondary to untreated Graves’ disease.

PZ0.01).

Addressed to the emergency unit with suspicion of acute coronary syndrome,

Conclusion

signs of lateral inferior apical ST-segment elevation were noticed on the ECG. At

N/L ratio was lower in Graves’ patients than in the control group. Slowing of

clinical examination: pale wet teguments, tachycardia, visible goiter and bilateral

granulopoiesis, shortening of the life span of circulating neutrophils, and the

exophtalmia. According to the Burch Wartofsky criteria for thyrotoxicosis the

development of anti-neutrophilic antibodies in autoimmune thyroid diseases may

patient had a score of 70, highly suggestive for thyreotoxic crisis, sustained by the

be responsible for this condition. N/L ratio should not be used as an indicator of

biological data (high free T4 5.27 ng/dl and free T3 7.47 pg/ml levels with

inflammation in hyperthyroid patients.

inhibited TSH

0.008 uUI/ml). She also associated anemia, inflammatory

DOI: 10.1530/endoabs.49.EP1343

syndrome and important hepatocytolisis. Echocardiographic she presented a

severely impaired left ventricular systolic function (ejection fraction 15%) with

apical ballooning and elevated left ventricular end diastolic pressure. Coronary

angiography revealed non-obstructive coronary atheroma. The final diagnosis of

Takotsubo cardiomyopathy was made on the basis of cardiac computer

EP1344

tomography. At the 7 weeks follow up, under antithyroid drugs there was an

improvement of thyroid hormone levels. Moreover, consistent with Takotsubo

Quality of life in patients with hyperthyreosis and hypothyreosis in

cardiomyopathy, at re-evaluation there was a cardiac function recovery with

slovak republic

normal ejection fraction (66%).

Jan Bielik¹, Emilia Slavikova² & Vladimir Melus¹

Conclusions

¹Trencin University of Alexander Dubcek, Trencin, Slovakia;

Thyrotoxicosis is associated with multiple implications in cardiovascular system.

²Faculty Hospital Trencin, Trencin, Slovakia.

Pathologically high levels of thyroid hormones cause exaggerated chronotropic

and inotropic response to cathecolaminee. One possible explanation could be the

Objectives

upregulation of beta adrenergic receptors by thyroid hormones in many tissues,

The prevalence of thyreoid diseases eg hyperthyreosis and hypothyreosis in

including cardiac.

Slovak Republic is about 240 000 patients. The objective of this study was to find

DOI: 10.1530/endoabs.49.EP1345

out the level of quality of life (QoL) in patients and other relevant characteristics

of diseaseas.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1346

Conclusion

Decrease in the disulfide/thiol ratio after levothyroxine sodium treatment in

The association of gene polymorphisms with the clinical outcome of

hypothyroidism may suggests that treatment plays a role in reducing both

Graves’ disease

oxidative stress and free radical mediated damage to the functional groups of

Dalia Dauksiene¹, Narseta Mickuviene² & Albertas Dauksa³

proteins. Thus, it may be possible to avoid the complications caused by oxidative

¹Institute of Endocrinology, Medical Academy, Lithuanian University of

stress. As a result disulfide/thiol ratio may contribute to the management of

Health Sciences, Kaunas, Lithuania;²Behavioral Medicine Institute,

treatment in hypothyroid patients.

Medical Academy, Lithuanian University of Health Sciences, Palanga,

Lithuania;³Institute for Digestive Research, Medical Academy, Lithuanian

DOI: 10.1530/endoabs.49.EP1347

University of Health Sciences, Kaunas, Lithuania.

The aim

Of this study was to investigate the association between two common CTLA-4

gene SNPs (49A/G in exon 1 and CT60 A/G in 3’UTR) and Graves’ disease

outcome in Lithuanian population.

EP1348

Methods

The role of vitamin D receptor gene FokI (rs2228570) polymorphism in

This case-control study was performed in the Hospital of Lithuanian University of

the pathogenesis of thyroid associated orbitopathy

Health Sciences. Graves’ disease patients (nZ105) were divided into remission

Adam Maciejewski¹, Michal Kowalczyk², Adam Czyzyk³,

and failed treatment groups according to the final outcome of the disease. The

Teresa Gasinska⁴ & Katarzyna Lacka¹

remission group (nZ49) - patients with euthyroid status minimum 1 year after

¹Department of Endocrinology, Metabolism and Internal Medicine, Poznan

antithyroid drugs

(ATD) withdrawal. The failed treatment group (nZ56) -

University of Medical Sciences, Poznan, Poland;²Department of

patients submitted radioiodine therapy or surgery due to poor response to ATD

Dermatology and Venereology, Poznan University of Medical Sciences,

therapy. Genomic DNA was extracted from the peripheral blood leukocytes with

Poznan, Poland;³Department of Gynecological Endocrinology, Poznan

kit Qiagen GmbH, Hilden, Germany.

University of Medical Sciences, Poznan, Poland;⁴Department of Internal

Results

Diseases and Oncologic Chemotherapy, Silesian Medical University,

The patients in failed treatment group had significantly higher frequency of GG

Katowice, Poland.

genotype and a lower frequency of AA genotype than patients in remission group.

Patients with GG homozygous genotype had more than four-fold (OR 4.94, 95%

CI 1.38-17.65) and more than sixteen-fold (OR 16.91, 95% CI 1.83-156.62)

Introduction

increase in risk of ATD treatment failure compared to patients with homozygous

Vitamin D, known mainly as a calcium-phosphorus homeostasis regulator, turned

genotype AA for 49A/G SNP and for CT60 SNP, respectively. When association

out to play also a significant role in the immune system modulation. Vitamin D

of 49A/G and CT60 genotypes on the outcome of Graves’ disease was analyzed

deficiency has been reported in some autoimmune disorders. It is also suspected

separately it provided significant prognostic information but after multiple

that polymorphisms of vitamin D-related genes comprise a risk factor for different

logistic regression analysis these genetic markers were not independent of other

autoimmune diseases. Therefore the aim of our study was to assess vitamin D

factors. Only TRAb levels before treatment was independently associated with

receptor

(VDR) gene FokI polymorphism in thyroid associated orbitopathy

elevated odds of failure (OR 1.05, 95% CI 1.02-1.08).

(TAO) in comparison to the controls among the Caucasian-Polish population.

Conclusion

Patients

the data shows significant association of two polymorphisms (A/G at position 49

The group studied consisted of 100 subjects diagnosed with TAO (mean age 53.8)

and CT60 in 3’UTR) in the CTLA-4 gene with Graves’ disease in Lithuania and

and 142 healthy age and sex matched controls. TAO was diagnosed by clinical

suggest that these genetic markers may provide important information in

examination, TRAb assessment and orbit MRI or CT. TAO group was further

predicting high risk patients for failure to ATD therapy.

divided into: A- orbitopathy from the onset of Grave’s disease, B- later

DOI: 10.1530/endoabs.49.EP1346

development of TAO. In the control group both TAO and autoimmune thyroid

diseases were excluded by clinical examination and thyroid ultrasound.

Methods

FokI polymorphism of the VDR was studied by PCR-RFLP analysis, randomly

selected patients were additionally analyzed by direct sequencing. The statistical

significance of differences between the allele and genotype frequencies in TAO vs

controls, as well as in subgroups of TAO were evaluated by c2 or Fisher’s exact

test. A P-value of !0.05 was considered significant.

EP1347

Results

The impact of levothyroxine sodium treatment on dynamic

Observed allele frequencies were in Hardy-Weinberg equilibrium. C allele and

thiol/disulphide homeostasis in overt hypothyroidism

CC genotype were more frequent in TAO compared to the controls (59.50 vs

Cemile Bicer¹, Ihsan Ates², Murat Aydin³, Mustafa Altay²,

55.28% and 34.00 vs 31.69%, respectively), although differences were not

Canan Topcuoglu⁴, Salim Neselioglu¹, Ozcan Erel¹ & Fatma Meric Yilmaz¹

statistically significant (PZ0.36 and PZ0.50). CCCCT genotypes (dominant

¹Yildirim Beyazit University Medical Faculty, Ankara, Turkey;²Ankara

inheritance model) were more frequent in the subgroup A compared to B (89.70%

Numune Training and Research Hospital, Department of Internal Medicine,

vs 75.00%), PZ0.07.

Ankara, Turkey;³Namik Kemal University Medical Faculty, Department of

Conclusions

Biochemistry, Ankara, Turkey;⁴Ankara Numune Training and Resaerch

There is no statistically significant difference in allele or genotypes distribution of

Hospital, Department of Biochemistry, Ankara, Turkey.

VDR FokI polymorphisms between TAO and the control group among the

Caucasian-Polish population.

DOI: 10.1530/endoabs.49.EP1348

Objective

Thiols are organic compounds that contain sulphydryl group (-SH) and have

important role in preventing oxidative stress especially in cells. The aim of our

study is to investigate the relationship between hypothyroidism due to HT and the

thiol disulfide homeostasis, the effect of treatment on this homeostasis and to

demonstrate the utility of thiol/disulphide homestasis as a marker for assessing the

damage to functional group of proteins and the oxidative balance in this group of

EP1349

patients.

Lymphoid hyperplasia in Graves’ disease: about 2 cases

Design, patients and measurements

Faten Hadjkacem, Dorra Ghorbel, Fatma Mnif, Hamza Elfekih,

Thirty-five patients with a new diagnosis of hypothyroidism due to HT who were

Nabila Rekik, Houcem Mrabet, Mouna Ammar, Nadia Charfi &

not yet under treatment is enrolled in the study. Serum samples were taken prior to

Mohamed Abid

the treatment and 6 months after initiation of levothyroxine sodium treatment to

The Department of Endocrinology and Diabetology of Hedi Chaker

compare clinical and laboratory parameters of patients. Thiol/disulfide

Hospital, Sfax, Tunisia.

homeostasis is evaluated by Erel & Neselioglu method.

Results

After

6 months of treatment the native thiol and total thiol levels were

Introduction

significantly increased

(PZ0.001 and PZ0.001). The disulphide level, the

Graves’ disease GD is an autoimmune disease, which can manifest with a variety

disulphide/native thiol and the disulphide/total thiol ratios showed a significant

of extrathyroidal clinical syndromes. Though quite rare, this disease can also

decline (PZ0.001, PZ0.001, PZ0.001 respectively).

manifest with lymphoid hyperplasia.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Case report

Introduction

Two cases are reported in the department of endocrinology and diabetology of

Radioiodine treatment (RAIT) is an effective definitive treatment for Graves’

Hedi Chaker hospital in Sfax-Tunisia from 2006 to 2016 associated GD with

Disease (GD) and Toxic Nodular Goiter (TNG). The aim of this study was to

lymphoid hyperplasia reaction. The first case was a 32 years old male with history

analyze demographic and clinical factors affecting the outcome of RAIT in

of GD 6 years back treated with propylthiouracil and beta blockers. He was

patients with hyperthyroidism.

admitted with follow complaints: dyspnea and edema of the lower limbs. The

Methods

diagnosis of cardiothyrosis with dilated cardiomyopathy has been confirmed by

Retrospective review of patients treated with RAIT for hyperthyroidism. A fixed

echocardiography. Neck-chest computerized tomography (CT) has been made to

dose of 10 mCi was administered to patients with GD and 15 mCi to patients with

explore swallowing disorder wich showed the presence of no compressed

TNG. Treatment success was defined as euthyroidism or hypothyroidism

heterogeneous goiter with mediastinal polyadenopathy and bilateral suspect lung

(subclinical/overt hypothyroidism) 12 months after RAIT.

nodules. The body scan revealed the same results with other deep localization of

Results

lymph nodes. The infectious and inflammatory etiological investigations were

217 patients were included; 122 with GD and 95 with TNG (52 patients with toxic

negatives. A total thyroidectomy with biopsy of mediastinal lymph node under

multinodular goiter and 43 with Toxic Adenoma). RAIT was more effective in

mediastoscopy confirmed histologically the presence of lymphocytic thyroiditis

TNG than in GD (94.7% vs 71.3%, P!0.05). Gender, previous thyroid function

with a lymphoid hyperplasia. The second case was a 47 years postmenopausal

and thyroid volume were significantly as-sociated with an effective outcome in

female followed for Graves’s disease complicated with cardiothyreosis. We have

patients with GD (P!0.05). No clinical or demographic factors affected the

discovered incidentally deep lymph nodes

(mediastinal, coeliomesenteric,

outcome in patients with TNG, although a higher Tc99 uptake on scintigraphy

aortocave) with lung nodules. The biopsy of the lung was not conclusive. The

was associated with persistent hyperthyroidism. Hypothyroidism was more

stability of these lesions for 10 years argues for a reactive lymphoid hyperplasia.

common in GD (62.3% vs 41.1%, PZ0.001). Hypothyroidism was significantly

Conclusion

more frequent in smaller nodules (26G8 mm vs 32G11 mm, P!0.05) and in

Reactive lymphocyte proliferation remains a histological diagnosis. It is

lower thyroid volumes (24.3G14 ml vs 37.7G19 ml, P!0.05).

necessary to complete with exhaustive etiology investigation in front of this

Conclusion

clinical presentation.

Thyroid volume seems to have a significant influence on the development of

DOI: 10.1530/endoabs.49.EP1349

hypothyroidism after the treatment and, in patients with GD, the efficacy of RAIT.

In GD, larger goiters may need a greater dose and beneficiate from a calculated

dose of radioiodine instead of a fixed predefined dose. In TNG, a fixed dose of

15 mCi successfully cured hyperthyroidism in almost all patients although in

selective patients with smaller thyroid nodules or smaller goiters a lesser RAIT

dose may restore euthyroidism.

DOI: 10.1530/endoabs.49.EP1351

EP1350

Effects of hypothyroidism on nutritional status: which impact?

El Mghari Ghizlane, Naima Bouznad & Nawal El Ansari

Department of Endocrinology, Diabetology, Metabolic Diseases and

Nutrition. PCIM Laboratory, FMPM, Mohamed VI CHU, Marrakech,

Morocco.

Introduction

EP1352

Hypothyroidism is a common disease in Morocco because of the iodine

An unusual case of subacute thyroiditis after alemtuzumab treatment

deficiency frequency. The metabolic and nutritional effects of hypothyroidism are

Philippe Baltzinger, Alina Dumitrescu, Clothilde Wagner,

known in the literature. The hypothyroidism is classically described among the

Nicolas Collongues, Jérôme De Seze, Thibault Bahougne &

causes of secondary obesity. The aim of the study is to evaluate the nutritional

Nathalie Jeandidier

status and anthropometric parameters in patients having hypothyroidism.

University Hospital of Strasbourg, Strasbourg, France.

Patients and methods

Patients were recruited from the out-patients clinics. All the patients with the

diagnosis of hypothyroidism and not receiving yet the L-thyroxin were included.

Introduction

All the patients were examined by the dietitian and the clinical and laboratory

Alemtuzumab, a humanized monoclonal antibody against CD52, is effective in

evaluation were carried on in all patients.

the treatment of early relapsing-remitting multiple sclerosis (MS). Thyroid side-

Results:

effects such as Graves’ disease have been already described. We describe one case

A total of .. were included. The mean age was 41 years. The sex ratio is 6/1.

of unusual subacute thyroiditis after alemtuzumab treatment.

Weight gain was found in 67% of patients with a mean gain of 8kg. The mean

Clinical case

weight was 80 kg for men and 68 kg for women for an average ideal weight of 64

A 38 year-old-female was treated by alemtuzumab for 2 years. She was referred

and 54 kg respectively. The BMI was normal in 43, 30% of cases, 26.60% were

for hyperthyroidism with 10 kg weight loss, diarrhea and palpitations. Clinical

overweight and 23.20% were obese. Waist circumference was pathological in

examination found cervical pain and fever. Thyroid function tests revealed low

92% of women and 80% of men. The body fat percentage was high in 60% of

TSH at 0.0170 mUI/l (N 0.270-4.20), increased fT4: 71.4 pmol/l (N 12-23) and

female patients and 80% of male patients. The average daily caloric intake for

fT3: 18.2 pmol/l (N: 3.84-7.07). Thiamazol (20 mg bid) and propranolol (20 mg

women was 2138.77 Cal while the caloric intake was 1856.6 Cal in men. High

tid) were started with daily neutrophil evaluation. First hypothesis was Graves’

intake in macronutrients was found in all patients.

disease, since it is currently described with alemtuzumab. Blood tests revealed

Conclusion

increased CRP: 156 mg/l (N!4 mg/l) without increased leukocytes. Ceftriaxone

Hypothyroidism is responsible for an important increase in body fat leading to

was started in front of a urinary infection suspicion. Finally, bacteriological

overweight and obesity. The hormonal replacement is an efficient way to

analyses (blood and urine) were negative and ceftriaxone was discontinued. After

overcome these nutritional and metabolic changes. The nutritional evaluation is

3 days under thiamazol treatment, fT4 increased up to 100 pmol/l and fT3 up to

critical for any patient consulting for hypothyroidism.

26.5 pmol/l without clinical improvement. Thyroid ultrasonography showed

DOI: 10.1530/endoabs.49.EP1350

isolated heterogeneous parenchyma. Technetium scintigraphy showed no uptake;

allow us to make the diagnosis of subacute thyroiditis. Finally, anti TSH receptor,

thyroglobulin and thyroperoxidase antibodies results came back negative.

Thiamazol was resumed, prednisolone (1 mg/kg per day) started. After 1 week,

neck pain and fever disappeared and fT3, like CRP, were normalized. After 2

weeks, fT3 and fT4 were in the normal ranges.

Discussion

Although subacute thyroiditis is not known as an auto-immune disease, an

increase of its incidence rate is found after alemtuzumab or INF-alpha treatment

EP1351

suggesting an immune participation. Moreover, this rise is not found after

Outcome of radioiodine therapy in patients with hyperthyroidism

alemtuzumab therapy for chronic B cell leukemia

(suggesting a specific

Catarina Machado¹, Patrícia Tavares¹, Sara Monteiro¹, Gustavo Rocha¹,

background in MS patient). We describe here the case of unusual severe subacute

Fernando Silva², José Manuel Oliveira² & Maria João Oliveira¹

thyroiditis after alemtuzumab treatment.

¹Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE, Vila Nova de Gaia,

DOI: 10.1530/endoabs.49.EP1352

Portugal;²HPP-MM-Lenitudes, Porto, Portugal.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1353

EP1355

Pattern of amiodarone-induced thyrotoxicoxis before and after

Perinatal outcome in graves-basedow disease during pregnancy

universal salt iodization

Snezana Mihajlovska & Marija Mihajlovska

Raluca Trifanescu^1,2, Cristina Popa², Andrei Goldstein², Florin Alexiu²,

¹Department of Nuclear Medicine, Clinical Center ‘D-R Trifun Panovski’,

Mariana Purice² & Catalina Poiana^1,2

Bitola, Macedonia;²Department of Endocrinology, General Hospital

¹‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania;

‘8-MI Septemvri’, Skopje, Macedonia.

²‘C.I. Parhon’ National Institute of Endocrinology, Bucharest, Romania.

The purpose of this study is to assess the treatment outcome of pregnant patients

Background

with Graves-Basedow disease. In the period of 20 years 59 pregnancies in

Prevalence and type of amiodarone-induced thyroid dysfunction in a population

hyperthyroid patients were registered with Graves-Basedow disease in the

depend on geographical iodine intake.

Department of Nuclear Medicine in Clinical Hospital Bitola. Thyrostatic therapy

Aims

was applied in 29 (56.5%) pregnant patients divided into 2 groups. The first group

To assess differences in amiodarone-induced thyrotoxicosis pattern before and

were patients who used methimazole therapy (MMT) or 50-400 mg propiltiuracil

after iodine supplementation.

(PTU). Of this group, 19 were born healthy infants (74.3%), 2 (5.12) with low

Patients and methods

birth weight, 5 (12.8) were premature but with no fetal malformations. The second

84 patients (41M/43F) with amiodarone-induced thyrotoxicosis, aged 60.1G11.9

group were patients who were not regularly controlled and treated. Of them all

years, were retrospectively reviewed. 28 patients were resident in former iodine-

three babies were born with malformations (two newborns died shortly after birth

deficient areas. TSH, FT₄ and total T₃ were measured by chemiluminescence;

and one newborn died six months after birth).

2 h and 24 h radioiodine (¹³¹I) uptake and color flow Doppler were performed.

Conclusion

Results

Our study suggests that patients treated with Graves-Basedow disease during

Type 1 amiodarone-induced thyrotoxicosis (AIT) was diagnosed in 21 cases

pregnancy with a low dose of thyrostatic therapy, provides a significant reduction

(25%), type 2 in 26 cases (30.9%) and mixed type in 37 cases (44%). Before

of fetal complications. Our study also indicated no significant difference in the

universal salt iodization were diagnosed 38 cases (type 1 AIT in 12 cases - 31.6%,

effects of both drugs - PTU and MMT in these doses although preferably PTU

type 2 in 14 cases - 36.8% and mixed type in 12 cases - 31.6%); after universal

because of reduced transplancental passage compared to MMT. In our study

salt iodization were diagnosed 46 cases (type 1 AIT in 9 cases - 19.6%, type 2 in

observed complications and mortality in newborns of mothers with uncontrolled

12 cases - 26% and mixed type in 25 cases - 54.3%); Patients with type 1 AIT

or inadequate and irregular treated hyperthyroidism.

were significantly younger (62.5G9.6 years vs 56.1G12.8 years, PZ0.05), with

DOI: 10.1530/endoabs.49.EP1355

significantly higher radioiodine uptake at

24 h (median 7% vs median 1%,

PZ0.022) and had higher thyroid volume (29.9G14.8 ml vs 19.9G8.6 ml,

PZ0.015) than patients with type 2 AIT. Patients with type 1 AIT had higher total

T₃ levels than patients with type 2 AIT (340.9G157.4 vs 246.7G135.9 ng/dl,

PZ0.06) and type 3 AIT (216.4G111.8 ng/dl, PZ0.003, respectively). There

were no statistically significant differences in body mass index, amiodarone

treatment duration, amiodarone cumulative dose, FT₄ levels between AIT type 1,

2 and mixed type.

Conclusion

After universal salt iodization, AIT type 2 and mixed type prevailed in our

geographical area.

EP1356

DOI: 10.1530/endoabs.49.EP1353

TSH receptor stimulating immunoglobulins - performance of an

automated immunoassay

Patrícia Tavares¹, Catarina Machado¹, José Carlos Pedroso², Joana Vieira²,

Gustavo Rocha¹, Sara Monteiro¹, Ana Margarida Sousa¹, Pedro Rodrigues¹,

Agostinho Lira² & Maria João Oliveira¹

Endocrinology Department, Centro Hospitalar Vila Nova de Gaia/Espinho,

Vila Nova de Gaia/Porto, Portugal;²Clinical Pathology Department, Centro

Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia/Porto, Poland.

Introduction

Graves’ disease (GD) hyperthyroidism is caused by autoantibodies against TSH

receptor (TRAb). Three varieties of TRAb are now recognized: stimulating (TSI),

EP1354

blocking and neutral antibodies. Current TRAb immunoassays detect and

They think it’s all ovar(ii)

quantify serum immunoglobulins that interact with the TSH receptor but without

Raj Tanday¹, Bonnie Grant¹, Premila Kollipara², Edel Casey¹ &

discriminating their function. An automated immunoassay for the detection and

Khash Nikookam¹

quantification of TSI is available.

¹Department of Endocrinology, King George Hospital, London, UK;

Objective

²Department of Obstetrics and Gynaecology, King George Hospital,

Our study objective was to determine the performance of TSI assay in patients

London, UK.

with thyroid autoimmune disease, nodular disease, and healthy individuals.

Methods

A 37 year old woman was referred to the endocrinology clinic from the

59 subjects were enrolled in the study: 37 samples of consecutive individuals

gynaecologists. She was awaiting an 8 cm left ovarian cyst removal and found to

referred to the endocrinology consultation with thyroid pathology and 22 healthy

be hyperthyroid (fT3 7.8 pmol/l, fT4 of 19.0 pmol/l, TSH !0.01 mU/l). She

subjects. The Immulite^w 2000 TSI (Siemens) was used to measure TSI.

described

4 months of palpitations, change in bowel habit and menstrual

Results

irregularity. She had no tremor or tachycardia. She had no palpable goitre or eye

Of the 37 patients, 30 (81,1%) were female and 7 (18,91%) were male, with a

signs. She had a past medical history of asthma on inhalers. There was no family

mean age of 58 (G14) years. 18 patients were diagnosed with autoimmune

history of thyroid disease. Repeat bloods confirmed T3 toxicosis, negative TPO

thyroid diseases (10 with untreated GD and 8 with Hashimoto thyroiditis (HT))

and TSH receptor antibodies. She was commenced on carbimazole 10 mg od. She

and 19 with nodular thyroid disease (12 with non-toxic goiter and 7 with toxic

underwent a successful left salpingo-ooperectomy. Histology showed a multi-

adenoma). Healthy subjects and those with nodular thyroid disease had a negative

loculated cyst containing hyperplastic thyroid tissue and no evidence of

TSI assay but one patient with HT had a positive TSI assay (specificity 98%). Of

malignancy. Following surgery she reported resolution of symptoms and had

the ten patients with diagnosis of Graves’ disease 10 had positive TSI assay

normalisation of thyroid function. Her carbimazole was reduced. At recent clinic

(sensitivity of

100%) with a median value of 3.6 IU/L (maximum of 90.1,

review she is clinically and biochemically euthyroid off carbimazole. Struma

minimum of 1.2). There was a positive correlation between the value of TSI assay

Ovarii is a rare finding of ectopic thyroid tissue in an ovarian teratoma. This case

and the amount of the free fractions of thyroid hormones.

illustrates the importance of checking thyroid function prior to gynaecological

Conclusion

surgery and to consider rarer causes of thyrotoxicosis.

This easy to perform assay method of TSI revealed high sensitivity and specificity

in the diagnosis of Graves’ disease.

DOI: 10.1530/endoabs.49.EP1354

DOI: 10.1530/endoabs.49.EP1356

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1357

not used as a mode of achieving euthyroid status with hyperthyroidism, though it

is often used in thyroid crisis.

Genetic variation in NFE2L2 and SEPS1S associated with increased

risk of Hashimoto’s thyroiditis

DOI: 10.1530/endoabs.49.EP1358

Liliana R Santos^1,2, Cecila Dura˜es1,3, Ana Pestana1,3, César Esteves4,

Celestino Neves^3,4, David Carvalho^3,4, Manuel Sobrinho Simo˜es1,3 &

Paula Soares^1,3

¹Institute of Molecular Pathology and Immunology of University of Porto

(IPATIMUP), Porto, Portugal;²Internal Medicine Department, Hospital de

Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal;³Faculty of

Medicine of the University of Porto, Porto, Portugal;⁴Department of

Endocrinology, Hospital of S. Joa˜o, Porto, Portugal.

EP1359

A slow but continuous growth: Case study of a thyroid nodule

Hashimoto’s thyroiditis (HT) is the most common chronic autoimmune thyroid

David Veríssimo, Vitória Pires, Dolores Passos, Filipa Serra, Joa˜o Silva,

disease, which is characterized by alteration of the thyroid function. HT is a

Luís Lopes, João Jácome de Castro & Mafalda Marcelino

multifactorial disorder and several candidate genetic loci have been identified as

Hospital das Forças Armadas, Lisboa, Portugal.

contributing to HT. The transcription factor Nrf2, encoded by the NFE2L2 gene,

is an important regulator of the cellular protection against oxidative stress. The

Thyroid nodules are a common clinical finding, with an estimated prevalence of

relevance of selenoproteins in follicular thyroid cell physiology and in molecular

palpable thyroid nodules to be approximately 5% in women and 1% in men. The

physiology have pointed to a putative role of the interaction of Nrf2

with

clinical importance of thyroid nodules rests with the need to exclude thyroid

selenoproteins in the pathogenesis of autoimmune thyroid diseases. In order to

cancer. The prevalence of malignancy reported for palpable thyroid lesions ranges

evaluate the role of a promoter variation in NRF2 and SEPS1 in the risk for

from 5.0% to 6.5%. Patients with benign thyroid nodules are unlikely to suffer

developing Hashimoto’s thyroiditis (HT), we performed a case-control study

morbidity or mortality due to thyroid cancer. A 53 aged man presented with a

comprising 997 individuals (HT patients and unrelated controls). Genetic variants

20-year history of a slow-growing nontender neck mass. He denied any

were discriminated by real-time PCR using TaqMan SNP genotyping assays.

compressive symptoms, such as dysphagia, dyspnea or hoarseness. On physical

Three polymorphisms (- 653A/G: rs35652124; - 651G/A: rs6706649 and -

examination of the thyroid, the patient had a right-sided soft, elastic nodule larger

617C/A: rs6721961 SNPs) in the NRF2 gene promoter were studied and no

than

10 cm of diameter. TSH, T4l were within normal range and thyroid

significant difference were found between HT patients and controls with regard to

antibodies were negative. CT scan of the neck indicated a solitary dominant

genotypic or allelic frequencies of the three NFE2L2 SNPs (PO0.05). The joint

nodule of the right thyroid lobe measuring 140!78!84 mm without invasion of

effect of genetic polymorphisms in NFE2L2 and SEPS1 was assessed considering

adjacent structures. A minor compression and tracheal deviation to the left was

the high-risk genotypes of NF2L2 and SEPS1. Our findings suggest that the risk to

also reported. Thyroid ultrasound indicated a large, heterogeneous nodule, solid

develop Hashimoto’s thyroiditis is not associate to a single NFE2L2

with some cystic component and well-defined contours, occupying the entire right

polymorphisms but increases with the combined effect of the number of risk

lobe of the thyroid gland. Left lobe also had a 1.4 cm solid nodule. FNAB of both

alleles in NFE2L2 and SEPS1. Individuals carrying two high-risk genotypes

nodules were benign. The patient remained asymptomatic throughout. Natural

present a significant increased risk for HT.

growth behaviour of thyroid nodules is controversially discussed. In our clinical

DOI: 10.1530/endoabs.49.EP1357

case, the slow progression and the absence of compressive signs was suggestive

of a benign lesion. However, the large dimensions and the progressive growth of

the nodule might also be indicative of malignancy. There are few studies about

long-term prognosis of thyroid nodules, including their malignant transformation.

Although well established that approximately 90% of non-functioning thyroid

nodules are benign, even in slow growth big nodules with benign FNAB, surgery

is crucial to the final diagnosis.

DOI: 10.1530/endoabs.49.EP1359

EP1358

Safety and efficacy of cholestyramine in the adjuvant management of

Graves thyrotoxicosis

Taimur Gulfam & Sath Nag

James Cook University Hospital, Middlesbrough, UK.

Introduction

EP1360

Graves’s disease is an autoimmune condition both cell and antibody-mediated,

which is associated with thyrotoxicosis and extra thyroid features.

Mirela Tirnovan¹, Anamaria Bursuc¹, Alina Daniela Belceanu¹,

Case report

Adina Manolachie¹, Ioana Armasu¹, Iulia Crumpei¹, Georgiana

A 35-year-old female presented with symptomatic hyperthyroidism due to graves

Constantinescu¹, Luminita Apostu², Carmen Vulpoi¹

thyrotoxicosis. She developed adverse reactions, including severe dermatitis and

Mirela Tirnovan¹, Anamaria Bursuc¹, Alina Daniela Belceanu¹,

hepatotoxicity, to two of the thionamide drugs (carbimazole and propylthiouracil).

Ioana Armasu¹, Iulia Crumpei¹, Adina Manolachie¹, Luminita Apostu² &

Eventually we decided for definitive treatment in the form of a total

Carmen Vulpoi¹

thyroidectomy, as it appeared to be the only option in a mother of a young

¹Department of Endocrinology, U.M.F. ‘Grigore T. Popa’, Iasi, Romania;

child, which precludes radioiodine therapy. Unfortunately, we were unable to

²Department of Biochemistry, Iasi, Romania.

treat her with a beta-blocker due to her history of severe Raynaud’s disease. We

arranged for her to undergo rapid thyroid blockade 10 days prior to her surgery

Introduction

with Lugol’s iodine. After she had Lugol’s iodine, she exhibited a paradoxical

Many causes of malabsorbtion of levothyroxine

(LT₄) in patients with

increase in her thyroid hormone levels, which was unusual and necessitated

hypothyroidism have been thoroughly described in literature. Pseudomalabsorp-

cancellation of her surgery. It appears she did not go through the Wolff-Chaikoff

tion, poor compliance of the patient is most common cause of failure of LT4

effect but instead showed Jod-Basedow effect, resulting in a significant rise in free

and/or liothyronine (LT₃) treatment.

T₄. We have agreed to commence her on cholestyramine 2 g three times a day and

Case report

prednisolone 40 mg once a day in order to improve her thyrotoxicosis. Eventually

27 years old woman, normopondeal, presented from the age of 11 years for short

she became euthyroid after a few weeks of starting the treatment and then

stature. Further investigations found pluritrope pituitary insufficiency (somato-

underwent total thyroidectomy.

trophic, gonadotroph, corticotroph and tireotroph) and substitutive treatment was

Comments

started (GH-treated off 17 years, actual height 168 cm, cortisol, esoprogestative

Thionamides are widely used as anti-thyroid drugs in the management of

and thyroid hormones). MRI described a small pituitary. Despite of increasing

hyperthyroidism but unfortunately they are also associated with serious adverse

dose of LT₄, ulterior in association with LT₃, and vitamic C for better absorption,

effects which was exhibited by this patient. In our case we have successfully used

THS remained high (13 mUI/ml, reference 0.4-4 mU/L) with constantly low fT₄.

adjunct treatment including steroids and cholestyramine to achieve euthyroid

Celiac disease, pernicious anemia, gastrointestinal, liver, pancreatic, heart disease

state and making patient ready to undergo thyroidectomy. Although steroids are

or pregnancy were excluded by laboratory and imagistic investigations, also were

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

excluded drugs and dietary interactions; To evaluate the hypothesis of

TSH (0,38-5,33 uUI/ml)

pseudomalabsorption, the patent was submitted to rapid LT₄ absorption test.

After an overnight fasting, it was administreted 1000 mg LT₄; We measured fT4 at

30⁰ , 2, 4, 6 h.Immediately fT4 serum increase, with the maximum serum level

after

2 h (basal fT₄Z0.56 ng/dl,

2 hZ1.72 ng/dl, peak fT₄O2.5). The test

showed a normal absorption of LT₄ and malabsorption was excluded.

34.02

Conclussion

30.76

28.44

27.39

Our case showed an inadequate thyroid hormone supplementation (3.3 mg/kg);

26.08

the literature suggested that after excluding organic cause or drug interaction, is

19.9

useful to make a malabsorption test, which confirms the diagnostic pseudoma-

16.9

16.1

labsorption; based on his historical attempts to stop the treatment, a psychological

10.7

counseling may be necessary. Once weekly oral thyroxine treatment, supervised,

can be a safe, well-tolerated, and effective therapy for patients with non-

2.1

3.2

2.3

2.6

2.7

compliance.

2.3

DOI: 10.1530/endoabs.49.EP1360

120

180

240

the graphic below. The patient remained with normal heart rate and normotensive

along LAT. The results showed a normal absorption of LT₄, so pseudo-

malabsorption was proven. Based on this diagnosis was prescribed 1 mg of LT₄

EP1361

weekly to improve therapeutic compliance. Nowadays, patient present normal

Oxidative profiles in patients with autoimmune thyroid diseases

TSH and FT₄ serum levels. In conclusion, pseudo-malabsorption is an important

Fatma Mnif, Hamza Elfekih, Mouna Elleuch, Faten Hadjkacem,

differential diagnosis in persistent hypothyroidism to achieve therapeutic success

Houcem Elomma Mrabet, Nabila Rekik, Dorra Ghorbel, Mouna Mnif &

and LAT is a simple, secure and useful tool in this cases.

Mohamed Abid

Hedi-Chaker University Hospital, Sfax, Tunisia.

DOI: 10.1530/endoabs.49.EP1362

Introduction

Autoimmune thyroid diseases are known to be associated with oxidative stress.

Objectives

We studied the oxidative profiles in plasma and thyroid tissue of 82 patients

having Graves’ disease (GD) or Hashimoto thyroiditis (HT) or hashitoxicosis

(HTX) vs 65 healthy controls in order to evaluate the antioxidant enzymes’

activity and the lipid peroxidation.

Results

The lipid peroxidation was objected with a significant higher level of

EP1363

Malondialdehyde (MDA) in the plasma of our patients vs healthy controls

Serum irisin level in different thyroid dysfunction states and its relation

(P!0.01 for HT, P!0.001 for GD and HTX). A very low antioxidative activity

to markers of muscle dysfunction

of Glutathione peroxidase (GPx) was found in our patients vs healthy controls

Mohamed Reda Halawa, Mona Mohamed Abdelsalam,

(P!0.001 for HT and HTX, P!0.01 for GD). The Selenium which is GPx-

Bassem Mourad Mostafa & Amira Galal Ahmed

cofactor and the Catalase were found to be reduced as well. For the proteins

Ain Shams University, Cairo, Egypt.

oxidation, we found a higher level in Carbonyl-group, MDA and a lower level of

thiol-group in our patients vs healthy controls. Similar results were found in the

thyroid tissue samples.

Introduction

Conclusion

Irisin is a myokin secreted by myocytes responsible for transmission of signals

This study shows clearly the presence of an oxidative stress in both plasma and

from muscles to other body tissues. It improves systemic metabolism by

thyroid tissue in patients with autoimmune thyroid diseases.

increasing energy expenditure and has a significant influence on the body

DOI: 10.1530/endoabs.49.EP1361

metabolism and thermogenesis. Thyroid disorders are characterized by a

disrupted thermo-metabolic state and muscular damage, and the underlying

mechanisms still not clear.

Aim

To evaluate serum Irisin levels in patient with hypothyroid and hyperthyroid

disease and its relation to creatinine kinase (CK) a marker of muscle damage.

Method

90 subjects participated in the study. They were divided into three groups: Group

1: 30 hyperthyroid patients, Group 2: 30 hypothyroid patients, Group 3: 30 normal

persons. They were submitted to history, medical examination (Weight, Height

EP1362

and BMI) and measurement of fasting serum Irisin, TSH, Free T₃, Free T₄, CK.

Levothyroxine absorption test in the management of a patient with

Results

persistent hypothyroidism

Irisin hormone level was lower in hypothyroid patients (16.60G4.07) Pg/ml than

Joana Monteiro, Marta Ferreira, Miguel Pires, Alexandra Vieira,

hyperthyroid patients (26.83G7.95) Pg/ml and controls (25.70G5.29) Pg/ml

Daniela Guelho, Teresa Pereira, Fernanda Pinhal & Célio Fernandes

(P!0.01). However, it was higher in hyperthyroid than (PO0.05). Creatine

Centro Hospitalar de Leiria, Leiria, Portugal.

kinase (CK) level decreased in hyperthyroid patients (33.80G1.49) m/l than

hypothyroid patients (196.26G4.53) m/l and controls (62.86G1.63) m/l (P!0.01).

However, creatine kinase increased in hypothyroid patients (196.26G4.53) m/l in

Nonadherence to levothyroxine therapy is one cause of persistent hypothyroid-

comparison with control

(62.86G1.63) m/l

(P!0.01). There is a negative

ism. To distinguish nonadherence from malabsorption, a levothyroxine

correlation between Irisin, TSH, Weight, BMI and CK (P!0.01), and a positive

absorption test (LAT) is sometimes required. The authors report a case of a

correlation with freeT₃ and free T4 (P!0.01) in hyperthyroid patients.

60-year-old female patient suffering from hypothyroidism resistant to oral

Conclusion

levothyroxine (LT₄) substitution after radioiodine therapy for Graves’ disease.

Lower Irisin hormone level was found in patients with hypothyroidism which

Despite the continuous increases of LT₄, over 10 years, to a maximum of

might be explained by muscles destruction demonstrated with high CK levels,

1 mg/day, she remained with high thyrotropin (TSH) and low free thyroxine

however the higher level of Irisin in hyperthyroidism might explained by

(FT₄). Extensive investigation excluded disease of the small bowel, liver and

hypermetabolic state.

pancreas as well us drugs interactions. After careful consideration was decided to

conduct a LAT. Serum levels of TSH, FT₄ and free triiodothyronine (FT₃) were

DOI: 10.1530/endoabs.49.EP1363

drawn at 0, 60, 120, 180 e 240 min after 1mg of LT₄. The results are presented in

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1364

supplementation as the first line of treatment. However, many of the symptoms

are unrelated to the failing thyroid function, but seem to be connected to the

Iodine deficiency is still prevalent in pregnant women from Romania

autoimmune disease, remain. Literature has reported on many of the

after universal salt iodization

environmental triggers of autoimmune response, however patients do not have

Monica Livia Gheorghiu^1,2, Horea Ioan Ursu^1,2, Irina Dumitrascu³,

a unified way to record, document, measure and understand their experiences and

Ionela Pascanu⁴, Carmen Georgescu⁵, Dan Mihu⁵, Corina Elena Delia⁶,

share them with their healthcare practitioners.

Geanina Mirela Toma⁶, Mihaela Stanciu⁷, Dragos Popescu⁷,

Objective

Corina Lichiardopol⁸, Mihaela Vlad⁹, Ramona Aldea¹⁰,

We aim to build a mobile phone application that would allow patients to record

Stefania Tudorache⁸, Mihaela Vasile⁸, Claudia Podia Igna¹¹,

and overview their symptoms as well as their compliance to medication.

Mariana Purice¹ & Adina Ghemigian^1,2

Design

¹C.I. Parhon National Institute of Endocrinology, Bucharest, Romania;

The app is build on a combination of thus far biomedical knowledge of symptoms

²C. Davila University of Medicine and Pharmacy, Bucharest, Romania;

related to Hashimoto’s as well as information gathered from interviewing

³Gr. T. Popa University of Medicine and Pharmacy, Iasi, Romania;

individuals diagnosed with Hashimoto’s. It enables individuals to record their

⁴University of Medicine and Pharmacy, Tirgu Mures, Romania;

experience on daily-weekly and monthly basis. No data are collected, the system

⁵I. Hatieganu University of Medicine and Pharmacy, Cluj Napoca,

is decentralized, and the recorded data are stored only on patient’s phones.

Romania;⁶Alessandrescu Rusescu National Institute for Mother and Child

Results

Care, Bucharest, Romania;⁷L. Blaga University, Faculty of Medicine,

Patient’s needs could be easily served through a mobile phone app, according to

Sibiu, Romania;⁸University of Medicine and Pharmacy, Craiova, Romania;

the first results. It could help the patients implement lifestyle changes that would

⁹V. Babes University of Medicine and Pharmacy, Timisoara, Romania;

serve as a first line of defence against non-thyroid related Hashimoto’s symptoms.

¹⁰Campulung Hospital, Campulung, Romania;¹¹Astra Clinic, Sibiu,

Conclusion

Romania.

Smart phone apps have a great value and potential in collecting a large pool of

worldwide data, however they need to be co-developed with biomedical scientists

Introduction

and healthcare professionals in order to fully serve to patients, medical healthcare

Even mild to moderate maternal iodine deficiency during pregnancy is associated

professionals as well as the research.

with impaired child cognition. Iodine deficiency is especially problematic in

DOI: 10.1530/endoabs.49.EP1365

pregnant women, who have a higher iodine requirement (250 mg/day) than non-

pregnant women (150 mg/day).

Objective

To assess iodine status (median urinary iodine concentration, UIC) in pregnant

women from multiple endemic or non-endemic areas in Romania, 13 years after

implementation of the Universal Salt Iodization (25-40 mg iodine/kg salt).

Subjects and methods

Median UIC in the morning urine was evaluated by spectro-photometry in 409

pregnant women in the third trimester from seven geographical regions in

Romania (age range 16-44 years, median age 29 years, none treated with

thyroxine, 80% from endemic regions, 59% from urban regions). Data regarding

iodized salt intake, bread intake (usually containing 6-9 mg iodine/slice) and

EP1366

iodine supplements were assessed. The study was approved by the local Ethics

Committee.

Dynamic risk stratification for predicting recurrence in patients with

Results

differentiated thyroid cancer treated without radioactive iodine

Iodized salt was consumed by 87% of women, iodine supplements during

remnant ablation therapy

pregnancy by 48% of women. Median UIC in the study group was 131 mg/l,

Suyeon Park, Won Gu Kim, Eyun Song, Hye-Seon Oh, Mijin Kim,

reflecting iodine deficiency during pregnancy (normal values R150 mg/l). Lower

Hyemi Kwon, Min Ji Jeon, Tae Yong Kim, Young Kee Shong &

median UIC (mg/l) were recorded in the endemic regions of Transilvania (92),

Won Bae Kim

Oltenia (114), Moldova (129) and Muntenia (149) as compared to Bucharest area

Department of Internal Medicine, Asan Medical Center, University of Ulsan

(206) and other non-endemic regions (206.6), except Timis (140); 55.7% of

College of Medicine, Seoul, Republic of Korea.

women had values below 150 mg/l, 13% below 50 mg/l, 1.7% had values over

500 mg/l. Higher median UIC was recorded in women with a daily intake of R5

Background

slices of bread, 166 vs 111 mg/l, P!0.01. Similar UIC were found in women

Increased incidence of small differentiated thyroid cancer (DTC) has emphasized

taking prenatal vitamins containing iodine and in those with no supplements. In

the need for risk stratification and individualized disease management for these

Transilvania region there is a discrepancy between schoolchildren

(normal

low risk DTCs. The aim was to validate a new dynamic risk stratification (DRS)

median UIC) and pregnant women (low median UIC). Urinary iodine/creatinine

system for prediction of structural recurrent/persistent disease in patients with

ratio was not significantly different from urinary iodine levels.

DTC treated without radioactive iodine (RAI) remnant ablation therapy.

Conclusions

Methods

Mild iodine deficiency is still prevalent in Romanian pregnant women from

This historical cohort study included

357 patients with DTC treated with

historical endemic regions after 13 years of universal salt iodization. Iodine

lobectomy or total thyroidectomy without RAI therapy. We stratified patient

supplementation during pregnancy should be encouraged in these regions.

response to initial treatment as excellent, indeterminate, biochemical incomplete,

DOI: 10.1530/endoabs.49.EP1364

and structural incomplete according to the DRS system.

Results

During a median 8.6 year of follow-up, 3.6% patients had structural recurrent

DTC. The response was excellent in 71.7% patients, indeterminate in 18.5%,

biochemical incomplete in 8.4%, and structural incomplete in 1.4%. There were

significant differences in disease-free survival among the DRS groups (P!0.001).

The hazard ratio (HR) of recurrent/persistent disease was significantly higher in

biochemical incomplete group (HR Z20.8, P!0.001) and structural incomplete

group (HR Z243.3, P!0.001) compared with the excellent group. However, the

tumor node metastasis

(TNM) staging system and the American Thyroid

EP1365

Association (ATA) initial risk classification did not effectively predict recurrence

The potential of smartphone applications in management and

of DTC.

compliance to recommended lifestyle in Hashimoto’s patients

Conclusions

Vedrana Hogqvist Tabor & Mikael Hogqvist Tabor

The new DRS system was effective for predicting risk of recurrent/persistent

Boost by VLM Health UG, Berlin, Germany.

disease in patients with DTC who underwent lobectomy or total thyroidectomy

without RAI remnant ablation.

DOI: 10.1530/endoabs.49.EP1366

Background

Hashimoto’s thyroiditis

(HT), a chronic autoimmune disease caused by an

interaction between genetic factors and the environmental is treated by thyroid

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1367

EP1369

Association between lymph node metastasis and patients’ age in

Differential diagnosis between Anaplastic Thyroid Cancer and

papillary thyroid microcarcinoma

Primitive Lymphoma of the Thyroid gland: A 66-cases study

Hye-Seon Oh, Min Ji Jeon, Suyeon Park, Mijin Kim, Hyemi Kwon,

Florence Kohler, Marie-Christine Vantyghem, Bruno Carnaille,

Eyun Song, Won Gu Kim, Young Kee Shong, Won Bae Kim &

Emmanuelle Leteurtre, Samuel Boury, Louis Terriou & Christine Do Cao

Tae Yong Kim

Centre Hospitalier Régional Universitaire de Lille, Lille, Nord, France.

Internal Medicine, Asan Medical Center, Seoul, Republic of Korea.

A rapidly growing neoplastic mass of the neck can either be caused by an

Background

anaplastic thyroid cancer (ATC) or a primitive lymphoma of the thyroid gland

Recent studies presented that younger patients with papillary thyroid

(PLT). These two malignancies share the same clinical features but vary widely in

microcarcinoma

(PTMC) had poorer clinical outcomes compared to older

their treatment and outcome. Only histologic criteria through biopsy can provide a

PTMC patients. The aim of this study is to investigate the impact of patient’s age

definitive diagnosis. The aim of this study was to assess biological and

on the lymph node metastasis (LNM) status of PTMC, a risk factor for recurrence

radiological differences between ATC and PLT in order to hasten differential

and poor clinical outcome of PTMC.

diagnosis. Sixty-six patients were included, 33 ATC and 33 PLT, diagnosed

Methods

between January 2000 and February 2016. Biological status (blood count, TSH,

The study evaluated 2068 PTMC patients who underwent thyroid operation with

antithyroid peroxidase antibodies, CRP, b2 microglobulin and LDH) and imaging

lymph node (LN) dissection from 2001 to 2009. All patients were allocated into

evaluation (Ultrasound (US) and computed tomography (CT) scanning) were

five groups by age; Group A (%35 years), Group B (35 !age%45), Group C

compared. ATC patients were all from Lille University Hospital. PLT being less

(45!age%55), Group D (55!age%65), and Group E (65!age). LNM status

common, 16 patients were included from Lille and 17 from other hospitals in

was divided into three groups by the number of metastatic LNs: no LNM, low

France. ATC was associated with higher leucocytes and neutrophils counts: over

volume LNM (%5 metastatic LNs), high volume LNM (O5 metastatic LNs). We

10000/ml and 7500/ml with positive predictive values (PPV) of 77.3 and 75%,

evaluated the correlation between patient’s age and high volume LNM in this

respectively. Neutrophils-to-lymphocytes ratio over 3,8 was noted in 77 and 48%

study.

of ATC and PLT patients, respectively. Thyroid tumor macrocalcifications and

Results

jugular vein thrombosis were found more frequently in ATC patients than in PLT

High volume LNM was found in 199 (8.9%) patients among whole study subjects

patients with PPV for ATC of 93 and 77.8% respectively, regardless of the

and was the most frequently found in the young age group (A 17.3%, B 8.4%, C

imaging technique (US or CT scan). PLT was associated with a thyroiditis history

7.2%, D 8.4%, and E 7.1%, respectively). Young age (Group A), male gender,

and/or high antithyroid peroxidase antibodies (PPV for PLT of 83 and 76.5%

larger primary tumor (O0.5 cm), multifocality, and extrathyroidal extensions

respectively). We conclude that blood count, antithyroid peroxidase antibodies

were significant risk factors for high volume LNM in univariate and multivariate

measurement, search for tumor calcifications and jugular vein thrombosis provide

analysis. In multivariate analysis, odd ratio (OR) of Group A for high volume

basic and relevant information in the initial work-up of thyroid mass to

LNM was 3.49 (95% CI, 1.67-8.06; P-value 0.002) compared to the Group E.

distinguish between ATC from PLT.

When analyzed only in women, young age (Group A) was also a significant risk

DOI: 10.1530/endoabs.49.EP1369

factor for high volume LNM (OR 6.00, 95% CI 2.73-20.76, P value 0.001). But

when analyzed in men, there was no significant difference in the incidence of high

volume LNM by different age groups (A 25%, B 18.1%, C 20.2%, D 22.0%, and E

22.7%, respectively).

Conclusion

High volume LNM was more frequently found in young aged female and male

patients. For patients under 35 years or male patients, immediate diagnosis and

surgical treatment for PTMC might be needed.

EP1370

DOI: 10.1530/endoabs.49.EP1367

The role of preoperative serum thyroglobulin values in the diagnosis of

differentiated thyroid cancer

Blertina Dyrmishi¹, Taulant Olldashi¹, Ema Lumi², Entela Puca³,

Dorina Ylli⁴, Majlinda Ikonomi¹ & Thanas Fureraj⁴

Hygeia Hospital Tirana, Tirana, Albania;²Regional Hospital Korca, Korca,

Albania;³Neo Style Clinic, Tirana, Albania;⁴UHC “Mother Teresa”,

EP1368

Tirana, Albania.

Breast cancer and family history for breast cancer in patients with

differentiated thyroid carcinoma

Safak Akin, Esra Tutal, Erkam Sencar, Melia Karakose, Ozgur Ozcelik,

Introduction

Mahmut Apaydin, Muyesser Sayki Aslan, Ilknur Unsal, Bekir Ucan,

Thyroglobulin (TG) is the most important protein produced by the thyroid. TG is

Mustafa Ozbek & Erman Cakal

considered a reliable marker of recurrent disease in patient with differentiated

Dı¸kapı Research and Training Hospital, Ankara, Turkey.

thyroid carcinoma (DTC). Before surgery, high serum TG values may be due to

an abnormally large thyroid, excessive thyroid stimulation, or physical damage to

thyroid etc.

Background and aim

Methods

The risk for breast cancer in patients with thyroid cancer has been investigated in

We evaluated in the retrospective study 20 patients (mean age 49.6G12 S.D.,

previous studies, and has been found to be increased. In this study we, therefore

range from 25-73 years old), with a histological diagnosis of DTC. Clinical

present retrospective analysis of the patients with differentiated thyroid

diagnosis before surgery was: 20% (4) solitary nodule; 10% (2) hyperthyroidism;

carcinoma in respect to breast cancer and family history for breast cancer.

5% (1) thyroid cancer with lytic bone metastasis; 65%(13) non toxic multinodular

Methods

goiter.

We conducted a retrospective study involving 455 patients with a diagnosis of

Results

differentiated thyroid carcinoma between January 2009 and March 2016.

Histological diagnosis: 85% (17) papillary thyroid cancer, and 15% (3) cases with

Results

follicular thyroid carcinoma. 25% (5) cases with micro DTC and 75% (15) of

The majority of them were female (403, 88.6%). Mean age at diagnosis was

cases with DTC more than 1 cm. We excluded from study one case with large

45.5G12.8 (range 10-81) years. We detected that 0.7% patients with thyroid

lytic bone metastasis because the serum TG value was very high 11096 ng/ml.

cancer had breast cancer and 13.4% patients had a family history of breast cancer

Mean TSH values were 1.4G0.9 IU/ml and mean TG values was 88.1G67 ng/ml

within three generations of the proband. There was no significantly differences

(range 16.7-255 ng/ml). In 20% (4) of cases with DTC less than 1 cm TG values it

between family history of breast cancer and gender, age at diagnosis, pathologic

were in the normal range. In 14 patients with DTC bigger than 1 cm: 42% (6) of

types, and RAI therapy.

cases had TG values more than 2 fold of normal range, 28% (4) of cases had TG

Conclusion

values in the normal range and 28% (4) of cases had TG values between normal

In the literature, there are many clinical, epidemiological, and experimental

and two fold normal range.

studies that show an association between thyroid cancer and breast cancer. Our

Conclusions

study is the first report showing history for breast cancer and family history for

In our study TG are more sensitive to detect DTC macro carcinoma, but we need

breast cancer is 0.7 and 13.4% this particular group of Turkish differentiated

to evaluate more cases, to compare TG values in cases with negative biopsy and to

thyroid cancer patients.

evaluate even the TG antibodies.

DOI: 10.1530/endoabs.49.EP1368

DOI: 10.1530/endoabs.49.EP1370

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1371

EP1373

Is there an impact of the concurrent presence of chronic autoimmune

Unilateral Graves’ disease with papillary carcinoma of the

thyroiditis in differentiated thyroid cancer patients?

hyperfunctioning lobe

Sorina Martin^1,2, Oana Budianu³, Oana Ion³, Andreea Grigore³,

Georgios Papadakis¹, Elena Gonzalez Rodriguez¹, Gilles Allenbach²,

Anca Sirbu^1,2, Carmen Barbu^1,2, Cosmin Giulea^4,5, Adrian Miron^4,5,

Marie Nicod Lalonde², Francois Gorostidi³, Kishore Sandu³,

Florin Andrei⁶ & Simona Fica^1,2

Massimo Bongiovanni⁴ & Gerasimos P. Sykiotis¹

¹Endocrinology Department, Carol Davila University of Medicine and

¹Service of Endocrinology, Diabetes and Metabolism, CHUV, Lausanne

Pharmacy, Bucharest, Romania;²Endocrinology Department, Elias

University Hospital, Lausanne, Switzerland;²Service of Nuclear Medicine,

Hospital, Bucharest, Romania;³Carol Davila University of Medicine and

CHUV, Lausanne University Hospital, Lausanne, Switzerland;³Service of

Pharmacy, Bucharest, Romania;⁴Surgery Department, Elias Hospital,

Otorhinolaryngology, CHUV, Lausanne University Hospital, Lausanne,

Bucharest, Romania;⁵Surgery Department, Carol Davila University of

Switzerland;⁴University Institute of Pathology, CHUV, Lausanne

Medicine and Pharmacy, Bucharest, Romania;⁶Pathology Department,

University Hospital, Lausanne, Switzerland.

Elias Hospital, Bucharest, Romania.

Background

Graves’ disease (GD) typically manifests as an autoimmune hyperfunction of

The association between differentiated thyroid carcinoma

(DTC) and auto-

both thyroid lobes. Less than 10 cases of unilateral GD have been described, and

immune thyroiditis (AT) has been reported in numerous studies, yet the impact of

the pathophysiology of unilateral GD remains unknown. Co-existence of

the concurrent presence of AT and DTC remains controversial.

malignancy has never been reported. We report a case of GD of the left lobe

Methods

with simultaneous discovery of a papillary carcinoma within the hyperfunctioning

We retrospectively analysed the files of 493 patients submitted to thyroidectomy

lobe.

in our surgery department between January 2012 and September 2015.

Case description

Results

A 49-year-old patient of Middle-Eastern origin was referred to our clinic in

A total of 86 patients with DTC were enrolled, mean age 53.99G13.91 years,

November 2016, one year after the diagnosis of symptomatic thyreotoxicosis,

83.7% females. 25 (29%) patients, all women, associated biochemical and/or

treated by carbimazole for the first

6 months. Subclinical hyperthyroidism

histopathological AT. We found no significant differences between patients with

recurred after treatment withdrawal. Thyroid isotope scanning with⁹⁹Tc in

DTC and AT compared to patients without AT regarding the ultrasound

September 2016 showed diffusely increased uptake of the left lobe (with the

characteristics of the thyroid nodules: nodule diameter (PZ0.330), echogenicity

exception of a low uptake zone) and minimal uptake of the right lobe. In

(PZ0.572), halo presence (PZ0.528), microcalcifications (PZ0.347), vascular-

November 2016, the patient was asymptomatic and had subclinical hyperthyroid-

ization

(PZ0.199) and lymph nodes involvement

(PZ0.418), nor the

ism. Thyroid gland ultrasonography

(US) showed a slightly enlarged and

histopathological characteristics of the DTC: tumor subtype (PZ0.100), tumor

heterogeneous left lobe with clearly increased vascularity. The right lobe was

diameter (PZ0.726), the presence of multifocality (PZ0.829), TNM staging

smaller, homogeneous, with normal vascularity confined to its periphery. Based

(PZ0.672), vascular invasion

(PZ0.149), capsular invasion

(PZ0.617),

on the imaging results and positive thyrotropin receptor antibodies, unilateral GD

extracapsular extension

(PZ0.713) or the presence of local lymph nodes

was diagnosed. The low uptake zone in the left lobe corresponded to a hypoechoic

metastasis (PZ0.888).

nodule with suspicious US features (central calcification, possible infiltration of

Conclusions

the thyroid capsule). Fine-needle biopsy of this lesion revealed papillary

Although our data showed a high prevalence of AT in patients with DTC, we

carcinoma (Bethesda class VI). Total thyroidectomy will soon be performed.

found no significant differences regarding the ultrasound and histopathological

Conclusion and perspectives

characteristics of DTC in patients that concurrently had AT compared to patients

GD can rarely present with an asymmetric involvement of the thyroid lobes. Our

without AT.

patient is the first case associating unilateral GD and thyroid malignancy in the

DOI: 10.1530/endoabs.49.EP1371

ipsilateral lobe. Given that total thyroidectomy is indicated, complete

histological, biochemical and genetic evaluation of both lobes will allow us to

test current hypotheses on the pathophysiology of unilateral GD.

DOI: 10.1530/endoabs.49.EP1373

EP1372

20,000 euros for diagnosis of one thyroid cancer case: It is not too much?

Marek Maciejewski¹, Agnieszka Sawicka¹, Michal Slomian¹,

Malgorzata Gasiorek¹, Renata Budzynska-Nosal¹ &

Krzysztof Marczewski^1,2

¹Pope John Paul II Regional Hospital, Zamosc, Poland;²University of

EP1374

Economy and Innovation, Lublin, Poland.

Trends in the clinicopathological features and clinical outcomes of

medullary thyroid carcinoma - an Israeli multicenter study

Introduction

Dania Hirsch^1,8, Orit Twito^2,8, Sigal Levy³, Gideon Bachar^4,8,

Thyroid cancer is a major public health problem, and fine-needle biopsy is an

Eyal Robenshtok^1,8, David J Gross⁵, Haggi Mazeh⁶ & Carlos Benbassat^7,8

established method of its early detection. However, there are still some

¹Institute of Endocrinology, Rabin Medical Center, Petach Tikva, Israel;

controversy about the indication for BACC depending on the clinical data and

²Institute of Endocrinology, Meir Medical Center, Kfar Saba, Israel;

the results of diagnostic imaging. An important role is also played by economic

³Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel;

criteria, including socially acceptable, so-called equitable cost of obtaining

⁴Department of Otorhinolaryngology, Rabin Medical Center, Petach Tikva,

additional year of life, which in our country is determined to three times the

Israel;⁵Neuroendocrine Tumor Unit, Endocrinology & Metabolism Service,

average national income per capita.

Department of Medicine, Hadassah-Hebrew University Medical Center,

Results

Jerusalem, Israel;⁶Department of Surgery, Hadassah-Hebrew University

We analyzed the results of fine needle biopsy of thyroid nodules taken in the years

Medical Center, Jerusalem, Israel;⁷Endocrine Institute, Assaf Harofeh

2008-2016 in ambulatory patients. In most cases, these people were targeted due

Medical Center, Zerifin, Israel;⁸Sackler Faculty of Medicine, Tel Aviv

to changes in the ultrasound detected by examination performed for other

University, Tel Aviv, Israel.

indications, the so-called incidentalomas. The most common indication was

evaluating the patency of the carotid arteries. We have performed total of 5347

Background

biopsy of thyroid focal lesions which led to the diagnosis of eight cases of thyroid

The massive use of neck sonography has led to a dramatic increase in the

cancer. Average cost detection of a single cancer case amounted to approximately

incidence of thyroid cancer detection, predominantly small papillary carcinomas.

20 000 Euro.

However, changes in the presentation and course of medullary thyroid carcinoma

Conclusion

(MTC) over time remain unclear.

This cost does not exceed three times the annual GDP per capita, but is high.

Objective

Therefore, it seems reasonable to discuss the criteria for performing the BACC in

To evaluate trends in the presentation and outcomes of MTC.

case of incidental thyroid focal changes, particularly in regions with a lower

Methods

incidence of thyroid cancer.

Patients treated for MTC at four medical centers in Israel were divided into two

DOI: 10.1530/endoabs.49.EP1372

groups by year of diagnosis, 1963-2005 (period A) and 2006-2016 (period B),

and compared for clinicopathological variables.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Results

EP1376

The cohort included 189 patients (55% female) of mean age 48.9G18.6 years

Differentiated thyroid cancer in patients taking lithium for bipolar

followed for 10.1G9.4 years. Of these, 104 patients (55%) were diagnosed in

affective disorder: a case series

period A, and 85 (45%) in period B. No significant between-group differences

Abbas Ali Tam, Cevdet Aydin, Didem Ozdemir, Muhammed

were found in primary tumor size at diagnosis (26.2G18.5 and 23.7G17.6 mm,

Cuneyt Bilginer, Reyhan Ersoy & Bekir C¸ akir

respectively), proportion of micro-MTCs (!1 cm) (18/74, 24.3% and 19/75,

Yildirim Beyazit University School of Medicine, Endocrinology and

25.3%, respectively), or TNM staging. Period A was characterized by a higher

Metabolism Diseases, Ankara, Turkey.

rate of familial MTC (28/98, 28.6% vs 6/73, 8.2%; PZ0.001) and lower age at

diagnosis (45.2G18.6 years vs 53.7G17.7 years; PZ0.002). Cervical lymph

node dissection was more commonly performed in period B (58/81, 71.6% vs

Aim

68/80, 85%; PZ0.05), but no concomitant increase in the rate of metastatic

Lithium bicarbonate is a drug used in the initial treatment of bipolar disorders.

lymph node excision (46/64, 71.9% and 45/70, 64.3% respectively, PZ0.36).

Lithium is an element of alcali metal group and besides being a causative agent

There was no significant difference between groups A and B in disease-free-

for goiter and hypothyroidism primarily, it has also some antithyroid effects.

survival

(DFS) at one year after diagnosis (34/87, 39.1% and 35/70, 50%,

Rarely, lithium may cause hyperthyroidism secondary to thyroiditis or probably

respectively PZ0.2) or at last follow-up, comparing patients with similar

autoimmune mechanisms. The association between lithium and thyroid cancer is

surveillance periods (11/28, 39.3% and 36/75, 48%, PZ0.5).

very little known subject. In this case series, we presented differentiated thyroid

Conclusions

cancer in five patients using lithium for the treatment of bipolar affective disorder

Unlike differentiated thyroid cancer, most presenting features of MTC have not

Cases

changed in recent years. The most significant temporal change is a decreased rate

Three of patients were female and two were male. Three patients had

of familial MTC. Despite the use of more extensive surgical procedures and new

hypothyroidism and were using levothyroxine and two patients were euthyroid.

treatment modalities, there has not been significant improvement in disease-

There was a solitary thyroid nodule in two, while multiple nodules were present in

related outcomes.

others. Preoperatively, thyroid fine needle aspiration biopsy was performed in all

DOI: 10.1530/endoabs.49.EP1374

patients and cytological results were suspicious for malignancy in three, atypical

cells in one and atypia of undetermined significance in one subject.

Histopathologically, one patient had minimal invasive follicular carcinoma, two

had papillary thyroid carcinoma, and two had concomitant papillary thyroid

carcinoma and papillary thyroid microcarcinoma. All patients were given

radioactive iodine ablation treatment postoperatively.

Conclusion

Thyroid dysfunctions can be observed in patients using lithium due to various

mechanisms. Among these, thyroid cancers are the least known and patients with

nodular goiter on lithium therapy should be evaluated carefully for the risk of

EP1375

development of thyroid cancer.

Association of preoperative neutrophil lymphocyte ratio and platelet

DOI: 10.1530/endoabs.49.EP1376

lymphocyte ratio with clinical features of differentiated thyroid cancer

Bengur Taskiran¹, Guven Baris Cansu¹, Goknur Yorulmaz² &

Ruya Mutluay¹

¹Yunus Emre State Hospital, Eskisehir, Turkey;²Osmangazi University,

Eskisehir, Turkey.

Introduction

EP1377

Platelets and neutrophils take part in proliferation of cancer cells, angiogenesis,

and metastasis. Studies on various cancer types showed relation between

Predictive value of CHAID Algorithm in the diagnosis of malignancy in

prognosis and absolute numbers of neutrophils, lymphocytes, and the ratio

thyroid nodules with Bethesda III (AUS/FLUS) cytology

in-between (NLR) and platelet/lymphocyte ratio (PLR). We aimed to evaluate

Reyhan Ersoy¹, Cevdet Aydin¹, Oya Topaloglu¹, Didem Ozdemir¹,

NLR and PLR and their relation with features of differentiated thyroid carcinoma

Husniye Baser², Fatma Neslihan Cuhaci¹, Abbas Ali Tam¹, Berna Ogmen²,

(DTC).

Sefika Burcak Polat¹, Fatma Dilek Dellal², Ahmet Dirikoc¹,

Materials and methods

Nagihan Bestepe², Mehmet Kilic³, Aysegul Aksoy Altinboga⁴ &

Electronic data of 330 patient with pathologic diagnosis of thyroid carcinoma

Bekir Cakir¹

were evaluated retrospectively. Two hundred and fifty five patients with other

¹Department of Endocrinology and Metabolism, School of Medicine,

chronic diseases and medullary thyroid carcinoma and whose pathology reports

Ankara Yildirim Beyazıt University, Ankara, Turkey;²Department of

and preoperative CBC data were unavailable were excluded. Clinical and

Endocrinology and Metabolism, Ankara Ataturk Education and Research

laboratory features of 75 patients (63 female, 12 male) were analysed.

Hospital, Ankara, Turkey;³Department of General Surgery, School of

Results

Medicine, Ankara Yildirim Beyazıt University, Ankara, Turkey;

The most common subtype was conventional type papillary thyroid cancer

⁴Department of Pathology, Ankara Ataturk Education and Research

(nZ46). Mean age was 46G12 years. 50 tumours were unifocal, 25 multifocal.

Hospital, Ankara, Turkey.

Forty-two patients had tumour less than 1 cm in size, 33 had 1 cm or larger. Forty

patients underwent radioactive iodine therapy or remnant ablation (RAI dose:

Introduction

92G32 mCi). Preoperative and postoperative NLR and PLR were not different

‘Artificial intelligence’ is an information-processing technology developed and

according to age (younger than or older than 45 years, focality (uni/multi focal),

inspired by the information processing technique of human brain. Artificial

RAI history (absence/presence), tumour size (less than 1 cm or larger), invasion

intelligence applications are used with an increasing ratio in medicine;

(nZ11). When 2.5 was chosen as cut-off value for NLR, preoperative and

particularly in the fields of breast cancer, radiology, cardiology, health

postoperative PLR was significantly (PZ0.0001 and PZ0.046) different; age at

management and drug effects analysis. There is not any study concerning thyroid

diagnosis was also significantly different

(PZ0.002). There was a positive

diseases and artificial intelligence applications in the literature. In this study, we

relation between preoperative and postoperative PLR (rZ0.575, PZ0.0001) and

aimed to use an artificial intelligence application

- CHAID (Chi-Squaered

NLR values (rZ0.431, PZ0.004). NLR was also positively correlated with PLR

Automatic Interaction Detection) algorithm- to predict malignancy risk in thyroid

both in pre- and postoperative period. Postoperative thyroglobulin data were

nodules with Bethesda III -atypia of undetermined significance/follicular lesion

available in 55 patients. It was negatively correlated with preoperative NLR

of undetermined significance (AUS/FLUS)- cytology.

(rZK0.354, PZ0.008). Age was positively correlated with NLR (rZ0.245,

Methods

PZ0.345). Tumour size was negatively correlated with postoperative PLR

Data of 3300 patients (6863 nodules) evaluated by our multidisciplinary council

(rZK0.102, PZ0.048).

and operated between 2005-2016 were analysed retrospectively. There were 364

Conclusion

patients with 385 nodules with AUS/FLUS cytology in. 65 parameters including

Preoperative NLR and PLR does not predict clinical features of DTC. Association

clinical, laboratory, ultrasonographical, cytological and histopathological features

between pre- and postoperative PLR and NLR may be due to a continuum instead

of each nodule were evaluated. The diagnostic value of CHAID algorithm was

of causal relation. Unlike high NLR associated poor prognosis in other cancer

determined considering histopathological diagnosis as the reference method.

types, higher NLR was observed in cases with lower thyroglobulin levels. CBC

Results

has no effect on thyroid cancer with indolent nature.

There were 75 male (20.6%) and 289 female (79.4%) patients. Histopathological

DOI: 10.1530/endoabs.49.EP1375

diagnosis was benign in 282 (73.2%) and malignant in 103 (26.8%) nodules.

Analysis with CHAID algorithm revealed that presence of thyroiditis/chronic

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

thyroiditis ultrasonographically, and presence of nuclear groove and intranuclear

¹University of Health Sciences Gazi Yasargil Education and Training

inclusions cytologically were predictive for malignancy. This algorithm had a

Hospital, Diyarbakir, Turkey;²Ege University Faculty of Medicine

sensitivity of

49.5%, specifity of

96.8%, positive predictive value of

85%,

Endocrinology Department, Izmir, Turkey;³Ege University Faculty of

negative predictive value of 16% and accuracy of 84.15%.

Medicine Department of Medical Biology, Izmir, Turkey.

Conclusion

The main issue in thyroid nodules is to differentiate benign and malignant lesions.

While doing this, clinician should try to avoid unnecessary ultrasonography

examinations, fine needle aspiration biopsy and surgical approach. Superfluous

Thyroid cancer is the most common malignant tumor of the human

interventions cause increased economical burden for both the patient and the

endocrine system. Recently, its incidence has increased significantly.

country. Use of artificial intelligence applications in clinical practice might help

Anaplastic cancer constitutes

2-4% of thyroid cancers and remains

aggressive. The life expectancy is 2-6 months. It is often beyond the

to reduce unnecessary diagnostic procedures and surgical interventions in thyroid

surgical margin. External radiation therapy or chemotherapy are the

nodules with AUS/FLUS. cytology.

treatment options. Therefore, new therapeutic approaches are needed.

DOI: 10.1530/endoabs.49.EP1377

Peroxisome proliferator-activated receptor

(PPAR) gamma is a DNA-

binding nuclear hormone receptor and regulates transcription effects in cell

energy metabolism. PPAR gamma agonists may inhibit tumor growth

through terminal cell differentiation induction, cell cycle arrest, apoptosis

induction and angiogenesis inhibition. PPAR gamma agonists show

significant antitumor activities against various cancers both in vitro and

in vivo. Metformin (1,1-Dimethylbiguanide) is the most widely used drug in

EP1378

treatment of type 2 diabetes patients. Preclinical data show its anticancer

Thyroid autoimmunity and risk of incidental thyroid microcarcinoma

effects. The molecular mechanisms of metformin in cancer cells is still

in non-toxic nodular thyroid diseases

unknown. In our study, we plan to evaluate effects of combination of

Dimitrios Askitis¹, Eleni I Efremidou¹, Michail A Karanikas¹,

metformin and pioglitazone on AMPK/mTOR signal pathway, p53 and

Grigorios Tripsianis¹, Alexandra Giatromanolaki²,

apoptosis in human anaplastic thyroid cancer cells. In C643 and SW1736

Alexandros Polychronidis¹ & Nikolaos Lyratzopoulos¹

cell lines, IC50 doses of metformin and pioglitazone were found as 17.69

¹First Surgical Department, University Hospital of Alexandroupolis, Faculty

and 11.64 mM, and 27.12 and 23.17 mM respectively. The combination of

of Medicine, Democritus University of Thrace, Alexandroupolis, Greece;

metformin and pioglitazone was determined as additive with isobologram

²University Pathology Department, University Hospital of Alexandroupolis,

analyses. Both of the compounds induce apoptosis separate or in

Faculty of Medicine, Democritus University of Thrace, Alexandroupolis,

combination. Consequently, we have evaluated the down regulation of the

Greece.

expression levels of oncogenic AKT3, CHUK, CDC42, EIF4E, HIF1A,

IKBKB, ILK, PIK3CA, PIK3CG, PLD1, PRKCA, RICTOR genes in MET

and PIO combination treated cells. Moreover, expression levels of tumor

Aim

suppressor DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8,

Thyroid cancer comprises the most common endocrine malignancy and a variety

GSK3B, MTOR, MYO1C, PTEN, ULK1, ULK2 genes were found to

of studies have investigated the role of thyroid autoimmunity as an independent

increase functionality. The results show that these agents can be used in the

risk factor for the manifestation of differentiated thyroid cancer in otherwise

treatment of thyroid cancer as novel therapeutic agents.

benign thyroid disorders. Objective of the current retrospective study is the

DOI: 10.1530/endoabs.49.EP1379

assessment of any possible correlation between thyroid autoimmunity, in terms of

elevated thyroid autoantibodies, and incidental thyroid microcarcinoma (ITC) in

non-toxic nodular thyroid diseases, subjected to total thyroidectomy (TT).

Patients and methods

In First Surgical Department between 1 January 2005 and 01 March 2010 a total

of 186 patients (146 females/40 males) underwent TT after referral for benign

non-toxic nodular thyroid diseases. Surgical specimens were evaluated in

University Pathology Department and the diagnosis of ITC was recorded.

Elevated thyroid autoantibody titers were assessed in patients without (group A)

and those with (group B) thyroid cancer. The results were also compared

EP1380

regarding preoperative diagnosis.

Vitamin D status and MPV changes in differentiated thyroid cancer

Results

Kevser Onbasi¹, Turkan Pasalı Kilit¹ & Aysenur Beyazıt Ucgun²

32 patients (17.2%) were diagnosed with microcarcinoma (females/males: 2.2/1),

¹Dumlupinar University, Kutahya, Turkey;²Suleyman Demirel University,

while 154 patients (82.8%) were free of malignancy. 9/34 patients with solitary

Isparta, Turkey.

thyroid nodule (STN) and 33/152 subjects with multinodular goiter (MNG) had

biochemical signs of thyroid autoimmunity. 9/32 (28.1%) cancer patients had

elevated thyroid autoantibodies preoperatively. The prevalence of thyroid

autoimmunity was higher

(non-statistically significant) in the cancer-group

Thyroid cancer is the most common cancer in the endocrine system. Thyroid

compared to the non-cancer cohort (28.1% vs 21.4% respectively; PZ0.41).

follicular epithelial-derived cancers are papillary, follicular, and anaplastic

Furthermore, the prevalence of thyroid microcarcinoma was also higher (non-

cancer. Risk factors for differentiated cancers are radiation exposure, and

statistically significant) in the autoimmunity subgroup compared to the non-

family history. Possible risk factors like occupational and environmental

autoimmunity subgroup (21.4% vs 16%; PZ0.41). These differences were

exposures, increased parity, late age at first pregnancy, and hepatitis C-

manifested solely in the MNG group.

related chronic hepatitis are potential but not proven risk factors. In order to

Conclusions

evaluate other potential risk factors have we investigated the vitamin D

Thyroid autoimmunity does not seem to feature an independent risk factor

status and MPV (mean platelet volume) in thyroid cancer patients and in

associated with thyroid microcarcinoma in non-toxic nodular thyroid diseases.

other benign thyroid disorders. 25-OH vitamin D3 levels were low and MPV

However, a non-significant higher correlation is recognized in the subgroup of

euthyroid multinodular goiter. Further studies are required to investigate the

potential association between thyroid autoimmunity and carcinoma, as a helpful

Table 1 MPV values and 25-OH vitamin D3 levels in benign and malign

indication for surgical referral.

thyroid disorders

DOI: 10.1530/endoabs.49.EP1378

Hashimoto

Graves

Thyroid cancer

thyroiditis

disease

Healthy con-

(nZ47)

(nZ30)

trols (nZ30)

Age (years)

45.96

(21-84)

41.43

(17K59)

42.37

(18-75)

45,37 (19K69)

Gender (male/

4/43

4/26

14/16

6/24

female)

EP1379

WBC (!10⁹/l)

7.42G2.19

7.34G1.42

7.92G1.91

7.39G2.16

0.174

Hb (g/dl)

13.11

(9.3-

13.47

(11.1K

13.98

(10.9-

13.55

(8.50K

0.035*

Effects of combination of metformin and pioglitazone on AMPK/mTOR

16.8)

15.3)

17)

16.80)

signal pathway, p53 and apoptosis in human anaplastic thyroid

Platelets (!10⁹/l)

279.14G81.98

293.43G66.27

272.8G67.90

266.57G61.10

0.145

cancer cells

MPV (femtoliters,fl)

8.22

(6-10.7)

8.41

(6.9K

8.38

(6.5-

8.56

(6.40K

0.001*

10.6)

11.2)

10.90)

Nilufer Ozdemir Kutbay¹, Mehmet Erdogan², Banu Sarer Yurekli²,

25-OH Vitamin D3

13.82G8.01

19.94G11.68

20.05G12.63

18.94G11.70

0.006

Cansu Caliskan Kurt³, Cumhur Gunduz³ & Cigir Biray Avci³

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

values have been found to be low. Low vitamin D may be a risk factor for

¹Holycross Cancer Centre, Kielce, Poland;²Jan Kochanowski University,

thyroid cancer. Decreased MPV values may be used as a predictor of thyroid

Kielce, Poland;³Medical University of Silesia, Katowice, Poland.

cancer.

Background

DOI: 10.1530/endoabs.49.EP1380

A dynamic risk stratification with modified initial estimated risk based on

response to therapy and disease course is one of the crucial changes adopted

recently by the American Thyroid Association (ATA). The analysis of BRAF

status is not routinely recommended by ATA, although this finding may be

advantageous to individualized risk-adapted approach in papillary thyroid cancer

(PTC). The methods used to detect the BRAF V600E are known of variation in the

sensitivities, variable susceptibilities for DNA degradation, and possible

equivocal results with direct DNA Sanger sequencing (Seq), particularly. The

aim of this study was to examine the relation between the BRAF status of PTC

detected applying three methods and ATA response-to-therapy categories

(excellent, indeterminate, biochemical/structural incomplete), and recurrence

EP1381

identified after no evidence of disease (NED) or persistence disease.

BRAFV600E status and Stimulated Thyroglobulin at ablation time

Methods

increase prognostic value of American Thyroid Association (ATA)

Unselected 723 PTC cases with known BRAF status diagnosed 2000-2013,

classification systems for persistent disease in Differentiated Thyroid

actively monitored at single institution, and reviewed retrospectively up to

Carcinoma (DTC)

December 31, 2015. Genotyping of BRAF was implemented using the algorithm:

Andrea Repaci¹, Valentina Vicennati¹, Alexandro Paccapelo¹,

Seq, followed by more sensitive allele-specific polymerase chain reaction (PCR),

Nicola Salituro¹, Ottavio Cavicchi², Fabio Monari³, Giovanni Tallini⁵,

and real-time PCR (quantitative PCR; qPCR). Considering various limitations of

Elisa Gruppioni⁴, Annalisa Altimari⁴, Michelangelo Fiorentino⁴ &

particular methods 639 specimens were available for the analysis by Seq, 638 by

Uberto Pagotto¹

ASA-PCR, and 705 by qPCR.

¹Endocrinology Unit, Department of Medical and Surgical Sciences,

Results

S. Orsola-Malpighi Hospital, Alma Mater University of Bologna, Bologna,

BRAF V600E was found in 51.6%, 67.7%, and 67% PTCs detected by Seq, PCR,

Italy;²Otolaringology Unit, S. Orsola-Malpighi Hospital, Bologna, Italy;

and qPCR, respectively. The indeterminate response was significantly more

³Radiation Oncology Center, Department of Experimental, Diagnostic and

frequent in BRAF-positive PTCs identified by SDefault (PZ0.03), but not by

Specialty Medicine-DIMES, S. Orsola-Malpighi Hospital, Alma Mater

ASA-PCR (PZ0.07), and qPCR (PZ0.06). There was no significant relation

University of Bologna, S. Orsola-Malpighi, Bologna, Italy;⁴Laboratory of

between BRAF-positive cases and other not-excellent response-to-therapy

Oncologic Molecular Pathology, S.Orsola-Malpighi Hospital, Bologna,

categories, recurrences and persistent disease regardless of the method used.

Italy;⁵Anatomic Pathology-Molecular Diagnostic Unit AUSL of

Conclusions

Bologna,Department of Medicine (DIMES), Bologna, Italy.

The BRAF V600E mutation identified by high sensitive methods (ASA-PCR,

qPCR) did not significantly alter a response-to-therapy category and out-come of

PTC. However, an indeterminate response was more frequent in BRAF-mutated

Background

PTC detected by direct sequencing.

Stimulated Thyroglobulin levels measured at the time of remnant ablation (Htg-

A) and BRAFV600E mutation were shown to have prognostic value in predicting

DOI: 10.1530/endoabs.49.EP1382

persistent disease in DTC. The aim of this study was to evaluate the prognostic

role of Htg-A combined with BRAFV600E status in association with revised

American Thyroid Association (ATA) risk stratification.

Patients and methods

620 patients treated for a DTC were included in this study with median follow-up

duration of 6.1

year. All patients were submitted to a total thyroidectomy,

followed by radioiodine ablation. Patients with positive antibodies anti-Tg were

excluded. The predictive value of Htg-A was calculated by receiver operating

characteristic curve analysis. Cox proportional hazard regression modeling,

including BRAF status, Htg-A and ATA classification system, was assessed to

EP1383

evaluate existing persistent disease risk.

Results

Thyroid nodules ultrasound classification and the importance of the

BRAF status and Htg-A levels together improve ATA risk classification in all

endocrinologist clinical feeling

categories. In particular in Low risk ATA only BRAFV600ECHtg-AO8.9 ng/ml

Bruno Madeo^1,2, Giulia Brigante^1,2, Anna Ansaloni^1,2, Erica Taliani^1,2,

was associated with persistent disease (PZ0.001 HR 60.2 CI 95% 5.28-687. In

Manuela Simoni^1,2 & Vincenzo Rochira^1,2

Intermediate ATA risk BRAFwt C Htg-AO8.9 ng/ml was associated with

¹Unit of Endocrinology, Department of Biomedical, Metabolic and Neural

persistent disease (PZ0.029 HR 2.71 CI 95% 1.106-6.670) and BRAFV600EC

Sciences, University of Modena and Reggio Emilia, Modena, Italy;

HtgO8.9 ng/ml was associated with persistent disease (PZ0.000 HR 5.001 CI

²Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

95% 2.318-10.790). In High risk ATA BRAFV600ECHtg-A!8.9 ng/ml was

associated with persistent disease (PZ0.042 HR 5.963 CI 95% 1.069-33.255)

Background and aim of the study

and BRAFV600ECHtg-AO8.9 ng/ml was associated with persistent disease

Several ultrasound (US) classifications for estimating thyroid nodules risk have

(PZ0.002 HR 11.564 CI 95% 2.543-52.576).

been proposed. Since most of them are hardly applicable in clinical practice, we

Conclusion

created a local tool, named Modena classification

(MC), considering US

BRAF status and Stimulated Thyroglobulin levels at ablation time improve the

characteristics and clinician subjective impression. The aim is to verify the

ATA risk stratification, so also Htg-A could be included in ATA risk

diagnostic accuracy of MC and to compare it to US classifications of American

classification.

Thyroid Association(ATA) (1) and British Thyroid Association(BTA) (2).

DOI: 10.1530/endoabs.49.EP1381

Methods

We prospectively enrolled 111 patients (33M, 78F; age 19-75; total 457 nodules)

with an indeterminate, suspicious for malignancy or malignant cytology. All the

patients underwent neck US before surgery and a score risk was assigned,

according to MC: low (not certainly nodular or not suspect); intermediate

(indeterminate); high

(suspect or very suspect). Then, we retrospectively

classified nodules according to ATA and BTA. The US pattern was related to

EP1382

hystology.

Results

High sensitivity of BRAF detection method does not alter response to

All the classifications had low sensitivity and positive predictive value (PPV), and

therapy of papillary thyroid cancer of known BRAF status

high specificity and negative predictive value (NPV) for low risk categories. For

Agnieszka Walczyk¹, Aldona Kowalska^1,2, Artur Kowalik¹,

the intermediate risk category, BTA had the highest accuracy (68%). For higher

Janusz Kopczynski¹, Iwona Palyga¹, Danuta Gasior-Perczak¹,

Estera Mikina¹, Katarzyna Lizis-Kolus¹, Dorota Szyska-Skrobot¹,

risk categories, MC had good sensitivity (62%), high specificity (89%) and

Monika Szymonek¹, Stefan Hurej¹, Maciej Kajor³, Magdalena Chrapek² &

accuracy (81%); ATA had high sensitivity (83%), low specificity (48%), accuracy

Stanislaw Gozdz^1,2

58%; BTA had high sensitivity (88%), low specificity (44%), accuracy 57%.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusions

The present study assessed the feasibility of evaluating tumor invasion into the

A classification that considers the subjective impression of the clinician, in

RLN using ultrasonography (US) and computed tomography(CT).

addition to the known US characteristics, has highest accuracy and specificity

Materials and methods

compared to guidelines classifications, particularly if the nodule has suspect US

Of 7,916 patients with a PTC who underwent surgery at our hospital, 35 with

features.

preoperative tumors that were %10 mm, without distal metastasis or lymph node

References

metastasis, and with surgical findings of RLN invasion were included. The

(1) Haugen et al. Thyroid. 2016, 26: 1-133.

location of the tumor and the degree of contact with the thyroid capsule (DCTC)

(2) Perros et al. Clin Endocrinol (Oxf). 2014; 81 (Suppl 1):1-122.

were examined by US and CT.

DOI: 10.1530/endoabs.49.EP1383

Results

Ten of the 35 patients were treated by combined resection of the RLN, and 25

patients were treated by shaving the RLN. US revealed that the tumor was located

at the dorsal side of the thyroid in 31 patients (88.5%). In all patients who were

treated by combined resection of the RLN, the tumor was located at the dorsal

side of the thyroid. Among these patients, the DCTC determined by US was

R25% in nine patients and !25% in one. Among those who were treated by

RLN shaving, the DCTC was R25 and !25% in nine and 16 patients,

respectively (PZ0.003). The DCTC was R25% in all patients who were treated

combined resection and in 15 of the 25 patients who treated by RLN shaving

EP1384

(RZ0.018) according to CT imaging. The tumor was located 1-1.5 cm from the

Five-year follow-up of thyroid cold nodules with somatic oncogene

cricoid cartilage in most patients who were treated by combined resection.

mutations in Hungarian patients

Conclusions

Bálint Tobiás^1,4, Bernadett Balla^1,4, Petra Soltész¹, János P Kósa^1,4,

When a PTC is located at the dorsal side of the thyroid with R25% DCTC,

János Horányi², Balázs Járay³, Eszter Székely³, Roland Istók³,

surgery should be selected for RLN invasion. Our results showed that the

Tamás Székely³ & Péter Lakatos¹

accuracy of predicting recurrent laryngeal nerve invasion can be improved by

¹1st Department of Internal Medicine, Semmelweis University, Budapest,

combining US with neck CT.

Hungary;²1st Department of Surgery, Semmelweis University, Budapest,

DOI: 10.1530/endoabs.49.EP1385

Hungary;³2nd Department of Pathology, Semmelweis University,

Budapest, Hungary;⁴PentaCore Lab Ltd, Budapest, Hungary.

Cold nodules are one of the most common findings on scintiscans and

ultrasound examinations of the thyroid gland. About 5-10% of these nodules

turn out to be histologically malignant. Our aim was to examine the

predictive value of somatogenetic alterations associated with thyroid cancer

in FNA samples of thyroid cold nodules being citologically benign at the

beginning of the study. These alterations included single nucleotide

mutations

(BRAF, HRAS, NRAS, KRAS) and genetic translocations

(RET/PTC1, RET/PTC3, PAX8ex7/PPARgamma, PAX8ex9/PPAR-

EP1386

gamma). The SNPs were tested by real-time PCR with fluorescence melting

curve analysis and the rearrangements were detected by Taqman probe-

Solitary metastasis of papillary thyroid cancer in the sellar region and

based quantitative real-time PCR. We have analyzed 779 consecutive FNA

cavernous sinus

samples and followed the patients up for 5 years. We identified 39 BRAF, 23

Lila Brakni, Lounes Haffaf, Yamina Aribi, F Hameg & Samia Ouldkablia

NRAS, 9 HRAS, 1 KRAS mutations and 1 RET/PTC3 rearrangement. No

Army Hospital, Algiers, Algeria.

PAX8/PPARgamma rearrangements were demonstrated in the nodules.

During the five-year follow-up, 57 cases (7.3%) were classified as malignant

by histology, from which we indentified genetic alterations in 27 (47.4%).

The commonest site of metastasis from papillary carcinoma is regional

The statistical performance of our genetic panel showed a specificity of

lymph nodes. Distant metastases are rare, most presenting synchronously.

93.6%, sensitivity of 47.4%, a negative predictive value of 95.8% and a

Brain metastases in papillary carcinoma are rare, reported with a frequency

positive predictive value of 37.0%. In summary, our test approach may be

of 0.1-5% and cavernous sinus metastasis is extremely rare.

used for the prediction of malignant transformation of thyroid cold nodules,

Case report

however, its sensitivity requires improvement.

A 62-year-old woman presented with a history of non-secretory pituitary

DOI: 10.1530/endoabs.49.EP1384

macroadenoma present with symptoms of hypopituitarism. MRI of the brain

revealed a 4.5!3.1!3 cm, extension into the cavernous sinuse. The tumorwas

not rescable, she Underwent a simple biopsy in view of the haemorrhagic nature

of the tumor. Histopathology revealed a tumor with diffuse papillary architecture.

On immunohistochemistry: positive for TTF1, PAX8, thyroglobulin, TPO;Ki67

(10-15%) and negative for GH, LH, FSH, ACTH, TSH. A diagnosis of metastatic

papillary carcinoma was made. Thyroid ultrasound revealed two hypoechoic

nodules. After thyroidectomy the histopathology was papillary micro- carcinoma

thyroid-follicular variant of 05 mm. She received radioiodine therapy.

Discussion

EP1385

The incidence of distant metastases from papillary carcinomas is reported to be 6-

Usefulness of preoperative ultrasonography and computed tomography

23%, the majority occurring within 5 years of the initial diagnosis. There have

for evaluation of recurrent laryngeal nerve invasion by Papillary

been case reports of papillary carcinoma with metastasis at unusual sites like the

Thyroid microcarcinoma

breast and cavernous sinus. All these cases were associated with a missed

Keiko Ohkuwa, Tadatoshi Osaku, Tetsuyo Maeda, Yuna Ogimi,

diagnosis of thyroid carcinoma, like our case, should be considered exceptional.

Chie Masaki, Junko Akaishi, Kiyomi Y Hames, Chisato Tomoda,

There have been five reports of papillary carcinoma with metastasis to the skull

Akifumi Suzuki, Kenichi Matsuzu, Takashi Uruno, Wataru Kitagawa,

base.

Mitsuji Nagahama, Kiminori Sugino & Koichi Ito

Conclusion

Ito Hospital, Tokyo, Japan.

There is no consensus for the treatment of papillary thyroid carcinoma with

cavernous sinus metastasis. Thus, that solitary distant metastasis from

Background

thyroidcarcinoma though rare, is a possibility, a difficult diagnosis to be made

Papillary thyroid microcarcinoma (PTMC) has low malignant potential and an

on radiology.

extremely good prognosis. However, surgical findings of asymptomatic PTC,

DOI: 10.1530/endoabs.49.EP1386

can occasionally reveal tumor invasion into the recurrent laryngeal nerve (RLN).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1387

thyroid cancer after three years of stable diasease showed a neuroendocrine

progression with multiple metastases. SSA treatment was started and we plan to

Calcitonin: clinical and laboratory evaluation in a tertiary hospital

perform peptid receptor radionuclide therapy (PRRT).

Catarina Silvestre, Maria João Bugalho, Joaquim Sampaio, Helena Proença

& Raquel Carvalho

DOI: 10.1530/endoabs.49.EP1388

Santa Maria Hospital, Lisbon, Portugal.

Background

Calcitonin is a hormone secreted by thyroid C cells, and is considered an excellent

marker for medullary thyroid carcinoma (MTC). However, the use of calcitonin to

screen patients with nodular thyroid disease (NTD) remains controversial.

Objective

Defining the frequency of hypercalcitoninemia among NTD patients followed at a

tertiary referral hospital.

EP1389

Methods

Cytohistologic correlation of thyroid nodules

Retrospective analysis of basal calcitonin measurements and corresponding

Ines Barka, Senda Ouerdani, Molka Chaieb, Asma Ben Abdelkrim,

patients’ records between January 2011-December 2015. The method used was

Amel Maaroufi, Maha Kacem & Koussay Ach

immunochemiluminescent assay. Hypercalcitoninemia was defined as O

Endocrinology Department, FARHAT Hached University Hospital, Sousse,

10 pg/ml.

Tunisia.

Results

In five years, there was a total of 6551 calcitonin measurements requested, by

different physicians from different services, to 5149 patients: median age 57

Background

years,

80.6% female. Calcitonin measurements were divided into 3 groups

The discovery of a thyroid nodule exposes the problem of the possibility of

according to their levels: GI %10 pg/ml; GII 10-100 pg/ml; GIII R100 pg/ml.

thyroid cancer. The difficulty of management of this situation is the fact that only

Excluding patients with no clinical information, there were

3097, with the

the histopathological examination can confirm or refute the malignancy. Fine-

following distribution: GI 2913, GII 158, GIII 26. Among these, calcitonin was

needle aspiration (FNA) is used as a diagnostic tool to assess thyroid nodules. The

requested in NTD context to 1504 patients: 69 patients had hypercalcitoninemia

purpose of our study is to correlate the clinical, ultasonographic, the FNA results

(GII and GIII). Of these, 21 underwent surgery (GI 12, GIII 9); a histological

and final pathology to determine the predictors of malignancy of thyroid nodules.

diagnosis of MTC was established in 12 (GII 3/25%, GIII 9/100%). Surgery was

Patients and Methods

decided based, solely, on calcitonin levels in 7 cases, since only 5 had a positive

We conducted a retrospective study on 33 patients with thyroid nodule. Data were

cytology.

obtained for FNA diagnosis, demographics, findings on ultrasound, and histologic

Conclusions

findings.

NTD was the reason for calcitonin measurement in less than 50% of total

Results

measurements. Hypercalcitoninemia was found in

4.6% of NTD patients.

The average age of our patients was

41.7yearsG15.6

SD with a female

Calcitonin levels R100 were associated to a greater CMT risk, comparative to

predominance (100%). Ultrasound findings were as follows: singles nodules,

values between 10 and 100 and reinforcing results from other groups. A cost-

multinodular goiter (MNG), and multiple nodules in respectively 48.5, 39.4 and

effective approach includes avoid unnecessary requests, adequate interpretation

12,1% of cases. Thyroid function tests prior to surgery were normal in all patients.

of results as well as appropriate selection of patients to surgery.

Among the 33 patients, 7 (21.2%)have malignant tumors in histological findings:

Two patients had signs of locoregional compression. A case of fixed nodule was

DOI: 10.1530/endoabs.49.EP1387

noted and one patient had cervical lymphadenopathy. On ultrasonogrqphy: the

average size of the nodules was

34.0G14.5 mm, three nodules were

hypoechogenic, and 1 case of mixed vascularity was diagnosed. The FNA was

benign in 90.9% of cases (nZ30), and indeterminate in 9.1% (nZ3). Of the 30

patients with a benign FNA result, 7 were found to have carcinoma on final

pathology for 23.3% false negative rate and sensitivity of 76.7%. 1 patient were

found to have incidental microcarcinoma which was located in the palpated

lesion.

Conclusion

EP1388

FNA biopsy is essential in the assessment and management of thyroid nodules.

Neuroendocrine progression of medullary thyroid cancer - case report

However, we report a high rate of malignancy among FNA diagnosed as benign

Krisztian Sepp¹, Zsuzsanna Besenyi², Laszlo Tiszlavicz³ &

lesions. This high rate of malignancy is the basis for our recommendation for a

Zsuzsanna Valkusz¹

surgical approach for benign lesions.

¹First Department of Medicine, University of Szeged, Szeged, Hungary;

DOI: 10.1530/endoabs.49.EP1389

²Department of Nuclear Medicine, University of Szeged, Szeged, Hungary;

³Department of Pathology, University of Szeged, Szeged, Hungary.

Thyroid cancers represent approximately 1% of new cancer diagnoses. Thyroid

malignancies are divided into papillary carcinomas (80%), follicular carcinomas

(10%), medullary carcinomas (5-10%), anaplastic carcinomas (1-2%) other rare

tumours (primary thyroid lymphomas, primary thyroid sarcomas). The main

therapeutic options are surgery

(mainly total thyreoidectomy), radioiodine

treatment (depending on the type and stage of the tumour), levothyroxine therapy

(thyroidea stimulating hormon - TSH suppression dose), others (external beam

EP1390

irradiation, chemotherapy, thyrosine kinase receptor inhibitors). Thyroid

Importance of central compartment neck metastasis in the

aspiration cytology was performed due to a rapidly growing neck mass of a 41

differentiated thyroid microcarcinomas

years old male patient, revealed a suspicion of neuroendocrine tumor. After the

Cátia Cunha¹, Vítor Guedes², António Garrão² & Olímpia Cid²

total removal of the thyroid gland and paratrecheal and upper mediastinal lymph

¹Hospital Beatriz Ângelo, Loures, Portugal;²Hospital da Luz, Lisboa,

node dissection histology showed medullary thyroid cancer and metastases in the

Portugal.

lymph nodes. Somatostatin receptor scintigraphy (SRS) was negative. PET-CT

showed suspicion of mediastinal metastases, at this time external beam

radiotherapy was performed. During the follow up calcitonin and chromogranin

A levels decreased presenting a stable disease, imaging investigations showed

Elective central compartment neck dissection in the treatment of differentiated

small remnant of the tumour without any progression or metastases. After three

thyroid carcinomas (CDT) remains controversial. In a series of 1500 patients

years of the operation the patient had weight loss and diarrhea, CT scan showed

undergoing thyroid surgery, the authors evaluated the prognosis related to central

cervical and mediastinal lymph node enlargement, hepatic and pancreas

compartment neck metastasis in differentiated microcarcinomas.

metastases, bone scintigraphy showed multiple bone metastases. SRS was

DOI: 10.1530/endoabs.49.EP1390

positive in these areas, somatostatin analogue

(SSA) treatment was started.

Histological verification of the metastases are in progress. In our case a medullary

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1391

Results

169 patients were included. Mean age: 40.05G6.20 years; \: 76.3%; Papillary

The impact of age and gender on the presentation and prognosis of

subtype: 89.3%.The great majority were classified as Stage I-II (81.1%). At the

medullary thyroid cancer - an Israeli multicenter study

end of the follow-up, 72.2% had achieved a complete remission. 6 to 12 months

Orit Twito¹, Simona Grozinsky-Glasberg², Carlos Benbassat^4,6,

after thyroid ablation, s-Tg was negative in 111 patients and WBS control showed

Sigal Llevy³, Gideon Bachar^5,6, David J Gross² & Dania Hirsch^6,7

negative uptake in 98 of these patients. In 13 patients (13/111), uptake remained

¹Institute of Endocrinology, Meir Medical Center, Kfar-Sava, Israel;

in the thyroid bed but no evidence of disease was found. In 4/111 subjects,

²Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service,

persistence of disease was detected by ultrasound scan, all of them with negative

Hadassah-Hebrew Universirt Medical Center, Jerusalem, Israel;³Academic

WBS. Of 58 patients with detectable s-Tg (O0.3 ng/ml), only 22 showed

College of Tel-Aviv Yaffo, Tel-Aviv, Israel;⁴Institute of Endocrinology,

pathological uptake in the thyroid bed (nZ16) or in the distance (nZ6). In 36

Assaf Harofe Medical Center, Zerifin, Israel;⁵Otorhinolaryngology, Rabin

patients with evidence of disease (62.1%) uptake was not observed. In 43 of these

Medical Center, Beilinson Hospital, Pethch-Tikva, Israel;⁶Sackler Faculty

58 patients disease-free status has not been reached. This facts reflect a low

of Medicine, Tel-Aviv University, Tel-Aviv, Israel;⁷Institute of Endo-

correlation between s-Tg level and results of the WBS

(I.KappaZ0.226;

crinology, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel.

PZ0.001). The diagnostic accuracy of WBS was founded to be low

((SensitivityZ0.36;

95% CI: 0.22-0.49) (SpecificityZ0.85;

95% CI: 0.79-

Background

0.91)).

Data regarding the effect of gender and age on medullary thyroid cancer (MTC)

Conclusions

presentation and prognosis is limited. Although older age and male sex were

WBS performed at 6-12 months after initial treatment is out of clinical utility,

found to correlate with poorer prognosis in some studies, this correlation may

especially in the presence of a s-Tg !0.3 ng/ml. WBS does not correlate with

reflect differences in MTC presentation between sex and age groups, or a mixture

results of s-Tg determination and its accuracy has turned out to be low.

of hereditary and sporadic MTC forms.

DOI: 10.1530/endoabs.49.EP1392

Objective

To evaluate the impact of age and sex on the presentation and outcomes of MTC.

Methods

Epidemiological and clinical data of MTC patients was extracted from a joint

registry of four medical centers in Israel.

Results

The study included 193 MTC patients (106 females, age 48.9G18.6, median 51),

who were followed for 10.1G9.4 years. Female gender was associated with

smaller tumor diameter (22.3 vs 28.7 mm, PZ0.032), lower rate of lymph nodes

involvement (42/70, 60% vs 49/64, 76.6%, PZ0.044) and lower rate of distant

metastases

(11/87,

12.6% vs

23/75,

30.7%, PZ0.007). Although females

achieved higher cure rates (47/97, 48.5% vs 20/72, 27.8%, PZ0.007), disease

related mortality and all cause mortality did not differ between the genders.

Patients aged !45 year at diagnosis had higher rates of hereditary familial forms

EP1393

of MTC (32/74, 43.2% vs 3/114, 2.6% .4%, P!0.0001). Analysis of the sporadic

Evolution in the management of thyroid cancer: an observational study

MTC cases (nZ137) revealed that younger age at presentation was associated

in two Belgian referral centres

with higher number of metastatic lymph nodes

(19.7G23.5 vs 10.2G9.3,

Bernard Peene¹, Annick Van den Bruel², Carolien Moyson¹ &

PZ0.05) and more therapeutic interventions during the follow-up (62.9% vs

Brigitte Decallonne¹

33.7%, PZ0.04). However, cure rate and disease related mortality were similar

¹University Hospitals Leuven, Leuven, Belgium;²General Hospital Sint

between the age groups.

Jan, Brugge, Belgium.

Conclusions

In concert with previous literature, female MTC patients present with milder

disease and achieve higher cure rates than males. However, younger age in the

Background

sporadic MTC form is associated with more advanced disease at presentation.

Thyroid cancer incidence is increasing, especially the cancers %1 cm (T1a).

Neither age nor gender affected disease related mortality.

Previous evidence suggests underuse of FNA. Several international guidelines for

the management of thyroid cancer have been published. Especially the year 2006

DOI: 10.1530/endoabs.49.EP1391

was a hallmark, with the publication of both the ETA consensus and ATA

guidelines.

Aim

Compare thyroid cancer subtypes and management before and after 2006.

Methodology

Retrospective observational study of non-medullary thyroid cancer patients

diagnosed after total thyroidectomy in two Belgian referral centres (University

Hospital Leuven, General Hospital StJan Bruges), comparing pre/per/postopera-

tive parameters of patient cohort1 (diagnosis 2004-2005, nZ69) and cohort2

(diagnosis 2011, nZ60).

EP1392

Results

Is post-treatment whole body scan useful in differentiated thyroid

The histology and tumor dimensions were comparable, with papillary thyroid

cancer after thyroid ablation?

cancer (PTC) as main histologic subtype (86% of cohort1, 82% of cohort2) and

Inmaculada Prior-Sánchez¹, María Rosa Alhambra Expósito¹,

T1a as most frequent dimension subtype (respectively 30 and 38%). In cohort2 a

Ángel Rebollo Román¹, Ana Barrera Martín¹, Estefania Moreno Ortega²,

comparable low proportion first presented following incidental finding at imaging

Juan Antonio Vallejo Casas² & María Ángeles Gálvez Moreno¹

(21 vs 17% in cohort 1). Pre-surgical FNA was performed in 91% in cohort1 and

¹Department of Endocrinology and Metabolism, Reina Sofia University

86% in cohort2. The indications for thyroidectomy were comparable, with

Hospital, Cordoba, Spain;²Department of Nuclear Medicine, Reina Sofia

Bethesda 5-6 as most frequent indication (44% in cohort1 and 53% in cohort2).

University Hospital, Cordoba, Spain.

The execution of a simultaneous lymph node dissection in the PTC subgroup was

not different, neither the frequency of postoperative hypoparathyroidism and

Background

recurrent nerve paresis after 1 year. However, radioiodine ablation was less

The short-term follow-up of patients with differentiated thyroid cancer (DTC)

frequently given in cohort2

(58

76% in cohort1, PZ0.03) and neck

after the initial treatment is based on the measurement of stimulated thyroglobulin

ultrasonography at

1 year was performed in a higher proportion of OT1a

(s-Tg) and the use of diagnostic whole body scan (WBS).

patients (73 vs 49% in cohort1, PZ0.02).

Objective

Conclusion

To evaluate the clinical utility of WBS performed at

6-12 months after

In two Belgian referral centres the use of FNA is high and established, and the

thyroidectomy. Examine the correlation between s-Tg and results of WBS.

proportion of T1a cancers is stable and low compared to the national data. A clear

Methods

change in the postoperative management of thyroid cancer patients is observed

We retrospectively evaluated all patients who were diagnosed with DTC

towards more restrictive use of radioiodine ablation and increased use of neck

(nZ213) at a tertiary hospital center in Cordoba (Spain), between January 2000

ultrasound.

and December 2013. The patients who had positive anti-thyroglobulin antibodies

DOI: 10.1530/endoabs.49.EP1393

microcarcinomas (Tumors ! 1 cm) were excluded from the study. Patients were

classified according to the new ATA- guideline.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1394

Results

The ongoing test has been performed on 17 patients, aged (23-67), 11 M, 6 F.

Retrospective analysis of unusual thyroid tumours with clear cell

Mean calcitonin values were: basalZ19.98 pg/ml (normal range: 1-11.8 pg/ml);

features: morphology and differential diagnosis

at 2 minZ209.159 pg/ml; at 5 minZ143.619 pg/ml, at 10 minZ100.557 pg/ml;

Alexander Abrosimov^1,2 & Alexei Sidorin³

10 subjects had a significant 2 min stimulated calcitonin (O100 pg/ml) and were

¹Federal State Institution, Endocrinology Research Center, Moscow, Russia;

operated, 3 subjects had an intermediate response (53.31-81.7 pg/ml) and 4

²National University of Science and Technology, MISIS, Moscow, Russia;

patients had low stimulated values(!54 pg/ml) therefore they are to be followed

³Federal State Institution, Medical Radiology Research Center, Obninsk,

up. C cell hyperplasia (CCH) and MTC was confirmed histologically in 4 out of

Russia.

10 patients (2 CCH and 2 MTC); 2 subjects had benign nodular goiter and 2

papillary thyroid microcarcinomas. More results are expected.

Background

Conclusions

In accordance with the WHO Classification of tumours of endocrine organs

Stimulated calcitonin may be useful in the early diagnosis and follow-up of MTC

(Lyon, 2004) clear cell thyroid lesions have not been separated in one category as

and could reduce false negative rate of basal calcitonin measurement.

they are occurred quite rare, characterized by various cellular origin,

DOI: 10.1530/endoabs.49.EP1395

heterogeneous morphological type, and malignant potential. Difficulties of

morphological diagnosis of clear cell thyroid lesions are also obvious.

Aim

Retrospective morphological study of clear cell thyroid tumours has been

performed by pathologists of two research centres (MRRC and ERC) for the

period of 10 years (2007-2016) to analyse difficulties of diagnosis related with

different histotype, and tumour grade.

EP1396

Materials and Methods

The relationship between extrathyroidal extension and BRAFV600E

Histological sections of paraffin blocks from 14 cases of clear cell tumours in 5

mutation in papillary thyroid cancer

male and 9 female aged from 15 to 78 years have been stained with H&E, and

Mehmet Celik¹, Buket Yilmaz Bulbul¹, Semra Ayturk¹, Nuray Can²,

immunohistochemistry (IHC) for Thyroglobulin (Tg), Thyroid Transcription

Ebru Tastekin², Atakan Sezer³, Funda Ustun⁴ & Sibel Guldiken¹

Factor

(TTF1), Calcitonin

(Cal), Chromogranin A

(Chr A), Parathyroid

¹Rakya University, Medical Faculty, Department of Endocrinology and

Hormone (PTH), CD10, and Ki-67.

Metabolism, Edirne, Turkey;²Trakya University, Medical Faculty,

Results

Department of Pathology, Edirne, Turkey;³Trakya University, Medical

Retrospective review of H&E and IHC stained sections allows to make diagnosis

Faculty, Department of Surgery, Edirne, Turkey;⁴Trakya University,

of 3 benign follicular thyroid adenomas (FTA), 2 follicular thyroid carcinomas

Medical Faculty, Department of Nuclear Medicine, Edirne, Turkey.

(FTC), 3 papillary thyroid carcinomas (PTC), 1 medullary thyroid carcinoma

(MTC), 2 poorly differentiated thyroid carcinomas

(PDTC) with clear cell

features,

2 intrathyroid parathyroid carcinomas

(ITPTC), and

1 renal cell

Aim

metastasis into thyroid (RCC metastasis). Tumour cells of FTA (2 pure clear

BRAF is one of the serine threonin kinases that activates mitogen activated

cell and 1 signet ring cell), FTC, PTC, and PDTC are Tg-, and TTF1-positive, in

protein kinase (MAPK) signal pathway.The aim of this study is to evaluatethe

comparison with negative Cal-, Chr A-, PTH-, CD10-staining. Ki-67 is expressed

relationship between extrathyroidal extension (ETE) and BRAFV600E mutation

by nucleus of more than 30% PDTC tumour cells in comparison with low

in the subjects with papillary thyroid cancer.

expression rate (less than 1%) of highly differentiated tumours. Tumour cells of

Materials and methods

MTC are Tg-, PTH-, and CD10-negative, but positive for TTF1-, Cal-, and Chr A-

Clinical and laboratory data of 455 patients, who had been followed-up in our

staining. Cells of ITPTC are Tg-, TTF1-, Cal-, CD10-negative, but Chr A-, and

clinic between the years 2010 and 2015 for PTC, were evaluated. The relationship

PTH-positive. Cells of RCC metastasis are positive for CD10, but negative for

between extrathyroidal extension and BRAFV600E mutation was examined in

Tg-, TTF1-, Cal-, Chr A-, and PTH.

the subjects enrolled in the study.

Conclusions

Results

Clear cell thyroid tumours are rare and should be distinguished in accordance with

Among 455 patients, 382 (83.9%) were female and 73 (16.1%) were males. The

their different cellular origin and histotype, as well as various tumour grade and

mean age of the participants was 49G11.8 years. While 368 (80.9%) of the

prognosis.

patients had no extrathyroidal extension,

(19.1%) of the patients had

DOI: 10.1530/endoabs.49.EP1394

extrathyroidal extension. 362 (79.6%) of the patients were BRAFV600E mutation

(K) and 93 (20.4%) patients were BRAFV600E mutation (C). 320 patients were

negative for both BRAFV600E mutation and extrathyroidal extension. The

prevalence of PTC larger than 1 cm was significantly more common among

BRAFV600E mutation and ETE (C) cases (P:0.004). The prevalence of capsular,

lymphovascular and perineural invasion, lymph node metastasis and ultrasono-

graphically detected pathologic lymphadenopathy was significantly higher among

EP1395

BRAFV600E mutation (C) and ETE(C) subjects (P:0.004, P!0.05, P!0.05,

P:0.05, P:0.01).

Stimulated calcitonin levels as a predictor of medullary thyroid cancer

Conclusion

Cristina Alexandra Gheorghiu¹, Cristina Corneci¹, Simona Jercalau¹,

In this study, BRAFV600E mutation and ETE positivity were found to be poor

Ruxandra Dobrescu¹, Daniel Mihai¹ & Corin Badiu^1,2

prognostic parameters in the patients with PTC. However, the evaluation of long

¹National Institute of Endocrinology, C.I. Parhon, Bucharest, Romania;

term follow-up data is required to more clearly understand prognostic effect and

²Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

especially to determine the effect of this situation on mortality.

DOI: 10.1530/endoabs.49.EP1396

Abstract

Medullary thyroid cancer (MTC) is a highly aggressive neuroendocrine tumour

originating in the thyroid parafollicular cells. Calcitonin measurement and RET

gene ascertainment have been used as markers for early diagnosis of MTC. Since

pentagastrin is not available, calcium stimulation test helps to preclude ‘gray

zone’ values of basal calcitonin, diagnose minimal residual disease and help the

early diagnosis of C cell hyperplasia.

Aim

To establish a gender specific threshold for positive calcium stimulation test as

EP1397

well as indication for thyroidectomy and therefore prevention of MTC through

Insulin resistance and BRAFV600E mutation in the patients with

early diagnosis.

differentiated thyroid carcinoma

Materials and methods

Mehmet Celik¹, Buket Yilmaz Bulbul¹, Semra Ayturk¹, Ebru Tastekin²,

We conducted the calcium stimulation test on a series of patients with either

Nuray Can², Atakan Sezer³ & Funda Ustun⁴

nodular goiter, single nodule, RET positive or history of MTC associated with

¹Trakya University, Medical Faculty, Department of Endocrinology and

elevation of basal calcitonin values. Calcium gluconate 25 mg/kg adapted on the

Metabolism, Edirne, Turkey;²Trakya University, Medical Faculty,

ideal BMI was administered over 3 min under ECG monitoring. Blood was

Department of Pathology, Edirne, Turkey;³Trakya University, Medical

collected before, at

5 and 10 min after calcium infusion. Calcitonin was

Faculty, Department of Surgery, Edirne, Turkey;⁴Trakya University,

measured using LIAISON XL assay.

Medical Faculty, Department of Nuclear Medicine, Edirne, Turkey.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Aim

¹Trakya University, Medical Faculty, Department of Internal Medicine,

The incidence of nodular thyroid disease is high among patients with insulin

Edirne, Turkey;²Trakya University, Medical Faculty, Department of

resistance. The aim of this study is to evaluate the relationship between

Endocrinology and Metabolism, Edirne, Turkey;³Trakya University,

BRAFV600E mutation and insulin resistance in the patients with papillary

Medical Faculty, Department of Pathology, Edirne, Turkey;⁴Trakya

thyroid cancer.

University, Medical Faculty, Department of Surgery, Edirne, Turkey;

Materials and methods

⁵Trakya University, Medical Faculty, Department of Nuclear Medicine,

We examined clinical and laboratory data of 103 patients who had been followed

Edirne, Turkey.

up by our department between the years 2010 and 2015. The diagnosis of insulin

resistance (IR) was made when the homeostasis model assesment of insulin

Aim

resistance (HOMA-IR) index was higher than 2.5.

ATA guideline recommends complementary thyroidectomy after thyroid

Results

lobectomy in case of tumor diameterO1 cm, in the presence of metastatic

(87.4%) of 103 patients were female, while 13 (12.6%) of them were male.

tumor, invasion, history of radiation therapy, familial history of thyroid cancer,

HOMA-IR was R 2.5 in 58 (56.3%) patients and !2.5 in 45 (43.7%) patients. 19

multifocal or agressive variant tumor. In this study, we aimed to evaluate the

of the patients were BRAFV600E mutation (C), while BRAFV600E mutation

relationship between the necessity of complementary thyroidectomy and post-

was (K) in 84 cases. Among 58 patients with insulin resistance, 46 (79.3%)

surgery clinical, radiologic and histopathologic results in the patients who

patients were BRAFV600E mutation

(K) and

(19.7%) patientswere

underwent complementary thyroidectomy for papillary thyroid cancer (PTC).

BRAFV600E mutation (K). There was no statistically significant relationship

Method

between BRAFV600E mutation and HOMA-IR in terms of demographic data,

We retrospectively evaluated the data of

110 patients who had undergone

clinical and histopathologic results.

complementary thyroidectomy following lobectomy and been followed-up by our

Conclusion

department between January 2010 and January 2017. 67 of these patients had

In this study, no statistically significant relationship was detected between insulin

unifocal and 43 had multifocal PTC. The relationship between demographic data,

resistance and BRAFV600E mutation among the patients with PTC.

histopathologic results, BRAF mutation status and complementary thyroidectomy

DOI: 10.1530/endoabs.49.EP1397

was evaluated.

Results

Among 110 patients, 85 (77.2%) were female and 25 (22.8%) were male. The

mean age of the subjects was 47.8G12.3 years. Following complementary

surgery, 70 (63.6%) of the patients were found to have benign pathology and 40

(36.4%) were found to have PTC on controlateral lobe. Parameters such as

gender, age, hormonal status, presence of Hashimoto disease, tumoral variant,

lymphocytic thyroiditis, tumor localisation, tumoral focality, number of tumoral

foci, perineural invasion, capsular invasion, lymphovascular invasion, extra-

thyroidal extension, lymph node metastasis and BRAFV600E mutation status

EP1398

were found to be insignificant for complementray thyroidectomy.

Beware a rapidly enlarging Thyroid mass- a case of Thyroid

Conclusion

Lymphoma

We suggest that unifocality or multifocality of single lobe tumor is not

Suhel Ashraff, Ahmed Al Sharefi & Satyajit Nag

determinative for complementary surgery during initial operation. However,

James Cook University Hospital, Middlesbrough, UK.

long-term follow-up data is required to determine the effect complementary

thyroidectomy on prognosis and mortality.

DOI: 10.1530/endoabs.49.EP1399

Primary Thyroid Lymphoma is rare comprising less than 5% among all

thyroid malignancies. It is historically associated with Hashimotos

thyroiditis. It typically presents as a rapidly enlarging, painless goitre

resulting in compression symptoms. Thyroid ultrasound and FNA cytology,

using flow cytometry and immunohistochemistry, remain the primary

modalities to confirm the presence of lymphoma. Treatment depends on the

immunohistology. The prognosis is subtype depended and is generally good.

A 53 years old female was seen in the Endocrine clinic with a right sided

EP1400

neck lump. On examination a smooth enlarged right thyroid lobe was noted.

A case report: co-occurence of medullary thyroid carcinoma and

Her history suggested Hashimoto’s thyroiditis but she has an enlarged right

papillary thyroid carcinoma

thyroid lobe. Biochemically her TSH was

11.87

with a FT4

being

Beliz Camur¹, Mehmet Celik², Buket Yilmaz Bulbul², Semra Ayturk²,

low/normal at 13. She had positive TPO antibodies. She was referred for

Ebru Tastekin³, Nuray Can³, Atakan Sezer⁴, Funda Ustun⁵ &

a Fine needle aspiration of the right lobe demonstrated lymphoid cells

Sibel Guldiken²

consistent with lymphocytic thyroiditis and was started on Levothyroxine

¹Trakya University, Medical Faculty, Department of Internal Medicine,

50mcg as she was symptomatic and an interval scan was recommended in 3

Edirne, Turkey;²Trakya University, Medical Faculty, Department of

months’ time. She was seen in a 4 months’ time with her scan results and her

Endocrinology and Metabolism, Edirne, Turkey;³Trakya University,

right sided thyroid swelling appeared to have increased in size. A repeat

Medical Faculty, Department of Pathology, Edirne, Turkey;⁴Trakya

ultrasound scan confirmed an increase in size compared to previous scans

University, Medical Faculty, Department of Surgery, Edirne, Turkey;

with level 6 and 4 lymph nodes. A core biopsy showed features consistent

⁵Trakya University, Medical Faculty, Department of Nuclear Medicine,

with an Extranodal marginal zone lymphoma (MALT-type). A staging CT

Edirne, Turkey.

showed stage 2E with FDH avid right thyroid lobe and 4 cervical lymph

nodes of

10mm. A bone marrow aspiration showed no lymhomatous

infiltrate. She underwent a radical radiotherapy with 24 Gy in 12 fractions

Introduction

with good effect. A repeat PET CT scan showed no residual disease. This

Co-occurence of medullary thyroid carcinoma and papillary thyroid carcinoma in

case demonstrates that a rapidly enlarging thyroid lump should be

the same patient is unusual. We report a case with this rare event.

investigated urgently to facilitate early diagnosis of the underlying cause,

Case

Thyroid lymphoma being one of them.

A 39 year old woman was presented with cough and shortness of breath. She had

DOI: 10.1530/endoabs.49.EP1398

no prior history of radiation exposure, cigarette or alcohol consumption and no

family history of thyroid cancer. On physical examination, a 3x5 cm thyroid

nodule was palpated in the middle portion of thyroid gland, which could be

noticed after neck extention. Laboratory examination revealed calcitonin 348

pg/ml(n:0-10), CEA 12,39 mg/L (n: ! 3,8 mg/L), FT3: 3,6 pg/mL (n: 1,71-3,81),

FT4:

1,41

ng/dl

(n:0,7-1,48), TSH:0,53

mlU/ml

(n:0,35-4,94). Thyroid

ultrasonografy examination demonstrated a hypoechogen 3*3*5 cm sized nodule

EP1399

invading thyroid gland. I131

thyroid uptake scintigraphy was negative and

autoantibodies were also found to be negative. Cytologic examination of fine

Complementary thyroidectomy in papillary thyroid cancer

needle aspiration biopsy was suspicious for follicular neoplasia. Therefore, she

Yusuf Durmus¹, Mehmet Celik², Buket Yilmaz Bulbul², Semra Ayturk²,

underwent total tyroidectomy. Pathologic examination of the specimen revealed

Ebru Tastekin³, Nuray Can³, Atakan Sezer⁴, Funda Ustun⁵ &

both medullary and papillary thyroid carcinoma. 3.5 cm sized classic variant

Sibel Guldiken²

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

papillary tyroid carcinoma was reactive for thyroglobulin and tumor stage was

¹Trakya University, Medical Faculty, Department of Internal Medicine,

reported as pT3pNxpMx; 5*3*3 cm sized medullary thyroid carcinoma was

Edirne, Turkey;²Trakya University, Medical Faculty, Department of

reactive for calcitonin. Investigation for multıple endocrine neoplasia (MEN)

Endocrinology and Metabolism, Edirne, Turkey;³Trakya University,

detected RET protooncogen mutation. She underwent 100 mCi radioactive I131

Medical Faculty, Department of Pathology, Edirne, Turkey;⁴Trakya

treatment. Since CEA and calcitonin levels were high during follow-up period,

University, Medical Faculty, Department of Surgery, Edirne, Turkey;

neck ultrasonography was performed, which revealed no pathologic lymphadeno-

⁵Trakya University, Medical Faculty, Department of Nuclear Medicine,

pathy. PET/CT examination detected metastasis in the upper lobe of the right

Edirne, Turkey.

lung, mediastinal lymph nodes and liver. The patient was given vandatanib

chemotherapy by medical oncology department. In conclusion, co-occurence of

medullary and papillary thyroid carcinoma in the same gland has rarely been

Ectopic thyroid tissue is the localization of thyroid tissue at any place other

reported. Occurence of medullary and papillary tyroid carcinoma are

than the normal localization of the thyroid during the migration of

independent; however, common points of pathogenic events can not be ruled

embryonic period. Concurrent normal thyroid tissue may accompany. It

out in their carcinogenesis.

usually is seen in women and in the midline. Very rarely thyroid carcinoma

DOI: 10.1530/endoabs.49.EP1400

can develop. Treatment is like normal thyroid carcinomas, suggesting

simultaneous thyroidectomy if accompanied by normal thyroid tissue. A

42-year-old female patient presented with complaints of swelling on the

right side of the neck for 3 months. There was no chronic disease or drug use

in her story. On physical examination, a painless, moving 30!30 mm mass

lesion was detected in the middle cervical region. Imaging revealed a mass

lesion in the lower right cervical region near the right lobe of the thyroid

EP1401

gland, 36!25!35 mm heterogeneous signal density same as the thyroid

Thyroid papillary carcinoma in the patients with resistance to

gland. Histopathological examination of the excised mass revealed TTF1

thyroid hormone

positive, galectin positive, CK19 positive, HBME1 positive and 36!30 mm

Mehmet Celik¹, Buket Yilmaz Bulbul¹, Sibel Guldiken¹, Hakan Gurkan²,

encapsulated follicular variant papillary carcinoma considered as thyroid

Semra Ayturk¹, Nuray Can³, Ebru Tastekin³, Atakan Sezer⁴ & Funda Ustun⁵

carcinoma and lymphoid tissue has not been observed. Thyroid function

¹Trakya University, Medical Faculty, Department of Endocrinology and

tests and laboratory findings were normal. Thyroid ultrasonography revealed

Metabolism, Edirne, Turkey;²Trakya University, Medical Faculty,

bilateral hypoechoic and isoechoic nodules maximal 1 cm in diameter and

Department of Genetic, Edirne, Turkey;³Trakya University, Medical

malignant lymphadenopathy 2 cm in the left cervical area. As a result of

Faculty, Department of Pathology, Edirne, Turkey;⁴Trakya University,

total thyroidectomy C neck dissection, 8 and 9 mm diameter papillary

Medical Faculty, Department of Surgery, Edirne, Turkey;⁵Trakya

thyroid carcinoma encapsulated follicular variant was detected in the right

University, Medical Faculty, Department of Nuclear Medicine, Edirne,

lobe and thyroid carcinoma metastasis were observed in 3 of 10 lymph nodes

Turkey.

removed in the left cervical area. This was evaluated as high-risk thyroid

carcinoma and treated with radioactive iodine (RAI-131) at 150 mCi. At

post-RAI whole body scan screening, 2 local foci were observed in the

thyroid location and were followed up. The patient was followed for 6

Resistance to thyroid hormone (RTH) is a genetic disease characterized by a

months with asymptomatic levothione suppression therapy. We aimed to

reduced target tissue responsiveness to thyroid hormones and increased or

present a rare case of ectopic thyroid carcinoma.

normal TSH level despite elevated levels of thyroid hormones. This

DOI: 10.1530/endoabs.49.EP1402

condition is mainly caused by mutations of thyroid hormone receptor beta

(THRB) gene. The role of THRB mutation in carcinogenesis is still unclear.

In here, we report a case of papillary thyroid carcinoma (PTC) with RTH,

with a past medical history of subtotal thyroidectomy due to diffuse goiter. A

61-year-old woman was referred to our hospital with recurrence of goiter

and displayed elevated serum thyroid hormones and unsuppressed TSH

levels. Genetic analysis of THRB identified a missense mutation, (Exon 7,

rs3752874, c.735COT) leading to diagnosis of RTH. The neck ultrasono-

graphy showed an isoechoic 9!11!11 mm sized nodule, a cystic 13!

13!15 mm sized nodule with microcalcification in the right lobe, a 7!9!

9 mm sized nodule with thin hypoechoic ring around in the right isthmus,

a 9!12!14 mm sized, iso-hypoechoic,uniformly restricted nodule with

cystic component in the left isthmus and a

17!25!29 mm sized

EP1403

hypoechoic nodule in the left lobe. Ultrasound-guided fine-needle aspiration

Co-occurrence of papillary and follicular thyroid carcinoma in a

biopsy was performed for microcalcific nodule in the right lobe. Cytologic

patient

examination of fine needle aspiration biopsy specimen was suspicious for

Ahmet Yigitbasi¹, Mehmet Celik², Buket Yilmaz Bulbul², Semra Ayturk²,

follicular neoplasm. Total thyroidectomy was performed. Pathologic

Nuray Can³, Ebru Tastekin³, Atakan Sezer⁴, Funda Ustun⁵ &

examination of thyroid tissue revealed capsulated oncocytic variant

Sibel Guldiken²

papillary thyroid cancer in 32 mm sized nodule in the left lobe and 7 and

¹Trakya University, Medical Faculty, Department of Internal Medicine,

2 mm sized nodules in the right lobe. The patient was scheduled for

Edirne, Turkey;²Trakya University, Medical Faculty, Department of

radioactive I-131 treatment. There is no consensus on the management of

Endocrinology and Metabolism, Edirne, Turkey;³Trakya University,

thyroid carcinoma in patients with RTH. The main concerns are the

Medical Faculty, Department of Pathology, Edirne, Turkey;⁴Trakya

relationship between differentiated thyroid cancer and thyroid hormone

University, Medical Faculty, Department of Surgery, Edirne, Turkey;

resistance, whether it is a coincidence, how to suppress TSH levels, which

⁵Trakya University, Medical Faculty, Department of Nuclear Medicine,

treatment regimen should be chosen and which parameters should be

Edirne, Turkey.

considered in the follow-up of these patients. Further studies are required to

find scientific answers to these questions.

DOI: 10.1530/endoabs.49.EP1401

Occurance of papiller carcinoma with foliculer thyroid carcinoma is a rare

situation. We report a 49-year-old male with asymptomatic goiter. The first

biopsy from the right tyroid lobe from a 6!6!4 cm iso-hypoechogen

heterogeneous nodule showed bening, hurthe cell and thyrocyte rich

cytology. Two months later the patient went through right lobectomy which

patology defined as 4.3 cm minimal invasive follicular carcinoma. Two

months after right thyroidectomy, a second operation was performed on the

left thyroid to complete the process of total thyroidectomy. The speciment

EP1402

was sent to patology which bore the following result: Papillary

A rare case: papillary thyroid carcinoma in the ectopic thyroid

microcarcinoma with follicular variant. This was evaluated as high-risk

Yusuf Durmus¹, Mehmet Celik², Buket Yilmaz Bulbul², Semra Ayturk²,

thyroid carcinoma and treated with radioactive iodine(RAI-131) at 100 mCi.

Ebru Tastekin³, Nuray Can³, Atakan Sezer⁴, Funda Ustun⁵ &

At post-RAI whole body scan screening, 2 local foci were observed in the

Sibel Guldiken²

thyroid location and were followed up. This work shows two different

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

carcinomas that belong to different lineages existing in two different lobes of

noninvasive techniques. Elastography is the imaging new technic,to evaluate the

the thyroid with no coheisive malignity triggering factors.

nodules. Aim of this study to evaluate the results of FNAB and elastography

performed in patients with thyroid nodules.

DOI: 10.1530/endoabs.49.EP1403

Methods

173 thyroid nodules were examined by Elastography and fine needle aspiration

biopsy. Strain elastography was performed with Siemens Acuson s1000 14L5

lineer transducer. Elastography findings were evaluated together with b-mode

ultrasonography. The susceptible nodules with an S/R ratio of over 2,6 were

accepted as malignant nodules.

Results

Results of 155 (89%) FNAB were benign, 18 (10.4%) were malignant. The

elastographic appearance was categorized at the time of the examination, 154

(89%) of them were categorised as benign and 19 (10.9%) of them were

EP1404

categorized as malignant. The sensitivity of Elastography for malignancy was

90.0%, specificity was 22%, PPV was 21%, NPV was 90% and accuracy was

A rare cause of respiratory failure: Anaplastic carcinoma

83.2%.

Ece Celik¹, Mehmet Celik², Buket Yilmaz Bulbul², Semra Ayturk²,

Conclusion

Nuray Can³, Bilkay Serez⁴ & Sibel Guldiken²

Elastography seems to require more experimentation in this regard with hope

¹Edirne Sultan 1. Murat State Hospital, Department of Chest Diseases,

being a technique. Our study strongly suggests, biopsy is still the most reliable

Edirne, Turkey;²Trakya University, Medical Faculty, Department of

method for the evaluation of nodules.

Endocrinology and Metabolism, Edirne, Turkey;³Trakya University,

Medical Faculty, Department of Pathology, Edirne, Turkey;⁴Trakya

DOI: 10.1530/endoabs.49.EP1405

University, Medical Faculty, Department of Chest Diseases, Edirne, Turkey.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal

human malignancies. The median survival time following diagnosis is

typically six months or less. Rapidly growing tumors may cause respiratory

failure by compressing trachea. A

71-year-old woman presented with

1-month history of dyspnea, cyanosis and rapidly enlarging neck mass for

the past 2 weeks. She had been suffering from multinodular goiter disease.

Physical examination revealed a large, fixed and mildy tender thyroid mass

EP1406

and cyanotic extremities. Breath sounds were bilaterally decreased on

Association of TIMP-3 expression and BRAF V600E mutation status in

auscultation. Arterial blood gas analysis showed hypoxia. Chest X-ray

papillary thyroid cancer

imaging revealed bilateral multiple nodular opacities, which were found to

Maryam Zarkesh¹, Mehdi Hedayati¹, Azita Zadeh-Vakili¹,

be bilateral metastatik nodular lesions involving all segments on thoracic

Afsoon Daneshafrooz¹, S Adeleh Razavi¹, S-Ahmad Fanaei²,

tomography. In addition, a 35!20 mm sized lingular metastatic lesion

Forough Foroughi³ & Fereidoun Azizi⁴

invading 5th rib was present in the left lung. Thyroid gland was slightly

¹Cellular and Molecular Endocrine Research Center, Research Institute for

larger than normal with heterogeneous parenchyma and there were multiple,

Endocrine Sciences, Shahid Beheshti University of Medical Sciences,

heterogeneous and hypoechoic nodules, the biggest one was being 30!

Tehran, Iran;²Association Professor of General Surgery, Erfan Hospital,

32!30 mm in size in the right thyroid lobe. In addition, 2 cm sized multiple

Tehran, Iran;³Department of Pathology, Shahid Beheshti University of

necrotic lymph nodes were visible. Laryngoscopic examination demon-

Medical Sciences, Tehran, Iran;⁴Endocrine Research Center, Research

strated externally compressed trachea. Tru-cut biopsy of left thyroid lobe

Institute for Endocrine Sciences, Shahid Beheshti University of Medical

detected anaplastic carcinoma with rhabdoid giant cell formation. Despite

Science, Tehran, Iran.

oxygen supplementation, hypoxic state worsened and the patient was

referred to intensive care unit following emergent tracheostomy. In

conclusion, although it is rare, anaplastic carcinoma should be considered

Background

in the patients presenting with respiratory failure. Anaplastic thyroid

The aim of this study was to assess the association between tissue inhibitor of

carcinoma should should be considered in patients presenting with rapidly

metalloproteinase-3

(TIMP-3) gene expression and B-Raf Proto-Oncogene

growing neck mass and respiratory failure.

(BRAF) V600E mutation in marginal and tumoral tissues of papillary thyroid

carcinoma (PTC) patients.

DOI: 10.1530/endoabs.49.EP1404

Methods

Sixty fresh frozen tissues of PTC including 55.3% women were collected during

thyroidectomy surgery. All clinicopathologic features of subjects were collected

which confirmed by a pathologist. The exon 15 of BRAF gene was genotyped by

sequencing, TIMP-3 gene expression was assessed using SYBR-Green Real-

Time PCR, and the protein level of TIMP-3 was measured using ELISA.

Results

The mean age in men and women was 39.6G15.6 and 37.5G11.6 years,

respectively. BRAF mutant was found in 24 (31.6%) of PTC samples. The mean

of TIMP-3 mRNA level was higher in marginal tissue compare to tumoral ones

EP1405

(PO 0.05). However, the mean of protein level of TIMP-3 was significantly

higher in marginal tissue compare to tumoral (PZ0.001). Moreover, in subjects

Our experience of strain elastography in the evaluation of thyroid

with BRAF positive mutation, the mean of TIMP-3 gene expression was higher in

nodules

marginal compare to tumoral tissues (PZ0.066). On the other hand, in subjects

Semin Melahat Fenkçi¹, Mehmet Co¸kun², Senay Topsakal¹ &

without BRAF mutation, the mean of TIMP-3 protein level was significantly

Guzin Fidan Yaylalı¹

lower in tumoral tissues compare to marginal tissue (PZ0.003). However, this

¹Pamukkale University Endocrinology Department, Denizli, Turkey;²Katip

difference was not significant in subjects with negative BRAF mutation

C¸ elebi University Ataturk Hospital Radiology Department, Izmir, Turkey.

(PZ0.084).

Conclusion

Introduction

This study showed that although the gene expression of TIMP-3 was marginally

Thyroid nodule is a common finding in neck ultrasonography performed in adult

different in two BRAF positive and negative mutation groups, it was significantly

age group. Appropriate management of patients with thyroid nodules accuretly is

different in protein levels.

very difficult process. Fine needle aspiration biopsy (FNAB), is the traditional

DOI: 10.1530/endoabs.49.EP1406

invasive method used to identify nodules. Investigations are continuing for

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1407

total thyroidectomy (TT). This study was aimed to describe clinical outcomes in a

retrospective large series of low and intermediate risk thyroid cancer patients

Histologically-proven Hashimoto’s thyroiditis significantly decreases

treated with LT or TT.

the risk of structural recurrence in patients with low risk

Methods

intra-thyroidal papillary thyroid cancer

We evaluated retrospectively 336 patients affected with differentiated thyroid

Vincenzo Marotta^1,2, Concetta Sciammarella², Maria Grazia Chiofalo³,

cancers (DTC); 292 of them were treated with TT and 44 with LT. The initial

Claudio Gambardella⁴, Claudio Bellevicine⁵, Marica Grasso⁶,

surgical treatment was not chosen based on the risk class. The median age was

Giovanni Conzo⁴, Gerardo Botti⁶, Simona Losito^6,7, Giancarlo Troncone⁵,

48 yrs, 274 were females and 62 males. Remission or persistent/recurrent disease

Luciano Pezzullo³, Annamaria Colao¹ & Antongiulio Faggiano³

was defined on the basis of biochemical and/or structural evidence of disease after

¹Department of Clinical Medicine and Surgery, Federico II University,

a median follow-up period of 65 months.

Naples, Italy;²IOS & COLEMAN s.r.l., Naples, Italy;³Thyroid and

Results

Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la Cura dei

Only 1/292 patients treated with TT needed additional therapy (surgery for

Tumori-IRCCS ‘Fondazione G. Pascale’, Naples, Italy;⁴Department of

malignant lymph node metastases), and none of them was submitted to

Anesthesiologic, Surgical and Emergency Sciences, Division of General and

radioiodine ablation. On the other hand, 15/44 patients treated with lobectomy

Oncologic Surgery, University of Campania Luigi Vanvitelli, Naples, Italy;

were submitted to following treatment (completion thyroidectomy alone in 3,

⁵Department of Public Health, University of Naples ‘Federico II’, Naples,

associated with lymphadenectomy and radioiodine treatment in 12 cases). As far

Italy;⁶San Giovanni di Dio e Ruggi D’Aragona, Universitary Hospital,

as the outcome concerns, remission was documented in 281/292 cases (96.2%)

Division of General Surgery, University of Salerno, Salerno, Italy;

and 30/44 cases (68.2%) in the TT and LT groups, respectively (P!0.0001).

⁷Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei

Conclusions

Tumori-IRCCS ‘Fondazione G. Pascale’, Naples, Italy.

Our data suggest that lobectomy should be performed only in patients with a very

low risk at diagnosis, in order to avoid the need for a second treatment. Moreover,

Introduction

since virtually all patients treated with TT were cured after surgery, our data

Due to the absence of randomized controlled trials, management of low risk

support the selective use of radioiodine ablation treatment.

papillary thyroid cancer (PTC), which represents the most commonly diagnosed

DOI: 10.1530/endoabs.49.EP1408

form of thyroid malignancy, remains controversial. Hashimoto’s thyroiditis (HT)

is significantly more frequent in patients with PTC, as compared with subjects

carrying benign lesions as well as different tumour histotypes. Despite still

controversial, HT is considered a protective factor in PTC being associated with

favourable tumour features and better outcome. Nevertheless, all studies dealing

with this issue included all PTC stages. We aimed to assess prognostic value of

histologically-proven HT in a large cohort of consecutive low-risk intra-thyroidal

PTC.

Patients and methods

Multicenter retrospective study including pT1/2 PTC without any evidence of

extra-thyroidal disease, who were subjected to surgery and follow-up within the

EP1409

involved centers. Pathological review of all specimens was performed.

Does the delayed risk stratification system help to evaluate the risk of

Co-existing HT was defined by the presence of diffuse/focal lymphoplasmacytic

unfavorable clinical outcome in pT1aN0/Nx stage patients with

infiltrate, oxyphilic cells, lymphoid follicles with germinal centers, and atrophic

differentiated thyroid cancer treated without radioactive iodine?

changes involving normal thyroid tissue, whereas isolated peri- and intra-tumoral

Danuta Gasior-Perczak¹, Iwona Palyga¹, Monika Szymonek¹,

lymphocytic infiltration was not considered as HT. Study endpoint was recurrent

Agnieszka Walczyk¹, Janusz Kopczynski¹, Anna Sluszniak¹,

structural disease.

Ryszard Mezyk¹, Stanislaw Gozdz^1,2 & Aldona Kowalska^1,2

Results

¹Holycross Cancer Centre, Kielce, Swietokrzyskie, Poland;

Two-hundred eighty-four patients

(156 without and 128 without HT) were

²Jan Kochanowski University, Kielce, Swietokrzyskie, Poland.

included. Mean follow-up was 75G61 months (6.3 years). Concomitant HT was

related to significantly lower rate of recurrent structural disease (PZ0.018, OR

0.33 95% CI 0.13-0.86). This finding was confirmed by survival analysis, where

Introduction

PTC with HT showed significantly higher recurrence-free time. After adjustment

In ATA recommendations (2016) a delayed risk stratification (DRS) system

for other variables affecting prognosis at univariate analysis (age at diagnosis,

proposed by D.P. Momesso et al. was accepted as a diagnostic tool for the risk

tumour size, multifocality, and post-surgery radiometabolic treatment), con-

stratification of unfavorable clinical outcome and for monitoring the clinical

comitant HT retained its protective effect (PZ0.036, OR 0.34 95% CI 0.12-0.93).

outcome in differentiated thyroid cancer

(DTC) patients treated without

Conclusions

radioactive iodine (RAI).

In our series of low risk intra-thyroidal PTC, concomitant HT independently

The aim of the study

predicted recurrent structural disease and may therefore represent a useful tool for

To evaluate the DRS system in patients with low clinical stage (pT1aN0/Nx).

the decision-making process of these patients.

Material

DOI: 10.1530/endoabs.49.EP1407

304 patients after total thyroidectomy (nZ202) or lobectomy (nZ102) without

adjuvant RAI therapy, with a follow-up period of at least 24 months, treated at a

single center were enrolled to the study. The median age was 50.5 years, 91.1%

were women, 100% at baseline had a low risk according to ATA, the median

follow-up was 4 years (2-24).

Methods

DRS of the treatment response was conducted, based on the medical records,

according to the criteria by Momesso et al. The course of the disease was

evaluated (recurrence, death) as well as the status on 31.12.2016, which is the end

of the follow-up

(remission, persistent disease). The relationship between

EP1408

unfavorable outcome and the DRS system was evaluated.

Evaluation of disease outcome in patients affected with differentiated

Results

thyroid carcinoma treated with total thyroidectomy or lobectomy

The response to initial therapy was excellent in

272

patients

(89.5%),

Carla Colombo¹, Simone De Leo¹, Michela Perrino¹, Marta Di Stefano¹,

intermediate in 31 patients (10.2%) and biochemically incomplete in 1 patient

Gianmaria Cantoni³, Leonardo Vicentini³ & Laura Fugazzola^1,2

(0.3%)

(increased concentration of TgAb). There was a recurrence in 2 patients

¹University of Milan, Milan, Italy;²Istituto Auxologico Italiano, Milan,

from the excellent response group at 6 and 7 years of follow-up (after lobectomy).

Italy;³Fondazione Policlinico Ca Granda, Milan, Italy.

No patients with intermediate and biochemically incomplete response were

diagnosed with the structural disease and none of the patients died during the

follow-up.

Abstract

Conclusions

An individualized risk-based approach to the treatment of thyroid cancer is being

The DRS system did not prove useful in predicting the risk of unfavorable clinical

extensively discussed in the recent literature, but controversies remain about the

outcome and cannot be used to personalize the monitoring method of the disease

ideal surgical approach. In particular, if some data showed that properly selected

in patients at pT1aN0/Nx, not treated with RAI.

thyroid cancer patients can be treated with lobectomy (LT) with excellent clinical

DOI: 10.1530/endoabs.49.EP1409

outcomes, other results demonstrated an increased incidence of persistent

recurrent disease in patients submitted to LT with respect to those treated with

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1410

Stage ICII:71.8 vs 49.8%, III:20.5 vs 27.6%, IV:7.7 vs 22.7%, PZ0.007) with

the difference remaining significant in both sporadic (PZ0.022) and familial

The impact of post-radioiodine therapy SPECT/CT on risk

MTC (PZ0.035). MTC-DTC group had marginally better disease prognosis

stratification in differentiated thyroid cancer; a bi-institutional study

compared to MTC alone (remission: 67.6 vs 48.7%, stable: 16.2 vs 25.2%,

Szabina Szujo¹, Livia Sira², Laszlo Bajnok¹, Beata Bodis¹, Ferenc Gyory⁵,

progression:

16.2

26.1%, PZ0.05). The 10-year probability of lack of

Orsolya Nemes¹, Karoly Rucz¹, Peter Kenyeres¹, Zsuzsanna Valkusz⁶,

progression of disease did not differ between the two groups. Size of DTC did not

Krisztian Sepp⁶, Erzsebet Schmidt³, Zsuzsanna Szabo³, Sarolta Szekeres³,

seem to affect the clinical course of MTC-DTC.

Katalin Zambo³, Sandor Barna⁴, Endre V Nagy² & Emese Mezosi¹

Conclusions

¹Ist Department of Medicine, University of Pecs, Pecs, Hungary;

Simultaneous occurrence of MTC-DTC is occasionally diagnosed. Even though

²Department of Medicine, Faculty of Medicine, University of Debrecen,

stage at diagnosis is better in MTC-DTC patients, there is no difference in 10-year

Debrecen, Hungary;³Department of Nuclear Medicine, University of Pecs,

probability of lack of progression of disease. We report for the first time an

Pecs, Hungary;⁴Department of Nuclear Medicine, Faculty of Medicine,

increased incidence of DTC in RET exon 8 (G533C) carriers. Whether this

University of Debrecen, Debrecen, Hungary;⁵Department of Surgery,

mutation-quite common in Greek MTC patients-might participate in shared

Faculty of Medicine, University of Debrecen, Debrecen, Hungary;

pathogenic mechanisms needs further investigation.

⁶Ist Department of Medicine, University of Szeged, Szeged, Hungary.

DOI: 10.1530/endoabs.49.EP1411

Objective

SPECT/CT has numerous advantages over planar and traditional SPECT images.

The aim of this study was to evaluate the role of post-radioiodine therapy

SPECT/CT of patients with differentiated thyroid cancer (DTC) in early risk

classification and in prediction of late prognosis.

Patients and Methods

EP1412

323 consecutive patients, 181 at the University of Pecs and 142 at the University

Concomitant thyroid inflammatory myofibroblastic and

of Debrecen, were investigated after their first radioiodine treatment (1100-3700

follicular tumors

MBq). Both SPECT/CT and planar camera images of the head, neck, chest and

Romena Laukiene, Audra Padlipskaite & Edvardas Zurauskas

abdomen regions were taken four days after radioiodine therapy. Patients were

Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.

re-evaluated 9-12 months later as well as at the end of follow-up (median 37

months).

Results

Abstract

Post-radioiodine therapy SPECT/CT showed metastases in 22% of patients.

We present a rare clinical case. Inflammatory myofibroblastic tumors (IMT) are

Lymph node, lung and bone metastases were detected in 61, 13 and 5 patients,

extremely rare neoplasms of unknown etiology and most commonly found in

respectively, resulting in early reclassification of 115 cases (36%). No evidence of

lungs and gastrointestinal tract. A rare clinical case of the thyroid IMT occurred in

disease was found in 251 cases at 9-12 months after radioiodine treatment and 269

a 50-year-old lithuanian female patient with clinical manifestation of breath-

patients at the end of follow-up. To predict residual disease at the end of follow-

lessness, dry cough, hemoptysis, neck mass, arrhythmia and loss of conscious-

up, the sensitivities, specificities and diagnostic accuracies of the current risk

ness. Because of elevated D dimers values, pulmonary artery thromboembolism

classification systems and SPECT/CT were: ATA: 77%, 47% and 53%; ETA: 70,

was suspected and CT scan was performed. CT showed no pulmonary embolism,

62 and 64%; SPECT/CT: 61, 88 and 83%, respectively. There was no difference

but revealed a large tumor in the neck. After patient was investigated in

between cohorts of the two institutions when data were analyzed separately.

cardiology department to exclude sick sinus syndrome, fine needle aspiration

Conclusions

cytology of thyroid nodus was done with non-diagnostic results. Thyroid

Based on our bi-institutional experience, the accuracy of post-radioiodine

scintigraphy showed cold node suggesting maligancy. All symptoms and findings

SPECT/CT outweighs that of the currently used ATA and ETA risk classification

indicated the need of surgical treatment. The patient underwent total

systems in the prediction of long-term outcome of DTC.

thyroidectomy. Histopathology analysis revealed two separative tumors:

DOI: 10.1530/endoabs.49.EP1410

follicular carcinoma and thyroid inflammatory myofibroblastic tumor. Because

of folicular carcinoma the patient was treated with radioiodine. She was

comfortable after treatment with thyroid hormone replacement therapy. We

managed to find only 20 cases of this type of tumor located in thyroid reported in

the literature. And we did not find reports with two concomitant thyroid tumors

including IMT.

DOI: 10.1530/endoabs.49.EP1412

EP1411

Clinical features of medullary thyroid carcinoma (MTC) in

simultaneous occurrence with differentiated thyroid cancer (DTC)

George Simeakis, Katerina Saltiki, Elli Anagnostou, Michalis Apostolakis,

Vasiliki Vasileiou & Maria Alevizaki

Endocrine Unit, Department of Medical Therapeutics, Alexandra Hospital,

Athens University School of Medicine, Athens, Greece.

EP1413

Is thyroid imaging reporting and data system useful in prediction of

Objective

malignancy in thyroid nodules with persistent nondiagnostic cytology?

Simultaneous occurrence of MTC and DTC is frequently found. It is unclear

Husniye Baser¹, Oya Topaloglu², Sevgul Faki², Afra Alkan³, Mustafa Omer

whether there is a common pathogenic mechanism. Aim of our study was to

Yazicioglu⁴, Hayriye Tatli Dogan⁵, Reyhan Ersoy² & Bekir Cakir²

characterize clinical features of MTC when coexisting with DTC.

¹Ataturk Education and Research Hospital, Department of Endocrinology

Methods

and Metabolism, Ankara, Turkey;²Yildirim Beyazit University Faculty of

Of 273 MTC patients followed-up in our department 39 (14.3%) had MTC

Medicine, Department of Endocrinology and Metabolism, Ankara, Turkey;

simultaneously with DTC. They were divided in 4 subgroups according to size.

³Yildirim Beyazit University Faculty of Medicine, Department of

Biostatistics, Ankara, Turkey;⁴Yildirim Beyazit University Faculty of

Clinical histopathological data were recorded.

Medicine, Department of General Surgery, Ankara, Turkey;⁵Yildirim

Results

Beyazit University Faculty of Medicine, Department of Pathology,

The patients were followed for 1-35 yrs (median:5). Median age at diagnosis was

Ankara, Turkey.

45 yrs (4-81 yrs). Simultaneous occurrence of distinct MTC-DTC was observed

more frequently in patients diagnosed after 2001 compared to earlier (16.7 vs

6.3%, PZ0.036). Sex and history of familial disease did not differ. In familial

Introduction

forms of MTC, DTC occurrence was higher in carriers of RET exon 8 (G533C)

Although malignancy rate is low in thyroid nodules with nondiagnostic (ND)

mutation compared to other RET mutations (17.6 vs 1.8%, PZ0.004). Patients

cytology, it is reported as higher in persistent ND nodules. We aimed to determine

with concomitant MTC-DTC had less frequently lymph node infiltration from

the role of ultrasonography (US) features and Thyroid Imaging Reporting and

MTC compared to those with MTC alone (26.3 vs 47.8%, PZ0.015), marginally

Data System (TIRADS) in the prediction of malignancy in patients with persistent

smaller MTC size (median (IQR) 0.9 (1.5) vs 1.2 (1.4) cm, PZ0.058) and more

ND cytology.

often c-cell hyperplasia (58.6 vs 31.5%, PZ0.006). No differences were found

Methods

regarding capsular and soft tissue invasion, multifocality, distant metastases at

246 patients who underwent thyroidectomy with an indication of at least two ND

diagnosis. Stage at diagnosis differed between groups (MTC-DTC vs MTC alone:

cytologies were included in this study. Suspicious US features (solid component,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

hypoechogenicity, irregular margin, microcalcification, and taller-than-wide

EP1415

shape) and TIRADS categories (TIRADS category 3, 4a, 4b, 4c and 5) of each

Primary thyroid lymphoma: a differential diagnosis to be considered

nodule were obtained from medical records.

M Teresa Gallego, Lucia Vera, Cristina Del Peso, Amparo Meoro,

Results

Manuel Martin, Marife Candel, Emilio Terol & Francisco Pastor

Of the 246 patients, 218 (88.6%) had benign and 28 (11.4%) had malignant final

Hospital General Universitario Reina Sofia, Murcia, Spain.

histopathology. Of these 28 patients with malignant histopathology, 25 (89.3%)

were evaluated as papillary thyroid carcinoma, 1 (3.6%) as follicular thyroid

carcinoma,

(3.6%) as medullary thyroid carcinoma, and

(3.6%) as

Introduction

undifferentiated thyroid carcinoma. Frequencies of taller-than-wide shape,

Primary lymphoma of the thyroid, although rare, should be considered in the

solidity, hypoechogenicity, microcalcifications, and irregular margins were

differential diagnosis of patients with thyroid nodules or goiter, because its

similar in benign and malignant groups (PO0.05, all). TIRADS categories of

prognosis and treatment differ substantially from that of the other disorders.

246 nodules with ND cytology were as follows; 12 (4.9%) TIRADS 3, 53 (21.5%)

Thyroid lymphomas are nearly always of the non-Hodking type (70-80% B cell

TIRADS 4a, 104 (42.3%) TIRADS 4b and 77 (31.3%) TIRADS 4c. There was not

lineage). There is a 4:1 female predominance and the mean and median ages at

any nodule with TIRADS 5 category. Malignancy rates of categories 3, 4a, 4b,

diagnosis are between 65 and 75 years. Hashimoto’s thyroiditis is the only known

and 4c nodules were 0, 13.2,

9.6

and 14.3%, respectively. No significant

risk factor.

differences were found in TIRADS categories between benign and malignant

Case report

nodules (PO0.05, all).

A 70 years old woman with a rapidly enlarging goiter without local symptoms or

Conclusion

signs. The patient presented a history of hypothyroidism on treatment with

In the present study, malignancy rate was found as 11.4% in nodules with

thyroxine. Her tiroglobulin antibodies were positives but not TPO. An ultrasound

persistent ND cytology. There was not any suspicious US feature that was

scan of the thyroid showed a 7-cm mass in the left lobe and istm. The fine needle

predictive for malignancy in ND nodules. Thyroid nodules in TIRADS 4a, 4b and

biopsy was nondiagnostic but suggestive of Hashimoto’s thyroiditis. The

4c categories had higher malignancy rates than estimated risk of malignancy

excisional biopsy confirmed the diagnosis of a diffuse large B-cell lymphoma.

reported by the Bethesda system in ND cytology.

Imaging studies demonstrated cervical and mediastinal lymph nodes and bilateral

DOI: 10.1530/endoabs.49.EP1413

pulmonary metastases.

Discussion

Thyroid lymphoma represents no more than 2% of all malignant thyroid tumors.

The vast majority are of the non-Hodking type, the most frequent the B-cell

lineage. The typical presentation is a rapidly enlarging goiter with symptoms or

signs of tracheal, esophageal or neck vein compression. In 10-20% there is a

known goiter often with hypothyroidism. Up to

10% have systemic (‘B’)

symptoms of lymphoma

(fever, night sweats, weight loss). Diagnosis is

established by cytologic examination; when the fine needle biopsy is

nondiagnostic the excisional biopsy is required. The treatment includes Radiaton

and Chemotherapy. Definitive surgery is not usally performed. Our patient was

EP1414

treated with six cycles of CHOP followed by radiation.

Significant difference between the prevalence of C cell hyperplasia

Conclusions

(CCH) in benign thyroid nodules without histological thyroiditis (HT)

Thyroid lymphoma is a rare cancer but must be considered in the differential

and in papillary/follicular thyroid cancers (PTC/FTC) at histology

diagnosis of patients with thyroid nodules or goiter specially if a Hashimoto’s

Letizia Pieruzzi¹, Eleonora Molinaro¹, Laura Agate¹, Valeria Bottici¹,

thyroiditis is present. The risk of Thyroid lymphoma is at least 60 times higher

Liborio Torregrossa², Clara Ugolini², Fulvio Basolo², Paolo Vitti¹ &

than in patients without thyroiditis. The treatment is not the surgery like in the

Rossella Elisei¹

others thyroid pathologies and the prognosis depends on the type and tumour

¹Medical Area and Experimental Medicine Department, Endocrinology

extension.

section, University of Pisa, Pisa, Italy;²Department of Oncology Section of

DOI: 10.1530/endoabs.49.EP1415

Cytopathology, Pathology, University of Pisa, Pisa, Italy.

Background

CCH and serum hypercalcitoninemia (iperCT) can be found in benign thyroid

diseases such as thyroiditis and in some cases of papillary (PTC) or follicular

(FTC) thyroid microcarcinomas. The question of whether the association with

these latter is related to the malignancy of the nodule is still unclear.

Aim of the study

EP1416

To evaluate the difference in the CCH prevalence, at histology, in a series of

Relation between TSH levels and the aggressiveness of differentiated

benign (BTN) and malignant (PTC/FTC) thyroid nodules. The correlation with

thyroid carcinomas

the serum CT was also analysed.

Esra Aydinli², Mustafa Kulaksizoglu¹, Ahmet Kaya¹ & Feridun Karakurt¹

Materials and methods

¹Necmettin Erbakan University, Meram Medical Faculty, Division of

We selected 315 consecutive cases surgically treated between 2012 and 2016 in

Endocrinology and Metabolism, Konya, Turkey;²Necmettin Erbakan

our Hospital: 137/315(43.5%) resulted to be BTN and 178/315(56.5%) to be

University, Meram Medical Faculty, Internal Medicine, Konya, Turkey.

PTC/FTC. In 27/315(8.5%) cases there was a serum iperCT (Immulite 2000,

Siemens). The definition of CCH was based on the presence of more than 50

C-cells at least in one microscope field, in a thyroid cross section.

Aim

Results

Differentiated thyroid carcinomas

(DTC) composes

95% of all thyroid

At a first analysis no differences were observed in the prevalence of CCH between

malignancies originating from thyroid follicular epithelial cells. DTC expresses

BTN and PTC/FTC. When we excluded from the analysis the cases with reported

TSH receptors so long time TSH stimulation may cause cancer occurrence or

HT, both benign and malignant, the prevalence of CCH was statistically

malignancy progression. So we aimed to assess the role of TSH levels in

significant more frequent and bilateral in PTC/FTC (32.6%) than in BTN (19.5%)

predicting thyroid cancer stage or aggressiveness.

(P!0.05). The cases with iperCT were exclusively in the PTC/FTC group and

Methods

among them those case with iperCT showed the highest prevalence of CCH

We retsopectively searched thyroid cancer patients fort he last 10 years in our

(P!0.001). In PTC/FTC with serum iperCT we observed that 11/21(52.4%) were

instution. Totally 329 patients record were eligible for the study. TSH levels and

follicular variant PTC(FVPTC) while this variant was present in only

disease stage, age and sex were evaluated.

30/84(35.7%) PTC/FTC without iperCT (P!0.05). The cases with iperCT

Results

were also more often multifocal (P!0.005).

322

(97.9%) were papillary thyroid carcinomas and 7 (2.1%) were follicular

Conclusions

carcinomas 261 79.3(%) were females, 68 (20.7%) were males. Median age was

CCH is more frequent in PTC/FTC than in BTN when the cases with HT were

(17-76) years old. Among the patients; 273 (83.0%) had stage 1 disease, 22

excluded; the serum iperCT was found exclusively in the PTC/FTC group and

(6.7%) had stage 2 disease, 11 had (3,3%) stage 3 disease and 23 (7.0%) had stage

these cases showed the highest prevalence of CCH; a higher prevalence of

4 disease. Median TSH level was 1.34 (0.01-9.97) mIU/ml. Serum TSH levels

FVPTC and multifocal cases were observed in the PTC/FTC group associated

were different when compared stage 1 and 4 patients (PZ0.004). But there was no

with CCH.

significant difference between other stages. Additionally, subjects with lymph

DOI: 10.1530/endoabs.49.EP1414

node at diagnosis had higher TSH levels according to patients who had not

(PZ0.0001).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Conclusion

Case report

Higher TSH levels were observed in patients with lymph node metastasis at the

A 46-yr-old man presented to the emergency department with a painful mass on

diagnosis and there was statistically higher TSH levels in stage

4 patients

the anterior side of his neck. Laboratory tests revealed leukocytosis, while thyroid

compared to stage 1 patients. But this relation was not seen in other stages.

functions tests, calcitonin, carcinoembryonic antigen and calcium levels were in

Further studies with larger number of patients could show the relation with TSH

the normal limits. Neck ultrasound revealed an enlarged thyroid gland with a

levels and thyroid cancer aggressiveness.

2.5 cm dominant nodule on the right thyroid lobe. Fine-needle aspiration cytology

DOI: 10.1530/endoabs.49.EP1416

showed ‘atypia of undetermined significance’ (AUS). The patient underwent total

thyroidectomy. Histological examination revealed a papillary carcinoma 1.4 cm

in diameter with central fibrosis, degenerative necrosis and the presence of foam

histiocytes. It also showed multiple solid cell nests, nodular hyperplasia and rare

lymphoid aggregates in the rest area of the thyroid.

Discussion

Rare cases of concurrent PTC up to 1 cm and SCNs have been described in the

literature. SCNs may harbour multipotent stem cells which after a combination of

EP1417

mutations affecting their differentiation and unlimited growth potential may

Ultrasonographic features of thyroid nodules with suspicious or

generate cancer stem cells predisposing to thyroid cancer. Immunohistochemical

malignant cytology

and molecular studies of neoplastic SCN lesions are needed to better understand

Vasileios Chambidis, Athanasios Siolos, Lazaros Lazarou,

the complexity of stem cells and their malignant counterparts, advancing our

Zoe Efstathiadou, Athanasios Panagiotou, Fotini Adamidou & Marina Kita

knowledge on thyroid pathophysiology, carcinogenesis, and treatment.

Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.

DOI: 10.1530/endoabs.49.EP1418

Introduction

Thyroid sonography has become the first line diagnostic procedure for thyroid

nodules. The characterization of specific sonografic patterns associated with high

risk of malignancy has enabled physicians to determine which nodules are more

likely to be malignant and thus merit further evaluation.

Aim

EP1419

We investigated whether the ultrasonographic nodule characteristics proposed in

Statistical analyses on thyroid cancer in Romania

the literature were able to predict cytology findings after ultrasound-guided fine

Mariana Purice¹, Andrei Liviu Goldstein¹, Iulia Andreea Chiriac¹,

needle aspiration biopsy (USg-FNAB), in our centre.

Monica Radulescu², Sorin Rusu², Alexandra-Cristina Mihai¹,

Materials and methods

Andreea Giurgi⁵, Madalina Olteanu³, Adina Mariana Ghemigian^1,4 &

A retrospective analysis of patients who had undergone USg-FNAB between Jan

Catalina Poiana^1,4

2014 and Nov 2015 was performed. Nodules were classified according to the

¹‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;

following sonographic characteristics a) size, b) solid hypoechoic nodule, c)

²SOFTWIN S.A, Bucharest, Romania;³Universite Paris I Panthéon

presence of microcalcifications, d) irregular borders, e) vertical growth (‘taller-

Sorbonne, Paris, France;⁴‘Carol Davila’ University of Medicine and

than-wide’ orientation), and, f) increased vascularity. Cytology reports were

Pharmacy, Bucharest, Romania;⁵Faculty of Biology, University, Bucharest,

classified, according to the Royal College of Pathologists guidance, as non-

Romania.

diagnostic for cytological diagnosis (Thy 1), negative for malignancy (Thy2),

neoplasm possible (Thy3), suspicious for malignancy (Thy4) and malignant

(Thy5). Category Thy1 nodules were excluded from the analysis. The association

of suspicious ultrasound characteristics with the composite cytology outcome of

For over 50 years the casuistic of patients with thyroid cancer registered in

possible neoplasm, suspicious or malignant (Thy3, Thy4, Thy5) was investigated.

the Nuclear Medicine Department of the National Institute of Endocrinology

Results

in Bucharest, Romania, has over 12 000 cases. In the last 6 years, a total of

During the study period, 736 nodules in 571 patients were biopsied. The most

2580 new cases have been added. They are organized in a ‘classic file’

common ultrasonographic feature was low echogenicity

(175/736,

23.8%),

format. As a necessity and the first step in order to build a digital national

whereas the most rear was the vertical nodule growth

(‘taller-than-wide’

database, we developed the BIOMAT-ENDO software as a Windows Forms

appearance, (28/736, 3.8%)). In a logististic regression model, where patient

application that stores all the main data regarding the patient hospitalized in

age was entered along with the ultrasonographic features, all variables emerged as

the department, starting with the first hospitalization, continuing with all the

predictors of the composite category Thy3, Thy4, Thy5 cytology, except vertical

periods of radioiodine therapy and the follow up. The patient-monitoring

nodule growth and increased vascularity.

MODULE contains: clinical parameters, surgery details, in vivo and in vitro

Conclusion

investigations, therapy information. Correlations can be done between any

Sonographic nodule characteristics proved to be accurate predictors of cytology

input data. We present preliminary results on 2000 cases of patients with

in the present patient series. Thyroid ultrasonography is a useful tool in

thyroid cancer digitalized during one year in this database. We used the

determining which nodules should be biopsied.

Structured Query Language in order to verify the functionality of the system,

DOI: 10.1530/endoabs.49.EP1417

the correctness of the existing data and for some preliminary statistics.

Results shows the following distributions: onset disease age: ! 18 year:

3%; 19-45 year: 37%; 46-65 year:42%; O66 year:18%; genders: F:84%;

M:16% M, area distribution: urban:74%; rural:26%, personal history: multi

nodular & nodular goitre:

81%, Graves’s

1%, Hashimoto:

1%; no

history:16%, risk factors: endemic area:70%; non-endemic area:30%,

histopathology: papillary/follicular:30%; papillary: 28%; follicular: 17%;

micro-carcinoma: 20%; others: 5%. Preliminary results on a target group

EP1418

with the onset disease age

!18 years (nZ58) show the following

Development of papillary thyroid carcinoma in a patient with multiple

distribution on: TNM: T1:7%; T2:14%; T3:19%; T4:5%; unclassified: 9%

solid cell nests of the thyroid

and on disease stage: STD1:57%; STD2:4%; STD3:23%; STD4a:10% and

Theodoros Liarigkovinos¹, Vasiliki Daraki¹, Paraskevi Floroskoufi¹,

STD 4b:6%.

Helen Moustou², George Kalikakis¹ & Stathis Papavasiliou¹

DOI: 10.1530/endoabs.49.EP1419

¹Department of Endocrinology, Diabetes and Metabolic Diseases,

University Hospital of Crete, Heraklion, Greece;²Laboratory of Pathology,

University of Crete, School of Medicine, Heraklion, Greece.

Introduction

EP1420

Solid cell nests (SCNs) of the thyroid are considered embryological remnants of

Prognostic value of preoperative serum calcitonin concentration on

the ultimobranchial bodies and the thyroid diverticulum. They are frequently (61-

primary surgery outcomes in medullary thyroid cancer

89%) detected in the thyroid gland, but their biological significance remains

Tomasz Gawlik, Aleksandra Kukulska, Zbigniew Wygoda,

disputable. According to the fetal cell thyroid carcinogenesis hypothesis SCNs

Jolanta Krajewska, Ewa Stobiecka, Agnieszka Czarniecka & Barbara Jarzab

may act as a source for specific thyroid cancer stem cells generating distinct

Maria Sklodowska-Curie Morial Institute and Centre of Oncology, Gliwice

thyroid cancer phenotypes. We report a case of a patient with concurrent SCNs

Branch, Gliwice, Poland.

and papillary thyroid carcinoma (PTC).

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1422

Calcitonin assessment in thyroid diseases is recommended when medullary

thyroid cancer (MTC) is suspected in fine needle biopsy, as well as in

Incidental thyroid uptake detected by⁶⁸Ga-DOTANOC positron

‘suspicious for a follicular neoplasm’ class, especially oxyphilic type, in

Emission Tomography: is it clinical significant?

patients with germinal RET proto-oncogene mutation and in nondiagnostic

Tiago Nunes da Silva¹, Joaquim Gomes Santos², Ana Catarina Matos¹, João

biopsy when no surgical treatment is planned. This assessment is also

Pedro Teixeira³, Carla Oliveira⁴, Joana Castanheira⁴, Susana Carmona^2,5,

suggested before any planned thyroid surgery to exclude MTC. Beyond

Hugo Duarte³, Durval Costa⁴, Luis Oliveira⁵, Ana Isabel Santos² &

diagnosis confirmation it is also suggested to take the concentration into

Jorge Portugal

account planning the extent of neck lymph node resection, although the

¹Endocrinology Department Hospital Garcia de Orta, Almada, Portugal;

threshold values are not precisely established. The aim of this work was to

²Nuclear Medicine Department Hospital Garcia de Orta, Almada, Portugal;

assess the prognostic impact of preoperative serum calcitonin concentration

³Nuclear Medicine Department - IPO Porto, Porto, Portugal;⁴Nuclear

on primary surgery outcomes in medullary thyroid cancer. Among 1575

Medicine department Champalimaud Centre for the Unknown, Lisboa,

MTC patients followed-up in single clinical centre 248 patients were

Portugal;⁵Nuclear Medicine Unit - Oncological Centre Dr.^a Natália

identified in whom serum calcitonin concentration before primary thyroid

Chaves/Joaquim Chaves Saúde, Carnaxide, Portugal.

surgery was available (63 men and 185 women). Its mean concentration was

3647.8G18862.7 pg/ml (median - 612 pg/ml, max. 286 643, min. 2 pg/ml).

Background

All patients underwent total thyroidectomy, and in 233 at least central and

The detection of thyroid incidental uptake of radiopharmaceuticals has been

unilateral neck lymph node resection. In postoperative assessment in 145

increasing. Those detected by

¹⁸F-fluorodeoxyglucose positron emission

patients serum calcitonin was undetectable and in 187 remained within

tomography (PET) have been associated with a significant risk of malignancy

normal ranges for healthy population (!10 pg/ml; in 11 of them in the

(8-64%). Gallium-68 (Ga-68) labelled peptides are now the standard imaging

follow-up calcitonin increased). In

217

patients after surgery no

modality for staging neuroendocrine tumours (NET). Its high sensitivity has

macroscopic cancer foci were visible in the imaging, and in further

increased the discovery of incidental findings. The aim of this study was to

follow-up in 11 metastases or recurrence were found. Maximal preoperative

evaluate the frequency and clinical significance of incidental thyroid uptake as

concentration in patients who had no nodal metastases and normal calcitonin

detected by⁶⁸Ga- DOTANOC PET in patients without a history of thyroid cancer.

after surgery was 2513.8 pg/ml. Maximal preoperative concentration in

Methods

patients in whom postoperative calcitonin was normal and were free from

A retrospective analysis was conducted over

patients who underwent

relapse in further follow-up was 15302.0 pg/ml. The minimal preoperative

⁶⁸Ga-DOTANOC PET as part of a work-up for non-thyroid cancer. The uptake

calcitonin in patients with histologiacally confirmed neck nodal metastases

in the thyroid gland (focal/physiologic) was evaluated and compared with the

was 23 pg/ml. Conclusions: High preoperative serum calcitonin concen-

uptake in the liver.

tration up to a value of almost 12 000 pg/ml does not exclude the possibility

Results

of radical surgical treatment in MTC patients. Neck nodal MTC metastases

(49%) of the 49 patients were female with a median age of 64 years (p25 53

can be found when serum calcitonin is as low as 23 pg/ml.

and p75 74). Thyroid nodules were known in 14 patients with a median size of

DOI: 10.1530/endoabs.49.EP1420

9.1G8.4 mm. The reasons for⁶⁸Ga-DOTANOC PET staging were: intestinal

NET in 29 (59.2%), bronchial NET in 10 (20.4%), pancreatic NET in 5 (10.2%),

paraganglioma in 2 (4.1%), an ectopic ACTH in one (2%), ectopic GH in 1 (2%)

and meningioma in 1 (2%). Eight patients (16%) had⁶⁸Ga-DOTANOC thyroid

uptake: one (2%) had anomalous focal uptake, and 7 (14%) had physiologic

uptake. The patient with focal uptake, had thyroid nodules on the corresponding

side, as detected by anatomic imaging with a final diagnosis of a benign nodule.

Of the seven patients with physiologic uptake, 3 (47%) had a corresponding

EP1421

nodule on ultrasonography and 1 (14%) had a papillary thyroid carcinoma. Ten

patients with known nodules did not have⁶⁸Ga-DOTANOC uptake, including a

Standardized mortality of thyroid cancer in Korea between 1985 and

follicular tumour.

2015: analysis of Korean national data

Conclusions

Yun Mi Choi¹, Won Gu Kim², Hyemi Kwon², Min Ji Jeon², Minkyu Han²,

In contrast to the published research of⁶⁸Ga-DOTANOC uptake in patients with

Tae Yong Kim², Young Kee Shong², Sang Mo Hong¹, Eun-Gyoung Hong¹

known thyroid cancer, in our short series, the incidental uptake in thyroid gland

& Won Bae Kim

does not seem to be related.

¹Hallym University Dongtan Sacred Heart Hospital, Seoul, Republic of

Korea;²Asan Medical Center, University of Ulsan College of Medicine,

DOI: 10.1530/endoabs.49.EP1422

Seoul, Republic of Korea.

Background

The prevalence of thyroid cancer has increased very rapidly in Korea. However,

there is no data focusing on thyroid cancer mortality in Korea. In this study, we

aimed to evaluate standardized thyroid cancer mortality using national data from

Statistics Korea.

Methods

Population and mortality data from 1985 to 2015 were obtained from Statistics

Korea. Age-standardized mortality rates (ASMR) of thyroid cancer per 100 000

EP1423

were calculated according to the standard population of Korea, as well as World

An association between breast cancer and the development of

Health Organization

(WHO) standard population and International Cancer

thyroid cancer

Survival Standard (ICSS) population weights.

Lila Brakni

Results

Hospital of Army MS Nekkache, Algiers, Algeria.

The ASMRs of thyroid cancer was increased from 0.19 to 0.87 between 1985 and

2004. And the ASMRs were decreased from 2005 until 0.43 in 2015. The

estimated annual percent change

(APC) from 1985 to 2004 was 7.64 and

Introduction

corresponding value from 2004 to 2015 was K4.28. These changes in the ASMRs

Women with breast cancer (BC) have an increased risk of developing thyroid

were similar patterns in males (APC 8.23, 1985-2003 and APC K4.33, 2003-

cancer (TC), specifically papillary and follicular thyroid carcinomas at a median

2015) and females (APC 7.33, 1985-2004 and APC K4.63, 2004-2015). These

of 5 years. The aim of the present retrospective study is to describe the clinical

patterns of the change of ASMR were also observed in elderly subgroup (R55

characteristics of women who present this association.

years). When ASMRs were calculated based on the WHO standard population

Results

and ICSS population weights, those was similarly increased until 2004, and

A total of 260 patients with an authenticated TC who were the median age at

decreased from 2004.

diagnosis is 41 years old (36-65). All our patients live in areas of moderate iodine

Conclusion

deficiency. The frequency of the association of BC-TC Z6/260 (4.3%). The

Thyroid cancer mortality in Korea was increased until 2004 and started to

median duration between the two diagnoses Z24 months (12-84). The BC has

decrease after then. The increase in early diagnosis of thyroid cancer might be

always preceded theTC. The histopathological aspects are respectively for the

associated with decrease of thyroid cancer mortality in Korea.

BC: invasive ductal carcinoma (nZ4) invasive lobular carcinoma (nZ2) and TC:

DOI: 10.1530/endoabs.49.EP1421

pure vesicular (nZ2); Papillary (nZ4). All these women underwent chemother-

apy, hormone therapy and radiotherapy for BC and total thyroidectomy and an

irradiation (100 mCI 131) for TC.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Discussion

Materials and methods

The coexistence BC and TC is not fortuitous but the related pathophysiological

Five hundred and thirty four patients done total thyroidectomy by general surgery

mechanisms remain poorly elucidated Exposure to estrogens and to thyroid-

were evaluated retrospectively from July 2015 to July 2016. Preoperative thyroid

stimulating hormones may play a role in the development of breast cancer or

function tests, anti-thyroid antibodies, thyroid ultrasonography findings, fine

thyroid cancer. Radiation exposure is also a well-known risk factor for the

needle aspiration biopsies of nodules and pathology results of total thyroidectomy

development of TC, so a germline mutation could be responsible for the

were examined. According to pathology results, HT was detected in 139 patients.

connection between breast and thyroid cancers.

Patients with PTC and HT (group 1) and PTC without HT (group 2) were

Conclusion

compared in terms of demographic characteristics, tumor size, focus number of

The association of these two pathologies is not incidental and should lead

tumor, invasion, extrathyroidal spread and lymphatic metastasis presence.

otherwise to the systematic screening of the thyroid cancer in women with breast

Findings

cancer.

PTC was detected in 70 (%50.4) patients in group 1 and 156 (%39.5) patients in

DOI: 10.1530/endoabs.49.EP1423

group 2 (PZ0.026). There was no statistically significant difference between

them in point of gender, age, tumor size, microcarcinoma-macrocarcinoma

distribution, focus number of tumor, invasion, extrathyroidal spread and

lymphatic metastasis. The number of patients with PTC who had at least 1 kind

of high anti-thyroid antibody was greater in group 1 then group 2 (P!0.001).

Results

In our study,we determined more PTC among HT patients but we find no

difference according to age, gender, tumor size, invasion and metastasis. By the

way anti-thyroid antibody positiveness was higher in cancer patients of group 1.

Long term follow-up studies are necessary for detecting the effect of HT to PTC

prognosis.

EP1424

DOI: 10.1530/endoabs.49.EP1425

Lung metastases from differentiated thyroid carcinoma: long term

outcome and its prognostic factors related to progression free survival

Seo Young Sohn¹, Hye In Kim², Sun Wook Kim² & Jae Hoon Chung²

¹Division of Endocrinology, Department of Medicine Seonam University

College of Medicine, Myongji Hospital, Goyang, Republic of Korea;

²Department of Endocrinology and Metabolism Samsung Medical Center,

Seoul, Republic of Korea.

Background

Distant metastasis rarely occurs in differentiated thyroid carcinoma (DTC), but

represents most common cause of death in patients with DTC. Lung and bone are

EP1426

the most frequent sites of distant metastases. This study investigated long term

A new strategy to estimate levothyroxine requirement after total

outcomes of lung metastasis in DTC patients and its prognostic factors

thyroidectomy and radioiodine remnant ablation for ‘intermediate’

influencing disease progression and cancer specific survival (CSS).

and ‘high’ risk differentiated thyroid cancer

Methods

Rosa Maria Paragliola, Annapina De Rosa, Vincenzo Di Donna,

A total of 134 DTC patients presenting with lung metastasis from 1994 to 2012

Giampaolo Papi, Alfredo Pontecorvi & Salvatore Maria Corsello

were retrospectively analysed. Factors predictive of the outcome were determined

Endocrinology, Università Cattolica del Sacro Cuore, Rome, Italy.

by Cox-proportional model.

Results

With a median follow up of 81 months after surgery, the 5- and 1-year CSSs were

Introduction

80 and 66%, respectively. The predictors of disease progression were older age

The approach for initial thyroid hormone suppression in patients who undergo

(R45 years),¹³¹I non-avidity and co-existing bone metastases other than lung.

surgery for differentiated thyroid cancer (DTC), is based upon the risk of disease

Similarly, older age (R45 years),¹³¹I non-avidity, co-existing bone metastases

recurrence. In particular, recent American Thyroid Association guidelines

and follicular pathology was associated with CSS. Cox proportional hazard ratio

suggest to maintain TSH levels between

0.1

and

0.5 mU/l and less than

for progression-free survival and disease-free survival showed that older age was

0.1 mU/l for patients with ‘intermediate’ and ‘high’ risk respectively. The aim of

the only independent predictive factor for poor prognosis.

the study is to identify the major predictive factors of LT4 requirement to obtain

Conclusions

semisuppressed or suppressed TSH levels and to elaborate a new method that

Older age, additional bone metastases,¹³¹I non-avidity and follicular histology

could improve the accuracy of the LT4 therapeutic starting dose in intermediate

were found to be significantly associated with poor clinical outcome. Therefore,

and high risk DTC patients.

strict surveillance should be tried in these patients.

Methods

DOI: 10.1530/endoabs.49.EP1424

Two hundred and nineteen patients who underwent total thyroidectomy and

radio-remnant ablation for DTC have been retrospectively evaluated. One

hundred and forty nine were on TSH suppressive therapy (TSH!0.1 mU/l) and

70 on TSH semisuppressive therapy (TSH: 0.1-0.4 mU/l). The results obtained by

this retrospective analysis were used to formulate a nomogram for the calculation

of the LT4 dose.

Results

For both groups

(suppressive and semisuppressive LT4

therapy) the best

parameters to predict the optimal LT4 starting dose are body mass index (BMI)

and age. On the basis of the nomogram, the LT4 dose in mg/kg to obtain

suppressed and semisuppressed TSH levels ranged from 1.6 to 2.1 mg/kg per day

EP1425

and from 1.5 to 1.9 mg/kg per day respectively. The dose is higher in younger

Is Hashimoto’s thyroiditis a risk factor for papillary thyroid cancer?

patients with lower BMI.

Zeynep Cetin¹, Ozden Ozdemir Baser¹, Dilek Berker¹ & Serdar Guler²

Conclusion

¹Numune Training and Research Hospital, Ankara, Turkey;²LIV Hospital,

In our study BMI and age represent important parameters to predict LT4 dose in

Ankara, Turkey.

intermediate and high risk DTC patients. LT4 requirement decrease with the

increase in age and BMI, probably due to the relative decrease of lean body mass.

Based on these data, a user-friendly nomogram, representing an efficient method

Aim

to calculate LT4 starting dose in patients who underwent thyroidectomy for

Hashimoto’s thyroiditis (HT) is the commonest autoimmune thyroid disease.

differentiated thyroid cancer, has been created.

Papillary thyroid cancer (PTC) is the most often thyroid cancer and its incidence

DOI: 10.1530/endoabs.49.EP1426

is increasing yearly. It is not clear that HT is a predisposing factor for PTC. We

studied PTC’s frequency among HT patients went to total thyroidectomy.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1427

Method

Data of patients diagnosed with DTC between 2007 and 2014 at our institution

Follicular thyroid carcinoma in a patient with graves’ disease

were analysed retrospectively. TNM, MACIS, EORTC, AMES, De Groot, ETA,

Nesrine Cheikhrouhou, Intidhar Elbez, Kaouthar Limam, Aida Mhiri,

LATS, and ATA staging systems were applied to patients according to their

Bechir Ltaeif & Mohamed Faouzi Benslimene

original description. In ATA risk classification system, we classified patients into

Department of Nuclear Medicine, Salah Azaiez Institute, Tunis, Tunisia.

four categories considering inappropriate postoperative thyroglobulin levels.

Results

Introduction

There were 983 patients (218 male and 765 female) with a mean age of 49.4G

Follicular cancer has a low incidence in Graves’ disease when compared to

12.5 and a mean follow-up of 42.6G24.3 months. Distribution of patients

papillary thyroid cancer. Some studies have not reported any follicular cancer in

according to the staging systems were as follows; TNM: 81.1%, 4.7%, 12.7%,

patients with Graves’ disease. We describe a rare occurrence of follicular cancer

1%, 0.3%, 0.2% of patients in stage I, II, III, IVA, IVB, IVC respectively;

in a patient with Graves’ disease.

MACIS: 91%, 5.9%, 2.2%, 0.8% of patients in group 1-4 respectively; EORTC:

Observation

39.4%, 36.7%, 19.8%, 4%, 0.1% of patients in group 1-5 respectively; AMES:

A 37-year-old female patient presented to our institute with symptoms of

82.2% of patients in low risk and 17.8% in high-risk group; De Groot: 81.6%,

thyrotoxicosis. She had no family history of thyroid cancer or of radiation

4.7%, 13.3%, 0.4% of patients in stages 1-4 respectively; ETA: 35.5%, 25.9%,

exposure in the neck area. She presented with typical clinical and biochemical

12.4%, 26.1% of patients in very low, low, high and undetermined risk groups

features of Graves’ disease. Tc-99m scintigraphy of the thyroid showed diffusely

respectively; LATS: 35.5%, 26.7%, 17.7%, 20.1% of patients in very low, low,

increased uptake with hypo functioning (cold) nodule. She underwent uneventful

high and undetermined risk groups respectively. According to ATA, distribution

surgery after achieving an euthyroid state. A total thyroidectomy was performed

of patients in low, intermediate, high and undetermined risk groups were

with resection of an enlarged lymph node detected on intra-operatively. A

respectively 26.4, 8.7, 40.8 and 23.6% in category 1, 39.7, 12.9, 23.8 and 23.6% in

follicular thyroid carcinoma was diagnosed on the cold nodule with metastatic

category 2, 46.7, 15.2, 14.5 and 23.6% in category 3, and 3.9, 19.2, 3.3 and 23.6%

lymph node. Patient was given an ablative dose of I131. Post-therapeutic

in category 4.

scintigraphy revealed a significant residual thyroid tissue/residual tumor in the

Conclusion

neck. The TSH-stimulated serum Thyroglobulin level measured by radio-

Variable scoring systems with variable risk assessments were suggested for DTC

immunoassay was 13 ng/ml. Being sensitive to iodine, patient will continue to

in the literature. A standardized categorization is required to overcome confusion

receive I-131cures to complete remission.

and help clinicians during management of these patients.

Conclusion

DOI: 10.1530/endoabs.49.EP1429

Surgical treatment should be indicated if graves disease is associated to suspected

nodule.

DOI: 10.1530/endoabs.49.EP1427

EP1430

EP1428

A rare association of thyroid micro carcinoma and thyroid tuberculosis

Papillary thyroid carcinoma in children: report of 15 cases

Intidhar Elbez, Nesrine Cheikhrouhou, Kaouthar Limem, Ihsen Slim,

Intidhar Elbez, Nesrine Cheikhrouhou, Kaouthar Limam, Aida Mhiri,

Aida Mhiri, Béchir Ltaeif & Med Faouzi Ben Slimene

Ihsen Slim, Bechir Ltaeif & Med Faouzi Ben Slimene

Department of Nuclear Medicine, Salah Azaiez Institute, Tunis, Tunisia.

Introduction

Papillary thyroid carcinoma is rare in young patients and have a good prognosis,

Thyroid tuberculosis is a rare disease, its frequency is 0.15-0.2% of autopsic data.

although it is often diagnosed at the stage of lung metastases. Our multicenter

We report a case of micro papillary carcinoma of thyroid revealed by thyroid

study included

children aged between

and

years with female

tuberculosis.

predominance, followed for differentiated thyroid cancer with lung metastases.

Observation

All these patients underwent a whole body scan with I-131, serum thyroglobulin,

Mrs. K.J aged 54 years presented a multinodular goiter without ultrasound signs

chest radiography and/or cervico-thoracic CT. Scintigraphy had shown

of malignancy. The patient underwent total thyroidectomy. Histological

pulmonary miliary among all patients. Iodine treatment was successful in all

examination revealed a granulomatous and giganto cellular inflammation which

patients, which proves the high sensitivity of these metastases to iodine treatment.

is in favor of a tuberculosis. The left lobe of the thyroid contained a 4 mm

The differentiated thyroid cancer is characterized by local aggressiveness and a

papillary microcarcinoma. No metastatic adenopathy was found. The tumor was

high frequency of distant metastases. Prognosis does not seem to be influenced by

classified pT1aN0Mx. The patient was addressed to department of nuclear

histology alone, but by its association with other prognostic factors: age,

medicine for supplementation of radioactive iodine treatment. In addition, the

metastases and surgery.

patient had benefited of anti-tuberculosis treatment for 7 months.

Conclusion

DOI: 10.1530/endoabs.49.EP1428

Thyroid tuberculosis is a rare entity. In the absence of other tuberculous sites,

diagnosis is often difficult. It is based on bacteriological and

/ or thyroid

anatomopathological evidence. The association with a microcarcinoma is also

rare and has to be carefully investigated by the anatomopathologist

DOI: 10.1530/endoabs.49.EP1430

EP1429

Evaluation of differentiated thyroid cancer patients according to

different scoring systems: a single center experience

Bekir Cakir¹, Cevdet Aydin¹, Berna Evranos Ogmen², Ali Abbas Tam¹,

Sefika Burcak Polat¹, Husniye Baser², Neslihan Cuhaci¹, Fatma

Dilek Kahramanca², Nagihan Bestepe², Cuneyt Bilginer¹, Sevgul Faki¹,

Mehmet Kilic⁴, Aydan Kilicarslan³ & Reyhan Ersoy¹

EP1431

¹Department of Endocrinology and Metabolism, Faculty of Medicine,

Ataturk Education and Research Hospital, Yildirim Beyazit University,

GA/GG Heterozygosity of ARG280HIS polymorphism in XRCC1

Ankara, Turkey;²Department of Endocrinology and Metabolism, Ataturk

GENE: Genetic susceptibility genotype in differentiated thyroid

Education and Research Hospital, Ankara, Turkey;³Department of

cancer?

Pathology, Faculty of Medicine, Ataturk Education and Research Hospital,

Nazli Gulsoy Kirnap¹, Neslihan Bascil Tutuncu¹, Yaprak Yalcin²,

Yildirim Beyazit University, Ankara, Turkey;⁴Department of Surgery,

Hasibe Verdi², Asli Nar¹ & Belgin Atac²

Faculty of Medicine, Ataturk Education and Research Hospital, Yildirim

¹Department of Endocrinology and Metabolism, Ba¸kent University Faculty

Beyazit University, Ankara, Turkey.

of Medicine, Ankara, Turkey;²Medical Biology, Ba¸kent University

Faculty of Medicine, Ankara, Turkey.

Introduction

True risk evaluation is important in the management of thyroid cancer. We aimed

Background

to evaluate patients with differentiated thyroid cancer (DTC) according to the

Thyroid carcinomas are the most frequent endocrine malignancies of which more

different staging systems.

than nighty percent are differentiated thyroid carcinomas (DTC). It’s known that

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

genetic variation plays

75% role in the development of papillary thyroid

EP1433

carcinoma (PTC).

Material and methods

In a case control setting subjects between January 2005 and December 2015 were

Abstract withdrawn.

evaluated for inclusion in the study. We aimed to compare the genotype

frequency distributions of three common X-ray repair cross-complementing

group 1 (XRCC1) SNPs in those with differentiated thyroid carcinoma (n: 228)

and cancer-free patirents with benign nodular goiter (n:100) and the healthy

controls (n:98) with regard to some predefined risk factors like existence of

Hashimoto’s thyroiditis, smoking, obesity, family history of thyroid cancer, and

radiation exposure. In the present study we tried to assess the genotype frequency

distributions of three common XRCC1 SNPs. Genomic DNA was extracted from

peripheral lymphocytes using phenol-chloro form extraction. XRCC1

Arg194Trp, Arg280His and Arg399Gln polymorphisms were detected by

amplification with real-time PCR followed by melting-curve analysis with

fluorescence-labeled hybridisation probes in a LightCycler.

EP1434

Results

Mutation analysis of papillary thyroid cancers using a newly developed

Heterozygous GA/GG genotype frequency of the Arg280His polymorphism in

targeted multi-gene panel in Hungarian population

DTC cases was significantly higher than in those with benign nodular goiter and

Barbara Kocsis-Deák¹, Kristóf Árvai¹, Bernadett Balla¹, Bálint Tóbiás¹,

in those in the healthy control group (64.5 and 3%, respectively; P!0.001). The

Andrea Kovesdi¹, János Kósa¹, Balázs Járay², Tamás Székely²,

frequency of homozygous AA genotype of Arg280His polymorphism was lowest

János Horányi³ & Péter Lakatos¹

in the DTC group (35.5%). The difference was statistically significant (P!0.001).

¹Department of Internal Medicine, Semmelweis University, Budapest,

Presence of family history of thyroid cancer was 7.9% in DTC group and 1% in

Hungary;²Department of Pathology, Semmelweis University, Budapest,

benign nodular group. The difference was statistically significant (PZ0.014).

Hungary;³Department of Surgery, Semmelweis University, Budapest,

Discussion

Hungary.

In conclusion, our study demonstrates that Arg280His GA/GG genotype of

XRCC1 gene polymorphism is more frequently encountered in DTC than in

cancer-free controls. GA genotype frequency is highest in those DTC cases with a

Thyroid cancer is the most common malignancy of endocrine organs and its

family history of thyroid cancer.

incidence is steadily growing worldwide. Approximately 80% of differentiated

thyroid tumors are papillary carcinomas. Next-generation sequencing (NGS)

DOI: 10.1530/endoabs.49.EP1431

allows for high-throughput sequencing analysis of large number of samples at a

time in a cost effective manner. We have developed a targeted sequencing parallel

testing panel for multiple mutations in genes involved in thyroid cancer

pathology. A custom-made AmpliSeq hot spot panel was designed to target 23

cancer genes (NRAS, MET, CTNNB1, PIK3CA, DICER1, VHL, BRAF, PTEN,

LPAR4, EIF1AX, HRAS, RET, GAS8-AS1, KRAS, TSHR, AKT1, GNAS,

TERT, TP53, AXIN1, APC, IDH1, SMAD4) which containes 357 known

mutational hot spot areas with COSMIC IDs. Semiconductor sequencing was

EP1432

performed to analyze DNA from 56 papillary thyroid carcinomas with matched

Expression analyses of HABP2 in neoplastic and normal thyroid tissues:

normal fresh frozen samples. The average coverage was 400X. BRAF, TSHR,

could this gene play a role in the pathogenesis of familial non medullary

APC, RET, LPAR4, TP53, AXIN1 and SMAD4 genes were the most mutated

thyroid cancer?

genes in our papillary thyroid cancer samples. Altogether, mutations, with at least

Marina Muzza^1,2, Carla Colombo^1,2, Maria Carla Proverbio^1,2,

5% variant coverage and less than

1% minor allele frequency in general

Giulia Ercoli^1,2, Michela Perrino^1,2, Valentina Cirello¹,

population, could be shown in all of the samples, while mutation could be seen in

Leonardo Vicentini^1,2, Stefano Ferrero^1,2 & Laura Fugazzola^1,2

seven control samples. The distribution of genetic alterations was similar to the

¹Division of Endocrine and Metabolic Diseases, Istituto Auxologico IRCCS,

published data. The sensitivity and the specificity of the method were 100% and

University of Milan, Milan, Italy;²Endocrine Unit, Division of Pathology,

90%, respectively with a positive predictive value of 87%. Our multi-gene panel

and Endocrine Surgery Unit, Fondazione IRCCS Ca’ Granda-Ospedale

testing approach allows parallel analysis for multiple mutations with high

Maggiore Policlinico, Milan, Italys.

accuracy and sensitivity, and short turnaround times.

DOI: 10.1530/endoabs.49.EP1434

Recently, the G534E variant of the HABP2 gene was reported as the underlying

genetic defect in large kindred with non-syndromic familial non medullary

thyroid cancer (FNMTC), but these data were not confirmed in additional cohorts.

Consistently, we found in our wide series of FNMTC that the HABP2G534E

variant is frequent, but does not segregate with the disease. Nevertheless, a

possible role for this gene in the pathogenesis of FNMTC cannot definitely ruled

out also because contrasting but interesting expression data are available in other

human tumors. To get more insights into the expression of this gene in thyroid

tumor and normal tissues, HABP2 expression levels were determined by non-

quantitative or quantitative Real-time PCR of RNA extracted from nine

neoplastic and matched normal thyroid tissues: seven sporadic papillary thyroid

EP1435

cancer (PTC) cases not carrying HABP2G534E, 1 FNMTC from a member

K1 cell line in vitro: the impact of diagnostic absorbed doses from¹³¹I

carrying HABP2G534E and 1 FNMTC from a member not carrying the variant.

Mariusz Stasiolek¹, Zbigniew Adamczewski², Boleslaw Karwowski³,

Immunohistochemistry for HABP2 was performed in 6 neoplastic and matched

Marek Dedecjus⁴ & Andrzej Lewinski²

normal thyroid tissues: 2 sporadic PTC cases, 2 FNMTC from members carrying

¹Department of Neurology, Polish Mother’s Memorial Hospital - Research

the HABP2G534E variant and 2 FNMTC from members not carrying the variant.

Institute, Lodz, Poland;²Department of Endocrinology and Metabolic

HABP2 mRNA had a very variable expression in tissues from FNMTC, sporadic

Diseases, Medical University of Lodz, Lodz, Poland;³Food Science

PTCs or contralateral normal tissues. In almost all cases, the gene appeared down-

Department, Medical University of Lodz, Lodz, Poland;⁴Department of

or up-regulated in tumors with respect to the corresponding normal tissue. At

Oncological Endocrinology and Nuclear Medicine, Maria Skłodowska-

immunohistochemistry, HABP2 was expressed in both tumor and matched

Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

control tissues, without differences between sporadic and familial cases. In

conclusion, our data confirm the apparent lack of co-segregation of the

Background

HABP2G534E variant with FNMTC. Nevertheless, the dysregulation of

Diagnostic whole-body scan is a standard procedure in patients with thyroid

HABP2 expression found in either sporadic or familial PTCs or normal thyroid

cancer prior to the application of therapeutic dose of

¹³¹I. Unfortunately,

tissues, suggests potential post-transcriptional and post-translational alterations,

administration of radioisotope in diagnostic dose may decrease further radio-

and is consistent with similar findings in other malignancies, possibly indicating a

iodine uptake

- the phenomenon called

‘thyroid stunning’. We estimated

role of this gene also in thyroid cancer.

radiation absorbed dose-dependent changes in genetic material, in particular

DOI: 10.1530/endoabs.49.EP1432

in sodium iodide symporter (NIS) gene promoter, and NIS protein level in K1

cell line.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Materials and methods

Antibodies) were within normal ranges. Thus, we did not find any evidence of

We used the K1 cell line derived from the metastasis of human papillary thyroid

thyroid disease. Two years later, the woman made an appointment at our clinic

carcinoma exposed to¹³¹I in culture. The different¹³¹I activities applied were

complaining of exercise - associated dyspnea. Her thyroid-stimulating hormone

calculated to result in absorbed doses of 5, 10, and 20 Gy.

(9.96 mU/l; normal, 0.4-3.6 mU/l) and TPOAb (685 kU/l; normal, 0-78 kU/l)

Results

were increased. The ultrasonography showed marked bilateral low parenchymal

Radioiodine did not affect the expression of NIS gene at the mRNA level,

echogenicity, inhomogeneous thyroid. In the left thyroid lobe, there were diffuse

however, we observed significant changes of the NIS protein level in K1 cells.

microcalcifications without focal mass. Sonographically, the thyroid lesions were

The decrease of NIS protein level, observed in the cells subjected to the lowest

indicative of chronic lymphocytic thyroiditis. A subsequent fine needle aspiration

absorbed dose, was paralleled by significant increase in 8-oxo-dG concentrations

biopsy was performed. The cytologic examination assessed a suspicion of

(P!0.01) and followed by late activation of the DNA repair pathways.

malignancy with chronic lymphocytic thyroiditis. The patient underwent the total

Conclusions

thyroidectomy with lymph node dissection. Histopathologically, a chronic

Our findings show that the impact of radiation on living cells, in the range

lymphocytic thyroiditis and 0.7 cm size papillary microcarcinoma in the left

compared to doses absorbed during diagnostic procedures in patients, does not

lobe were detected. Numerous stromal psammoma bodies, lymphatic intralobular

show the linear dose-effect.

spread with lymph node metastasis were revealed. We have demonstrated a very

DOI: 10.1530/endoabs.49.EP1435

rare case of PTC with chronic lymphocytic thyroiditis ultrasonographically

presenting with diffuse microcalcification without thyroid nodes. In our case, an

atypical sonographic appearance of papillary microcarcinoma was associated

with lymphatic intralobular spread and numerous stromal psammoma bodies in

the thyroid. We conclude, in a case of ultrasonographically detected diffuse

microcalcification without focal lesions, a careful examination for thyroid

malignancy should be proposed.

EP1436

DOI: 10.1530/endoabs.49.EP1437

Massive thyroid gland metastasis from nonsmall cell lung cancer

Diana Simoniene^1,2, Milda Daneliene^1,2, Raimonda Klimaite^1,2 &

Rasa Mikalauskaite²

¹Hospital of Lithuanian University of Health Sciences, Kauno Klinikos,

Kaunas, Lithuania;²Lithuanian University of Health Sciences, Kaunas,

Lithuania.

EP1438

Columnar cell variant of papillary thyroid carcinoma

Despite that the thyroid gland is one of the most vascular organs of the body but

Marie Hlavá

ˇková

thyroid gland is an uncommon site for metastasis [1]. It represents less than 4% of

Institute of Endocrinology, Prague, Czech Republic.

thyroid malignancy in clinical and surgical studies [2, 3]. 58-year-old male, a

prior smoker, was diagnosed with nonsmall cell lung cancer T4N3M1 St IV,

histopathological findings - infiltrative adenocarcinoma, G1. About eight months

Columnar cell variant is rare variant of papillary thyroid carcinoma. It occurs in

he was treated with chemotherapy. At the beginning of the disease, the patient

both genders with the most common occurence in the middle age of life. It differs

was examined by the endocrinologist and diagnosed a nodule thyroid. A fine

from common PTC both in morphology and especially in biological behavior.

needle aspiration (FNA) revealed a cystic degeneration. It was intended to repeat

The cancer cells also commonly harbor BRAF mutation. We describe a case of

the FNA after three

- 6 months. After

2 months, a patient presented to

young women, who came for the examination of the thyroid gland before in vitro

Endocrinology department of Hospital of Lithuanian University of Health

fertilization. We found normal thyroid function tests, negative antibodies. A small

Sciences Kauno klinikos because of increasing volume of the neck, shortness of

cystic lesion in the middle line of her neck under hyoid bone was seen at

breath, changes in voice and swallowing disorder. Thyroid ultrasound

ultrasound. The small primary tumor in pyramid lobe of thyroid gland was found

examination showed an enlarged thyroid gland, its structure was hypoechogenous

and cystic lesion was identified as the metastatic lymphonode. We scrutinized the

and non-homogenous. Because of rapid tumor growth, we differentiated between

genetic background of this more aggresive PTC variant and BRAF mutation was

lymphoma, anaplastic and hypopharyngeal cancer, lastly metastatic lesion.

found. We mentioned the necessity of the differential diagnosis of cystic lesion of

Metastasis from primary lung cancer was confirmed by thyroid fine-needle

the neck. This case has happy end untill now thanks to early diagnosis.

aspiration, cervical lymph nodes and laryngeal biopsies. After

week

DOI: 10.1530/endoabs.49.EP1438

complications progressed. Thyroid was dramatically enlarged, acute respiratory

failure evolved and the patient was unsuccessfully treated at Intensive Care Unit.

In conclusion, a diagnosis of metastatic disease should be considered when new

thyroid lesion is identified in any patient with a known history of malignancy until

such a diagnosis can be ruled out. Because detection of metastasis to the thyroid

gland often indicates a poor prognosis, aggressive treatment in time may be

EP1439

sufficient.

A higher frequency of papillary thyroid carcinoma in

DOI: 10.1530/endoabs.49.EP1436

myotonic dystrophy

Adrien Ben Hamou^1,2, Claire Marie Dhaenens^1,4, Stephanie Espiard^1,2,

Kanza Benomar^1,2, Vincent Tiffreau^1,5, Robert Caiazzo^1,3,

Sebastien Aubert^1,4 & Marie Christine Vantyghem^1,2

Lille University Hospital, Lille, France;²Endocrinology, Diabetology and

Metabolism, Lille, France;³Endocrine Surgery Unit, Lille, France;⁴Institute

of Biochemestry and Molecular Biology - Biology and Pathology Center,

Lille, France;⁵Neuromuscular Reference Center, Lille, France.

EP1437

Papillary thyroid cancer and chronic lymphocytic thyroiditis present-

Background and purpose

ing with diffuse microcalcifications without focal mass on ultrasound

Type 1 myotonic dystrophy (MD), associates neuromuscular, cardiac, respiratory

Jelena Vainikonyte-Kristapone, Jurgita Makstiene, Raimondas Valickas,

and endocrine disorders. The aim of this study was to determine the prevalence of

Neli Jakuboniene, Dalia Kozloviene & Gintaras Kuprionis

thyroid disorders and of any causal factors.

The Hospital of Lithuanian University of Health Sciences Kauno klinikos,

Methods

Kaunas, Lithuania.

A retrospective single centre study was conducted, between 2000 and 2016, in

127 MD patients, diagnosed by familial genetic screening after informed consent.

The detection and characterization of PTC are based on the evaluation of specific

Clinical examination, TSH assay, 120-min glucose and insulin levels post-OGTT,

ultrasonographic features of thyroid nodes. However, there is limited data

number of CTG repeats and ultrasound thyroid exam were performed. Eleven

regarding diagnostics without typical malignant-appearing nodules. We report a

patients refused the assessment. The 116 remaining were divided into 2 groups

very rare case of PTC in underlying chronic lymphocytic thyroiditis

according to the presence of a goiter defined as an ultrasound volume ! (usNG)

ultrasonographically manifested with diffuse microcalcification without focal

or O (usG) 18 ml, whatever the presence of nodules.

mass. A 22-year-old woman visited our institution complaining of weight loss,

Results

general weakness, and headache. A physical examination revealed a painless, firm

The whole population (61.2% female) was aged 45.1G12.2 years; the BMI was

thyroid without a palpable mass. In an ultrasonography of the neck, the pathology

26.2G6.5 kg/m²; at least one palpable nodule or a goiter was present in 33.6%,

was not assessed. The thyroid hormones concentration, TPOAb (Thyroperoxidase

and hypothyroidism in 8.6%. The percentage of usG was 38.8%. Age (46.6G9.6

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

vs 44.1G13.6 years), BMI (28.1G7.1 vs 24.9G5.9 kg/m²), and frequency of

advanced disease to the palliative care stage. However, chronic and escalating

papillary thyroid carcinoma (PTC) (17.8% vs 1.4%) were significantly higher in

somatic symptoms during the treatment may promote the appearance of

usG than in usNG. UsG was associated with BMI increase (P 0.017, IC 95%

depressive reactions. It can be expected that a cognitive image of the disease,

(K5.609 to K0.556), and hyperinsulinism (trend: PZ0.069), but not with CTG

as a collection of subjective beliefs concerning patient’s own illness and

repeats. 11 (24.4%) of the 45 usG patients had a total thyroidectomy. Six micro

treatment, will be an important determinant of mental functioning. The aim of the

(whose one had a capsule rupture) and 3 macro-PTC (with a high-risk level for 2

study was to define a mutual dependence between the intensity of somatic

of them (pT2N1aM0, pT3N0M0) were diagnosed. 80% of these 9 PTC were

problems, self-image of the illness and depression in patients receiving an

associated with a palpable thyroid anomaly.

experimental treatment of TC.

Conclusion

Material and methods

A third of these 116 MD patients had a palpable thyroid anomaly and 7.7% a PTC

The study included 32 patients treated with MKI due to TC for at least one year.

vs respectively 10% and 0.1% of the general population. The risk of usG was

The study was cross-sectional and it based on different questionnaires: List of

more related to a high BMI than to CTG repeats. Clinicians should be aware of

Somatic Problems, Beck’s Depression Inventory and Short Questionnaire of

this high prevalence of PTC in MD.

Diseases Perception (B-IPQ).

DOI: 10.1530/endoabs.49.EP1439

Results

Nineteen patients showed severe somatic symptoms

(HSS; High Somatic

Symptoms), whereas 13 patiens demonstrated none or mild physical symptoms

(LSS; Low Somatic Symptoms). The depression intensity was higher in HSS

patients than in LSS group. In HSS group a mediating role of self-image

relationship to disease somatic symptoms and depression was noticed. The direct

EP1440

effect of somatic symptoms on depression severity was insignificant. While, the

belief about a negative impact of physical symptoms on the daily functioning was

Management of treatment-related toxicity caused by multi kinase

an important mediator of relations between somatic symptoms and depression in

inhibitors administered due to advanced thyroid carcinoma

the study group.

Jolanta Krajewska, Aleksandra Kukulska, Daria Handkiewicz-Junak,

Conclusions

Ewa Paliczka-Cieslik, Tomasz Olczyk, Tomasz Gawlik,

The inclusion of interaction aimed at changing the perception of a negative

Aleksandra Ledwon, Barbara Michalik & Barbara Jarzab

impact of the disease and its treatment on daily life in TC patients can reduce the

M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,

risk of deterioration in depressive symptoms. The role of a nurse in psychologist-

Gliwice, Poland.

physician-nurse team is crucial for better patients care and quality of life.

DOI: 10.1530/endoabs.49.EP1441

Multi kinase inhibitors (MKIs) constitute a new therapeutic option in advanced

RAI-refractory differentiated thyroid cancer

(DTC) and medullary thyroid

carcinoma (MTC). To date four different MKIs demonstrated a beneficial effect

on progression free survival in DTC (sorafenib, lenvatinib) and MTC (vandetanib

and cabozantinib). However, the treatment related toxicity, which potentially may

limit their clinical use and lead to a negative impact on the quality of life, have

been widely discussed recently.

Material and methods

The study group involved 81 patients with advanced thyroid cancer, who received

different MKIs:

patents

- lenvatinib,

20-vandetanib,

22-sorafenib,

4-cabozantinib,

4-motesanib and

3-axitinib. All side effects were classified

according to the Common Terminology Criteria for Adverse Events (CTCAE),

version

4.0. Median treatment duration was

21.3

months (range 0.7-100.0

EP1442

months).

Malignancy risk stratification in thyroid nodules according to the

Results

Bethesda system for reporting thyroid cytopathology

Among the most common adverse effects were hypertension (73%), skin reactions

Aldona Kowalska^1,2, Agnieszka Suligowska¹, Janusz Kopczynski¹,

(70.3%), diarrhea (54.1%), weight loss (54.1%) and stomatitis (43.2%). The

Kornelia Niemyska¹ & Stanislaw Gozdz^1,2

majority of side effects fulfilled G1 (mild) and G2 (moderate) criteria except of

¹Holycross Cancer Center, Kielce, Poland;²The Faculty of Health Sciences

hypertension mainly classified as G3 (the necessity of the administration of at least

of the Jan Kochanowski University, Kielce, Poland.

2 antihypertensive drugs). The management of treatment related side effects was

based mainly on cautious follow-up (wide panel of laboratory examinations,

regular ECG monitoring, echocardiography and other examinations, if necessary),

Introduction

non-pharmacological methods (sun blockers, moisture creams), concomitant

Fine needle aspiration biopsy (FNAB) plays a crucial role in the diagnosis of

pharmacotherapy (antihypertensive drugs, loperamide and other depending on

thyroid nodules. The choice of further therapeutic strategy depends largely on its

different side effects) and dose modifications: 52.7% of patients needed dose

result. Knowledge of the risk of malignancy in each diagnosis class in the

reduction. Multidisciplinary team involving oncologists, internists, dermatolo-

population is necessary. The aim of the research was to analyse the risk of

gists, cardiologists, nurses and psychologists was also an important part of our

malignancy in thyroid nodules in each diagnosis class according to Bethesda

successful patients care. Only 14.5% of patients required drug withdrawn due to its

system.

poor tolerability.

Materials and methods

Conclusion

Retrospective research included 1001 patients with thyroid nodules diagnosed

The proper management of MKI-related side effects is essential to keep patients

and treated surgically between

2002 and 2015 in one department. Women

on therapy as long as the treatment is beneficial without an unfavorable impact on

accounted for 86% of the research group. The median age was 52 years. The

their quality of life.

results of the guided FNAB performed before the introduction of the Bethesda

scale (621) were re-evaluated and qualified to the appropriate group according to

DOI: 10.1530/endoabs.49.EP1440

the new criteria.

Result

The preoperative FNAB results presented as follows: non-diagnostic material

(class I)

- 6

(0.6%); benign

(class II)

- 522

(52.1%); follicular lesion of

undetermined significance

(class III, FLUS)

- 62

(6.2%); suspicious for a

follicular neoplasm (class IV, SFN) - 138 (13.8%); suspicious for malignancy

EP1441

(class V) - 74 (7.4%), malignant (class VI) -199 (19.9%). The postoperative

Cooperation between an endocrine nurse, psychologist and physician

histology follow-up in the research group were spread as follows: benign - 708

and their mediating role in the care of depression in patients treated

(70.7%); malignant - 292 (29.3%). Malignancy risk for each class according to

with multi kinase inhibitors due thyroid cancer

Bethesda system amounted to respectively: I - 33%, II - 4.21%, III - 11.2%, IV -

Alina Rozanska, Anna Syska-Bielak, Justyna Kraus, Malgorzata Ocieczek,

13.04%, V - 59.46%, VI - 100%.

Ewa Wojtyna & Jolanta Krajewska

Conclusions

M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,

The present study shows that the risk of malignancy in class III and IV is low. The

Gliwice, Poland.

diagnosis of FLUS or SFN in the absence of clinical indications is not a basis for

surgical treatment.

The treatment with multi kinase inhibitors (MKI) under clinical trials due to

DOI: 10.1530/endoabs.49.EP1442

advanced thyroid cancer

(TC) may postpone moving on the patients with

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1443

present in

104 patients. Extrathroidal extension was present in 32 patients.

In logistic regression analysis, age

(!45 years old (P!0.001 OR:4.193)),

The sensitivity and positive predictive value (PPV) of 131I-post-therapy

lymphovascular invasion

(P!0.001 OR:7.762), capsule invasion (P!0.002

whole body scan is higher than serum Tg values in detecting metastases

OR:3.054), extrathyroidal extension (P!0.001 OR:6.450) and bilaterality (P !

in early stage of differentiated thyroid cancer patients

0.001 OR: 0.217) involvement were significantly associated with cervical lymph

Alfredo Campennì¹, Salvatore Antonio Pignata¹, Massimiliano Siracusa¹,

node metastasis.

Teresa Manuela Vicchio², Francesco Trimarchi³, Rosaria

Discussion

Maddalena Ruggeri² & Sergio Baldari¹

We found that the risk of cervical lymph node metastasis was high in the presence

¹University of Messina, Department of Biomedical and Dental Sciences and

of extrathyroidal extension, multifocality and lymphovascular invasion. In

Morpho-functional Imaging, Nuclear Medicine Unit, Messina, Italy;

contrast to previous reports, the risk was found to be high for the age group

²University of Messina, Department of Clinical-Experimental Medicine and

lower than 45. Clinically, lymph node metastasis does not develop in all patients,

Pharmacology, Division of Endocrinology, Messina, Italy;³University of

knowing risk factors of cervical lymph node metastasis can determine the

Messina, Accademia Peloritana dei Pericolanti, Messina, Italy.

operation type, the treatment and the follow-up.

DOI: 10.1530/endoabs.49.EP1444

The work-up of Differentiated Thyroid Cancer (DTC) patients includes thyroid

surgery, thyroid remnant ablation (TRA) with 131-radioiodine and long life

follow-up. 131I-post therapy whole body scan (pT-WBS) and thyroglobulin (Tg)

are used in identifying metastatic patients. Some authors suggested to use post-

surgical Tg (ps-Tg) values in deciding for or against TRA. The aim of our study

was to verify the sensitivity and PPV of 131I-pT-WBS compared to serum Tg

levels in detecting metastases in early stage of DTC patients.

Material and method

We retrospectively reviewed the records of 570 patients affected by pT1-pT3

DTC (FZ450, MZ120, mean age 48.5G13.2; F/M ratioZ3.7:1) referred to our

Nuclear Medicine Unit in the last five years. None of our patients had: 1) loco-

regional or distant metastases at the time of recruitment; 2) age %16 years; 3)

EP1445

positive thyroglobulin-antibody (Tg-Ab); 4) pT₄ stage, 5) poorly-differentiated

Theranostic management of medullary thyroid cancer (MTC) with

thyroid cancer. The majority of patients (98.2%) were affected by papillary

(111In/177Lu) CP04: how close are we to a clinical solution?

carcinoma. Before TRA, all patients underwent neck-ultrasonography, laboratory

Alicja Hubalewska-Dydejczyk¹, Paola Erba², Clemens Decristoforo³,

test and, if treated in hypothyroid state (321/570, 56%), radioiodine thyroid

Katja Zaletel⁴, Renata Mikolajczak⁵, Helmut Maecke⁶, Theodosia Maina-

uptake. Both ps-Tg and Tg values obtained at TRA were matched with 131I

Nock⁷, Mark Konijnenberg⁸, Petra Kolenc-Peitl⁴, Malgorzata Trofimiuk-

pT-WBS results.

Muldner¹, Elwira Przybylik-Mazurek¹, Irene Virgolini², Dariusz Pawlak⁵,

Results

Marion de Jong⁸, Alide C Froberg⁸, Christine Rangger³, Georg Goebel³,

131I pT-WBS discovered metastases in 82 out of 570 (14.4%) patients. Seventy-

Lorenza Scarpa³, Konrad Skorkiewicz⁹, Luka Lezaic⁴, Pirotr Garnuszek⁵,

three out of these patients (90.2%) showed ps-Tg levels %1 ng/ml. At TRA, forty

Anna Sowa-Staszczak¹, Berthold A Nock⁷, Damijan Bergant⁴,

of them (54%) maintained Tg levels %1 ng/ml. The majority of these patients

Sebastijan Rep⁴ & Boguslaw Glowa⁹

(38/40, 95%) showed lymph-node metastases at 131I-pT-WBS while three had

¹Jagiellonian University Medical College, Krakow, Poland;²Azienda

lung metastases (one of them showed lymph-node metastasis). The metastases

Ospedaliero-Universitaria Pisana, Pisa, Italy;³Innsbruck Medical

were confirmed by targeted morphological studies.

University, Innsbruck, Austria;⁴University Medical Centre Ljubljana,

Conclusion

Ljubljana, Slovenia;⁵Radioisotope Centre Polatom, NCBJ, Otwock,

ps-Tg cannot be used to decide for or against TRA. In early stage of DTC, 131I-

Poland;⁶University Hospital Freiburg, Freiburg, Germany;⁷Molecular

pT-WBS is an accurate method in detecting metastases also in patients with

Radiopharmacy, INRASTES, NCSR Demokritos, Athens, Greece;

stimulate Tg values %1 ng/ml, showing sensitivity and PPV significantly higher

⁸Erasmus MC, Rotterdam, The Netherlands;⁹University Hospital, Krakow,

than Tg (100% vs 29.3% for both).

Poland.

DOI: 10.1530/endoabs.49.EP1443

Effective targeted therapy for advanced endocrine malignancies is a goal of

modern endocrinology. We herein present promising results of the first phase

of clinical part of European project (Gran-T-MTC) aimed to assess the safety of

gastrin analogue CP04

(DOTA-(DGlu)₆-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH₂)

i.v. administration in dose (50 mg) useful for translation to 177In-CP04 for PRRT.

CP04 has been selected for MTC therapy based on a high CCK-2 receptor

expression in MTC and superior pharmacokinetics properties among gastrin

EP1444

analogues tested. Positive results of preclinical part of the study confirmed

Evaluation of clinicopathological factors in papillary thyroid cancer

possibility of 111In-CP04 applying in humans.

with cervical lymph node metastasis

Aim

Betul Aydin Buyruk¹, Medine Nur Kebapci¹, Goknur Yorulmaz¹,

To assess¹¹¹In-CP04 safety, biodistribution and dosimetry.

Aytug Buyruk² & Mahmut Kebapci³

Material and methods

¹Department of Endocrinology, Eskisehir Osmangazi University Medical

Four patients: three with progressive/metastatic MEN2A-related MTC (¹⁸F-FDG-

Faculty, Eskisehir, Turkey;²Department of Ear, Nose, Throat, Eskısehır

PET/MRI positivity), one with sporadic MTC (short calcitonin doubling time)

State Hospital, Eskisehir, Turkey;³Department of Radiological,Eskisehir

were enrolled. Basal calcitonin levels ranged between 279 and 824 pg/ml.

Osmangazi University Medical Faculty, Eskisehir, Turkey.

Study design

During the first clinical trial phase each patient received 111In-CP04 (200 MBq)

Introduction and purpose

in 2 different doses: a low (10 mg) and high (50 mg). Biodistribution and dosimetry

More than 90% of differentiated thyroid cancers are papillary thyroid cancer

data were assessed based on serial planar and SPECT/CT images over time.

(PTC). Lymph node metastasis is common in PTC and has been reported to have

Results

no effect on prognosis. The risk of cervical metastasis is high in the presence of

No side effects were observed during injection of either CP04 dose. In all patients

clinicopathologic factors including extrathyroidal extension, multifocality and

111In-CP04 uptake was confirmed in MTC lesions regardless of peptide dose (in

lymphovascular invasion. In this study, it was aimed to evaluate the

one patient uptake was low). The compound showed both a renal clearance and

clinicopathological features of lymph node metastasis development.

uptake in the stomach wall with subsequent intestinal clearance with for both

Materials and methods

peptide doses similar kinetics and little variation across patients. The Effective

Patients with papillary thyroid carcinoma diagnosed between 1995 and 2016 were

dose was 6 mSv/200 MBq, irrespective of the amount of peptide. The kidney

retrospectively reviewed. Patients who previously had another cancer story were

absorbed dose for the 50 mg therapeutic amount of CP04 if labeled with 177Lu

excluded from the study. The demographic characteristics and pathology findings

was estimated at 0.32Gy/GBq and the stomach absorbed dose at 0.13Gy/GBq.

(histopathology, tumor size, lymph node metastasis, lymphovascular invasion,

Conclusions

multifocality, capsule invasion, bilaterality) and antiTG, antiTPO values were

MTC metastases can be detected with 111In-CP04. Biodistribution and dosimetry

compared in patients with and without cervical lymph node metastasis.

data show CP04 promising radiopharmaceutical for MTC therapy if labeled with

Results

177Lu. The confirmatory second part of clinical phase of trial has just begun.

In 419 papillary thyroid cancer patients, 52 lymph node metastases were detected.

DOI: 10.1530/endoabs.49.EP1445

Lymphovascular invasion was present in 24 patients and capsule invasion was

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1446

without cervical adenopathies. The patient had a total thyroidectomy whose

anatomopathology returned without anomaly. The hormonal assessment showed

Medullary thyroid carcinoma - diagnosis and outcome of patients

an undetectable level of thyroglobulin (TG). (TSH: 30.24 Uu/ml, TG: 0.55 mg/l

treated in a tertiary center

and anti-TG antibody: 1.2 IU/ml). Levothyroxine was increased to 150 mg/day.

Joanna Prokop, Ana Palha, Teresa Sabino, Carolina Neves, Luísa Cortez,

Iratherapy is considered for our patient.

José Silva-Nunes, Cristina Santos, Lurdes Matos, Natércia Candeias,

Conclusion

António Afonso, Fernando Fonseca & Ana Agapito

The papillary cancer on TDC is an exceptional localization. It can develop at the

expense of residues of thyroid follicles within the cyst of the TDC, or may be

secondary to thyroid papillary carcinoma metastasis. Its management consists of

Medullary thyroid carcinoma (MTC) is a rare tumor of C cell origin, that may be

an excision of the cyst. Hormone replacement therapy is systematic. Total

sporadic or familial. Diagnosis is often delayed and its course variable.

thyroidectomy is indicated in cases of thyroid suspicious of malignancy, also if

Objectives

extra-cystic extension. Lymph node dissection is indicated in the presence of

Evaluation of clinical characteristics and outcome of patients diagnosed with

adenopathy. A complement by Iratherapy is not systematic, however in our

MTC.

patient it is indicated because the presence of a lymph node metastasis. The

Methods

monitoring will be on long term and generally the evolution is favorable.

Retrospective analysis of clinical records of patients with MTC between 2005 and

DOI: 10.1530/endoabs.49.EP1447

2016. We considered undetectable serum calcitonin as criteria of cure.

Results

Sixteen patients (12 women) were observed: mean age at presentation 63.8 years

(46-79), mean follow-up: 2.2 years. Thyroid nodules were present in all. Four

patients had compressive symptoms, three lymphadenopathy and one chronic

diarrhea. Eight patients were diagnosed on the basis of histological examination

without previous clinical suspicion of MTC. Genetic testing for RET proto-

oncogene mutations was performed in nine patients and in one germinative

mutation was detected (isolated familiar MTC). Eight patients with previous

suspicion of MTC underwent total thyroidectomy with central lymph node

dissection, and in five of these also lateral lymph node dissection. Among patients

diagnosed after surgery: two had undergone total thyroidectomy with central

lymph node dissection, in one of these combined with lateral node lymph

EP1448

dissection, three total thyroidectomy and three hemithyroidectomy. One

Impact of RAC1/1b signalling on Sodium Iodide symporter regulation

completed thyroidectomy and the other two maintain undetectable calcitonin

Márcia Faria^1,2, Paulo Matos^1,3, Maria João Bugalho^4,5 & Ana Luísa Silva^4,5

(follow-up: 0.5-1.3 years). After surgery seven patients were cured. One of them

¹Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute,

suffered recurrence with hepatic metastases 4 years later. Among patients with

University of Lisbon, Lisboa, Portugal;²Research Unit of Molecular

disease persistence there were six with progression in serum calcitonin, one with

Pathobiology, Portuguese Institute of Oncology of Lisbon - Francisco Gentil

radiologic evidence of metastases. This patient had cervical lymph node

E.P.E., Lisboa, Portugal;³Department of Human Genetics, National Health

metastases

(calcitonin doubling time-CDT:6

months)

years after MTC

Institute ‘Dr. Ricardo Jorge’, Lisboa, Portugal;⁴Department of Endo-

diagnosis and underwent reoperation without cure.

crinology, Diabetes and Metabolism, Centro Hospitalar Lisboa Norte E.P.E

Discussion

- Hospital de Santa Maria, Lisboa, Portugal; ⁵ISAMB, Genetics Laboratory,

In this cohort of patients MTC diagnosis was made often after surgery (50%),

Faculty of Medicine, University of Lisbon, Lisboa, Portugal.

which raises the question of presurgical calcitonin testing. MTC may have

indolent or aggressive course as observed in this study, and turns difficult optimal

treatment and follow-up strategy in the individual patient.

The Sodium Iodide Symporter (NIS) is responsible for active transport of iodide

DOI: 10.1530/endoabs.49.EP1446

into thyroid cells. Its expression in thyroid tumors allows the use of radioactive

iodine (131I) as co-adjuvant therapeutic tool to eliminate remaining tumor cells

and metastases after total thyroidectomy. Nevertheless, certain subsets of patients

with advanced forms of thyroid cancer lose the ability to respond to radioiodine

therapy, which drastically reduces their survival rates. Recent studies have

implicated the Rac1/p38 pathway in the stimulation of NIS expression through a

mechanism that remains unclear. Additionally, the overexpression of RAC1b, a

hyperactive splicing variant of RAC1, was recently shown to be overexpressed in

a subset of papillary thyroid carcinomas carrying the activating mutation

BRAFV600E and to be associated with unfavorable outcome. BRAFV600E

mutation, in turn, has been associated with the downregulation of NIS. Here, we

further investigate the role of RAC1/RAC1b on NIS expression levels, and

developed new cellular models to functionally assess the impact of these GTPases

EP1447

on NIS-mediated iodide uptake. To evaluate whether RAC1b has a role in NIS

expression modulation, we determined NIS transcript levels in a cohort of 64

Papillary carcinoma of thyroglossal duct cyst with cervical lymph

follicular cell-derived thyroid tumors, comparing tumors presenting RAC1b

node metastasis

overexpression (nZ32) to those that did not (nZ32). RAC1b-overexpressing

Si Youcef Hafsa, Boussata Amani, Azzoug Said & Fedala Nora Someya

tumors were defined as those with expression levels above a defined threshold

CHU Mohamed Lamine Debaghine Bab El Oued, Algiers, Algeria.

(corresponding to the mean value plus two SDs of RAC1b expression level in a

normal thyroid group). RAC1b and NIS expression was assessed by quantitative

Introduction

RT-PCR. We found that samples negative for RAC1b expression presented

Neoplasias in the thyroglossal duct cyst (TDC) are rare, their prevalence varies

higher levels of NIS in comparison to RAC1b-overexpressing samples (4.402G

from 1 to 1.5%. The most common cancer is papillary cancer representing 85% of

1.271 vs 1.916G0.5423, respectively; PZ0.0384, two-tailed Student’s t-test).

cases. The diagnosis is often fortuitous following to the anatomopathological

Thus, our results show an inverse correlation between RAC1b and NIS expression

examination of the surgical specimen.

levels, suggesting that RAC1b might antagonize RAC1

effectiveness at

Patient and method

stimulating NIS expression. To further explore the impact of RAC1/1b signalling

Our patient has 33-years-old, with no previous medical history, which underwent

on NIS expression regulation, we established a halide-sensitive YFP-based

a resection of a TDC of 29 mm in diameter, diagnosed by an anterior cervical

reporter in a normal thyroid cell line system, allowing us to detect differences on

tumefaction. The anatomopathological examination of the cyst was in favor of

iodide influx upon TSH stimulation. Our preliminary results support the relevance

papillary carcinoma. The evolution is marked by the appearance of a left cervical

of further studying the impact of RAC1/1b on NIS regulation.

adenopathy. The patient has benefited by a biopsy excision, and histology was in

DOI: 10.1530/endoabs.49.EP1448

favor of a metastasis of a papillary carcinoma. Cervical ultrasound: normal,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1449

abnormalities were detected in the thyroid on ultrasound, the patient was referred

for total thyroidectomy. The histopathological specimen revealed the presence of

The usefulness of the study of sodium iodide symporter expression in

multifocal PTC within the thyroid, the largest being 1 mm, and one metastatic

thyroid primary tumors

lymph node. Due to the increased post-surgical thyroglobulin concentration and

Catarina Tavares^1,3, Maria João Coelho^1,4, Catarina Eloy^1,2, Miguel Melo^1,5,

the suspicion of metastasis to other cervical lymph nodes on ultrasound

Adriana Gaspar da Rocha^1,7, Ana Pestana^1,3, Rui Batista¹, Luciana

examination, the patient required two subsequent lymphadenectomies followed

Bueno Ferreira^1,3, Elisabete Rios^1,3, Bruno Cavadas^1,2, Luísa Pereira^1,3,

by radioiodine therapy to achieve remission. No further recurrence of the disease

Samia Selmi-Ruby¹⁰, Manuel Sobrinho Simo˜ es1,3 & Paula Soares1,3

was observed in a 6-year follow-up period.

¹Instituto de Investiga

˜o e Inova

¸a˜o em Saúde (i3S), Universidade do

Conclusions

Porto, Porto, Portugal;²Institute of Molecular Pathology and Immunology

In such patients two scenarios should be considered: (i) PTC in BCC is a primary

of the University of Porto, Porto, Portugal;³Medical Faculty of the

lesion arising from ectopic thyroid tissue concomitant with multifocal PTC of the

University of Porto, Porto, Portugal;⁴Institute of Biomedical Sciences of

thyroid or (ii) neck cyst is a cystic degeneration of a metastatic lymph node, while

Abel Salazar, Porto, Portugal;⁵Department of Endocrinology, Diabetes and

primary site is located in the thyroid. Detection of PTC in BCC requires

Metabolism, University and Hospital Center of Coimbra, Coimbra,

verification of the thyroid for concomitant neoplastic lesions. Despite normal

Portugal;⁶Medical Faculty, University of Coimbra, Coimbra, Portugal;

thyroid on ultrasonography, histopathological examination may reveal the

⁷University and Hospital Center of Coimbra, Coimbra, Portugal;⁸Depart-

presence of multifocal occult PTC in the thyroid. Therefore, following

ment of Pathology and Oncology, Medical Faculty of the University of

the diagnosis of PTC in BCC, completion total thyroidectomy should be the

Porto, Porto, Portugal;⁹Department of Pathology, Hospital de S.Joa˜o, Porto,

recommended procedure.

Portugal;¹⁰Inserm UMR-S1052, CNRS UMR5286, Centre de Recherche en

Cancérologie de Lyon, Lyon, France.

DOI: 10.1530/endoabs.49.EP1450

Thyroid cancer therapy is based on surgery followed by radioiodine treatment of

tumor remnants and metastases. The incorporation of radioiodine by cancer cells

is mediated by sodium iodide symporter (NIS), normally present in thyroid

follicular cells’ membrane. We studied the expression of NIS in a series of 229

thyroid primary tumors using real time PCR and immunohistochemistry, and

searched for possible associations between NIS expression and clinicopatholo-

gical features, molecular data, response to therapy and prognosis. NIS mRNA

levels were significantly lower in carcinomas than in normal adjacent thyroid;

EP1451

carcinomas from males or with vascular invasion presented significantly less NIS

Comparative analysis of clinicopathological characteristics between

mRNA expression than carcinomas from women and non invasive carcinomas.

Korean and Italian thyroid cancer patients

BRAFV600E tumors and those presenting extrathyroidal extension had a

Jee Hyun An¹, Sin Gon Kim¹, Hoon Yub Kim², Kwang Yoon Jung³,

tendency to display lower NIS mRNA expression than tumors BRAFWT and

Yang Seok Chae⁴, Gianlorenzo Dionigi⁵, Stefano Rausei⁵,

no extrathyroidal extention. Regarding immunohistochemistry, only 12/211 of

Maria Laura Tanda⁶, Eliana Piantanida⁶ & Stefano La Rosa⁷

the cases demonstrated NIS in the basolateral membrane of tumor cells; these

cases showed variable outcomes concerning therapy response and prognosis. All

¹Division of Endocrinology, Department of Internal Medicine, KUMC

but one of the aforementioned cases were wild type for BRAF, NRAS and TERT

Thyroid Center, Korea University College of Medicine, Seoul, Republic of

promoter mutations. NIS immunohistochemical expression in primary tumors did

Korea;²Department of Surgery, KUMC Thyroid Center, Korea University

not predict tumor behavior or response to therapy. NIS mRNA expression was

College of Medicine, Seoul, Republic of Korea;³Department of

more informative of tumor aggressiveness than NIS protein expression. In order

Otolaryngology-Head and Neck Surgery, KUMC Thyroid Center, Korea

to validate our data we also searched possible associations between NIS mRNA

University College of Medicine, Seoul, Republic of Korea;⁴Department of

expression and clinicopathological and molecular features on

378 primary

Pathology, KUMC Thyroid Center, Korea University College of Medicine,

papillary thyroid carcinomas of the TCGA database. Further studies are needed to

Seoul, Republic of Korea;⁵Endocrine Unit, 1st Division of General Surgery,

confirm the association observed between the presence of the oncogenic

Department of Medicine and Surgery, Research Center for Endocrine

mutations (BRAF, NRAS and TERT promoter) and both lower mRNA expression

Surgery, University of Insubria, Varese, Italy;⁶Endocrine Unit, Department

and diminished membrane targeting of NIS protein.

of Medicine and Surgery, University of Insubria, Varese, Italy;⁷Institute of

Pathology, University Hospital of Lausanne (CHUV), Lausanne,

DOI: 10.1530/endoabs.49.EP1449

Switzerland.

Background

The incidence of thyroid cancer in South Korea has increased rapidly. Increase in

medical surveillance and access to health care services have enhanced the

detection of asymptomatic tumors. We investigated the differences of tumor

characteristics between South Korean patients and Northern Italian patients

subject to different healthcare systems.

EP1450

Methods

Concomitant occurrence of papillary thyroid cancer (PTC) in a

The demographic, histopathologic and management features of thyroid cancer

branchial cleft cyst (BCC) and an occult multifocal PTC in the

operated in two tertiary referral hospitals in Seoul, South Korea (nZ4,474) and

thyroid gland

Varese, Northern Italy (nZ2,897) from years 2000 to 2015 were analyzed.

Ewelina Szczepanek-Parulska¹, Martyna Borowczyk¹, Alina Kluk¹,

Results

Grzegorz Dworacki², Marcin Orłowski³, Katarzyna Ziemnicka¹ &

The mean age of diagnosis was similar (49 years) among the Korean and Italian

Marek Ruchała¹

patients. However, the proportion of female was higher among Korean patients

¹Department of Endocrinology, Metabolism and Internal Medicine, Poznan

(81.3 vs 74.2%, P!0.001). The proportion of papillary subtype was higher (99.2

University of Medical Sciences, Poznan, Poland;²Department of Clinical

vs 92.6%, P!0.001) and the size of tumor was smaller (1.03G0.83 vs 1.79G

Immunology, Poznan University of Medical Sciences, Poznan, Poland;

1.01 cm, P!0.001) in the Korean subjects. Interestingly, the prevalence of

³Department of Pathology, Provincial Hospital in Poznan, Poznan, Poland.

multifocality (37.8 vs 8.2%), extrathyroidal extension (41.6 vs 13.1%) and lymph

node metastasis (34.8 vs 6.7%) was also higher in the Korean patients (P!0.001).

Introduction

Most of the Italian cases received total thyroidectomy (96.0%). In comparison, a

BCC is a congenital epithelial neck cyst, which occurs due to failure of the second

considerable number of the Koreans (21.9%) received hemithyroidectomy as

branchial cleft to obliterate during embryogenesis. Development of PTC inside

initial surgical treatment (P!0.001). The proportion of the patients who received

the cyst is extremely rare.

radioactive iodine therapy was significantly higher among the Korean patients

Case description

(53.3 vs 29.7%, P!0.001).

A 29-year-old female presented to the endocrinology clinic with a gradually

Conclusion

increasing painless mass in the right lateral region of the neck, identified on

We have identified distinct lineaments of thyroid gland cancer between the two

ultrasound examination as an anechoic cyst of size 2!2!5 cm with a smooth

different nationalities which could not be explained entirely by early detection

wall. Despite repeated biopsies and evacuation of the fluid, the cyst was a

from screening. Further prospective studies with controlled treatment strategies

recurrent problem. Hence, a decision for surgical removal was made. The

are needed to determine long-term prognosis.

histopathological examination revealed a cystic structure with lymphatic weaving

DOI: 10.1530/endoabs.49.EP1451

in the wall and PTC in both the lumen and lymphatic weaving. Despite no

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1452

body mass index (BMI) were measured prior the surgery. A fasting blood sample

obtained from all study participants prior the surgery to measure serum neopterin

Malignant struma ovarii and synchronous tumour of thyroid gland in

levels. Post-thyroidectomy, according to pathology results patients were divided

the same patient: a single pathway for two different tumours?

into two groups,as DTC and benign pathology.

Ricardo Capita˜o, Catarina Saraiva, Francisco Santos, Cátia Férrinho,

Results

Catarina Roque, Carlos Bello & Carlos Vasconcelos

Of thesepatients, 39 were diagnosed with DTC and 47 had benign pathology

Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal.

according to postoperative histologic evaluation. There were no significant

differences between the two groups in terms of age, weight, height and body mass

Background

index. Demographical data and laboratory results are given in the table. There was

Struma ovarii (SO) is the presence of thyroid tissue as a major cellular component

a positive correlation with neopterin levels and tumor size (rZ0.776, P!0.001).

in an ovarian tumour.

Discussion

Case report

Our study indicates that there is a strong association between plasma neopterin

A 35-year-old, Caucasian female, asymptomatic and with normal physical

levels and DTC. Thus, if it is supported with high volume larger studies, neopterin

examination was submitted to left oophorectomy due to an ovarian mass (8.2!

may be a useful marker forpredicting the DTC preoperatively.

7.0!6.0 cm) detected in routine pelvic examination. Her mother also had history

of oophorectomy for an ovarian tumour and partial thyroidectomy for benign

DOI: 10.1530/endoabs.49.EP1453

thyroid nodule. The histological examination of the mass showed a totally intra-

ovarian neoplasia predominantly composed of thyroid tissue (95%) with areas of

follicular variant of papillary thyroid carcinoma (FVTPC) which was compatible

with malignant SO. She was tested for thyroid function which was normal and

thyroid ultrasound revealed a slightly hypoechogenic nodule with 1.7 cm in the

right lobe. Fine needle cytology of this nodule was performed and was compatible

with FVTPC. She underwent total thyroidectomy and histology revealed a well

EP1454

differentiated thyroid tumour of uncertain malignant potential. No vascular or

Unexpectedly low thyroglobulin levels in differentiated thyroid

capsular invasions were recorded. She was treated with¹³¹I and suppressive doses

carcinoma - case report

of levothyroxine and remains asymptomatic, without signs of clinical or

Francisco Norton-Branda˜o1, Teresa Ferreira1, Manuel Rio Carvalho1,

biochemical recurrence of thyroid and ovarian tumours. The search for BRAF

Inês Patrocínio Carvalho¹, Rita Sousa¹, Pedro Ratão¹, Lucília Salgado¹,

mutations was negative.

Joana Simo˜es-Pereira2 & Valeriano Leite2

Discussion

¹Nuclear Medicine Department, Portuguese Oncology Institute - Lisbon,

Three other cases of synchronous thyroid and ovarian thyroid tumours have been

Lisbon, Portugal;²Endocrinology Department, Portuguese Oncology

described so far to the best of our knowledge. In this case, since both tumours

Institute - Lisbon, Lisbon, Portugal.

were confined and no invasion was documented they were probably synchronous

tumours instead of metastasis. These two tumours are embryologically related so

we cannot exclude a common mechanism of genomic origin that possibly

Case report

explains the synchronous tumours and even the familiar history.

66 year old male with a neck growing mass performed an ultrasonography and

DOI: 10.1530/endoabs.49.EP1452

fine-needle aspiration biopsy which was suspicious for papillary carcinoma. The

patient was submitted to total thyroidectomy and central and left lateral

compartments lymph node dissection. The histological report showed a follicular

carcinoma of 9 cm, with multiple lymphovascular invasions and skeletal muscle

invasion. There was a focally positive surgical margin and resected lymph nodes

had no metastases. Thoracic CT showed multiple lung nodules; PET showed faint

uptake in a single nodule in the upper lobe of the right lung. Five months after

EP1453

surgery, 5,5 GBq (150 mCi) of iodine-131 (RAI) were administered. Forty-eight

hours after therapy whole-body scintigraphy (WBS) was performed: moderate

Does Preoperative Serum Neopterin Level Predict Differentiated

thyroid remnant and faint uptake in the lower third of the right thoracic area were

Thyroid Carcinoma?

visible. Non-stimulated serum thyroglobulin

(Tg) was undetectable and

Mazhar Muslum Tuna¹, Narin Nasırog˘lu İmga2, Mehtap Navdar Ba¸aran2,

stimulated levels were

1.5 ng/ml; anti-thyroglobulin antibody

(ATg) was

Berçem Ayçi

¸ek Do

˘ an², Canan Top

¸uog˘ lu3, Dilek Berker2 &

negative. Two years after RAI, Tg levels increased to 15.2 and to 43.1 ng/ml

Serdar Guler²

six months thereafter. ATg remained negative. Neck and thorax CT showed a new

¹Umraniye Training and Research Hospital, Endocrinology and Metabolism

lesion in D3 and no progression of lung nodules. The patient referred light

Clinic, Istanbul, Turkey;²Ankara Numune Training and Research Hospital,

numbness in his left arm and hand. A second RAI was performed under thyroid

Endocrinology and Metabolism Clinic, Ankara, Turkey;³Ankara Numune

hormone withdrawal. Stimulated serum Tg was 229.0 ng/ml. PET-CT (Default 1)

Training and Research Hospital, Biochemistry Clinic, Ankara, Turkey.

was performed just before RAI administration: uptake in lytic lesions in D3 and

D4 was found (SUVmax Z11.3). Post-therapeutic WBS (Default 2) also showed

Introduction

intense uptake in the dorsal spine and faint uptake in pulmonary lesions.

The frequency of thyroid surgery for suspected malignancy but postoperative

Conclusion

resulted with benign pathology tends to increase in the worldwide. Therefore,

Serum thyroglobulin is usually useful to monitor disease progression. In patients

additional preoperative markers are needed to prevent excessive surgery.

with aggressive differentiated thyroid carcinoma, Tg alone may not reflect

Neopterin is a new molecule secreted by monocytes and macrophages and

indicates the activation of cellular immunity. Therefore it can be used as a marker

of immune activation. We aimed to evaluate the diagnostic value of serum

neopterin levels to determinedifferentiated thyroid cancers (DTC).

Material and method

This prospectivestudy included

86 patients

(67

female and

19 male) who

underwent thyroidectomy due to nodular goiter between March

2015 and

November 2015. Patients who had overt hyperthyroidism or hypothyroidism

Fig. 1 18F-FDG PET-CT.

andrenal or hepatic dysfunction were excluded from the study. Weight, height and

Table The comparison of demographical data and neopterin levels

between groups.

Group 1 (n:39) Group 2 (n:47)

Age (year)

47.2G12.8

48.4G12.9

0.719

Weight (kg)

79.3G15.5

76.6G15.5

0.455

BMI (kg/m²)

30G5.9

28.8G5.2

0.362

Preoperative TSH (mIU/lt)

1.57G1.47

1.21G1.27

0.127

Plasma neopterin (ng/ml)

50.8G48.2

22.1G20.7

0.009

Fig. 2 WBS.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

accurately disease progression, as in this patient with documented bone and

chest and abdominal lesions were described. Fine needle aspiration of the thyroid

pulmonary disease that is both differentiated and aggressive.

and the supraclavicular mass revealed anaplastic carcinoma, with no expression

of the thyroid transcription factor 1, mamoglobin 1 and positive expression for

DOI: 10.1530/endoabs.49.EP1454

CK7, CK19 and CK5. The tumour was considered unresectable and the patient

was started on chemotherapy with paclitaxel and carboplatin for 4 months. After

the first

2 rounds of chemotherapy she had an initial good response, with

shrinkage of the supraclavicular mass. The CT after the completion of

chemotherapy showed an increased volume of both the thyroid gland and the

supraclavicular mass, with thrombosis of the internal jugular vein and

supraclavicular bone erosion. She is under evaluation for external radiotheraphy.

The association between a toxic nodular goiter and anaplastic thyroid carcinoma

EP1455

after cervical radiotherapy, with no distant metastases has apparently not been

Papillary thyroid microcarcinoma: is it worth ablating the patients with

reported so far.

radioiodine?

DOI: 10.1530/endoabs.49.EP1456

Muammer Urhan, Eylem Cagiltay & Ferhat Deniz

Sultan Abdulhamid Training Hospital (Former Gata Haydarpasa Training

Hospital), Istanbul, Turkey.

Objective

Recently, radioablation has been offered for patients with thyroid microcarci-

noma, however some authors favor just follow-up as the prognosis of this disease

EP1457

is excellent. In this study, we compared the long-term follow-up results, for a

Evaluate the effectiveness of the Bethesda system for reporting thyroid

period of 16 years, in patients with thyroid microcarcinoma in a group of patients

cytopathology in the prediction of thyroid cancer (TBSRTC) on fine

with thyroidectomy only and in another both thyrodectomized and radioablated.

needle aspiration (FNA) in Moscow region, Russia

Methods

Timur Britvin, Olga Nechaeva, Alexey Krivosheev, Larisa Bavykina,

Two hundred sixty five patients with a proven diagnosis of thyroid cancer

Armine Kazaryan & Alexander Dreval

!10 mm among 1755 thyroid cancer cases were included in the study. Any

Moscow Regional Research Clinical Institute, Moscow, Russia.

patients with unfavorable characteristics such as capsular or perithyroidal

invasion, intrathyroidal spread, lymph node invasion or multicentirity were

excluded. In group IA, 18 patients (14 female, 4 male; mean age 74), patients

Aim

were hemi-thyroidectomized only and 64 patients (43 female, 21 male, mean age

To evaluate the effectiveness of the Bethesda system for reporting thyroid

66) in group IB had total or near-total thyroidectomy. In group II, 183 patients

cytopathology in the prediction of thyroid cancer on fine needle aspiration (FNA).

(123 female, 60 male; mean age; 61) underwent total or near total thyroidectomy

Materials and methods

and ingested I-131 (dose range; 30-85 mCi) while they were in ahypothyroid state

This is retrospective study of 70 detected thyroid cancer. Thyroid ultrasound and

(TSH O40 uIU/L). In the surveillance period, all patients were monitored with

FNA were performed on all patients. 66 of them with cancer suspicion were

periodical serum Tg/ATg measurement and ultrasound of the neck for a period of

communicated to the thyroid surgeon, 4 cases of papillary carcinoma were

two to 16 years.

accidentally diagnosed after hystological investigation. 65 patients underwent

Results

total thyroidectomy with or without lymph node dissection. One patient refused

In group IA and IB, lymph node metastasis was detected in 9 patients (11%) with

surgical treatment.

69 intraoperative samples were subjected to hystological

US-guided fine needle aspiration in the surveillance period. No patient asked for

examination.

additional treatment including surgical intervention and followed by L-T4

Results

suppression only. Serum Tg levels were less than 2 ng/dl (range; 0.2 to 3.9 ng/dl)

In the group with cancer suspicion category VI by TBSRTC was assigned in 51

in 56 patients an in the remaining 26, ranged from 2.0 to 9.8 ng/dl. Serum Tg

(77.3%) cases, category V in 13 (19.7%) cases, 1 case (1.5%) with category V and

levels decreased to lower values than 9.8 ng/dl after no more than one year. In

VI with multinodular goitre, and 1 case (1.5%) with category VI and IV with

group II, lymph node invasion were detected in 19 patients (10%) and 9 of them

multinodular goitre too. Hystological examination of 60 (91%) cases confirmed

had neck dissection for a complete cure. Initial serum Tg levels ranged from 2.1 to

thyroid cancer: papillary carcinoma in 56 (85%) cases; medullary carcinoma in 3

19.8 ng/dl in those patients. In 19 patients with lymph node invasion serum Tg

(4.5%) cases; mixed follicular and papillary carcinoma in 1 (1.5%) case. In 6 (9%)

levels ranged between 2.2-19.8 ng/dl.

cases the cancer wasn’t detected. 2 (3%) of these 6 cases were classified as

Conclusion

category VI and 4 cases (6%) as category V. Thyroid cancer was not detected in

In both groups, approximately 1/10 of patients presented with recurrent or

all the cases of categories II-III found after thyroidectomy for other reasons.

metastatic disease to regional lymph nodes. As the difference between

Conclusion

radioablated and not ablated groups is statistically not significant, we do not

Category VI corresponds with 97% of diagnosed thyroid cancer, and category V -

recommend completion thyroidectomy and radioablation for patients with thyroid

94%. Thyroid cancer was confirmed in only 4 of all cases with category IV. This

microcarcinoma (excluding any poor prognostic factor) and follow-up unless the

result indicates the need for additional diagnostic methods in the preoperative

disease becomes clinically apparent.

period for category IV - for which molecular genetic tests may have potential. To

DOI: 10.1530/endoabs.49.EP1455

determine the risk of malignancy of thyroid nodules with categories II-III requires

long-term monitoring.

DOI: 10.1530/endoabs.49.EP1457

EP1456

Anaplastic thyroid carcinoma and multinodular toxic goiter

Oana-Maria Capraru

EP1458

Saint Constantin Hospital, Brasov, Romania.

Outcomes and imaging results in patients with medullary

thyroid cancer

Thein Htay¹, Mansour TA Sharabiani², S Nimalasena², Kate Newbold² &

A 69 years old female with cervical radiotherapy 25 years ago for an unknown

Daniel Morganstein^1,2

condition, known with multinodular goitre and hyperthyroidism for 6 years,

¹Diabetes and Endocrinology Department, Chelsea and Westminister

presented with a 6 months history of enlarged right supraclavicular mass, local

Hospital NHS Trust, London, UK;²Thyroid Unit, Royal Marsden Hospital,

pain with difficulty in mobilization of the right arm and weight loss. She also

London, UK.

reported progressive bilateral exophtalmia especially on the right side, no

dysphagia, hoarseness or dyspnoea. Thyroid hormone levels were normal on

antithyroid drugs and the thyroid auto-antibodies and parathyroid levels were all

Medullary Thyroid Cancer (MTC) is sporadic in approximately 75% whilst 25%

normal. Neck CT showed an inhomogeneous large gland with several hypoechoic

of MTC occurs as hereditary forms due to RET mutations. Prognosis is relatively

nodules, compression of the trachea and oesophagus, severe compression of the

good with 10-year survival rates of 65%. However, many patients develop

right internal jugular vein with collateral blood flow and a right supraclavicular

recurrent disease and imaging is critical to localise the site of recurrence. Eighty-

adenopathy with no cleavage plan from the thyroid tissue. No significant head,

eight MTC patients, attending the Royal Marsden Hospital NHS Trust were

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

included in an analysis of overall survival. Median Follow-up duration was 7.5

Thyroid cancer is the most frequent endocrine cancer. Its incidence has been

years (IQR: 4.5-13.5). Twenty cases were hereditary and had a median survival

found to increase in recent years. Additionally, environmental factors, which may

12 year (7.7-22.5 95%CL). Sixty-eight patients with Sporadic MTC had a shorter

be implicated in the pathogenesis of thyroid disorders, such as iodine deficiency

survival outcome, median survival 5. 7 year (5.0-7.7 95%CL). Overall median

and salt iodine supplementation are changing and may have an impact on the

survival rate was

7.3

years

(5.3-9.3

95%CL). Hazard Ratio for Sporadic

epidemiology of thyroid cancer. The aim was to study the epidemiology of

Hereditary is 2.1 (1.2-3.5, PZ0.005). According to Kaplan-Meier estimate,

thyroid within a center of excellence in Athens in the modern world setting. A

65%(nZ13) of these Hereditary MTC survive 10 years. In contrast, 10 year

cohort of 63 patients, aged 46.3G1.77 (meanGS.E.M), range 16-81 years with

survival rate of sporadic cases was 28% (nZ19). We also evaluated the sensitivity

thyroid cancer was studied. The histology of the cancer was recorded. The

of different imaging modalities within three bands of calcitonin levels (0-100,

histological subtypes of papillary thyroid cancer were evaluated and recorded.

100-400, and O 400 ng/l). The findings demonstrated that USS neck had a

Within a cohort of 63 patients with thyroid cancer 60 were found to have papillary

superior sensitivity for localising diseases in those with calcitonin with less than

thyroid cancer, three were found to have follicular thyroid cancer, one was found

400: 0.25 (.0.073-.0.524 95%CL, calcitonin 0-100), 0.857 (0.421-0.996 95%CL

to have a mixed medullary follicular-derived thyroid cancer and one was found to

calcitonin 100-400,) and .0 556 (.0.308-785 95%CL calcitonin O 400). In

have a B cell lymphoma of the thyroid. Within the group of the patients with

contrast, in patients with calcitonin O 400, CT neck and body has a higher

papillary thyroid cancer, 39 (67.24%) were found to have papillary, 19 (32.8%)

sensitivity

0.667

(.0.49-0.814

95%CL) and .0745 (.0.604-0.857

95%CL)

were found to have the follicular variant of papillary thyroid cancer, 1 (1.72%)

respectively. Thus, USS neck should be considered as first line imaging modality

had encapsulated papillary thyroid carcinoma, and 1 (1.72%) was found to have

in follow-up in MTC in those with calcitonin ! 400 and CT should be considered

the tall cell variant of papillary thyroid carcinoma. It appears that in the modern

at higher calcitonin levels in order to identify site of disease relapse. In addition,

world setting within a center of excellence in Athens papillary thyroid cancer was

Hereditary MCT has better prognosis than sporadic cases.

the commonest type. Although papillary thyroid cancer and the follicular variant

DOI: 10.1530/endoabs.49.EP1458

of papillary thyroid cancer were the commonest forms of thyroid cancer recorded,

more aggressive types of thyroid cancer such as the tall cell variant were also

recorded.

DOI: 10.1530/endoabs.49.EP1460

EP1459

Lymph node metastasis of differentiated thyroid cancer: role of

thyroglobulin in the washout fluid of fine-needle aspiration biopsies

Bernardo Marques, Raquel Martins, Nuno Cunha, Joana Couto,

Jacinta Santos, Teresa Martins, Ana Paula Moniz, Olga Ilhéu, Joana Bastos,

Paulo Figueiredo, Frederico Valido & Fernando Rodrigues

EP1461

Instituto Português de Oncologia de Coimbra FG, EPE, Coimbra, Portugal.

Is thyroglobulin at ablation a good predictor of the thyroid remnant size

in differentiated thyroid cancer?

Introduction

Helder Martins¹, Gracinda Costa¹, Jorge Isidoro¹, Paulo Gil¹,

Thyroglobulin (Tg) measurement in needle washouts from fine-needle aspiration

Rodolfo Silva^1,2 & João Pedroso de Lima^1,2

biopsies

(FNA-Tg) increases the sensitivity of lymph node (LN) metastasis

¹Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;

diagnosis in differentiated thyroid cancer (DTC). However, the cutoff value for

²Instituto de Ciências Nucleares Aplicadas à Saúde, Coimbra, Portugal.

FNA-Tg has not been clearly established and there are large differences between

clinical studies, which hinders its interpretation. Our study aimed to investigate

the optimal cutoff value of FNA-Tg and evaluate its utility in the diagnosis of LN

Aim

metastasis of DTC.

Stimulated thyroglobulin (sTg), measured at radioiodine remnant-ablation (RRA)

Methods/design

in patients with differentiated thyroid cancer(DTC), is an important predictive

This was a retrospective study of 211 consecutive cases of FNA from 143 patients

factor of persistent disease. However, Tg produced by normal thyroid cells may

identified from our institutional database, who underwent FNA citology and Tg

also contribute to the sTg value.

measurement in needle washout for suspicious LN, between 2012 and 2016.

We aimed to study the relationship between sTg-level in RRA and the thyroid

Results

remnant size

(TRs), using post-therapy whole-body scan

(131I-ptWBS), at

From the total of 211 cases, 121 (57%) had personal history of DTC. FNA

different TSH stimulation method.

citology was benign in 114 (54%) and malignant in 64 (30%). The median FNA-

Materials and methods

Tg was 1168 ng/ml (interquartile range

27-11974) in malignant LNs, and

We review DTC cases referred for RRA, either prepared with recombinant-

0.1 ng/ml

(interquartile range

0-0.27) in benign LNs. LN ressection was

human TSH (rhTSH) or after 4-weeks levothyroxine withdrawal (hipo). Anti-

performed in 55 patients (38.4%), based on the combined results of FNA-Tg

thyroglobulin antibodies (TgAb) and sTg were measured. Patients with positive

and FNA citology. Histology reported LN metastasis of DTC in 45 of these (81%).

TgAb, 131I-uptake outside the thyroid bed and suspected to have persistent

Compared to FNA-Tg values above 0.2 ng/ml, FNA citology showed superior

disease on the first 6-12 months were excluded. Four hundred patients (331

specificity (95.4% vs 67.1%) but slightly inferior sensitivity (88.7% vs 91.5%).

women, 69 men;mean age sd:49.8 14.1 years-old) were selected. TRs was

FNA-Tg values above 10 ng/ml showed 80.3% sensitivity and 100% specificity.

assessed by 131I-ptWBS, using a fixed circular region-of-interest (ROI) placed in

Combining both diagnostic strategies

(FNA citology and FNA-Tg above

thyroid bed. The geometric mean (GM) of the total counts (cts) in the ROI was

0.2 ng/ml) showed superior diagnostic power than using either strategy alone

calculated, corrected for the thigh background and normalized for the treatment

(specificity 96.4% and sensitivity 91.5%). We evaluated the optimal cutoff values

activity (nGM). Based on nGM, remnants were classified into small(S)-nGM!Z

of FNA-Tg in determining malignant LNs from ROC analysis and the optimal

10cts/MBq; medium(M)-10cts/MBq!nGM!Z50cts/MBq and large

(L)-

cutoff value was 0.98 ng/ml (sensitivity, 85%; specificity, 95.4%).

nGMO50cts/MBq. Spearman’s rank correlation coefficient was used to test the

Conclusion

association between TRs and the sTg normalized for TSH(nTg). SPSS version-23

Our results show that combining FNA citology and Tg measurement is useful for

was used for statistical analyses.

the investigation of LN metastasis of DTC. A FNA-Tg cutoff value above 1 ng/ml

Results

should lead to its diagnosis.

A moderate positive correlation between nGM and nTg was found in rhTSH and

hipo patients (rsZ0.55, P!0.001 and rsZ0.59, P!0.03 respectively). For the all

DOI: 10.1530/endoabs.49.EP1459

population we found a strong positive correlation(rsZ0.61,P!0.002). A positive

moderate correlation was found in group-S and L (rsZ0.58, P!0.01; rsZ0.42,

P!0.034 respectively); a weak positive correlation in group-M

(rsZ0.08,

P!0.19).

Conclusion

EP1460

Radioiodine-scintigraphy and sTg are important tools to evaluate the functional

The epidemiology of thyroid cancer within a center of excellence in

status of both normal and neoplasic thyroid tissue. Our results suggest that TRs

Athens: Real life data

and sTg values are correlated, in the absence of clinical/imagiological disease,

Eleni Pantazi¹, Alexios Travlos¹, Evaggelia Vogiatzi¹ &

regardless the method of TSH stimulation. We hypothesize that sTg values are a

Ifigenia Kostoglou-Athanassiou²

better predictor of TRs in patients with less TRs.

¹Department of Endocrinology, Alexandra Hospital, Athens, Greece;

DOI: 10.1530/endoabs.49.EP1461

²Department of Endocrinology, Red Cross Hospital, Athens, Greece.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1462

(44.9% of N1b patients vs 46.3% of N1a patients; PZ0.812), tumour size (mean

size was 23.3 vs 23.2 mm; PZ0.958), persistence of disease (29.4% vs 21.1%;

Prevalence of thyroid cancer in malaga and province

PZ0.163), recurrence of disease (14.5% vs 9.1%; PZ0.182) and disease specific-

Carmen Hernández-García, Araceli Mun˜oz-Garach, Viyu Doulatram,

mortality (5% vs 1.5%; PZ0.1).

Lidia Pérez-Villa, J Mellado-Soria, L Robles-Cabeza, C González-Hermoso

Conclusion

& Francisco Tinahones-Madue

˜o

Our results suggest that there is no difference in patients’ outcome with LN

Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain.

metastasis in the central neck compared to LN metastasis in the lateral neck or

mediastinum, namely disease specific mortality, recurrence and persistence of

Introduction

disease. These data support the recently updated TNM classification in which

Thyroid cancer is the most common endocrine neoplasia, being its papirally

lymph node metastases location is not considered for staging purposes.

version the most frequent. (90% of all differentiated thyroid neoplasms). It is

DOI: 10.1530/endoabs.49.EP1463

usually multifocal and metastasizes normally to regional lymph nodes.

Objectives

To describe the prevalence of thyroid cancer and its histopathological variants in

the different regions of the province of Malaga.

Material and methods

We performed a retrospective descriptive study. We collected the thyroid cancer

EP1464

diagnoses in the databases of pathological Anatomy of the different hospital

Two cases with metastatic thyroid cancer

centers of the province between 2010 and 2015.

Murat Dagdeviren¹, Mustafa Altay¹, Ozge Safak² & Tolga Akkan³

Results

¹Endocrinology and Metabolism, Kecioren Education and Research

545 cases were collected, it is more frequent in women (79.63%) than in men

Hospital, Ankara, Turkey;²Sanatoryum Education and Research Hospital,

(20.37%); the average age at diagnosis was 50G15 years. Analyzing in different

Ankara, Turkey;³Internal Medicine, Kecioren Education and Research

areas: 30.1% East Málaga; 12.5% West Málaga, 30.1% Costa del Sol, 1.3%

Hospital, Ankara, Turkey.

Guadalhorce Valley,

1.5% Serranía de Ronda/ Sierra de las Nieves,

7.3%

Axarquía, 3.1% Antequera, 2.4%, 2.7% Melilla. The most frequent histological

Although the thyroid gland has an abundant blood supply, metastasis to the

variant was papillary (69.72%) and in the different areas: East Málaga: 76.22%

thyroid gland is a rare condition. Its incidence varies from 0.1% and 3% in clinical

papillary,

9.15% follicular,

6.71% micropapillary,

3.65% medullary, 1.83%

series. First case. A

56-year-old man presented to emergency service with

anaplastic,

1.22% Hurtle cel, 1.22% oncocytic. West Málaga; 63.25% were

neurological symptoms. CT of brain revealed multiple hyperdens lesions.

papillary,

11.76% were follicular, 13.23% were micropapillary, 4.41% were

Posteroanterior chest X-ray showed increased opacity in the left lung. Metastatic

medullary, 4.41% were oncocitic, 2.94% were Hurtle; Or anaplastic. Axarquia

lung cancer was considered as a preliminary diagnosis and PET/CT was

73.17% papillary, 4.88% follicular, 9.76% micropapillary, 9.76% medullary,

performed. PET/CT showed a mass lesion of 15.8!7.6!8.5 cm in the upper lobe

2.44% anaplasic. Gualdalhorce Valley 77.59% were papillary, 6.89% follicular,

of the left lung and multiple pathologic involvements with metastatic appearance

10.34% micropapillary, 1.72% medullary, 3.45% no data. Antequera, 64.71%

were present in many organs, especially in thyroid gland. A biopsy was performed

papillary; 17.65% follicular, 11.76% micropapillary, 5.88% medullary. Serranía

from the mass lesion and biopsy revealed squamous cell lung cancer. FNA was

Ronda/Sierra Nevis: 75% papillary, 12.5% follicular, 12.5% micropapillary. In

performed from a nodule located in the right thyroid lobe and cytopathological

Costa del Sol 59.76% papillary, 12.20% follicular, 8.54% micropapillary, 1.22%

analysis of aspiration material showed metastatic epithelial carcinoma. Second

medullary, 0.61% anaplastic, 4.27% Hurtle cel, 13.41% no data. Melilla: 80.02%

case. A 42-year-old man presented with fatigue, dyspnea and cough. Thorax CT

papillary,

6.66% follicular,

6.66% micropapillary, 6.66% anaplasic In other

revealed a nodular lesion of 27!17 mm in posterior segment of the right upper

provinces: 84.62% papillary, 7.14% follicular, 7.14% medullary. Tumor tissue

lobe. PET/CT showed increased FDG uptake in the lung, mediastinum and

was noticed to surpass the resection capsule in 19.08% (without data 11.93%).

abdominal multiple lymph node regions, thyroid gland and skeletal system.

33%, no ganglia were removed,

21.6% of affected nodes and distant

Biopsy was performed with fiberoptic bronchoscopy and the result was consistent

metastasesO1%.

with primary adenocarcinoma of the lung. FNA was performed from a nodule

Conclusions

located in the right thyroid lobe and from a suspicious right cervical lymph node

The prevalence of thyroids cancer in our population was similar to those

in level III. Cytopathological analysis of both aspiration materials revealed

described in Spain. In the analysis of different types, papilar was the most

metastasis of malign epithelial carcinoma. It was thought that medical palliative

frequent, followed by follicular and micropapillaries. The overall prognosis is

approach would be more appropriate treatment option for two cases when

good.

presence of multiple synchronous metastases, absence of local symptoms,

DOI: 10.1530/endoabs.49.EP1462

characterization of primary diseases, general condition and life expectancies of

the patients considered. Discussion. It should be known that the treatment

approach in patients with metastatic thyroid cancer affects survival and treatment

should be individualized.

DOI: 10.1530/endoabs.49.EP1464

EP1463

Lymph node metastases location (central vs lateral neck) in

well-differentiated thyroid carcinoma: Is it important?

Bernardo Marques, Raquel Martins, Joana Couto, Jacinta Santos,

Teresa Martins & Fernando Rodrigues

EP1465

Instituto Português de Oncologia de Coimbra FG, EPE, Coimbra, Portugal.

Isolated bone metastases: a rare form of presentation of papillary

thyroid carcinoma

Introduction

Mariana Peyroteo, Cátia Ribeiro, Pedro C Martins, Ana Ferreira,

Regional lymph node

(LN) metastases have prognostic significance in

Laurinda Giesteira, Rui Barbosa, Machado Carvalho, António Ramalho,

differentiated thyroid cancer (DTC). Several studies demonstrated that lateral

Augusto Moreira & Abreu de Sousa

neck LN metastasis, classified as N1b, have a greater impact on overall survival

IPO Porto, Porto, Portugal.

than central LN metastasis. Our study aimed to assess the risk of N1a vs N1b

involvement on outcome in patients with differentiated thyroid cancer (DTC),

Background

according to the 7th edition of the TNM staging system.

Papillary thyroid cancer (PTC) is the most frequent type of well-differentiated

Methods/design

thyroid cancer

(WDTC) and frequently poses a management dilemma. Its

This was a retrospective study of 276 patients identified from our institutional

indolent behavior associated with high long term survival support the trend

database, who underwent surgery for DTC between 2000 and 2013. All patients

towards a more conservative management approach. The authors present a case of

had: lymph node metastasis, apparent complete tumour resection, without distant

isolated bone metastases as the form of presentation of papillary thyroid

metastasis at diagnosis and nonaggressive histologic variant. The association

carcinoma. A 61-year-old man was admitted with complaints of lower back pain

between variables was assessed using chi-square and Student’s t-tests.

for the previous

3 months. A lumbosacral spine CT and sacral MRI were

Results

performed, showing a 9!9!7,5 cm mass centered on the sacrum infiltrating the

All patients were followed for a minimum of 3 years postoperatively (146.3G

sacral canal, with soft tissue density associated with extensive lytic lesions of the

87.1 months). Most patients had papillary thyroid cancer (99%). One hundred and

sacral vertebra, suggestive of chordoma. The patient was submitted to a

twenty seven patients (46%) were classified as N1b and mean age was similar in

sacrectomy with reconstruction. The histology of the removed specimen revealed

both groups (46.6 years in N1b patients vs 47.5 in N1a; PZ0.560). There was no

involvement of the sacrum by thyroid cancer, namely papillary type (follicular

significant association between N1b classification and extra-thyroid extension

variant), with positivity for thyroglobulin and TTF-1

on the

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

immunohistochemistry study. The thyroid ultrasound showed multiple nodes

Introduction

bilaterally and the FDG-PET scan showed increased uptake in the left thyroid

Follicular Thyroid Carcinomas (FTCs) and Follicular Variant Papillary Thyroid

lobe and in the area of the sacral surgery, without other areas of high uptake. The

Carcinomas

(FVPTCs) may present absence of suspicious ultrasonography

patient was submitted to a total thyroidectomy, with the histologic study of the

features more frequently than classic papillary carcinomas. Thus, some cases may

thyroid revealing a multifocal papillary thyroid cancer (follicular and oxyphilic

be identified with the pattern of ‘low suspicion’ rather than intermediate or high

variants). Ablative treatment with radioactive iodine was administered after the

suspicion defined in the American Thyroid Association (ATA) guidelines of

surgery.

2015. These guidelines establish a size cutoff of 1.5 cm to recommend fine-needle

Conclusion

aspiration in nodules belonging to this category of low suspicion, justified because

Distant metastatic disease at presentation is rare in WDTC, with these patients

the probability of distant metastasis in FTCs !2 cm is rare. The aim of this study

having less favorable outcomes. For this reason, many risk stratification

is to analyze the perithyroidal extension and the presence of variables associated

algorithms include metastatic disease as a high risk factor. This clinical case

with greater aggressiveness in cases of FTC and FVPTC as a function of the initial

reports a rare form of presentation, showing us that, although most PTC are

size.

indolent, there are still factors about this type of tumor we need to study in order

Description of methods

to be able to single out these specific cases for more aggressive treatment.

A retrospective study of 76 patients with diagnosis of FTC or FVPTC was

DOI: 10.1530/endoabs.49.EP1465

conducted. The presence of the followings clinical and histological parameters

were evaluated: initial perithyroidal extension; aggressive histologic variants

(extensive capsular invasion, oncocytic features, undifferentiated foci); presence

of vascular invasion, presence of lymph node metastases and distant metastases at

diagnosis and during follow-up. The differences between the 2 groups were

analysed according to nodular size: !1.5 cm (group A) and R 1.5 cm (group B).

EP1466

Results

Association between preoperative serum MMP-9 and histopathological

76 cases with a mean age of 53G16 years, 75% women. Group A: 40 cases, size

features of thyroid tumors

0.72G0.34 cm, 8% FTC and 92% FVPTC. Group B: 36 cases, size 2.76G

Ruxandra Dobrescu¹, Catalina Picu¹, Sorina Schipor¹, Adriana Padure¹,

1.04 cm, 33% FTC and 67% FVPTC. Extrathyroidal extension 5% vs 19.4%

Liliana Parvu¹, Dana Manda¹, Dumitru Ioachim¹, Corin Badiu^1,2 &

(p0,052); aggressive histologic variants 0% vs 22.2% (P0.002); vascular invasion

Andra Caragheorgheopol¹

0% vs 19.4% (P0.003), lymph node metastases 10% vs 13.9% (P0.6); distant

¹‘CI Parhon’ National Institute of Endocrinology, Bucharest, Romania;

metastasis 0% vs 2.3% (P0.28).

²‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania.

Conclusion

The presence of aggressive histologic variants and vascular invasion was

Introduction

significantly greater in the carcinomas R1.5 cm. None of the carcinomas

Matrix metalloproteinase-9 (MMP-9) is a zinc dependent proteolytic enzyme

!1.5 cm presented aggressive histological, vascular invasion or distant

used by cells for degradation of the extracellular matrix during invasion and

metastases at diagnosis or during follow-up. Our data agree with the

recommendation established by the ATA to choose a size cutoff of 1.5 cm for

migration. There are only a few reports regarding the role played by MMP-9 in

low suspicion pattern nodules.

papillary thyroid carcinoma (PTC).

Aim

DOI: 10.1530/endoabs.49.EP1467

To evaluate the association between MMP-9 secretion, reflected by preoperative

serum levels and the histopathological features of thyroid tumors.

Materials and methods

We assessed serum MMP-9 in 329 subjects: 309 patients with thyroid tumors and

20 healthy controls (C). Patients were divided into 2 groups, following the

EP1468

pathology report: benign disease group (BD) (nZ176, aged 50.5G12.88 years)

Ten years of TSH suppression therapy in differentiated thyroid cancer

and PTC group

(nZ133, aged

48.6G14.92

years). In the PTC group

analysed by HR-pQCT

histopathological features of thyroid tumors were analyzed according to

Natacha Germain, Katia Nadin, Bruno Estour & Bogdan Galusca

pathological stage, histological subtype, multifocality and invasion. The histology

Endocrinology Department, University Hospital of Saint Etienne,

showed classic PTC (cPTC) in 49 patients, follicular variant (fvPTC) in 52 and

Saint Etienne, France.

aggressive forms (AGR) in 32 patients. Sera were collected before patients

underwent surgery. MMP-9 was measured by Quantikine Elisa kit (R&D System).

The study was approved by Ethics Committee of the Institute.

Introduction

Results

TSH suppression therapy by thyroid hormones

(TST) in patients with

We found a significant difference in serum MMP-9 levels between controls and

differentiated thyroid cancer (DTC) could be associated with adverse effects on

thyroid tumors (BDCPTC) (meanGS.E.M.: 561.45G49.37 ng/ml vs 787.47G

bone metabolism in post-menopausal women. Recent recommendations suggest

31.24 ng/ml, P!0.0001). According to the pathology tumor stage (T1-T4), we

therefore to minimize time passed under TSH suppression therapy. However data

found higher MMP-9 levels in T3

(869G79.48 ng/ml) compared to more

in literature are controversial and few shows results on microarchitecture. This

incipient stages (T1 vs T3 P!0.01, T2 vs T3 P!0.03 respectively). fvPTC

study evaluated bone microarchitecture using High-resolution peripheral

showed lower MMP-9 levels vs cPTC or AGR (596.38G34.76 ng/ml vs 760.35G

quantitative computed tomography

(HR-pQCT, XtremeCT; Scanco Medical

70.54 ng/ml or vs 835.75G109.9 ng/ml, respectively, P!0,05). There was no

AG, Switzerland), in post-menopausal women under TST for more than ten years.

significance between cPTC and AGR. There was no difference in MMP-9 in terms

Patients and methods

of multifocality, but patients with invasive tumors had significantly higher serum

We conducted a descriptive, case-control, cross-sectional study, in

MMP-9 than non-invasive ones (838.14G80.3 ng/ml vs 618.68G30.9 ng/ml,

menopausal women under TST for more than 10 years (patients), compared

P!0.02).

with 32 menopausal women without any bone disease (controls). We measured

Conclusions

Bone Mineral Density (BMD) by Dual-energy X-ray absorptiometry (DXA),

Preoperative serum MMP-9 might differentiate patients at risk for invasive and

Bone Microarchitecture by HR-pQCT, bone markers (serum osteocalcin and

more aggressive tumor behavior, with implications in post-surgical radioiodine

cross laps).

treatment and follow-up.

Results

DOI: 10.1530/endoabs.49.EP1466

BMI were similar in both groups. PTH was higher in patients (37.2G2.2 ng/l)

compared with controls

(29.4G2.4 ng/l), PZ0.03. TSH was at

0.10G

0.03 mUI/L, with duration of TST of 17.9G1.2 years. No differences were

observed between the two groups for bone markers. Hip and lumbar spine BMD

were not impaired in patients group. However radial cortical bone density value

(Dcomp) was lower in patients (Dcomp at the radius: 816.7G24.5 g/cm³ vs

EP1467

863.3G11.3 g/cm³ in controls, PZ0.04).

Follicular thyroid carcinoma and follicular variant papillary thyroid

Conclusions

carcinoma: Clinical and histological features depending on the

This preliminary study shows an adverse effect of TST on radial Dcomp, while

initial size

BMD is not affected. The trabecular micro architecture is preserved. These

Fernando García Pérez¹, Guillermo Martínez de Pinillos Gordillo¹, Mariana

preliminary results need to be confirmed and impact of bone breaks need to be

Tomé Fernández-Ladreda², Eyvee Arturo Cuéllar Lloclla¹, José Álvaro

studied.

Romero Porcel¹, Carmen Carretero Marín¹ & María Victoria Cózar León¹

DOI: 10.1530/endoabs.49.EP1468

¹Hospital Universitario de Valme, Sevilla, Spain;²Hospital Punta de

Europa, Gibraltar, Spain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP1469

¹Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece;

Metastatic papillary thyroid carcinoma with intraglandular

²Microdiagnostics Ltd, Thessaloniki, Greece;³St Luke’s Hospital,

dissemination in remission of Graves’ disease

Thessaloniki, Greece.

Dubravka Brdar, Davor Eterović, Gordana

ˇ ošo, Tina Majstorovi

´ &

Ante Punda

Background

University Hospital Center Split and Split University School of Medicine,

Lymph node metastasis from papillary thyroid cancer without detectable primary

Split, Croatia.

within the thyroid gland is extremely rare. We describe a case of a young woman

with a cervical metastasis, without detectable orthotopic or ectopic thyroid focus.

A 26-year-old woman was referred to our outpatient clinic, presenting with

Case report

A 30-year old woman with a history of adenocarcinoma of the ascending colon six

growing left sided neck mass. She was in remission of Graves’ disease for the last

years previously, presented at the 15th week of a normal second pregnancy, for

two years.Ultrasound examination revealed isoechogenic nodule with micro-

management of subclinical Hashimoto’s thyroiditis. She had received thyroxine

calcifications in the upper third of the left thyroid lobe measuring 9!6!6 mm

replacement during her first pregnancy 2 years earlier. She had a family history of

and conglomerate of lymph nodes on the left side of the neck, the largest node

colon cancer in her maternal grandmother and her mother’s two cousins. On

measuring 37!21!13 mm. Behind the lower pole of the left thyroid lobe we

examination she had a palpable node at the right lateral compartment and her

found lymph node. Fine needle aspiration of the isoechogenic nodule in the left

thyroid was not palpable. Ultrasound examination of the neck showed a small,

thyroid lobe, conglomerate of lymph nodes on the left side of the neck and lymph

mildly hypoechoic, heterogeneous gland and a well-defined, hypoechoic mass

node behind the lower pole of the left thyroid lobe revealed papillary carcinoma.

30!15!13 mm, lateral to the right carotid artery at level IV. The mass was

Total thyroidectomy with left modified radical neck dissection was performed.

finally excised one year postpartum and was found to be a lymph node occupied

Histopathological examination confirmed papillary thyroid carcinoma with

extensively by follicular variant of papillary thyroid cancer. She subsequently

intraglandular dissemination and metastases to 18 out of 26 lymph nodes. Patient

underwent total thyroidectomy with central and right lateral node dissection

recived ablative-therapeutic dose of 3.83 GBq of I-131. Now, 6 years later, the

without complications. Thorough histologic examination of the thyroid failed to

patient is disease free.

reveal cancer, central compartment nodules were negative (0/17) and one more

DOI: 10.1530/endoabs.49.EP1469

node harbored microscopic metastasis (1/18) on the right side. The contralateral

nodes dissected were negative (0/9). MRI of the oropharynx, mediastinum,

abdomen and pelvis and non-contrast CT of the lungs (scheduled for follow up of

the bowel carcinoma) were normal. The patient has been referred for radioactive

iodine treatment.

Conclusions

Papillary thyroid cancer presenting as a cervical mass in the absence of a thyroid

EP1470

primary, needs to be differentiated from ectopic thyroid cancer in the neck or

Thyroid nodule size and the risk of malignancy

elsewhere. A picocarcinoma or one that has spontaneously regressed cannot be

Entela Puca¹, Ema Lumi⁴, Blertina Olldashi², Sonila Bitri¹, Dorina Ylli³,

excluded.

Agron Ylli³ & Edmond Puca³

DOI: 10.1530/endoabs.49.EP1471

¹American Hospital 2, Tirana, Albania;²Neo-Style Clinic, Tirana, Albania;

³UHC Mother Teresa, Tirana, Albania;⁴Regional Hospital Teni Konomi,

Korce, Albania.

Introduction

Thyroid nodule size is routinely assessed and has been a cause for concern, if it is

a carcinoma or not.

EP1472

Aim

Birt-Hogg-Dubé and papillary thyroid carcinoma: a case report

Our aim was to evaluate the relationship between thyroid nodule size and cancer

Ines Barka¹, Katherina Krompa¹, Camille Baudry¹, Frédéric Caux² &

risk. It was a retrospective analysis of 386 patients with thyroid nodules who

Hélène Bihan¹

referred to surgery in our hospital from January 2011 to March 2016. Patient’s

¹Endocrinology, Diabetology and Metabolic Disease, Hôpital Avicenne -

demographic data, nodules size, and final pathology were recorded. All data were

Hôpitaux Universitaires Paris, Seine-Saint-Denis, France;²Dermatology,

analyses using SPSS18.

Hôpital Avicenne - Hôpitaux Universitaires Paris, Seine-Saint-Denis,

Results

France.

From the total of 386 patients, female were 86% and male 14%, with mean age of

46.75

years old G14.24 DS were included for this study. Based on final

pathology

179 patients

(46.5%) had malignant nodules. The mean size of

Background

malignant and benign nodules were

3.07G1.52

cm and 3.6G1.59 cm

Birt-Hogg-Dubé (BHD) syndrome has been reported to be associated with

respectively (P!0.003). For the purposes of this investigation, thyroid nodules

neoplastic conditions. Its association with thyroid carcinoma has been reported

!1 cm in diameter provided baseline cancer risk for comparison (5.6% risk of

but remains controversial. Here we report the case of a BHD patient with a thyroid

cancer). The overall prevalence of cancer in nodules 1.0-1.9 cm was 20.1%; 2-

papillary carcinoma.

2.9 cm was 30.8%; in nodules 3.0-3.9 cm, 23.4%; and in nodules R4.0 cm,

Case report

20.1%. The primary influence of this association was the low malignancy rate in

A 47-year-old man presented with asymptomatic facial papules, which had been

nodules under 1.0 cm. When comparing nodules 1.0-1.9 cm, 2.0-2.9 cm, 3.0-

gradually increasing in number for 6 years. A biopsy was taken from a papule on

3.9 cm, no difference in malignancy rate was demonstrated (PZ0.5). For nodules

the nose and histology examination showed epithelial proliferation. Mutation in

O4 cm the differences was statistically significant (OD: 3.17; CI95%: 1.01-

exon 4 of FLCN was identified which confirmed the diagnosis of BHDS. A

10.02; P!0.04).

systematic ultrasound examination of his neck showed a 2 cm solid isoechoic

Conclusion

nodule of the right thyroid lobe. The left thyroid lobe and the isthmus appeared to

These data provide strong evidence that thyroid nodule size O4 cm is associated

be normal. Serum levels of free thyroxine, and thyrotrophin were within normal

with an increased risk (three fold) of well-differentiated thyroid cancer and can be

ranges. Fine needle aspiration of the nodule revealed papillary clusters that had

applied in medical decision for thyroid surgery.

atypical nuclei and intranuclear inclusions and that appeared to be a papillary

carcinoma. Our patient underwent a total thyroidectomy with neck exploration.

DOI: 10.1530/endoabs.49.EP1470

The pathologic examination confirmed the diagnosis of papillary carcinoma

classified T1NXMX. The patient was put on L-thyroxine and a radioiodine

therapy will be considered.

Discussion

Birt-Hogg-Dubé syndrome consists of multiple fibrofolliculomas traditionally

associated with trichodiscomas and acrochordons. Medullary carcinoma of the

thyroid was the most reported type of cancers. Eventhough, other types of

EP1471

carcinoma as papillary carcinoma et carcinoma were not the common form of

Lateral cervical lymph node metastasis from papillary thyroid cancer of

BHD syndrome could also occur. Our report is of high scientific interest because

undetected primary: a case report

it will increase awareness of BHD in the medical community, as this syndrome is

Athanasios Panagiotou¹, Fotini Adamidou¹, Panagiotis Anagnostis¹,

too often overlooked even when obvious clinical manifestations are present. So

Mattheos Bobos², Dimitris Hatzibougias², Keraso Tzelepi³ & Marina Kita¹

the neck ultrasound is recommended for BHD patients and family members.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Among others BHD patients followed in our hospital, we will look for the

under control of endocrinologist and oncologist. In May 2014 patient was again

frequency and results of ultrasounds.

hospitalized and next lymphadenectomy was done. At that moment histopathol-

DOI: 10.1530/endoabs.49.EP1472

ogy of the lymph nodes indicated CASTLE (HMWCKC, p63C, CD5C, bcl2C,

CEAC, synaptophysinC, CalcK, THYK, TTF1K). Therefore, the thyroid

specimens were reevaluated again, and the presence of CASTLE in the gland was

also confirmed. In subsequent follow-ups there were no signs and symptoms of

the disease recurrence. Thyroid CASTLE might be easy overlooked because of its

rarity and similarity to some thyroid cancers like squamous cell carcinoma or

anaplastic carcinoma. Complete thyroid resection and lymphadenectomy are

important to improve the long-term survival and the locoregional recurrence rate,

EP1473

although CASTLE course is usually clinically indolent. The short review of the

Diagnosis of papillary thyroid carcinoma: Is it time to reconsider?

already published data regarding CASTLE was done.

Panagiotis Panousis, Stella Vasileiadou, Michael Katsamakas,

DOI: 10.1530/endoabs.49.EP1474

Maria Boudina, Anastasia Nikolaidou, Alexandra Chrysoulidou,

Kalliopi Pazaitou-Panayiotou & George Zafeiriou

Theagenio Cancer Hospital, Thessaloniki, Greece.

Aim

The aim of this retrospective study was to evaluate the diagnostic significance of

presurgical thyroid ultrasound in comparison with FNAC of thyroid nodules and

EP1475

their contribution in detecting thyroid cancer.

Minimally and widely invasive follicular thyroid carcinomas: are there

Patients and methods

significant differences in clinical behaviour and prognosis?

We retrospectively studied the files of 118 thyroid cancer patients, 18 men

Diana Martins¹, Cristina Ribeiro¹, Miguel Melo¹, Joana Saraiva¹,

(15.2%) and 100 women (84.8%), who underwent thyroidectomy from January

Maria Joa˜o Martins2, Carla Baptista1, Diana Oliveira1, Mara Ventura1,

2013 until December 2016, in the Department of Surgical Oncology of Theagenio

Adriana Lages¹, Nelson Cunha¹, Diana Catarino¹, Lúcia Fadiga¹,

Cancer Hospital, Thessaloniki, Greece. All patients were diagnosed and followed

Gracinda Costa³ & Francisco Carrilho¹

up by the Section of Endocrinology and were operated upon by the same surgical

¹Endocrinology, Diabetes and Metabolism Department of Coimbra Hospital

team. The mean patient age was 55 years (G12.26). We evaluated the suspicious

and University Centre, Coimbra, Portugal;²Anatomic Pathology Depart-

ultrasound findings according to the ATA Guidelines of 2015 (hypogenicity,

ment of Coimbra Hospital and Universitary Centre, Coimbra, Portugal;

microcalcifications, taller than wide shape, irregular margins, extrathyroidal

³Nuclear Medicine Department of Endocrinology, Diabetes and Metabolism

extension) and the results of FNAC (in accordance to Bethesda Score), in

Department of Coimbra Hospital and Universitary Centre, Coimbra,

association with the pathology report. All ultrasounds were scored based on the

Portugal.

suspicious characteristics.

Results

Mean tumor size was 7.1 mm (G8.73 mm), multifocallity was found in 69

Introduction

patients (58.5%). The Bethesda score was positive for malignancy in 45% of the

The existence of clear differences between the biological course and clinical

cases. On the other hand, the suspicious ultrasound findings were in accordance

behaviour of minimally invasive (MI) and widely invasive (WI) follicular thyroid

with the pathology report in 78.8% of the cases. Almost all patients with Bethesda

carcinomas (FTC) is still debatable. The present study was conducted to outline

II or III presented at least one or more suspicious ultrasound characteristics and

the clinical differences between MI and WI-FTC and evaluate outcomes in both

those with Bethesda VI at least three or more suspicious for cancer

tumors.

ultrasonographic findings. Based on our statistical analysis, ultrasound as a

Methods

diagnostic tool is more significant (P!0.05) and has a more positive predictive

We conducted a retrospective cohort study involving 80 cases of FTC. The

value in detecting thyroid cancer compared to FNAC.

comparison between MI-FTC and WI-FTC included an evaluation of clinic-

Conclusions

pathologic characteristics, including tumor staging, and outcome assessment.

Ultrasound characteristics and clinical suspicion are considered more valuable

Results

in the diagnosis of papillary thyroid carcinoma, especially for small lesions

The cohort included 65 patients with MI-FTC and 15 patients with WI-FTC.

(!10 mm) and multinodular goiter. Therefore, an ultrasound scoring system

Patients whose age at diagnosis was R45 years more frequently had WI-FTC

should be adopted by the clinicians coping with thyroid cancer.

(27.3% Vs 4.0%, PZ0.023). Mean tumor size was significantly greater in

WI-FTC patients than in the MI-FTC (43.07 vs 30.94 mm, PZ0.007). At

DOI: 10.1530/endoabs.49.EP1473

univariate analysis, vascular invasion, infiltrative margins and invasion of thyroid

capsule were significantly related to the presence of WI-FTC

(P!0.001,

P!0.001 and PZ0.010, respectively). A higher cancer stage (III-IV) was also

associated with the occurrence of WI-FTC (50% vs 8.6%, P!0.001). After a

mean follow-up of 52.6 and 76.4 months in MI and WI-FTC, respectively, one

patient of the first group and two patients of the second died of FTC. Patients with

MI and WI tumors respectively presented a disease-free survival of 100% and

EP1474

84% at 10 years.

Patient with thyroid carcinoma showing thymus-like

Conclusions

differentiation: a case study

The study reported a good outcome in both MI and WI patients, probably related

Małgorzata Kałuz˙na1, Adam Janicki1, Jacek Sygut2, Andrzej Marszałek2,

to an aggressive therapeutic strategy and strict follow-up. Our data confirm

Katarzyna Ziemnicka¹ & Marek Ruchała¹

previous studies which showed that WI-FTC are typically larger tumors with

¹Department of Endocrinology, Metabolism and Internal Medicine,

higher stage, more frequent vascular invasion and invasion of the thyroid capsule.

University of Medical Sciences, Poznan, Poland;²Greater Poland Cancer

Accordingly, we believe that the tumor grade of invasiveness must be taken into

Centre, Poznan, Poland.

account on the staging process of disease.

DOI: 10.1530/endoabs.49.EP1475

Thyroid carcinoma showing thymus-like differentiation

(CASTLE) is an

extremely rare thyroid neoplasm. This type of tumour may arise from branchial

pouch remnants or ectopic thymus and is considered as independent

clinicopathological entity of thyroid neoplasms. There have been only about

100 cases described in the literature, so far. Here, we have retrospectively

analyzed the data from histopathology and clinics of a 70 year old female patient

with thyroid CASTLE who underwent total thyroidectomy in 2009 due to thyroid

nodule in the right lobe (25!25!30 mm) and suspicion of papillary thyroid

carcinoma in the fine needle aspiration biopsy. At that time histopathological

EP1476

examination suggested presence of metastasis to the thyroid likely from the ovary

or thymus however, the detailed clinical and imaging study did not confirm that

Cystic masses of neck: a case report

these organs could be the source of this lesion. In February

2011 patient

M Teresa Gallego, Lucia Vera, Amparo Meoro, Cristina Del Peso &

underwent neck lymphadenectomy that revealed metastases to the lymph nodes

Manuel Martin

with unknown origin but thyroid carcinoma was ruled out. Patient was all time

Hospital General Universitario Reina Sofia, Murcia, Spain.

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Introduction

EP1478

Cystic masses of neck consist of a variety of pathologic entities. The age of

Cystic nodule and carcinoma of thyroid gland, diagnosis and treatment

presentation and clinical examination narrow down the differential diagnosis. In

of cistic nodule

adults are considered to be malignancies until proven otherwise (thyroid lesions,

Snezana Mihajlovska & Marija Mihajlovska

salivary gland neoplasms, metastatic squamous cell carcinoma and lymphatic

¹Department of Nuclear Medicine, Clinical Center ‘D-r Trifun Panovski’,

malformations such as the cystic lymphangioma. Ultrasound (US) is often used

Bitola, Macedonia;²Department of Endocrinology, General Hospital

for initial evaluation. Computed tomography (CT) and MRI provides additional

‘8-mi Septemvri’, Skopje, Macedonia.

information. FNAC has a supplementary role for confirmation of diagnosis but its

accuracy may depend on the experience of the cytopathologist.

Case report

The cystic nodule is by its origin a real or pseudo cyst. According to the date of

A 41 years old woman presented with a left-side neck mass that had slowly

literature the papillary thyroid carcinoma is being detected in the cystic nodule in

enlarged over the past

months with a serious burner. MRI showed a

up to 27% of the cases. Ultrasound is the best diagnostic method of the cystic

72*57*47 mm septate mass, with solid and cystic components with contralateral

nodule and fine needle aspiration under ultrasound examination is a diagnostic

airway displacement and posterior displacement of the carotid. Thyroid US had

method for cytological diagnosis.

revealed a normal gland. FNAC was nondiagnostic but the inicial diagnosis was a

Results

cystic lymphangioma and the patient was treated with Picibanil (OK-432) without

Seventy patients with detected cystic nodule underwent fine needle aspiration and

any result. Six months later she underwent surgical excision. The histopathology

the aspirational content was cytopathologically examined. In 31/70/ (44.3%) of

report came out as Cystic metastatic lymph node from Papillary carcinoma of the

patients there was a complete discharge of the cyst. In 4/70/ (5.7%) there was

thyroid. US demonstrated a poorly defined nodule with micro-calcification in the

partial discharge but without recidivans and in 35/70/ (50%) of patients there were

left lobe of the thyroid. One week later she underwent a total thyroidectomy and

recidivates of cystic contents. According to the fine needle pathohystological

bilateral cervical lymphadenectomy. The final diagnosis was a 12 mm Papillary

findings in nine patients was detected a malignancy (eight patients had papillary

Carcinoma with bilateral metastatic lymph nodes.

and one follicular carcinoma).

Discussion

Conclusion

Metastatic nodes from head-and-neck malignancy, especially papillary carcinoma

Cystic nodule in thyroid gland is diagnosed by using ultrasound. Fine needle

of the thyroid, are the most common types of nodal metastases presenting as

aspiration is used for discharging of the cyst. Cysts which recidivate after few

cystic masses in the neck. Eighty percent of the cystic masses in patients over 40

needle aspiration should be operated surgically, and the patient with proved

years of age are due to necrotic lymph nodes. On US presence of punctate

carcinoma are cured according to the protocol for the treatment of thyroid

calcification within the solid component of the cystic node warrants careful search

malignant disease.

for primary papillary carcinoma in the thyroid gland. In our patient the diagnosis

DOI: 10.1530/endoabs.49.EP1478

unfortunately was a challenge.

Conclusions

Cystic lesions of the neck are commonly encountered on imaging studies. Clinical

presentation along with imaging features as assessed by Doppler US or CT help in

accurate diagnosis. These imaging modalities also aid in optimal pre-operative

EP1479

planning. Imaging is essential for accurate diagnosis and pretreatment planning.

Incidence of thyroid cancer in the gray bethesda categories

DOI: 10.1530/endoabs.49.EP1476

Berta Barbosa, Moreira da Costa, Vitor Valente, Fatima Borges &

André Carvalho

Centro Hospitalar Porto, Porto, Portugal.

Objective

The recommendations for action in a Bethesda category III are to repeat the

cytology or to perform molecular tests, and if these are inconclusive, surveillance

EP1477

or surgical indication may be maintained, depending on the risk factors,

Staging of thyroid cancer at the time of its diagnosis in a single

ultrasound characteristics of the nodule and patient preference. In case of category

clinical centre

IV of Bethesda, the recommendation is the surgery. The objective of this study

Agata Bałdys-Waligorska¹, Maciej Kolodziej¹, Monika Buziak-Bereza¹,

was to evaluate the impact of age, gender and nodule size on the incidence of

Michal Koziara¹ & Andrzej Sokolowski²

malignant lesions in patients with thyroid nodules with Bethesda III and IV

¹Jagiellonian University College of Medicine, Krakow, Poland;

classification.

²University of Economics, Krakow, Poland.

Material and methods

Retrospective observational study of patients undergoing Total Thyroidectomy

between July 2014 and June 2016. Totalizations were excluded. Descriptive

Medical documentation of 976 patients treated and followed-up over the years

analysis and statistical treatment with SPSS 20.

2001-2006 at our 131- radioiodine treatment centre was analysed with respect to

Results

their thyroid cancer staging. The mean age at their time of diagnosis was 59G

Four hundred ninety two patients were submitted to Total Thyroidectomy after

15.1 years. From histopathology, papillary, follicular or poorly differentiated

their presentation at the Multidisciplinary Thyroid Group consultation. The mean

cancer was diagnosed in 87.6, 11.7, and 0.7% of these patients, respectively. The

age of the patients was 54.6 years, being 82.7% female. Bethesda III was

mean ages of patients with papillary, follicular or poorly differentiated cancer

indicated in 52 patients, and Bethesda IV in 125 patients. In category III, in seven

were

58.4G15.0,

62.9G15.7

and

70.6G14.6

years, respectively, the age

patients (13.5%) the histology revealed to be a malignant lesion, 71.4% female,

differences between these patient groups being statistically significant

mainly in the 5th decade of life; the majority of patients were T1b. In category IV,

(PZ0.0014). On their admission, patients were TNM- staged. Patients with

in 20 patients (16%) the histology revealed a malignant lesion, 65% female,

microcarcinoma pT1a formed the largest group - 38.9%, followed by T1b-

mainly in the 6th decade of life; the majority of patients were T1b.

32.3%, T2K 10.0%, T3K12.3%, T4K3.0%, and Tx - 3.5%. In the last case the

Conclusions

tumour diameter was not established by the surgeon or pathologist. Most patients

In our series, 13.5 and 16% of patients with a category III and IV Bethesda

were staged at N0 - 88.9%, followed by N1aK 9.7%, and N1aCb - 1.4%. At the

surgical indications were found to be malignant lesions, respectively, according to

time of diagnosis, distant metastases to lungs or bones was staged as M1in only

the literature (5-15% for Bethesda III, 15-30% for Bethesda IV). It was not

0.6% of patients. On chi-square analysis of percentage distribution of tumour size

possible to find a statistically significant difference between the variables tumor

(T) in papillary cancer patients, pT1a was most frequent (42.8%), while T₂

size, age group of patients and gender.

dominated in the follicular cancer group (32.3%). This difference was statistically

DOI: 10.1530/endoabs.49.EP1479

significant

(PZ0.0000). No differences were found with respect to N or M

classes. In the follow-up of this patient group, 77 patients were re-operated due to

lymph node or lung metastases, and 23 patients were operated three times.

Multiple I-131 treatment (2-6 times) was applied in this last group. Three patients

died due to thyroid cancer progression.

Conclusion

EP1480

On their diagnosis, patients with papillary cancer and follicular cancer

Sentinel lymph node biopsy in medullary thyroid microcarcinoma after

significantly differed with respect to age and stage of disease.

methylene blue dye mapping - a pilot study

DOI: 10.1530/endoabs.49.EP1477

Radan Dzodic^1,2, Nada Santrac¹, Marko Buta^1,2, Merima Goran¹,

Igor Djurisic¹ & Ivan Markovic^1,2

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Surgical Oncology Clinic, Institute for Oncology and Radiology of Serbia,

Table 1

Belgrade, Serbia;²Medical Faculty, University of Belgrade, Belgrade,

Serbia.

LN Number

N1a

N1b

(1-22)

0.01

50%

75%

80%

0.002

Introduction

Remission

(0-2)

100%

50%

25%

20%

The aim was to analyse usefulness of sentinel lymph node (LN) biopsy of jugulo-

carotid regions after methylene blue dye mapping for selection of clinically N0

patients with medullary thyroid microcarcinomas

(MTMC) and lateral LN

reached remission was 0%(0/5) with extracapsular involvement vs 50%(5/10)

metastases for one-time modified radical neck dissection (MRND).

Materials and methods

without extracapsular involvement

0.053). Among

patients with

From 2007 to 2016^th, 15 patients were operated in our institution due to MTMCs

N1category, only three were cured (all had! 5 LN and a size LN! 2 cm).

with serum calcitonin levels lower than 1000 pg/ml, tumors under or 10 mm in

Conclusion

size and clinically negative regional LNs. Total thyroidectomy with central neck

In our case series we observed that N category and number of LN is associated

dissection was done in all patients. Sentinel LN mapping was performed by

with PD in the long term. Furthermore, there was a linear trend between the size

injecting 0.2-0.5 ml of 1%-methylene blue dye in the thyroid lobes. Blue stained

of the greatest LN and the extracapsular imvolvement with the PD. This

sentinel LNs were removed from II/III levels and examined by frozen section. In

reinforces the importance of a correct characterization of LN involvement.

case sentinel LNs were benign, additional non-colored LNs were removed for

standard pathological analysis. If sentinel LNs were positive on frozen section,

DOI: 10.1530/endoabs.49.EP1481

one-time MRND was performed.

Results

One patient had hereditary form of medullary thyroid carcinoma, with bilateral

subcentimeter tumors, while others had sporadic, unilateral MTMC. Sporadic

MTMCs showed neither central nor lateral LN metastases on bilateral sentinel LN

biopsy, with no indication for MRND. Hereditary MTMC had central LN

metastases, with positive sentinel LNs on both sides, thus one-time bilateral

EP1482

MRND was performed. This patient had metastases in other dissected LNs, as

A case of bilateralmetastaticrenal tumorof thyroid carcinoma

well, and serum calcitonin level of

221 pg/ml. Frozen section and definite

Lila Brakni

pathological analysis were 100% match.

Endocrinology, Algiers, Algeria.

Conclusion

Sentinel LN biopsy after methylene blue dye mapping can be precisely used for

intraoperative assessment of lateral neck LNs. It optimizes surgery of MTMCs,

Introduction

selecting clinically N0 patients with metastases on frozen section for one-time

Distant metastasis caused by thyroid carcinoma is common and usually found in

MRND. This pilot study is the first reported experience with sentinel LN biopsy of

lung or bone. Clinically detectebale, welldifferenciated metastatic thyroid

jugulo-carotid regions in medullary thyroid carcinomas using methylene blue

carcinoma to the kidney is rare. Only 16 cases have been reported in the

dye, focusing on the subgroup of microcarcinomas.

littérature. We describe a case of metastatic vesicular thyroid carcinoma to the

DOI: 10.1530/endoabs.49.EP1480

bilateral kidneys in a 61 years women, with bone, pulmonary lever and lynph

nodes metastasis.

Case report

A 61 old women with a past history of thyroid tumor that had been surgically

treated

19 years earlier She underwent a total thyroidectomy, radiotherapy,

s ablation treatment with iodine

131

and thyroxin suppression therapy

(200 mg/day) and has been diagnosed as vesicular thyroid cancer developped a

left renal metastasis with chest pain. The lesion was detected with iodine 131

scintigraphy which measured in the CT Scan 68/60/13 mm. Biological tests

EP1481

showed: The thyroglobulin 3000 ng/ml (0.8-55) - TSHZ0.02 mUI/ml. Sub-

Lymph node categorization as a prognostic factor in a historical series

sequent surgery and histopathology analysis of the renal lesion confirmed the

of medullary thyroid cancer cases within a regional hospital

diagnosis of vesicular thyroid metastatic carcinoma. Four years later a second

Nerea Aguirre Moreno, Elena Fernandez Gonzalez, Sandra Campos Mena,

metastasis of the right kidney appeared with pulmonary, bone, leaver and lymph

Monica Marazuela Azpiroz & Marcos Lahera Vargas

nods metastasis. She underwent surgery where metastatic carcinoma was

La Princesa Hospital, Madrid, Spain.

confirmed (3 cm of diameter).

Discussion - Conclusion

Only few cases of metastatic spread to the kidneys are described in the literature.

Introduction

16 cases have been reported. They are mostly unique and rarely bilateral. The

Medullary thyroid cancer (MTC) TNM classification categorizes lymph nodes

common use of the ultrasound and the CT Scan in assessment of monitoring of a

(LN) according to their location, but does not consider number and size of LN.

cancer, patient allowed bringing to light more frequently this kind of lesion. The

Objective

concomitant existence of metastasis in the other sites is variously appreciated in

To analyze the relationship between number and size of LN in MCT persistent

the literature. They varies from 50 to 100% observed cases and pejorative from

disease (PD).

the point of view of the prognosis. The most frequent locations are pulmonary,

Material and methods

mediastinal and bone. The patient has benefited a dialysis treatment and deceased

Retrospective study of patients with MTC followed up in a regional hospital from

a year later.

1985 to 2015. The main variables (expressed as qualitative in frequency and

quantitative as meanGS.D. or median (min-max)): size of largest LN, number of

DOI: 10.1530/endoabs.49.EP1482

node, extracapsular involvement and number of LN surgical procedures

undertaken. Univariate analysis was used to assess the relationship between LN

number and TMN stage with PD or remission. A P-value less than !0.05 was

considered significant.

Results

Thirty-five patients were included (age at diagnosis 51G18 years; 57% women).

Time to follow up:8.6G7.2 years. Presentation: 24% cervical mass, 38% through

EP1483

family screening, 8% as incidentalomas. Before surgery, calcitonin levels were

Is prophylactic central cervical dissection in papillary carcinoma of the

391 pg/ml (2-46022) and carcinoembryonic antigen levels were

11.8 ng/ml

thyroid justified?

(0-2009). TNM stage: I:47%; II:6%; III:12%; IV:35%. N0:37%; NX:20%,

Berta Barbosa, Moreira da Costa, Vitor Valente, Fátima Borges &

N1:43%(N1a:33%; N1b:67%). Size of greatest LN:2.5G1.6 cm (! 1 cm: 23%;

André Carvalho

1-3 cm: 46%; O3 cm: 31%). Number of node: 1(0-22) (! 5 LN:64%; 5-9

Centro Hospitalar do Porto, Porto, Portugal.

LN:14%;R10 LN:22%). Extracapsular involvement:

29%. Number of LN

surgery: 1G0.67 (0-4). At the last visit, 47% had PD.

Univariate analysis:

Objective

We found clinical differences, although they were not significant, in LN size (PD

Thyroid cancer is the most common of the endocrine tumors, with papillary being

31G15 mm vs remission 10G14 mm (P 0.058)). The percentage of patients who

the most frequent. There is no consensus about prophylactic central cervical

dissection in patients with papillary carcinoma of the thyroid. The aim of this

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

study is to analyze surgical complications and the rate of recurrence of papillary

carcinoma was diagnosed histologically following reassuring cytology and

carcinoma in patients undergoing total thyroidectomy and prophylactic central

radiological examination. This is a case of 28-year-old female who presented with

cervical dissection, and patients submitted to total thyroidectomy alone.

neck swelling. ThyUSS showed an enlarged left thyroid with cystic and solid

Material and methods

components; FNA was Thy2. Surveillance ThyUSS showed additional right-sided

Prospective study of consecutive patients submitted to total thyroidectomy and

nodules without pathological features; FNA was Thy1. The patient opted for

prophylactic central cervical dissection between January 1993 and December

thyroidectomy; histology showed two small foci of papillary carcinoma. 53-year-

1999, and consecutive patients submitted to total thyroidectomy alone, in the

old female referred with a right dominant nodule following ThyUSS; FNA was

same period of 7 years, for papillary carcinoma of the thyroid. The groups were

Thy2. Subsequent ThyUSS showed a mildly hypoechoic, vascularised nodule

compared in relation to surgical complications and the rate of disease recurrence.

with peripheric halo; FNA was Thy1. The patient opted for right thyroid

Totalizations of thyroidectomy were excluded. Statistical analysis with SPSS 20

lobectomy; histology showed benign follicular nodules with the dominant nodule

Results

containing an incidental papillary microcarcinoma. 60-year-old female had an

Fifty-nine patients underwent total thyroidectomy and prophylactic central

incidental finding of a left thyroid nodule on CT neck on a background of

cervical dissection (mean age 46.3 years, 86.4% female), 43 patients underwent

autoimmune hypothyroidism and a family history of thyroid cancer. ThyUSS

total thyroidectomy alone

(mean age 46.2 years, 95.3% female). Recurrent

showed a left-dominant nodule with increased peripheral vascularity and smaller

laryngeal nerve injury occurred in 10 patients after CCD and in two patients after

right-sided nodules; FNA was Thy2. The patient opted for a left thyroid

TT. Hypoparathyroidism occurred in 24 patients (20.8% definitive) after CCD

lobectomy; histology showed papillary thyroid carcinoma and subsequent right

and in seven patients (14.3% definitive) after TT. Disease-free survival rates were

thyroidectomy histology also showed papillary micro-carcinoma. 41-year-old

of 84.3% of patients 10 years after CCD, and 88.6% after TT alone.

female presented with T3-thyrotoxicosis with positive thyroglobulin antibodies

Conclusions

and swelling corresponding to the thyroid. ThyUSS showed a right-sided, solid

In our series, it was not possible to establish a statistically significant difference

homogenous nodule and two small left-sided nodules. Repeated ThyUSS over

between groups regarding recurrence of the disease, but a statistically significant

nine months were stable; FNA was Thy2 and Thy1c. Technetium scan showed a

difference regarding surgical complications. According to our results, we consider

right-sided toxic nodule and co-existent cold nodule. Following right hemi-

prophylactic central cervical dissection in papillary carcinomas thyroid not

thyroidectomy histology showed benign follicular adenoma and an incidental

justified.

papillary microadenoma.

DOI: 10.1530/endoabs.49.EP1483

Conclusion

These cases demonstrate that whilst the U- and Thy-Classifications are reassuring

they do not exclude malignancy. This uncertainty should be highlighted to

patients when discussing management of thyroid nodules.

DOI: 10.1530/endoabs.49.EP1485

EP1484

Thyroid cancer frequency over three decades

Cecilia Sanchez-Ragnarsson, Silvia Gonzalez & Edelmiro Menendez-Torre

HUCA, Oviedo, Spain.

Aim

EP1486

To investigate the frequency of thyroid carcinoma and its subtypes in one region

Timing to repeat thyroid fine-needle aspiration after a follicular lesion

over three decades.

of undetermined significance result - does it matter?

Material and methods

Francisco Sousa Santos¹, Cátia Ferrinho¹, Ricardo Capitão¹,

Data retrospectively collected from a tissue bank where all hospitals in a region

João Sequeira Duarte¹, Martinha Chora˜o2, Clotilde Limbert1 &

with a little above 1 million inhabitants should send samples from all operated

Carlos Vasconcelos¹

tumors, from 1981 to 2010.

¹Centro Hospitalar Lisboa Ocidental - Servic¸o de Endocrinologia, Lisbon,

Results

Portugal;²Centro Hospitalar Lisboa Ocidental - Serviço de Anatomia

From 1981 to 1990 there where 156 thyroid cancers; 206 from 1991 through 2000

Patológica, Lisbon, Portugal.

and 362 from 2001 through 2010, with a 132% rise from the first decade to the last

one. Papillary cancer accounted for just 42% in the first decade, rising to 65% in

the 2000s. There was also an absolute 50% rise in follicular cancer incidence,

Introduction

although the relative percentage fell from 40% in the first decade to 26% in the

Regarding thyroid nodules, in case of follicular lesion of undetermined

last one. Medullary cancer incidence rised by 150%, but relative percentage

significance

(FLUS), performing repeat fine-needle aspiration

(FNA) is a

remained stable between 3 and 4%. Frequency of other rare types of thyroid

common follow-up strategy. It has been suggested that a waiting period of at

neoplasms such as anaplastic, lymphoma or squamous carcinoma remained

least 3 months between FNAs would increase the diagnostic yield. Our study aims

stable.

to clarify the optimal time for repeat FNA in case of an initial FLUS result.

Conclusions

Methods

Thyroid carcinoma incidence is rising, mainly due to a rise in papillary

We identified retrospectively all thyroid FNA FLUS results that occurred in our

carcinoma, as previously reported, but we also observed an increased incidence in

institution in 2016 and analysed only the patients who were submitted to repeat

follicular cancer.

FNA. We recorded cytologic diagnosis, time between FNA and histologic results

in case of surgery.

DOI: 10.1530/endoabs.49.EP1484

Results

A total of 79 patients were included, with ages between 34 and 86 years. Mean

nodule diameter was 26.7G11.7 mm. After the second FNA, 8 (10.18%) patients

also underwent a third one. A total of 6 (7.6%) had surgery performed at some

time during follow-up - 2 cases with malignant histology results. The result of the

second FNA was non-diagnostic in 27.8% of cases and remained FLUS in 26.6%.

Mean time interval between the first and second FNA was 3.8G1.4 months. We

EP1485

did not find a statistically significant difference in diagnostic yields (PZ0.267) or

Thyroid nodules: a huge dilemma!

diagnostic non-FLUS results (PZ0.523) between second FNA’s performed 3

Bonnie Grant¹, Bethan Goulden¹, Raj Tanday¹, Edel Casey¹,

months or earlier (36 patients) compared to those preformed later (43 patients).

Antony Pittathankal², Akin Ojo², Imran Syed³ & Khash Nikookam¹

Timing (as well as sex, age and nodule diameter) remained not correlated with

¹Diabetes and Endocrinology Department, Barking Havering and Redbridge

diagnostic yield or diagnostic non-FLUS results after regression analysis using

University Trust, Greater London, UK;²Surgery Department, Barking

time between FNAs as a continuous variable.

Havering and Redbridge University Trust, Greater London, UK;³Radiology

Conclusion

Department, Barking Havering and Redbridge University Trust, Greater

Although our study had limited numbers, its results suggest that in case of a first

London, UK.

FLUS FNA result, and if the decision to repeat is considered by the clinician, the

timing of the second FNA does not seem to affect its diagnostic yield or the

likelihood of another FLUS result.

Current UK guidelines for thyroid nodules advise a thyroid ultrasound (ThyUSS)

with U-Classification with or without Fine Needle Aspiration (FNA) with Thy-

DOI: 10.1530/endoabs.49.EP1486

Classification to determine malignancy risk. We report four cases where thyroid

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Author Index

Aancute, A EP213, EP260

Ackermann, D EP820

Aguiar-Oliveira, MH

Akman, S EP673

& GP34

& OC13.5

EP949 & GP178

Akram, M EP205, EP761,

Aancutei, A EP809

Acosta-Calero, C EP105,

Aguilar, C EP3

EP1092 & EP1225

Abacar, KY EP266

EP170, EP193, EP390,

Aguilar-Diosdado, M EP714,

Aksyonova, E EP670

& EP440

EP530, EP621

EP715 & EP1278

Akturk, M EP1144

Abbas, A EP280 & EP334

& EP757

Aguirre, N EP180

Akyıldız, AB EP266

Abboud, D EP928

Acu, B EP427

Ahbab, S EP86

Akyurek, F EP1167

Abd elbaky, RS EP425

Ada¸, M EP113

Ahern, T EP1169

Al Kadi, H EP292

Abdalaziz, A EP395

Adam, M EP692

Ahlem, B EP762

Al-Attas, O GP77

Abdallah, NB EP87,

Adamczewski, Z EP1325

Ahmadpour, F GP164

& EP263

EP147, EP482, EP832

& EP1435

Ahmed, A EP552

Al-Daghri, N GP46, GP77

EP1232 & EP1233

Adamidou, F GP40, EP68,

Ahmed, AG EP1363

& EP263

Abdallah, RB EP167

EP771, EP827, EP828,

Ahmed, KS EP70 & EP339

Al-Saleh, Y GP46 & EP263

& GP113

EP1303, EP1307,

Ahmed, M EP1150,

Al-Sharefi, A EP89

Abdelkrim, S EP633

EP1417 & EP1471

EP1153 & EP487

& EP1230

Abdelsalam, MM EP1363

Adamska, A EP1104

Ahmed, S GP180

Al-Trawneh, O EP489

& EP497

& EP466

Ahmeti, A EP585

Alaguney, ES EP427

Abderrahmane, SA

Adaramoye, O EP1095

Ahmetov, I GP170

Alaguney, S EP69, EP90

EP219, EP450

Adaway, J EP1169

Ahn, C EP738 & EP1100

& EP264

& EP633

Adebayo, O EP1095

Ahn, CW EP452, EP531,

Alam, M EP534

Abdulkhaliq, A EP652

Adesanoye, O EP1095

GP54 & GP87

Alaminos, MEL EP920

Abduvakhabova, M

Adhikari, P EP692

Ahn, HJ GP162

Alapi, T EP742

EP686, EP1106,

Adomnicai, V EP1209

Ahn, SV EP236

Alarcón, E EP302

EP1186 & EP1187

& EP792

Ai Thu, B GP142

Alba, A EP99

Abe, S EP1029

Adorini, L EP377

Aichler, M OC1.1

Albani, A EP1056

Abell, S EP1115

Adrian, M EP148

Aida, BS EP762

Albert, C EP641

Aberer, F EP609

Af¸ar, ZT EP538

Aires, I EP599

Albert, L EP165 & GP238

Abernethie, A EP802

Afanasyev, D GP86

Aithal, G OC3.5

Albiger, N EP1042

Abeygunasekara, S EP575

Afentoulidi, A EP1202

Ajabnoor, G EP652

Albu, A EP943, EP1137,

Abid, D GP28

& EP859

& EP657

EP1138 & EP1147

Abid, M GP113, EP66,

Afonso, A EP32, EP1323

Ajdzˇanović, V EP359

Albu, AI EP307 & EP947

EP77, EP135, EP167,

& EP1446

Ajdinovic, B EP787

Albu, D EP1138 & EP1147

EP189, EP335, EP667,

Afonso, C EP887

Ajdzanovic, V GP62,

Albuquerque, JL EP841,

EP770, EP1128,

Afshan, K EP1092,

GP202 & EP779

EP899 & EP975

EP1349 & EP1361

EP1225, EP205

Ajmi, S EP355

Alcaide-Torres, J GP71

Abizanda, EP EP862

& EP761

Akın, O EP673

Alcantara-Aragon, V

& GP240

Afzal, N EP761

Akaishi, J EP1385

EP681

Abolaji, A EP1095

Agapito, A EP10, EP133,

Akalin, A EP12, EP244

Aldea, R EP1364

Aboshady, MM EP513

EP181, EP251, EP253,

& EP1033

AlDwairi, A GP88

Abouleka, Y EP1310

EP599, EP1000,

Akarsu, E EP1003

Alefishat, E EP360

Abraitiene, A EP990

EP1006, EP1049,

Akbar, S EP1262

Alegria, S EP996

Abreu, A EP984 & EP1005

EP1062

Akbiyik, F GP212

Alejandro, R OC6.2

Abreu, S GP98

& EP1446

Akcan, E EP1033

Aleknaite, A EP990

Abrosimov, A EP1394

Agate, L EP1414

Akdader-Oudahmane, S

Aleksic, M EP693

Abs, R EP884

Agersø, H GP152

EP1234 & EP6

Alemany, PA GP179

Abuin, J EP755

Aggarwal, R EP661

Akdeniz, CS EP296

Alevizaki, M EP1411

& EP808

Aghajanova, Y EP893

Akdeniz, YS EP1099

& GP230

Abushady, MM EP497

Aghajanova, YM EP422

Akdere, G EP418

Alevras, TM EP76

Abusoglu, S EP1167

Aglony, M OC5.1

Akgul, G EP344

Alexander, B EP1248

& EP419

Agoulnik, A EP754

Akin, S EP1097 & EP1368

Alexandra Ambarus

Ach, K EP441 & EP1389

Agoulnik, I EP754

Akkan, T EP1060,

Popovici, I EP813

Acierno, J GP153

& OC7.5

EP1343, EP1464

Alexandra Gheorghiu, C

Acik, ME EP296

Agrawal, S EP701

& EP186

EP1395

Acikgoz, SB EP1066

Agreda, J EP1030

Akkaya, L EP675

Alexandra Smarandoiu, G

Acikgoz, A EP378

Aguiar, A GP133

Akladious, C EP583

EP137

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Alexandraki, K EP176

Alors-Perez, E GP128

An, JY GP42, EP248,

Anjum, B EP741

& EP1253

Alpagat, G EP937

EP727, EP738 & EP1100

Anna, D EP989

Alexiu, F EP1221

Alpergin, ESS GP172

Ana, A EP1133

Ansaloni, A EP1166

& EP1353

Alqudah, M GP88

Anagnostis, P GP40,

& EP1383

Alfaqih, MA GP63

Alramadan, M EP443,

EP68, EP214, EP827,

Ansari Nawal, E EP309,

Alhambra-Expósito, M-R

EP524 & EP593

EP828, EP1084

EP311 & EP711

EP819 & EP907

Alshboul, O GP88

& EP1471

Ansari, NE EP1334

Alhambra-Expósito, MR

Altay, M EP186, EP1060,

Anagnostou, E GP45,

& EP476

EP500, EP941

EP1343, EP1347

GP230 & EP1411

Anselmo, J EP255

& EP1159

& EP1464

Anandappa, S EP134

& EP596

Ali Tam, A EP1250,

Altieri, B GP22 & EP161

Anastasia, L EP1047

Antal, I EP508

EP1258, EP1376

Altimari, A EP1381

Anastasiou, E GP230

Antic, IB EP177, EP75

& EP1377

Altinboga, A EP1326

Anaya-Torres, FJ EP437

& EP80

Ali, J EP762

Altinboga, AA EP1377

Anchutin, P EP539

Antic, J EP80

Ali, MS GP84

Altinok, A GP96

Andalib, A EP661

Antic, S EP64

Ali, N GP30, EP254,

Altinova, AE EP1144

Andereggen, L EP986

Anton, G EP1176

EP525 & EP1306

Altintas, YE EP834

Anders, H-J EP1027

& EP1180

Ali, S EP1318 & S11.2

Altun, I EP1194

Anders, S S2.2

Antonik, M EP1433

Alibrandi, A GP175,

Altuntas, Y EP109

Andersen, M OC8.3,

Antonini, S EP7

GP208, EP1056

Altunrende, B EP296

GP59, EP63 & GP181

Antonio Vallejo Casas, J

& EP1118

Altunta¸, S EP836

Anderson, C GP58

EP1392

Aliev, P GP92

Álvarez-Escolá, C EP886

Andersson, E GP9

Antun˜ ano, ML EP869

Alieva, D EP1106

Alves, I EP791

Andersson, I-L EP557

Antunes, P GP23, EP82

Alikasifoglu, M GP212

Alves, M EP106, EP706

Anderwald, C-H EP638

& EP772

Alimova, K EP965

& EP707

Andia, V EP1030

Antunes, S EP44

Alisik, M EP429

Alves, MG EP1179

Andjelkovic, M EP484

Antwi, K GP185

Alissa, E EP292

Alviggi, C EP1107

Andoskin, P GP92

Anyfantakis, A EP625

Aljohani, N GP46

Alzoubi, A EP424

Andrés, AL-d EP431

Anyfantakis, D EP625

& EP263

Amado, A GP228, GP229,

Andrés, AV EP1072

Aouiche, S EP629

Alkan, A EP1326

EP350, EP496,

Andrè, V GP130

Apaydın, M EP999

& EP1413

EP1049 & EP1279

Andrada, P EP227

Apaydin, M EP964

Alkebro, C GP117

Amani, B EP1447

Andrade, M OC4.3

& EP1368

Allakhverdieva, Y EP695

Amani, MEA EP1267

& EP807

Apicella, M EP238

Allenbach, G EP1373

& EP1268

Andrade, S EP816

Apostolakis, M GP230

Allende, F OC5.1

Amano, A EP273

Andrade, V EP235

& EP1411

Allinson, K GP27

Amar, L OC7.2, GP2

Andreassen, M GP150

Apostu, L EP1360

Allo, G GP73

& GP15

Andreea Oprea, A EP813

Appenzeller, S GP119

Allouh, M GP88

Amaral de Carvalho, G

Andrei, F EP148

Araújo, A EP1340

Allwood, W OC3.3

EP1244

& EP1371

& EP300

Almacioglu, S EP601

Amaral, A EP255

Andres, R EP986

Araújo, AN EP1255

Almaev, D EP1069

Amaral, C EP30, EP496,

Andrew, R EP802

Araújo, J EP573 & EP548

Almaraz, JH EP91

EP921 & EP1049

Andrey, S EP1248

Aragón-Alonso, A EP708

Almaraz, MC EP868

Amarawardena, WKMG

Androulakis, I OC4.5

& EP717

Almeida, C EP578

EP879

Andrusiewicz, M EP1252

Aragués, JM EP1204

& EP626

Amarilla, V EP1029

& EP1275

Arakelyan, L EP893

Almeida, CFT GP224

Ambroziak, U GP122

Andrysiak-Mamos, E EP230

Aranburu, M EP869

Almeida, JMG EP406

& EP48

Ang, T-L OC11.4

Aranda, G GP24

& EP407

Amel, M EP646 & EP1229

Angela Condorelli, R

Aranda, J EP1218

Almeida, M GP6

Amengual, A EP184

OC13.4

Aranda-Regules, S EP443,

Almeida, R EP350, EP460,

& EP185

Angelo Giagulli, V GP214

EP524 & EP593

EP462, EP496,

Amin, A OC3.5

Angelopoulos, N OC4.5

Arapova, S EP917

EP1049, EP1071

Ammar, M EP66, EP77,

Angelousi, A EP67

Araujo, A EP1012

& EP1080

EP135, EP167, EP770,

& GP236

Araz, M EP1003

Almeida-Coelho, J GP217

EP1128 & EP1349

Angrisani, E EP1064

Arbizu, J GP198

Alokail, M GP77 & EP263

Amer, HM EP425

Anile, C EP997

Arca, M EP397 & EP713

Alonso-Gordoa, T EP784

Amzar, D GP53, EP153,

Anisie, E GP34

Arcano, K EP891

Alors-Pérez, E EP178

EP306 & EP1068

Anisimowicz, S OC7.1

Archambeaud-

& EP472

An, JH EP1451

& GP118

Mouveroux, F GP120

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Ardeleanu, I EP1345

Arteaga, M EP1130

Aulinas, A EP944

Babajko, S GP142

Arefjeva, A GP92

Arteiro, C EP613

Auriemma, RS EP34

Babazono, T EP1014

Arefyeva, I EP1057

Artham, S EP1306

& GP184

Babenko, A GP92

Aretini, P EP348

Artola, YM EP1237

Austgulen, S EP794

Babic, KK EP1161

Argente, J EP435 & EP655

Arutyunova, M EP521

Austin, E EP1259

Baccini, M EP669 & EP671

Arhire, A EP262

Árvai, K EP1434

Avci, CB EP1379

Bacelar, C EP496 & EP887

Arhire, AI EP148

Arvaniti, A GP125

Avdikos, G EP423

Bachar, G EP1374

Ariander, A EP680

Arvat, E GP231

Avilés, AM EP432, EP433

& EP1391

Aribi, Y EP1386

Asanin, M GP197

& EP705

Bacigaluppi, S EP1251

Arici, B EP942

Asghari, G OC5.2, EP662

Awan, Z EP652

Baciu, I EP980 & EP1007

Arif Jadoon, N EP316

& EP642

Ayçiçek, B EP538 & EP1122

Backeljauw, P GS1.4

Arifjanov, I EP15

Ashawesh, K EP453,

Ayala-Cuellar, AP GP144

& GP66

Arikan, IH EP851

EP534, EP597

Aycicek, B EP56

Baculescu, N GP137

Arizanovic, Z EP127

& EP1004

Aydin, C GP233, EP1002,

Bacun, T EP23

& EP42

Ashraff, S EP89, EP1230

EP1250, EP1258,

Badak, B EP69, EP264

Arkan, T EP1066

& EP1398

EP1264, EP1320,

& EP90

Arlt, W OC1.3, OC3.3,

Asik, M EP1099

EP1326, EP1376,

Badak, I EP1316

OC3.5, GP69, GP122,

Asimakopoulou, A

EP1377 & EP1429

Badalyan, M EP304

GP180, EP798,

EP1098

Aydin, F EP884

Badenhoop, K EP5 & GP83

EP1051, EP1150

Askaoui, S EP640

Aydin, H EP440

Badiu, C GP21, EP108,

& EP1153

& EP888

Aydin, K EP289

EP830, EP1046,

Armasu, I EP188, EP792,

Askitis, D EP1378

Aydin, M EP1347

EP1094, EP1176,

EP809, EP1209

Aslan, MS EP1368

Aydinli, E EP1416

EP1180, EP1216,

& EP1360

Asoglu, V EP201, EP271

Aydogan, BI EP1487

EP1220, EP1395

Armbrecht, G EP353

& EP848

Aydogdu, A EP1165

& EP1466

Armignacco, R GP8

Assadi-Porter, F GP172

Aye, M EP83

Bae Kim, W OC14.5

Armstrong, M OC3.5

Assem, M EP1240

Aykut, E EP249

Bae, KH GP56, EP383,

Armstrong, P EP259

Assié, G OC7.2, GP28

Aylwin, S EP985

& EP506

Arnás-León, C EP530

& GP160

Ayoub, MA EP1123

Bae, S-J EP514

Arnés, JAG EP868

Assmann, T GP79, GP94

Aytekin, C EP362

Baek, K-H EP554 & EP690

Arnas-Leon, C EP105,

& EP411

Ayturk, S EP118, EP121,

Baena-Nieto, G EP1174,

EP170, EP193, EP390,

Assmann, TS OC2.1, GP93

EP201, EP271, EP848,

EP1200 & EP1203

EP621 & EP757

& EP457

EP981 EP1198,

Baena-Nieto, M EP535

Arnau-Vives, MJ EP944

Assonitis, N EP67

EP1396, EP1397,

& EP1287

Arnoriaga, M EP1030

Assumpta, C EP641

EP1399, EP1400,

Baena-Nieto, MG EP858

Aronov, D EP598

Assyov, Y EP699

EP1401, EP1402,

& EP915

Aronov, DM EP598

Astaf ’eva, L EP220

EP1403 & EP1404

Baetu, M GP21

Arosa, V EP1332

& EP895

Ayuk, J GP180 & EP1051

Baffoni, C EP268

Arosio, M GP43, EP20,

Astafieva, L EP799

Azad, K EP428

Bagci, B EP675

EP924 & EP1043

Atac, B EP1431

Azal, O EP362 & EP1165

Bagci, G EP675

Arpaci, DK EP282

Ataoglu, E EP86

Azcona-Monreal, I EP619

Bagdonaite, K EP637

Arqués, PB EP183

Atasoy, A EP86

Azevedo, A EP1058

Bagg, W EP1314

Arranz, MTH GP240

Atencia, J EP1030

Azevedo, I EP100

Bagir, GS EP963 & EP969

& EP862

Ates, I EP1061 & EP1347

Azevedo, T EP106

Bahçeci, M EP937

Arranz, S EP1218

Athanaselis, S GP80

Aziz, N EP115

Bahadir, B EP282

Arrieta, AY EP1023

Athanasiou, V EP859

Azizi, F EP1406

Bahia, H EP379

Arrizabalaga, C EP128,

& EP1202

Azizyan, V GP157

& EP488

EP1040 & EP1217

Athanassiou, L EP275

Azkutia, A EP184 & EP185

Bahijri, S EP652 & EP657

Arrizabalaga, JJ EP1332

& EP366

Aznar, PT EP920

Bahlous, A EP482

Arroyo, SQ EP107

Athanassiou, P EP136,

Azoicai, D EP439, EP811

Bahougne, T EP1352

Arsene, AL EP376

EP222, EP275, EP366,

& EP1231

Bahri, M EP743

& EP1137

EP368 & EP1300

Azpiroz, MM EP574,

Baik, SH GP91 & EP1116

Arsenescu-Georgescu, C

Atkinson, M EP926

EP1072 & EP1481

Bailleux, D EP179

EP1345

Atkinson, MJ OC8.1

Azzoug, S EP743

Baitman, T EP1316

Arslan, M EP1097

Atmaca, M EP834

Bajkin, I EP116, EP245,

& EP673

Aubert, S EP1439

EP709, EP1024

Bałdys-Waligorska, A

Arslan, MS EP327

Audi, L EP1090

& EP1089

EP1477

Artas, H EP249

Auernhammer, C EP154

Ba¸aran, MN EP1453

Bajnok, L EP1410

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Bajraktari, G EP585

Baranowski, E OC1.3

Barros, E OC5.1

Bayrasheva, V GP92

Bak, AM EP654

Barbakadze, G EP315

Barros, L EP45

Bazán, AA EP125

Bakar, F EP344

& EP658

Barroso, F EP923

Bazyka, D GP86

Baker, E EP386

Barbano, B EP537

Barrros, R EP30

Bchir, N EP482

Baker, K EP1145

Barbaro, G EP702

Barsiene, L EP164

Bdeoui, N OC11.2

Baki, S EP476

Barber, T EP668

& EP839

Beauchet, A GP189

Bakiner, O EP963 & EP969

Barbier, N EP1015

Bartalena, L EP688,

Beaufaron, J GP148

Baksanskaite, J EP173

Barbieri, AM EP1043

EP691 & S12.2

Beck, J EP986

Bakstyte, V EP173

Barbosa, AP EP1083,

Bartfai, G EP731

Beck, K EP802 & EP822

Bala, C EP560

EP232, EP234

Bartholdi, D GP153

Beck, P EP609

Balaceanu, R EP813

& EP243

Bartonkova, I EP805

Beck-Peccoz, P EP912

& EP961

Barbosa, B EP1029,

Bartoshevich, O EP749

Beckers, A EP928 & OC8.1

Balas, M GP53, EP153,

EP1479 & EP1483

Basaran, Y EP1165

Bęczyk, M EP1433

EP306 & EP1068

Barbosa, D EP1037,

Baser, H EP1264, EP1326,

Bednárová, A EP1173

Balasko, A EP71 & EP81

EP1083, EP1085,

EP1377, EP1413

Bednarczuk, T EP48

Balcere, I EP931

EP243, EP310, EP320,

& EP1429

& MTE7

Baldaia, H EP53

EP95, GP237 & GP239

Baser, OO EP1035,

Bednarek-Tupikowska, G

Baldane, S GP96, EP256,

Barbosa, R EP1465

EP1317, EP1329,

GP165

EP419, EP421,

Barbot, M EP1042

EP1425 & EP287

Beer, S EP597

EP1101, EP1167

Barbu, C EP1048,

Bashir, M EP160

Begolli, L EP585

& EP1214

EP1371, EP215,

Basile, V EP26 & GP123

Beguin, Y EP883

Baldari, S EP1443

EP262 & EP943

Basinski, P EP1282

Behan, L-A EP1150,

Baldeiras, I EP704

Barbu, CG EP1137, EP148

Baskal, N EP967

EP1153, EP487,

Baldeweg, SE EP1075

& EP947

Basker, K GP125

EP572 & EP70

Baldweg, S EP985

Barcala, J EP1278

Baslund, B EP40

Bejinariu, E EP272

Baleanu, F EP225

Barcin, C EP362

Basmaz, SE EP109

Bekaert, M EP1191

Balin, M EP249

Barenholz-Goultschin, O

& EP836

Bel Pen˜ a, N EP401

Balkan, MB EP265

EP624 & OC4.1

Basolo, F EP1414

Belaid, R EP1232,

Balla, A EP804

Bárez-López, S GP217

Bassetti, M GP27

EP1233, EP147

Balla, B GP37, EP1384

Bargi-Souza, P EP716

Bassi, I OC8.2

& EP87

& EP1434

& GP224

Basta-Kaim, A GP158

Belaya, J EP1069

Ballano, DA EP920

Bargiota, A EP483,

Bastos, J EP1459

Belaya, Z EP1028,

Ballarino, C EP385

EP559, EP618, EP861

Bastos, M EP887

EP1034, EP220,

Bally, M EP942

& EP864

Bastyr, MP EP733

EP345, EP346

Balsa, A EP428

Bari, FD EP1118

Batagelj, E EP385

& EP881

Balsa, AM EP106

Barka, I EP1389, EP1472

Batchelor, JM EP1192

Belceanu, A EP792

Baltzinger, P EP1352

& EP441

Bates, A EP1259

Belceanu, AD EP1073,

Bampilis, A EP1008

Barkan, A EP1039

Bathelt, C OC9.2

EP1076 & EP1360

& EP38

Barmpa, E EP559

Bathon, K GP1, GP28 & GP5

Belgundi, P EP1140

Banakh, I EP426

Barna, S EP1410

Batista, L GP213

Belis, C EP1202

Bancos, I GP122 & GP3

Barnaeva, E EP754

Batista, R EP1449

& EP859

Bandurska-Stankiewicz, E

Barnes, E OC3.5

& OC14.3

Bellarbi, D EP1315

EP17

Barnett, J EP1433

Batman, A EP109

Bellastella, G EP1121

Banerjee, R EP254,

Baron, F EP883

& EP836

& EP1293

EP272, EP525

Barrasso, M EP1121

Battaglia, C EP370

Belle, EV OC5.3

& EP732

Barreiros, E EP1049,

Baudin, E EP179, GP123

Bellevicine, C EP1407

Banfi, G EP653 & EP777

EP896, EP897, EP898

& OC7.2

Bellis, AD EP1121

Banik, S EP343

& EP974

Baudrand, R OC5.1

Bello, C EP1088, EP1177,

Banisauskaite, I EP173

Barreiros, L EP1049,

Baudry, C EP1472

EP1207, EP1311,

Bankovic, J EP166

EP896, EP897, EP898

Bauer, A GP79

EP1452 & EP414

Baptista, C EP175, EP392

& EP974

Bauer, AC GP93

Bello, CT EP258 & EP951

& EP1475

Barrera Martín, A EP1392

Bautista, C EP302

Bellusci, L GP223

Baptista, L EP723

Barrera-Martín, A EP159,

& EP341

Belo, C EP57

Bar, J EP1185 & EP405

EP776, EP819, EP907

Bavykina, L EP1457

Belo, F EP1009

Barabash, N EP983

& EP941

Bayburdyan, G EP893

Belo, G EP1330

Baranda, C EP952

Barreto, F EP235

Bayburdyan, GM EP422

Belo, S EP1079, EP194,

Baranowska, B EP908

Barrios, V EP435 & EP655

Bayraktarli, RY EP113

EP477, EP493, EP564,

Baranowska-Bik, A EP908

Barroca, H GP227

Bayraktaroglu, T EP282

EP576 & EP719

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Belousov, I EP1164

Berthon, A OC1.2

Bilen, A EP261

Bodart, G EP883

Belousova, L EP978

Bertolucci, C EP789

Bilen, H EP261

Bodis, B EP1410

Belska, L EP622

Besenyi, Z EP1388

Bilezikian, JP GP47

Bodnar, P EP1146, EP622

Belyavskaya, E EP13

Beshyah, S EP28

Bilgen, OF EP752

& GP60

& GP68

Bestepe, N EP1152,

Bilgen, S EP752

Body, J EP225

Ben Abdelkrim, A EP1389

EP1377, EP1429,

Bilgic, B OC12.1

Boemi, I OC7.4

Ben Hamou, A EP1439

EP331, EP843

Bilginer, C EP1429

Bogalho, P EP10, EP181,

Ben Slimene, F EP1290

& EP856

& EP843

EP253 & EP599

Benítez, IC EP769

Betivoiu, M EP943

Bilginer, MC EP1264

Bogavac, T EP1114,

Benbassat, C EP1374,

Betivoiu, MA EP947

& EP1376

EP166, EP177, EP191,

EP1391 & EP199

Betsi, G EP1008 & EP38

Bilha, SC GP34

EP75, EP80 & GP139

Benbassat, CA EP1313

Bettaieb, J EP207

Bilic-Curcic, I EP23

Bogazzi, F EP970

Bendacha, Y OC11.2

Bettany, E EP103

Bilir, B EP446 & EP842

Bogdanet, D EP70

Benecke, A GP15 & GP2

Bettencourt-Silva, R

Biller, B EP1010 & GP192

Bogdanova, S GP170

Benedict, C S28.1

EP477, EP564, EP576,

Biller, BMK EP1015 & GP187

Bogner, E-M OC8.1

Benedini, S OC6.2

EP630, EP719, EP773

Billig, H EP1096

Boguszewski, C EP1013,

Benli, AR EP1228

& EP872

Bilora, F EP1042

EP1029, EP235

Bennet, A GP7

Bettikher, O EP485

Bilovol, O EP489 & OC2.2

& GP187

Benomar, K EP1439

Betz, M OC9.2

Bima, C EP991 & EP997

Boj-Carceller, D EP619

& OC5.3

Beun, J N2.3

Bin-Nabhan, AS EP513

Bokal, EV EP1105

Bensing, S GP9

Beuschlein, F EP20, EP52,

Binart, N S3.1

Bolanowski, M EP1135,

Benslimene, MF EP1427

GP1, GP122, GP123,

Biondo, C EP1029

GP165, GP72 & S8.3

Bento, J EP100

GP160, GP5, OC7.2

Birgisson, G EP19 & EP21

Bollerslev, J GP155, GP181

Benvenga, S EP1118

& S30.3

Biscarini, F EP1342

& OC8.3

& EP1171

Bevan, C OC3.2

Bisogno, F EP1064

Bolotko, Y GP78

Berdal, A GP142

Bevan, JS GP191

Bitri, S EP1470

Bolt, JW EP155

Berea, HO EP365

Béu, G EP490 & EP492

Bjorkman-Burtscher, I

Bondarenko, I EP659

Beregova, T GP60

Bex, M GP187

EP1070 & GP182

& EP685

Berends, MA EP155

Beyan, E EP1060 & EP186

Bjarne Christiansen, O

Bone, HG GP47

Beretta, E GP130

Bhagwat, N EP844

OC13.2

Bonea, M EP215

Berg, Gvd EP1045

Bhardwaj, C EP1277

Bjekic-Macut, J EP1114,

Bongiovanni, M EP1373

Bergamim, A EP794

& EP526

GP139 & GP140

Boniakos, A OC4.5

Bergant, D EP1445

Bhudia, J EP525

Blánquez Martínez, D

Bonne, G OC5.3

Berger, M GP90

Biagetti, B EP944

EP581

Bonner, C EP103 & EP58

Berges-Raso, I GP238

Bialas, P EP1252

Black, D D3.2

Bonneville, JF S8.2

Berinder, K GP9

Bianchi, A EP991, EP997

Black, K EP592

Bonomi, M OC8.2 & OC9.5

Berker, D EP1035,

& OC12.5

Blanchard, A GP19

Bonora, E S29.3

EP1317, EP1329,

Bianco, A S6.1

Blanco-Acevedo, C EP929

Bontea, VF EP399

EP1425, EP1453,

Bianconi, E EP688

Blaschke, M EP353

Borai, A EP652 & EP657

EP287, EP538, EP56,

& EP691

Blasio, C GP184

Boran, G EP1150,

EP589, EP810

Bicer, B EP131

Blazekovic, A EP595

EP1153, EP487,

& EP977

Bicer, C EP1347 & EP429

Bleicher, L OC4.3

EP572 & EP70

Berlik, H EP362

Bicho, M EP1083, EP232,

Bliddal, S OC13.2

Borba, V EP235 & EP79

Bernaczyk, P OC7.1

EP234, EP243, EP562,

Bloom, S GP131

Bordogna, P GP43

Bernal, MDF EP708

EP632 & OC5.4

Bloomer, L EP534

Borges, F EP1049,

& EP717

Biczysko, M EP1275

Boama, V EP597

EP1279, EP1479,

Bernarde, K EP142

Bidlingmaier, M EP639

Bobillo, J EP1331

EP1483, EP496,

Bernardes, I EP1077

& GP196

Boboridis, K EP827

EP921, GP228

& EP1078

Biebermann, H OC2.3

& EP828

& GP229

Bernardi, S GP204

Biehl, M OC1.3 & OC3.5

Bobos, M EP1471

Borges, T EP818, EP887,

Berruti, A GP231

Bielecka, A EP826

Bobronnikova, L EP489

EP899, EP923

Bertagna, F OC10.3

Bielik, J EP1344 & EP734

& OC2.2

& EP975

Bertagna, X EP1015

Bielohuby, M GP105

Bobrov, A EP1069

Bornikowska, K EP469

Bertelli, E EP922

Bihan, H EP1472

Boccard, J EP782

Bornstein, S S20.2

Berthaut, I GP148

Bik, W EP908

Bocheva, Y EP1271

Borovecki, F EP595

Bertherat, J EP20, GP12,

Bilbao, I EP869

Bochud, M EP820

Borowczyk, M EP1433

GP120, GP13, GP160,

Bilem, O EP1099

& OC13.5

& EP1450

GP28, GP5 & OC7.2

Bilem, Y EP1099

Bock, O EP353

Borozan, S EP857

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Borresen, SW EP40

Brøndstad, I EP59

Brouze, M OC7.1

Burlacu, MC EP1342

Borretta, G EP268

Bruning, J GP105

Brovkina, O EP220

Burlacu, NP EP1137

Borsari, S EP278 & EP348

Brabant, G EP800

Brucker-Davis, F GP120

Burman, P GP9 & OC12.2

Borson-Chazot, F EP966,

& GP183

Bruckert, E GP189

Burnadze, K EP315

GP177 & S14.2

Bracaccia, ME EP991

Brue, T GP192

& EP658

Boscaro, M EP1042,

Bradnová, O EP1143

Brunner, B GP105

Burnier, M EP820 & OC13.5

GP123 & GP3

Bragança, G EP887

Bruno, C EP1260

Bursuc, A EP1073,

Boskovic, O EP1283

Braham, A EP355

Brutskaya-

EP1076, EP1209,

& EP857

Brailly-Tabard, S GP148

Stempkovskaya, E

EP1360 & EP188

Bossowski, A EP1046

& GP19

EP269, EP286, EP312,

Buruiana, A EP117

& EP1226

Braithwaite, V S5.2

EP480 & EP737

Burulday, V EP529

Bost, F EP745

Brakni, L EP1386,

Bryngelsson, I-L GP9

Burumkulova, F EP50

Botelho de Sousa, A EP133

EP1423, EP1482,

Brzozowska, M EP577

Busquets, J EP150

Botella, S EP227

EP219, EP450

Buades-Rotger, M EP800

Buta, M EP1480 & GP225

Botezatu, A EP1176,

& EP633

Bubnoa, M EP598

Butaru, M EP1068

EP1180 & EP1216

Bram, Z GP12

Bubnova, MG EP598

Butz, H GP3

Botfield, H EP798

Brancatella, A EP238

Buchfelder, M GP192

Buyruk, A EP1444

Bothou, C OC4.5

& EP274

& S13.3

Buyruk, BA EP110,

Botling, J GP194

Branco, CC EP567

Bucur, M EP1048

EP1444 & EP69

Botoula, E EP1047

Branco, SC EP519

Budek, A EP283

Buyukkaragoz, B EP815

Botti, G EP1407

Brandi, M-L S22.1

Budianu, O EP1371

Buzas, EI GP3

Bottici, V EP1414

Brandi, ML GP33

Budziszewska, B GP154

Buzduga, C EP961 & GP34

Bouc¸as, AP EP457 & GP94

Branisteanu, D EP213,

Budzynska-Nosal, R

Buziak-Bereza, M EP1477

Bouc, YL GP19

EP260, EP838, EP961

EP1372

& EP283

Boucelma, F EP633

& GP34

Buey, GG EP227 & GP198

Byrne, J GP180

Bouchard, P GP148

Branisteanu, DD EP252

Bugalho, MJ EP1037,

Byrne, MM EP1318

& MTE10

Brasoveanu, D EP1221

EP1083, EP1085,

Boudiba, A EP629

Brassil, C EP720

EP119, EP1204,

Cabac, M EP1076

Boudina, M EP1473

Bravenboer, B GP41

EP1255, EP1269,

Cabanelas, C EP723

Boudouvi, E EP885

Bray, BFG EP862 & GP240

EP1340, EP1387,

Cacic, M EP43

Bouillon, R S27.3

Braycotton, L EP409

EP1448, EP157,

C´aćić,M EP172

Bouizammarne, I EP847

Brdar, D EP1469

EP174, EP243, EP300,

C´aćić P EP463 & EP549

Bouligand, J GP45 & GP7

Breault, D OC1.2

EP320, EP896, EP897,

C´aćićM EP463 & EP549

Boulkroun, S GP15 & GP2

Breen, N EP295

EP898, EP95, EP974,

Cáceres, LD EP574

Boulmarka, I EP450

Brehar, A EP206

GP226, GP237

Cadirci, K EP478, EP566,

Boulo, T EP1123

Brenda, VB EP74

& GP239

EP710 & EP873

Bouloux, P EP985

Bresciani, G EP196

Bukowski, S GP41

Caeiro, C EP773

Bourcigaux, N GP148

& EP197

Bula, G EP349

Caetano, J EP1227

Bourdeau, I GP123

Brezean, I EP16

Bulbul, BY EP118,

Cagiltay, E EP1455

Bourko, I EP1308

Brianso-Llort, L EP753

EP1198, EP121,

Cagir, BB EP1060

Bourko, O EP1308

Briet, C GP143

EP1399, EP1400,

Cagir, Y EP1060

Boury, S EP1369

Brigante, G EP1383

EP1401, EP1402,

Cagliani, R GP77

Boutzios, G EP1253,

& GP245

EP1403, EP201,

Caiazzo, R EP1439

EP176 & GP80

Briganti, S OC6.2

EP271, EP848

Cailleux, A GP177

Bouvier, C EP192 & EP746

Bright, GM GP65 & GP66

& EP981

Caimari, F EP1075

Bouzid, A EP246 & EP381

Briner, M EP1087

Bulusu, R GP27

Caixàs, A EP165 & GP238

Bouznad, N EP1350

Brismar, K EP557

Bulbul, BY EP1404

Cakal, E EP1060, EP1097,

Boyle, J EP747

Brito, M EP451

Bumbu, A EP1310

EP1368, EP327

Boysan, SN EP296

Britvin, T EP126, EP1457

Bunte, K OC1.3

& EP999

Bozek, T EP1161 & EP595

& EP50

Buranasupkajorn, P

Cakir, B EP1002, EP1152,

Bozhinovska, N EP285

Brom, Rvd EP1045

EP1288

EP1258, EP1264,

Bozic Antic, I EP191

Bromin´ ska, B EP1433

Burbridge, W EP409

EP1320, EP1326,

Bozic-Antic, I EP1114,

Brondani, L GP94

Burcak Polat, S EP1152

EP1377, EP1413,

EP166, GP139

Brondani, LA EP457,

& GP49

EP1429, EP237,

& GP140

GP90 & OC2.5

Burcea, I EP1007

EP331, EP843, EP856,

Bozkirli, E EP963 & EP969

Bronstein, M EP1039

Burekovic, A EP976

GP233 & GP49

Bozkurt, N EP384

Broutin, S EP179

Burggraf, M EP747

C¸ akir, A EP101

Bozkus, Y EP39

Brouwers, AH EP155

Burgos-Ramos, E EP655

Cakir, E EP86

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Cakir, SD EP109 & EP836

EP1401, EP1402,

Caragheorgheopol, A

Carvalho, A EP1279,

Caklili, OT EP447

EP1403, EP1404,

EP1007, EP1018,

EP1479, EP1483,

Cakmak, GK EP282

EP271 & EP981

EP1063, EP1216,

EP496 & GP228

Calıskan, M EP327

Canale, D EP274

EP1220, EP137,

Carvalho, B EP1077

Calan˜ as-Continente, A

Canani, L EP411

EP1466, EP206,

Carvalho, D EP1058,

EP776

Canani, LH GP93, GP94

EP240, EP817

EP1077, EP1078,

Calabrò, V GP204

& OC2.1

& EP911

EP1079, EP1081,

Calabretto, M GP168

Canaz, F EP69 & EP90

Caragheorghopol, A EP16

EP1181, EP1206,

Calafell, MA EP1023

Candan, F EP675

Carceller, DB EP920

EP1289, EP1357,

Calanchini, M EP1145

Candeias, N EP1446

Cardinale, S EP60

EP140, EP169, EP194,

& GP138

Candel, M EP1415

Cardoso, C EP632

EP195, EP305, EP477,

Calatayud, M EP1044

Cander, S EP1017, EP102,

Cardoso, H EP818, EP921

EP493, EP53, EP54,

Caldara, R OC6.2

EP131, EP132,

& EP923

EP564, EP576, EP613,

Calderón-Vicente, D

EP1335, EP332,

Cardoso, I EP841, EP899

EP630, EP719, EP773,

EP443, EP524

EP333, EP336, EP601,

& EP975

EP870, EP871, EP872,

& EP593

EP608, EP679, EP72

Cardoso, L EP392

GP199 & GP217

Calebiro, D GP1, GP28,

& EP852

Cardoso, MH EP146

Carvalho, I EP486

GP5 & OC4.4

Candido, DFF EP389

& EP496

Carvalho, IP EP1454

Calejo, L EP1155

Canelles, S EP435

Cardoso, R EP1227

Carvalho, L GP18

Calejo, M EP567

& EP655

& GP109

Carvalho, M EP1465

Calero, CA EP107

Canlar, S¸ EP277

Cardoso, S EP807 & EP84

Carvalho, MR EP1340,

Calhau, C EP403

Canlar, S EP1059, EP1487

Cardoso, SC OC4.3

EP1454, EP157,

Calhaz-Jorge, C GP133

& EP967

Cardoso, T EP841

EP300, EP896, EP897,

Calle-Pascual, A EP900

Cannarella, R EP1163

Cardot-Bauters, C GP120

EP898 & EP974

Calle-Pascual, AL GP179

& OC13.4

Caric, B EP168

Carvalho, R EP119,

Calleja, A EP227

Cannavò, S GP175

& EP767

EP1387, EP921

Calles, L EP1040 & EP112

Cannavo, S EP1056

Cariou, B S16.1

& GP226

Calles, LA EP1217

& EP26

Carlessi, R GP94

Casa, SD EP161

Callewaert, B EP812

Cano, A EP165 & GP238

Carlioglu, A EP1108,

Casadio, E EP669 & EP671

Calmarza-Calmarza, P

Canpolat, A EP967

EP1113, EP429,

Casals, G GP24

EP619

Canpolat, AG EP1059,

EP529 & EP873

Casamitjana, L EP165

Calogero, AE EP1163,

EP1199 & EP277

Carlos, C EP1133

& EP641

EP35 & GP127

Canpolat, IP EP296

Carmina, E D4.2

Casanova, ME EP1005

Caltık Yılmaz, A EP815

Cansu, GB EP1375

Carmona, S EP1298

Casar-Borota, O GP155

Camacho-Hubner, C

& EP244

& EP1422

& GP194

EP748, EP884, GP192

Cantante, H EP1323

Carnaghi, C OC7.4

Casares, MLdlT EP581

& OC8.4

& EP32

Carnaille, B EP1369

Casarini, L EP1107,

Camargo, A EP472

Cantinho, G EP1269

Carnovali, M EP653

EP1112, EP1123,

Camargo, JL OC2.5

Cantini, G GP8

Caro, AC EP544

EP1131 & GP245

Camilo Fernandes, A

Cantoni, G EP1408

Caron, P GP191 & GP7

Casciano, O EP1121

EP791

Cantrell, D EP1313

Carra, S EP1222

& EP1293

Camozzi, V GP33

Canu, L EP92, EP93, GP25

Carracedo, A EP725

Casey, E EP103, EP1213,

Campana, C OC14.1

& GP8

Carrano, M EP1064

EP1354, EP1485,

Campennı`, A EP1443

Cap, J EP1197 & EP837

Carrasco, A EP636

EP308, EP58 & GP115

Campigotto, F GP187

Capatina, C EP911

& GP132

Casey, R GP27

Campino, C OC5.1

Capel, I EP165 & GP238

Carrasco, R EP1331

Casini, G EP1247

Campos, A EP460, EP462

Capita˜ o, R EP1088,

Carrasco-Valiente, J EP790

Cassar, S EP747

& EP904

EP1177, EP1207,

Carrilho, F EP1009,

Cassatella, D GP153

Campos, S EP180

EP1311, EP1330,

EP1195, EP1475,

Cassiolato, JLB EP380

& OC10.2

EP1452, EP1486,

EP175, EP203, EP392,

Castan˜ o, J-P EP182

Campos, VC EP949

EP414 & GP222

EP394, EP44, EP444,

& EP819

& GP178

Cappabianca, P EP927

EP445, EP45, EP61,

Castan˜ o, JP EP178,

Camur, B EP1400

Cappellani, D EP274

EP922, GP35 & OC14.3

EP472, EP698, EP790,

Camussi, G OC11.1

& EP970

Carroll, P EP985

EP929, GP128 & S3.3

Can, B EP1317

Capraro, J EP18

Carsote, M EP117

Castan˜ o, O EP1005

Can, N EP1198, EP121,

Capraru, O EP1456

& EP846

& EP984

EP1396, EP1397,

Car, N EP585

Carujo, A EP1289

Castan˜ o-Fuentes, JP

EP1399, EP1400,

Cara, J EP884 & OC8.4

Carvajal, C OC5.1

EP941

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Castan˜ o-León, AM

Ceccato, F EP1042

Chambidis, V EP1303,

Chianetta, R GP108

EP1044

Celebi Tayfur, A EP815

EP1307 & EP1417

Chiara Zatelli, M EP196,

Castanheira, J EP1422

C¸ elik, A EP440

Chambidou, E EP1303

EP197 & EP789

Castedo, J EP1181

Celik, C EP1101

Chambo, JL GP6

Chiellini, G GP172

Castedo, JL EP1077,

Celik, E EP118, EP1404

Chamera, K GP158

& GP223

EP1078, EP630 & EP870

& EP848

Champion, B EP1265

Chihaoui, M EP1193,

Castela, A EP490 & EP492

Celik, H EP1327

Chander Wasoori, S

EP1201, EP1208,

Castellano, E EP268

Celik, M EP118, EP1198,

EP1277

EP1212, EP1322,

& GP33

EP121, EP1396,

Chang, Cy GP63

EP1324, EP1328,

Castellino, G GP108

EP1397, EP1399,

Chang, HB EP700

EP207, EP340

Castelo-Branco, M EP704

EP1400, EP1401,

Chanson, P GP189

& EP570

Castro Oliveira, S EP1289,

EP1402, EP1403,

& GP19

Chikalova, I GP86

EP194 & EP195

EP1404, EP201,

Chantzichristos, D EP55

Chikhrouhou, N EP441

Castro, AMG EP406

EP271, EP848

& GP9

Child, T EP1145

& EP407

& EP981

Chapurlat, R S22.3

Chiloiro, S EP991, EP997

Castro, C EP1058 & EP146

Celiker, D EP1343

Charazac, A EP745

& OC12.5

Castro, JJ EP139

Celikmen, M EP1281

Charfi, N EP1128,

China, D EP1079

Castro, JJd EP1359

Cellai, I EP377

EP1349, EP167,

Chini, M EP239

Castro, M EP7

& GP147

EP189, EP335 & EP77

Chiodini, I EP1043, EP20

Castro, MA EP948

Cenci, V EP60

Charles-Obi, D EP525

& GP33

Castro, R EP1177, EP329,

Cenik, F EP1327

Charlton, C EP728

Chiofalo, MG EP1407

GP228 & GP229

Can˜ izo-Gómez, FJd EP431

Charlton, RW GP65

Chiotinis, N EP1098

Castro-Correia, C EP403

Centanni, M EP825

& GP66

Chira, RI EP114

& GP227

& GP221

Charneco, MQ EP581

Chiriac, A EP1231

Castro-Feijóo, L EP725

Centeno, RG EP1030

Chatterjee, K GP27

& EP811

Catak, M EP1317,

Cepero, D GP111

Chatzi, A EP588

Chiriac, AE EP1231,

EP1329, EP287

Cerina, V EP43

Chatzipanagiotou, S

EP439 & EP811

& EP589

Cerovic, S EP787

EP417, EP442

Chiriac, IA EP1221

Catalano, R EP20

Cerqueira, L EP1000

& EP509

& EP1419

Catapono, A S16.3

& EP1062

Chatzistergiou, V EP1084

Chisalita, SI OC6.4

Catarino, A GP242

Cerqueira, ML GP224

Chavda, S GP180

Chiti, A GP231

Catarino, AL EP174

Certo, R GP208

Chaves, C EP596 & OC5.4

Chlebus, M EP577

Catarino, D EP1195,

Cerveira, F EP1330

Chaves, YD EP365

Cho, D-H EP438 & EP514

EP1475, EP444

Cesario, F EP268

Chee, D EP494

Cho, HA EP590

& EP445

César, R EP255 & EP596

Chefu, S GP92

Cho, NH GP56

Catheline, JM OC11.2

Cetani, F EP278, EP288,

Cheikh, C EP616

Cho, Y-W EP516

Cátia, R EP1133

EP348 & GP33

Cheikhrouhou, N EP1290,

Chochishvili, N EP650

Catalán IP GP48

Cetin, K EP289

EP1427, EP1428

Choi, E EP236

Caune, O EP931

Cetin, Z EP1317, EP1329

& EP1430

Choi, HS GP207

Caux, F EP1472

& EP1425

Chekanova, A EP50

Choi, J EP1256 & EP960

Cavaco, B GP126 & GP23

Cetinkaya, G EP968

Chen, G GP171

Choi, K-C EP1109,

Cavadas, B EP1449

C¸ etinkaya, S EP1241

Chen, K EP1263

EP1189, EP151,

Cavalcante, I GP6

Chabbert, M GP143

Chen, M-J OC14.2 & OC4.2

EP739 & GP144

Cavallo, LM EP927

Chabre, O GP12, GP120

Chen, P-L EP1319

Choi, KM GP91

Cavicchi, O EP1381

& OC7.2

Chen, Y-T EP1319

Choi, YK EP383, EP506

Cavun, S GP112 & GP161

Chae, YS EP1451

& EP551

& GP56

Cayón-Blanco, M EP1174,

Chafer-Vilaplana, J EP900

Chenegreha, M EP450

Choi, YM EP1421

EP1200, EP1203,

Chagunava, K EP647

Cheng, S-P OC14.2

& EP517

EP290, EP372, EP374,

Chaieb, M EP1389

Chentli, F EP1267

Chong, LT OC6.4

EP610, EP611, EP612,

& EP441

& EP1268

Chora˜ o, M EP1486

EP858 & EP915

Chaker, F EP1193,

Cherebillo, V EP978

Chortis, V GP122 & S30.2

Cay-Melero, S EP619

EP1201, EP1208,

Chernenkov, Y EP1224

Chou, C GP129

Cayon-Blanco, M EP1287

EP1322, EP1324,

Chertko, E EP286

Choulia, M EP1296

& EP535

EP1328, EP207,

Chevalier, N EP745

Chow, B EP916

Cazares, J OC6.5

EP340 & EP570

Chew, SL EP985

Chow, BKC EP894

Ceausu, RA EP935

Chalasani, S EP592

Cheyne, E EP85

Chowen, JA EP655

Ceccarini, G EP238

Challa, A EP299

Chi, H-C GP64

Chrapek, M EP1382

& EP397

Challis, B GP27

Chi, Y-T EP1319

Christ, E EP986 & GP185

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Christ-Crain, M EP687,

Claessens, F S11.3

EP1073, EP1076,

Costache Outas, M EP817

EP889, EP918, EP942,

Clara, JG OC5.4

EP1209 & EP1345

Costantini, D EP702

OC11.3 & OC9.2

Clark, J EP124

Conzo, G EP1407

Coudenys, E GP41

Christensen, LL GP59

Clarke, BL EP291 & GP47

Corapcioglu, D EP1059,

Coutant, R GP143

Christin-Maitre, S GP148

Clarke, I GP135

EP1273, EP277,

Couto, J EP1459

Christou, M EP1172

Clarke, S GP131

EP967 & EP988

& EP1463

Christou, P EP1172

Claro, I EP174

Corbett, R EP386

Covelli, D EP1342

Chronopoulou, G EP1098

Clavel, S EP745

Corbetta, S GP130 & GP33

Coves, M8J OC12.3

Chrousos, G GP46

Clemente, H EP392

Corbin, CJ EP1190

Covic, A GP34

Chrusciel, M GP118

C¸ akir, a EP101

Corcetto, F GP147

Cowley, M EP373

& OC7.1

Clerici, M GP77

Corcoy, R EP586

Cox, R EP730

Chrysoulaki, M GP32

Clu-Fernández, C GP71

Cordan, I EP545

Cozzolino, A EP1050

Chrysoulidou, A EP1473

Coín-Araguez, L GP71

Cordeiro, J EP1143

& EP1056

Chudecka, A GP190

Co¸kun, M EP1405

Cordeiro, MC EP1298,

Cranston, T OC10.5

Chudek, J EP726

Cobbold, J EP682 & GP138

EP226 & EP996

Crespo, I GP36

Chula, D EP235

Cobzac, G EP328

Cordeu, MPdC EP1023

Crespo-Hernández, I

Chung, CH EP236

Codella, R OC6.2

Cordido, F EP891

EP900

Chung, DJ EP554

Cody, D EP696

Cordova, RSM EP581

Crisan, D EP114

Chung, JH EP1424

Coelho, MJ EP1449

Coremans, P EP393

Crisosto, N EP1120

& OC9.4

Coelho, P GP200

Corlan, AS EP935

Crisostomo, T EP216

Chuvashova, M EP1266

Coelho, R EP613

Cormack, AM GS2.2

Crispim, D EP411, EP457,

Cianferotti, L GP33

Coelho, TH GP227

Corneci, C EP1220

EP648, GP79, GP90,

Cianflone, K EP701

Coeli-Lacchini, F EP7

& EP1395

GP93, GP94 & OC2.1

Cianga, P GP34

Cohen, R EP616 & OC11.2

Cornejo-Pareja, I EP614

Crista, C EP945

Ciccantelli, B EP713

Colao, A EP1056, EP1407,

Cornejo-Pareja, IM GP71

Cristani, M GP208

Cicciarella, F GP123

EP34, EP786, EP839,

Cornianu, M EP153

Cristea, C EP961

Cid, M GP242

GP184 & OC9.5

& EP306

Cristina Staicu, D EP1157

Cid, O EP1390

Coles, T EP1263

Corno, C GP147

Crock, P GP176

Cifci, A EP1280, EP529,

Colet, AM EP76

Corona, M GP238

Crowley, R EP259

EP604 & EP683

Colita, A EP763

Corone, C GP148

& EP430

Cima, L EP148, EP262

Colkesen, F GP96

Correia, CC EP512

Crujeiras, AB NSA6

& EP855

Collombat, P S20.3

Correia, F EP313

Crumpei, F EP188

Cima, LN EP763

Collongues, N EP1352

Corsello, SM EP1341

& EP792

Cimino, L EP35

Colombo, C EP1408

& EP1426

Crumpei, I EP1073,

Cimpean, A EP935

& EP1432

Cortes, SN EP76

EP1076, EP1209,

C¸ inar, B EP101

Colpo, A EP927

Cortez, L EP1006,

EP1360, EP792

Cinel, M EP967 & EP988

Colucci, G EP1342

EP1049, EP1062

& EP809

Ciobanu, D EP188

Combarnous, Y EP1123

& EP1446

Cruz, I EP794

Cipri, C GP33

Comeglio, P EP377

Cosar, R EP1280

Cruzado-Begines, C EP535

Cipriani, S EP370

& GP147

Cosma, DT EP398, EP399

Cuéllar, EA EP298

Circo, E EP1301, EP1302

Comenda, E EP1323

& EP400

& EP623

& EP1304

& EP32

Cosma, DT EP114, EP158

Cuatrecasas, G OC12.3

Circo, R EP1301

Comite, P OC14.1

& EP328

Cucinotta, D EP1118

& EP1304

Comninos, A GP131

Costa, A EP1279

Cucu, A-P EP1132

Cirello, V EP1432

Conaglen, H EP1312

Costa, C EP100, EP1012,

Cudal, I EP216

Ciresi, A EP1056

Conaglen, J EP1312

EP1021, EP1255,

Cudlip, S GP180

Ciric, J EP111 & EP1261

Conceiça˜ o, F EP794

GP213 & GP222

Cuellar, L EP603

Ciric, V EP64

Conceiça˜ o, I EP1204

Costa, D EP1422

Cuesta-Hernández, M

Cirkovic, V EP1184

Conde, JB EP725

Costa, G EP1461, EP1475,

EP900

Cirla, A EP206

Condorelli, RA EP1163,

EP198, EP203

Cuhaci, FN EP1326

Ciubotaru, V EP1063

EP35 & GP127

& OC14.3

& EP1377

& EP1073

Conley, A EP1190

Costa, HS EP562

Cuhaci, N EP1429

Ciudin, A EP944

Connell, JM GP58

Costa, J EP1323 & EP32

Cuixart, G EP586

Ciurea, A EP158 & EP328

Conry, B EP134

Costa, MM EP1077,

Cullen, D EP295

Civita, P EP348

Constantinescu, A EP1073

EP1078, EP1181,

Cuneyt Bilginer, M

Cláudia , A EP253

& EP1076

EP630, EP719, EP870,

EP1258

Claahsen-van der Grinten,

Constantinescu, D GP34

EP871, GP18 & GP227

Cunha, AL EP100

H GP10

Constantinescu, G

Costa, UMM GP178

Cunha, C EP1390 & GP199

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Cunha, F EP305

da Costa, M EP1479

Das, S EP520, EP552

de Miguel-Yanes, JM

Cunha, N EP1009,

& EP1483

& EP555

EP431

EP1195, EP1459,

da Rocha, AG EP1449

Dash, K EP552

de Oliveira, SNP EP389

EP1475, EP203,

da Silva, AP OC5.4

Dato, CD EP537 & OC9.5

de Pinillos Gordillo, GM

EP392, EP394, EP44,

da Silva, TN EP226

Dauksa, A EP1346

EP769

EP444, EP445, EP45,

& EP486

& GP244

de Pinillos, GM EP298

EP61 & GP35

Dabrowska, A EP547

Dauksiene, D EP1346

& EP623

Cunha, V EP807 & OC4.3

Dae Moon, S EP690

& GP244

de Quirós, JMG EP298,

Cunningham, K EP720

Dagdelen Duran, İ EP810

Daumerie, C EP1342

EP623 & EP769

Cuocolo, A GP231

Dagdeviren, M EP1060,

Davey, L EP295

De Quiros, JMG EP270

Curic, N EP1024

EP1343, EP1464

David, J GP203

de Rijke, YB GP116

& EP709

& EP186

& GP206

De Rosa, A EP1341

Curkovic, S EP64

Dahl, SR EP59

Davidenko, I EP415

& EP1426

Currò, M GP175

Dahlgren, C GP117

& EP73

de Sanctis, L GP43

Curria, M EP211

Dahlqvist, P GP9

Davies, E GP58

De Schepper, J EP812

Cusini, C EP688

Dal, J GP181

Dbouk, R OC11.2

De Seze, J EP1352

& EP691

Dalama, B EP944

de Agredos, ÁG-MV EP11

de Sousa, A EP1465

Cvetkovic, S EP470

Dalar, L EP296

& EP955

& EP98

Cvijovic, G EP694

Dallenga, AHG GP116

de Almeida, MM GP226

de Sousa, JA EP82

Człapka-Matyasik, M

Dalmatova, A EP978

de Alonso, IA EP632

de Souza, B EP411

EP1074

Dalvi, F EP130

de Angelis, C EP786

de Souza, BM EP457

Czajka-Oraniec, I GP173

Dalvi, M EP130

de Angulo Martín, DR

de Souza, PB GP128

Czarniecka, A EP1420

Dalwadi, P EP844

EP708

de Valk, H EP635

Czarnywojtek, A EP1275

Daly, A EP928

de Carvalho, AC GP229

De Vathaire, F GP148

& GP220

Daly, AF OC8.1

de Castro, DO EP714

De Vincentis, S GP146

Czech, M EP577

Damas-Fuentes, M EP614

de Castro, RV EP1204

De Waure, C EP1341

Czekanska, P EP1148

Damasceno, M EP54

& EP1269

˘irmenciog˘lu, S EP971

& EP371

Damjanovic, S EP166,

de Ciriza, MP EP869

De, P EP409, EP501,

Czepczyn´ ski, R EP1433

EP177, EP191, EP75,

de Courten, B EP1115,

EP558 & EP584

Czepielewski, M EP919

EP80, GP197

GP135 & GP141

Deak, K EP731

Czyzyk, A EP1348

& S25.1

De Feo, ML GP33

Debono, M EP879

Danciu, M EP792

De Francia, S EP26

Decallonne, B EP1393

Daneliene, M EP1436

De Geyter, C GP153

& OC14.4

D’Allagnol, A OC2.5

Daneshafrooz, A EP1406,

De Giorgi, F EP702

Decaroli, MC EP1166

D’Aluisio, D GP16

EP642 & EP662

de Heide, L EP402

& GP146

D’Amelio, P S7.1

Dang, M GP195

de Jong, M EP1445

Deciu, D EP1067

D’Angelo, A GP33

Dani, C GP7

de Krijger, RR EP155

Decmann, A GP3

D’Antongiovanni, V EP92,

Daniela Belceanu, A

& OC7.2

Deconde Le Butor, C

EP93 & GP25

EP188

de la Higuera, M GP198

EP745

D’Sa, S EP1075

Danieluk, M EP1433

de la Mata, M EP698

Decourtye, L OC5.5

d’Uscio, CH EP820

Daniil, G GP15

de la Morena, LH EP125

Decristoforo, C EP1445

Díaz, JA EP184 & EP185

Danila, R EP252

& EP886

Dedecjus, M EP1435

Díaz, PRC EP125

Dantas, IA EP389

de la Rúa Franch, ER

Dedov, I EP1036, EP220,

Díaz-Guerra, GM EP8

Dantas, R EP106

EP569

EP568, EP881, EP913

Díaz-Perdigones, C EP614

Danyarova, L EP436

De La Torre, FJM EP401

& EP914

& GP71

Danyte, E EP1321, EP434

de la Vega, IR GP179

Deeks, J GP122

Díaz-Yelamos, A EP715

& EP543

De la Vieja Escolar, A

Defreyne, J EP1032

Díez, A EP863

Daphne, FA EP1032

GP235

degli Uberti, E EP789

Díez, JJ EP784, EP891

Daraki, V EP1418 & GP32

De Leo, S EP1408

Dehara, Y EP840

EP94 & GP241

Daramilas, C EP588

de Lima, JP EP1461

Dekkers, O GS2.1

Dundar, M EP1129

Darashkevich, I EP540

de Linares, LUL EP603

Dekkers, OM GP17

da Conceiça˜o Pereira, M

& EP541

De Linares, UL EP3, EP9

& OC12.2

EP816

Daroszewski, J EP775

& EP952

del Mar Moreno, M EP790

da Costa, AM GP228

& GP72

De Marinis, L EP991,

del Olmo, MI EP99

& GP229

Darstein, C GP177

EP997 & OC12.5

del Olmo, RC EP99

da Costa, JM EP706

Darwis, I EP363

De Martino, MC EP34

Del Peso Gilsanz, C EP432

& EP707

das Oliveiras, P EP794

De Miguel Novoa, P GP179

& EP705

Das, J EP1296

de Miguel-Díez, J EP431

Del Peso, C EP1415

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Del Prato, S D6.1

Di Sante, S OC9.5

do Vale, S EP281, EP898,

Dragomir, L EP979

del Río-Moreno, M EP178,

Di Stefano, M EP1408

EP96 & GP213

Drakopoulou, A EP217

EP698 & EP790

Diaconescu, MR EP764

Dog˘an, BA EP1453

Drakopoulou, M EP62

Del Val-Zaballos, F EP456

Diaconescu, S EP764

Doblas, IM EP998

Draman, MS EP1342

& EP955

Diamanti-Kandarakis, E

Dobrescu, R EP1395

Dravec, D EP1265

Delemer, B GP7

EP1098 & EHM1

& EP1466

Drelon, C OC1.2

Delerue-Matos, C EP403

Diamonde, A OC11.5

Dobrinja, C GP204

Dreval’, A EP936

Delgado, CG EP1023

Diana Ilie, M EP1220

Dobrota, VD EP1161

Dreval, A EP1141,

Delgado, L EP1289

Dias, C GP199

Doga, M OC10.3

EP1457, EP50, EP905

& GP199

Dias, D EP1142, EP297,

Dogan, F EP182, EP332

& GP193

Delgado-Lista, J EP472

EP783, EP788

& EP933

Drews, M EP388

Delia Santana-Suarez, A

& EP816

Doganay, M EP968

Drosdzol-Cop, A EP1119

EP193

Dias, S EP100

Dogansen, SC EP1038

Dušková, M EP1143,

Delia, CE EP1364

Diazzi, C GP146

& OC12.1

EP1170 & EP14

Delibasi, T EP1039

Dick, B EP820 & OC13.5

Dokmetas, HS EP834

Duarte, G EP411

Dellal, FD EP1377

Dieter, C EP411 & GP79

Doknic, M EP1046,

& GP79

& GP233

Diez, JJ EP88

EP892, EP953, EP954,

Duarte, H EP1422

Demaj, E EP634 & EP765

Diez-Perez, A GP84

EP956 & GP188

Duarte, I EP51

Demidowich, A EP13

Dik, W S12.1

Domínguez, ÓM EP886

Duarte, JS EP1486, EP414

Demir, O EP277

Dima, L EP774

Domínguez, M EP756

& EP951

Demir, O EP1165, EP962

DiMarchi, R OC2.3

Dombrovska, N GP86

Duarte, N EP243

& EP967

Dimitrijevic-Sreckovic, V

Domingues, A EP313

Duarte, R EP562

Demirba¸, T EP1122

EP367, EP677

Domingues, V EP403

Duarte, V EP139

Demircan, S EP249

& EP678

Donadille, B GP148

Dublang, M EP112,

Demirci, I EP1165

Dina, R EP123

& GP19

EP1217 & EP128

Dempster, N EP682

Dinc, M EP1165

Donath, MY EP687

Duceac, A EP1063

& EP730

Dinccag, N EP821

& OC11.3

Dudich, O EP1308

Demura, M OC3.1

Dinis, A GP109

Donato, I EP288

Dudina, M EP1248

den Bruel Annick, V

Dinis, I EP1227 & GP109

Donato, S EP1142,

Dudler, V OC13.5

OC14.4

Dinu Draganescu, D

EP1219, EP258,

Dudzinska, M EP144

Dendale, R GP189

EP1176

EP772, EP783, EP788,

Dugonjic, S EP787

Deng, Y EP1

Dinu-Pirvu, CE EP376

EP816 & GP23

Dukhan, K EP1004,

Denham, DS GP47

Dionigi, G EP1451, EP688

Dong, X EP551

EP453 & EP597

Deniz, F EP1455

& EP691

Donini, L EP713 & GP168

Duma, D EP547

Derya Bulus, A EP815

Diosdado, MA EP544

Donini, LM EP702

Dumanovic, MS EP470

Descombes, X EP745

Dirikoc, A EP1320

Donnay, S EP1332

Dumeige, L OC5.5

Desmet, C EP883

& EP1377

Donsa, K EP609

Dumitrache, C EP319

Detka, J GP154

Dirikoc, M EP1320

Dores, J EP460, EP462

Dumitrascu, A EP1007,

Dettoraki, A EP885

Ditsiou, A EP785

& EP921

EP137, EP352, EP911

Deutschbein, T EP932

Diz, Y GP52

Dorfman, L GP79

& EP980

& GP160

Diz-Chaves, Y GP156

Doroszewska, K EP1111

Dumitrascu, I EP1364

Devia, DG GP187

& GP75

& EP141

Dumitrescu, A EP1352

Devosa, I EP731

Dizdarevic-Bostandzic, A

Doroszko, M GP118

Dumitrescu, C EP206

DeVries, H MTE6

EP976

& OC7.1

& EP352

Dexneit, T GP121

Djamila, M EP279

Dotan, I EP661

Dumitrescu, I-B EP376

Dey, A EP1117

Djelic, M EP470

Dottore, GR EP1247

Dumitru, N EP117

Deyneli, O EP47 & EP851

Djerrou, Z EP743

Dottorini, M GP231

Dunauskas, V GP31

Dhaenens, CM EP1439

Djordjevic, M EP528

Doulatram, V EP1462,

Dunn, W OC3.3

Dharan, SS EP115

Djukic, A EP484

EP755, EP756

Duntas, L OC4.5

Dhayat, NA EP820

Djurdjevic, SP EP956

& EP808

Duparc, C GP12

Dhillo, W GP131 & S28.3

& GP153

Doulgeraki, A GP99

Dupuis, N EP928

Di Bari, F EP1171

Djurisic, I EP1480

Dounousi, E EP299

Dura˜ es, C EP1357

Di Dalmazi, G GP1 & GP5

& GP225

Dousset, B OC7.2

Dura˜ es, J EP394

Di Donna, V EP1341

Djurovic, MN EP956

Doyle, C GP131

Dural, AC EP1235

& EP1426

& GP188

Dozio, E EP688 & EP691

Duran, ID EP977

Di Franco, A GP8

Dmitriev, Y GP92

Draganescu, DD EP1180

Duran, P EP1130

Di Gennaro, G EP34

Do Cao, C EP1369

Dragoi, CM EP1137

Duranteau, L GP19

Di Martino, M EP713

do Han, K EP554

& EP376

Durmaz, S EP873

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Durmaz, SA EP1280,

El Ansari, N EP1065

Elouarradi, N EP1065

EP758, EP759, EP778,

EP529, EP604, EP683

& EP1350

Eloy, C EP1449

EP852 & GP102

& EP684

El Azeem, NEDA EP416

Elston, M EP1312

Ersoy, O EP1264, EP856

Durmic, T EP470

El Houda, KN EP149

Elyousfi, A EP534

& GP49

Durmus, I EP427

El Kareem, HA EP416

Emini, M EP585

Ersoy, R EP1002, EP1152,

Durmus, Y EP121,

El Mghari, G EP1065

Emous, M EP402

EP1250, EP1258,

EP1399, EP1402

El Zein, R GP2

Emral, R EP1273, EP277,

EP1264, EP1320,

& EP848

Elías, E EP869

EP967 & EP988

EP1326, EP1376,

Duro, D EP704

El-Khouly, G EP513

Emre, AU EP282

EP1377, EP1413,

Dursunoglu, D EP1101

El-Koussy, M EP986

Encica˘, S EP328

EP1429, EP237,

Dusan, V EP1089

Elaffandi, A EP160

Endelman, M EP1237

EP331, EP843, EP856,

Dusceac, R EP1018

Elamid, M EP7

Enderle, G EP1020

GP233

Dusek, T EP71 & EP81

Elamin, Y EP430

Eneva, N EP1141

& GP49

Duvvuru, S EP555

Elansari, N EP847

Engeli, R EP781

Ersoz Gulcelik, N EP1175

Dvorak, Z EP805

Elasaify, W EP1230

Engels, M GP10

Ertan, Y EP1194

Dworacki, G EP1433

Elbuken, G EP446

Engstrom, BE GP9

Erten, S EP843

& EP1450

& EP842

Eraydin, A EP1003

Ertorer, ME EP963

Dwyer, A GP153 & N1.2

Elbasan, O EP608

Erba, P EP1445

& EP969

Dydyshka, Y EP737

Elbere, I OC6.3

Ercan, O EP101

Ertugrul, DT EP1343

Dyrmishi, B EP2 & EP1370

Elbez, I EP1290, EP1427,

Ercoli, G EP1432

Erturk, E EP1017, EP132,

Dzantieva, E EP1164

EP1428 & EP1430

Ercolino, T EP92, EP93

EP332, EP336, EP608,

& EP695

Elbuken, G EP265

& GP8

EP72 & EP852

Dzeranova, L EP1034,

Eldin, AMB EP1299

Erdélyi, L EP804

Escalada, J S9.3

EP1036, EP913,

Elena, G EP989

Erdem, B EP815 & GP74

Escher, G OC13.5

EP914 & GP157

Elena, M EP591

Erdemir, RU EP282

Escobar-Morreale, H

Dzherieva, I EP539

Elena, S EP591

Erden, E EP967

MTE12

& EP760

Elena-Iuliana, P-G EP587

Erdogan, M EP1379

Escola, CÁ EP125

Dzib, FG GP15

Elewa, A EP1299

Erdogan, MF EP1199,

Escolano, E OC10.2

Dzivite-Krisane, I EP1046

Elewa, AA EP513

EP1487, EP277

Escola, CÁ EP125

Dzodic, R EP1480 & GP225

Elezovic Kovacevic, V

& EP967

Espín, MlBG EP705

EP191

Erek, M EP533 & GP102

Espín, NVG-T EP432

Eastell, R MTE5

Elezovic, V EP1114,

Erel, O EP1347

& EP433

Ebbehoj, AL OC1.4

EP166, EP177, EP75

Erel, O EP1108 & EP1320

Espada, M EP1332

Ebrahimi, F EP687

& GP139

Eremkina, A EP257,

Espallardo, MÁC EP708

& OC11.3

Elezovic, VK EP80

EP318 & EP347

& EP717

Echiburu, B EP1120

Elfaleh, E EP482

Erfurth, E-M EP1070

Esperto, H EP392

Eckstein, A EP1342

Elfekih, H EP1349,

& GP182

Espiard, S EP1439, GP120

Economou, E GP32

EP1361, EP189,

Erfurth, EM GP9

& GP28

Ediboglu, E EP277

EP335, EP66

Ergang, P EP1082

Espiart, S OC5.3

Efaishat, R EP360

& EP770

Ergur, AT EP1223

Espiga, J EP128

Efe, B EP264, EP418,

Elhadd, T EP160, EP453

& EP724

Espinosa-Nava, MA EP437

EP427 & EP90

& EP597

Eriksen, EF S1.3

Esposito, I EP692

Efremidou, EI EP1378

Elhem, BJ EP762 & EP780

Erkutlu, I EP1003

Esposito, K EP1121

Efstathiadou, Z EP1303,

Elias, N EP211

Erlic, Z EP104

& EP1293

EP1307, EP1417

Eliasson, B EP55

Ermetici, F OC6.2

Esteves, C EP1181,

& EP223

Elisabet, G EP641

Eroglu, M EP1099

EP1289, EP1357,

Egan˜ a, N EP869

Elisei, R EP1414, EP288

Erol, RS EP109

EP576, EP613, EP773,

Ehret, G EP820 & OC13.5

& GP231

?& EP836

EP870, EP871

Eisa, M EP83

Elleuch, M EP1128,

Ersoz Gulçelik, N EP810

& GP199

Eisenhofer, G EP92, EP93

EP135, EP1361,

Ersoy, A EP533, EP751,

Esteves, CM EP887

& GP25

EP167, EP66, EP77,

EP752, EP758, EP759,

Estevez, LT EP365

Ekberg, NR EP557

EP770 & GP113

EP778 & GP102

Estorninho, J EP133

Eker, EP673

Elleuch, N EP355

Ersoy, C EP1017, EP102,

Estour, B EP1126, EP1468

Ekiz-Bilir, B EP446

Elli, FM GP43

EP131, EP132,

& OC11.5

& EP842

Elmghari, G EP1337,

EP1335, EP332,

Eterović, D EP1469

Ekman, B EP1070, EP22,

EP711 & EP847

EP333, EP336, EP533,

Etxeberría, E EP1217

GP11, GP182, GP20

Elo, L EP692

EP601, EP608, EP679,

Etxeberria, E EP1040

& GP9

Eloranta, E GP50

EP72, EP751, EP752,

& EP112

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Eugenio Calogero, A

Fanni, E EP370

Fernández, F EP99

Ferreira, L EP350 & EP57

OC13.4

Farahan, AH GP164

Fernández, HG EP294

Ferreira, LB EP1449

Eugenio, B EP641

Farahani, P EP579, EP583

Fernández, I EP298

Ferreira, M EP1362,

Eun Song, D OC14.5

& GP110

& EP623

EP267, EP57 & GP98

Evans, JMM EP481

Faraldi, M EP777

Fernández, J EP1044

Ferreira, MA EP1269

Evason, J GP195

Fardella, CE OC5.1

Fernández, LP GP235

Ferreira, PA GP234

Evliyaoglu, O EP101

Fareleira, A GP234

Fernández, M EP863

Ferreira, T EP1454

Evora, F EP578 & EP626

Farha, RA EP360

Fernández-Amigo, PM

Ferrer, FM EP365

Evran, M EP1241

Farhat, K EP883

EP224

Ferrer, M EP754

Evranos Ogmen, B EP1152

Faria, C EP1037, EP1083,

Fernández-Cancio, M

Ferrero, S EP1432

& GP49

EP1085, EP1133,

EP1090

Ferrigno, R EP34

Evranos, B EP331

EP1340, EP243,

Fernández-Ladreda, MT

Ferrinho, C EP1088,

Evren, B EP330, EP620

EP320, EP95, GP237

EP1331, EP1467,

EP1177, EP1207,

& EP703

& GP239

EP563 & EP769

EP1311 & EP1486

Expósito, A EP128

Faria, M EP1448

Fernández-Marmiesse, A

Ferrinhos, C EP414

Expósito, MRA EP474,

Faria, T GP200

EP725

& EP951

EP602 & EP882

Farkash, R OC4.1

Fernandes, A EP706,

Feuchtinger, A EP52

Faro, ACN EP949

EP707 & GP200

& GP22

Férrinho, C EP1452

& GP178

Fernandes, AC EP140

Feuvret, L GP189

Furstenberger, C EP781

Farooqi, S S4.2

& EP54

Fezoulidis, I EP559

Fabbri, A EP1145

Fassnacht, M EP161,

Fernandes, C EP1362

Fian˜ o, RS EP725

& GP138

EP932, GP1, GP119,

Fernandes, G EP773

Fica, S EP1371, EP143,

Fabre, JM OC11.2

GP121, GP122,

Fernandes, I EP174

EP763, EP817, EP855,

Fabregat, J EP150

GP123, GP22, GP5,

Fernandes, L GP222

EP943 & EP947

Fabris, B GP204

OC1.1 & OC7.2

Fernandes, V EP57

Figueiredo, P EP1459

Fadiga, L EP1195,

Fattorini, G GP149

Fernandes-Rosa, F GP15

Figurová, J EP1127

EP1475, EP444

Fauconnier, A EP1126

Fernandes-Rosa, FL GP2

Filetti, S GP231

& EP445

Faucz, FR GP236

Fernandez, B EP3

Filho, JCC GP163

Fafa, N EP718

Favaro, E OC11.1

Fernandez, E EP180

Filice, A GP231

Fagg, C EP807

Fawzi, M EP1240

Fernandez, EG EP459

Filipa Martins, A GP213

Faggiano, A EP1407,

Fayzullaev, R EP15

Fernandez, LP EP920

Filipe, E EP519

GP33 & OC9.5

Fazal-Sanderson, V GP114

Fernandez, M GP111

Filipović, B EP212

Fahad Arshad, M EP190

Fazel, J GP160

Fernandez-Ladreda, MT

& EP359

& EP316

Fazzini, A EP1166

EP270

Filipović-Grcˇić, M EP172,

Fahmy, E EP412

Fechner, PY GP65

Fernandez-Real, JM GP24

EP463 & EP549

Faillot, S GP28

Fedala, NS EP1315

Ferone, D GP177

Filipovic, B GP202

Fajardo-Araujo, ME EP437

Fedala, S EP718

Ferrín, G EP698

Filipovic-Grcic, M EP43

Faki, S EP1002, EP1152,

Fedorenko, E EP749

Ferraù, F GP160 & GP175

Filippi, S EP377 & GP147

EP1250, EP1258,

Feelders, R EP182, EP933

Ferrante, E EP1043

Filisan, C EP1137

EP1264, EP1413,

& GP187

Ferrari, F EP397

Finan, B OC2.3

EP1429, EP237

Feelders, RA GP116

Ferrau, F EP1056

Finucane, FM EP720

& EP843

Feki, H EP77

Ferreira, A EP1465

Fiore, D EP537

Fakra, E OC11.5

Feldt-Rasmussen, U EP40,

& EP599

Fiore, E EP238

Falalyeyeva, T GP60

EP63, GP150, GP181

Ferreira, AG EP1298,

Fiorelli, M EP1054

Falca˜ o-Pires, I GP217

& OC13.2

EP226, EP486

Fiorentino, M EP1381

Falch, CM OC8.3

Felicia, B EP939

& EP996

Firat, SN EP384

Falcon-Perez, J NSA2

Felipe, GDJ GP2

Ferreira, AS EP660

Fish, D EP134

Falkowski, B EP388

Feller, K EP1090 & GP153

Ferreira, B EP30

Fjalldal, S EP1070

Falletta, S EP196 & EP197

Felsenberg, D EP353

Ferreira, D GP205

& GP182

Falzacappa, CV EP825

Felsinger, J EP426

Ferreira, E EP267

Fluck, C EP1090 & GP153

& GP221

Fenichel, P EP745 & S21.1

Ferreira, F EP1055,

Flamant, F NSA4

Fambrini, M EP370

Fenkçi, SM EP1405,

EP1204, EP329,

Flegg, P EP83

Fanaei, S-A EP1406

EP656, EP971

EP791, EP887, EP897

Fleseriu, M GP187

Fandin˜ o, J GP156, GP52

& EP972

& EP898

Fletcher, C EP682

& GP75

Feola, T EP1050 & EP537

Ferreira, J EP1083

Flitsch, J EP932 & GP176

Fanelli, F EP1166, EP669

Feraru, L EP813 & EP961

Ferreira, JA EP923

Florea, S EP143, EP215

& EP671

Ferjan, S GP136

Ferreira, JL EP129

& EP855

Fani, M GP185

Ferla, ML EP348

& EP337

Florentino, CA EP74

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Flores, PM EP1072

Frara, S GP231 & OC10.3

Gunes, SO EP1223

Garay, IB EP1023

Florian, S EP979

Frattini, F EP688 & EP691

& EP724

Garbis, S GP46

Floroskoufi, P EP1418

Freel, EM GP58

Gunes-Ciftci, H EP842

García, C EP869

& GP32

Freitas, C EP1279, EP496,

Guvenç, G EP964

García, CH EP627

Fokina, N EP142

GP228 & GP229

Gabalec, F EP1197 & EP837

García, CR EP406

Foldesi, I EP731

Freitas, J EP232, EP234,

Gabery, S EP1070

& EP407

Folin, C GP9

EP818 & EP923

& GP182

García, DS EP1237

Follin, C EP1070, GP182

Freitas, M GP163

Gacic, J EP367

García, F EP298 & EP623

& MTNE2

Freitas, P EP1081, EP140,

Gadaleta, R OC3.2

García, IR EP756

Fonseca, AC EP1204

EP169, EP194, EP195,

Gadawska-Juszczyk, K

García, JE EP948

Fonseca, F EP1000,

EP493, EP53, EP54,

EP1274

García, M EP9

EP1006, EP1049,

EP576, EP630

Gadelha, M S8.1

García, MIDO EP183

EP1062, EP1446,

& EP719

Gadelha, MR GP160

García, ML EP1237

EP181 & EP251

Frey, J EP986

Gadelha, P EP841, EP899

& EP1251

Fonseca, L EP567, EP824

Friis-Hansen, L EP40

& EP975

García, MTG EP432,

& EP921

Froberg, AC EP1445

Gagliano, T EP196,

EP433 & EP705

Fonseca, M EP887

Frolova, A EP1266

EP197, EP785

García, NP EP948

Fonseca, R EP414

& EP1316

& EP789

García, PdD EP920

Font, A EP1330

Fuentes, MD EP406,

Gahete, MD EP178,

García-Almeida, JM EP224

Font, MN EP294

EP407 & EP627

EP472, EP698, EP790

García-Fernandez, E

Font, P EP486

Fuentes-Fayos, AC EP929

& GP128

EP944

Fontoura, M EP1058,

Fugazzola, L EP1408

Gaillard, D GP45

García-García-Doncel, L

EP403, EP512, EP887

& EP1432

Gajate, P EP784

EP858 & EP915

& GP227

Fujikawa, N EP1242

Gajdosiik, M EP638

García-Giralt, N GP36

Forleo, R EP60

Fujimoto, S EP643

Gajkowski, P EP48

García-Jurado, P-B EP819

Formenti, AM GP231,

Fukagawa, M EP4

Gala-Błędzin´ ska, A

& EP907

OC10.3, OC12.5

Fumarola, A OC9.5

EP1338

García-Notario, P EP443,

& S22.2

Fuqua, JS GP65

Galanis, P EP1084

EP524 & EP593

Fornai, F GP223

Fureraj, T EP1370, EP2,

Galdiero, G EP786

García-Ruiz, R EP11,

Fornari, G EP1112

EP495 & EP765

Galdiero, M GP184

EP456 & EP955

Forni, D GP77

Furtado, I EP350 & EP824

Galesanu, C EP957

García-Sancho, P EP88,

Forno, I GP130

Fustinoni, S EP1043

& EP961

EP891 & EP94

Foroughi, F EP1406

Futeran, C EP228

Galfi, M EP742

García-Talavera Espín, NV

Forsgren, M GP117

Fysekidis, M OC11.2

Galie, N EP16

EP705

Foster, P GP125

Gallagher, F GP27

Goreía-Talavera Espin, MB

Foti, M EP692

Gallardo, GL EP1218

EP705

Fotinou, A EP62 & EP885

Gálvez-Moreno, M-Á

Gallego, MT EP1476

Garcia, C EP952

Foukaki, M EP625

EP159, EP500, EP941

Gallo, D EP688 & EP691

Garcia, E GP73

Fourtanier, G OC11.2

& EP1159

Gallwitz, B S9.2

Garcia, MM EP920

Fruhbeck, G S24.2

Gálvez-Moreno, MA

Galofré, JC EP227, EP733,

Garcia-Eguren, G GP24

Frade, J EP44

EP178 & EP929

GP198 & GP235

Garcia-Garcia-Doncel, L

Frago, LM EP435

Gérard, S OC11.2

Galoiu, S EP1007 & EP980

EP1174, EP1200,

& EP655

Gómez, JF EP365

Galusca, B EP1126,

EP1203, EP1287

Fragoso, MC GP6 & GP160

Gómez, JTC EP125

EP1468 & OC11.5

& EP535

Fraile, ES EP76

Gómez, MF EP708

Galva˜ o, S EP152

Garcia-Ramirez, J-R

Fraile, MR EP227

& EP717

Galvez-Moreno, MÁ

EP666

Francaite-Daugeliene, M

Gómez, NS GP179

EP819, EP907

Garcia-Segura, LM GP156

EP448 & EP449

Gómez, RC EP183

& EP1159

Gargallo, J EP227

Franceschi, S EP348

Gómez-Alfonso, FJ EP11,

Gama, P GP224

& GP198

Franceschini, SS EP1247

EP456 & EP955

Gambardella, C EP1407

Gargantini, E OC11.1

Franco, C EP100

Gómez-Gómez, E EP790

Gambaro, G EP1260

Garnelo-Caban˜ as, S EP666

Francou, B GP45

Gómez-García, I EP11

Gamian, A GP72

Garnuszek, P EP1445

Francque, S OC3.5

& EP955

Gan, KJ EP259

Garoufalia, Z EP1253

Franek, E EP577

Gorar, S EP1053

Gangemi, S GP208

Garra˜o, A EP1390

Frankel, M EP228

Gulçelik, NE EP977

Gangitano, E EP702

& GP242

Franklin, R EP682

Gulcelik, NE EP854

Gannon, A-L GP4

Garrahy, A EP1318

Franks, S EP1110

Guler, S EP1453, EP538,

Gar, C EP639 & GP196

& EP768

Franzén, S EP55

EP810 & EP977

Garach, AM EP627

Garrido, S EP57

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Garrote, S EP603

Germak, J EP291

Gielerak, G OC12.4

Gluvić, Z EP1245 & EP356

Garzón, RD GP240

Gesmundo, I GP151

Giessen, H EP18

Gluvic, Z EP484

Gasinska, T EP1348

& OC11.1

Giesteira, L EP1465

Gnanalingham, K EP1022

Gasior-Perczak, D EP1274,

Gethings, L OC3.2

Giger, O GP27

Gnessi, L EP702, EP713

EP1382 & EP1409

Ghagre, R EP844

Giglio, RV GP108

& GP168

Gasiorek, M EP1282

Ghanem, A EP649

Gil, EP632

Gon˜ i, F EP1040 & EP112

& EP1372

Ghanmi, S EP1238

Gil, A OC5.4

Go, R-E EP739

Gaspar da Rocha, A

Gharbi, R EP570

Gil, P EP1461

Godbole, A OC4.4

OC14.3

Ghasemi, A EP615

Gil, SM EP385

Godinho, C EP1330,

Gasparini, DI EP669

Gheibi, S EP615

Gilioli, L EP1131

EP750, EP795, EP796

& EP671

Gheludcova, O EP1057

Gilis-Januszewska, A

& EP829

Gastaldello, A EP802

Ghemigian, A EP117

EP1026

Godsland, I EP1084

Gaston-Massuet, C OC8.5

& EP1364

Gilleron, J EP745

Goebel, G EP1445

Gata, L GP109

Ghemigian, AM EP1221

Gillies, R EP682

Goena, MM EP869

Gateva, A EP699

& EP1419

Gilligan, L EP798, GP125

Goffin, V S23.1

Gathercole, L EP730

Ghemigian, MV EP1221

& OC3.5

Gogitidze, T EP983

& GP69

Gheorghe, I EP1138

Gilsanz, CDP EP433

Goitia, MS EP1332

Gattlen, C EP1087

& EP1147

Giménez-Palop, O EP165

Gokalp, D EP937

Gatu, A EP213 & EP260

Gheorghiu, CA EP108

Gimenez-Roqueplo, A-P

Gokcay Canpolat, A

Gatu, C EP252

Gheorghiu, ML EP1364

S17.2

EP1273 & EP1487

Gautier, J-F GP19

& GP137

Gioia, I GP214, GP215

Gokce, M EP282

Gautier, JF MTE13

Gherasim, I EP143

& GP216

Gokkaya, N EP261

Gavira, IM EP544

Gherlan, I EP1221, EP206

Giordano, C EP1056

Golchert, J OC3.4

Gavriilidou, S EP1202

& EP352

Giordano, T S17.1

Golda, A EP826

& EP859

Ghervan, C EP846

Giorgio, MRD GP16

Goldstein, A EP1353

Gavris, C EP774

& EP979

Giovinazzo, S GP208

Goldstein, AL EP1221

Gawlik, A GP67

Ghigo, E GP151 & GP192

Girdziute, M EP156

& EP1419

Gawlik, T EP1420

Ghizlane, E EP845

Giritharan, S EP1022

Goldstein, D EP1221

& EP1440

Ghizlane, EM EP1350,

Gissler, M EP1285

Golic, I EP693

Gawrychowski, J EP349

EP379, EP387

Gittoes, N EP1051

Golu, I EP1068, EP153,

Gay, S OC14.1

& EP488

& GP180

EP306 & GP53

Gaysina, L EP617

Ghorbel, D EP1128,

Giubbini, R GP231

Gomes, A EP1133, EP119,

Gazizova, G EP617

EP1349, EP1361,

& OC10.3

EP897 & EP898

Gedik, V EP967

EP167, EP189, EP66

Giudici, F GP204

Gomes, AC EP157, EP896

Geelhoed-Duijvestijn, N

& EP667

Giuffrida, G GP208

& EP974

EP635

Ghosh, M EP1296

Giugliano, D EP1121

Gomes, ARC EP1083

Geenen, V EP883

Ghyselinck, NB GP2

& EP1293

& EP243

Gehrig, A GP119

Giagulli, VA GP215

Giulea, C EP1371

Gomes, B EP899

Gelmini, S GP8

& GP216

Giulietti, K EP745

Gomes, L EP1009,

Gen, R EP835

Giamas, G EP785

Giulio, MD EP278

EP1049, EP1195,

Gener, I EP1094

Giampietro, A EP991,

Giurgi, A EP1419

EP444, EP445 & EP45

Genest, J EP661

EP997 & OC12.5

Giusti, M OC14.1

Gomes, M EP468

Gennaro, GD EP786

Giandalia, A EP1118

Giustina, A EP1020,

Gomes, R EP548

Genser, B GP107

Gianfrilli, D EP1054,

GP231, OC10.3

& EP573

Gentilin, E EP196

EP537 & GP149

& OC12.5

Gomes, V EP1055,

& EP197

Giannetta, E EP1050,

Giveon, S EP735

EP1083, EP1204,

Georgescu, C EP1364

EP537 & OC9.5

Gluer, C-C EP353

EP1269, EP243,

Georgescu, CE EP114,

Giannetta, V GP149

Glatz, P EP734

EP329, EP791, EP897

EP158, EP328 & EP846

& OC9.5

Glazunova, A EP521

& EP898

Georgescu, O EP855

Gianotti, L EP268 & GP33

Gleeson, H EP1052

Gomez Balaguer, M

Georgiou, E EP864

Giardino, E EP20 & EP924

Gligic-Kuzmanovic, A

EP1178

Georgiou, T EP1303,

Giatra, C EP1047

EP694

Gomez, R EP1046

EP1307, EP68, EP771,

Giatromanolaki, A

Glinianowicz, MO EP726

Gomez-Hoyos, E EP900

EP827 & EP828

EP1378

Glintborg, D GP59

Gomez-Sanchez, C EP37

Georgiu, C EP158

Gibney, J EP1150,

Glombik, K GP154

Gomez-Sanchez, CE EP52

Gerasimov, A GP78

EP1153, EP487,

& GP158

& GP2

Germain, N EP1126,

EP572, EP70 & EP798

Gloor, B GP185

Gomez-Sanchez, E EP37

EP1468 & OC11.5

Gibson-Helm, M EP747

Glowa, B EP1445

Gonçalves, A EP586

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Gonçalves, F EP548

Gountios, I EP861

EP985, GP114, GP138

Guldiken, S EP118,

& EP573

& EP864

& GP180

EP1198, EP121,

Gonçalves, H EP567

Gourdin, L GP143

Grothey, A EP785

EP1396, EP1399,

Gonçalves, HS EP468

Gourgiotis, D GP99

Group AMTCO, EP719

EP1400, EP1401,

Gonçalves, J EP567

Gouveia, P EP1279,

Groussin, L OC7.2

EP1402, EP1403,

Gonçalves, JA EP30

GP228, GP229

Grove, J OC3.5

EP1404, EP201,

Gonca Tamer, H EP447

& GP98

Grozinsky-Glasberg, S

EP271, EP848

Gondal, A GP125

Goyogana, A EP3, EP9

EP1391

& EP981

Gonen, MS EP296

& EP952

Gruppioni, E EP1381

Guler, S EP1317, EP1425

Gontijo, MdCD EP1011

Gozdz, S EP1382, EP1409

Grussendorf, M OC10.1

& EP56

González, A EP1218

& EP1442

Grycova, A EP803

Gulfam, T EP1358

González, CL EP862

Gozel, N EP249

& EP805

Gullu, S EP1059, EP1487,

& GP240

Graça, L EP54

Grytaas, MA EP33

EP277 & EP967

González, D EP302

Graça, S EP1291

Grzymislawski, M EP721

Gumeniuk, O EP1224

González, DM EP886

& EP1292

Gu Kim, W OC14.5

Gumuscu, HH EP467

González, EF EP1072

Grama, MA EP319

Gualtieri, A OC8.5

Gumuskaya Ocal, B GP49

& EP574

Granata, R GP151

Guan, M EP801

Gunasekara, R EP103

González, J EP863

& OC11.1

Guaraldi, G EP1166

Gundogan, R EP1223

González, L GP52

Granberg, D GP194

& GP146

Gunduz, C EP1379

González-Hermoso, C

Granda, MJD EP569

Guarnieri, V GP130

Gunes, Y EP362

EP1462

Grande, D GP214, GP215

Guarnotta, V EP1056

Gungor, K EP447

González-Lázaro, P EP11,

& GP216

Guastamacchia, E GP214,

Gungunes, A EP1280,

EP456 & EP955

Grande, E EP784

GP215 & GP216

EP529, EP604, EP683

González-Matías, L GP156

Granieri, L GP184

Guasti, D GP25

& EP684

& GP75

Grant, B EP1213, EP1354,

Gubaidullina, S GP170

Gunnarsdottir, H EP19

González-Pereira, C EP456

EP1485 & EP308

Guclu, M GP112

& EP21

González-Rubio, S EP698

Granzotto, PCD EP1244

Gudermann, T MTBS1

Gunness, A EP1150,

Gonzalez, C EP681

Grasso, LFS GP184

Gudmundsson, J EP19

EP1153 & EP487

Gonzalez, D EP341

Grasso, M EP1407

& EP21

Guntaite, V GP31

Gonzalez, EF EP1481

Gratiana, G EP199

Guedes, V EP1390

Guo, Y EP1

Gonzalez, JV OC5.1

Gravholt, CH GS1.1

Guelho, D EP1362

Gupta, A EP701

Gonzalez, S EP1484

Graziadio, C EP1054

& EP267

Gupta, P EP1039

Gonzalez-Molero, I EP755,

Grazie, GL EP537

Guerra, AL EP1030

Gupta, SK EP520

EP756, EP808

Grebennikova, T EP220

Guerra, E EP807

Guran, T OC1.3

& EP868

Greco, E OC9.5

Guerra-Navarro, L EP443,

Gurkan, H EP1401

Gonzalez-Rodriguez, E

Green, C GP69

EP524 & EP593

Gurlek, A GP212

EP170

Green, P GP124 & OC7.3

Guerreiro, S S28.2

Gurnell, M EP877 & GP27

Gonzalo, M EP808

Greenman, Y D1.1

Guerrero, F EP88

Gursel, BE EP752

Goodwin, L EP83

Gregová, J EP1086

Guessous, I EP820

Gursel, E EP752

Goran, M EP1480

Grieve, J GP195

& OC13.5

Gusova, Z EP695

& GP225

Griffin, H EP720

Gueye, M EP745

Gutiérrez, CA EP574

Gordillo, GMdP EP1331,

Grigore, A EP1371

Gugenheim, J OC11.2

Gutiérrez, MC EP8

EP1467, EP270

Grigore, C EP376

Guglielmi, G EP288

Gutiérrez, MT EP1217

& EP563

Grigorescu, F GP137

Guha, N OC3.5

Gutierrez-Aguirre, K-I

Gordon, DM EP876

Grigorie, D EP16

Guimara˜es, J EP106

EP666

Gorostidi, F EP1373

& EP240

& EP57

Guy, T EP1032

Gorska, M EP1104, EP31

Grigoriev, A EP220, EP917

Guimara˜es, JA GP90

Guzel, H EP362

& EP466

& GP157

Guimara˜es, JT GP205

Gyory, F EP1410

Gorukmez, O EP322

Grigorovici, A EP252

Guiochon-Mantel, A GP7

Gorvin, CM OC10.5

Grineva, E EP200, EP978,

Gul, AE EP289

Hána, V jr EP208

Goschnik, M EP1188

GP78 & GP92

Gul, OO EP1017, EP102,

Hána, V EP1046 & EP208

Gothilf, Y OC8.2

Grira, W EP207

EP1335, EP332,

Hanninen, A GP167

Gotovac, K EP595

Groeneweg, S S26.3

EP333, EP336, EP679

Haring, H-U P4

Gougoura, S EP618

Groma, V GP209

& EP852

Hofner, K GP22

Goulart-Silva, F GP224

Groop, L GP76

Gul, Z GP112 & GP161

Holl, B EP609

Goulden, B EP1485

Gross, DJ EP1374

Gulcelik, MA EP344

Horsch, D GP177

Goulis, D EP1084

& EP1391

Gulcelik, NE EP344

Hoybye, C EP912 & GP9

& EP214

Grossman, A EP1145,

& EP384

Haak, H GP123

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Hacker, N EP1188

Hanson, P EP668

Hernández, MC GP179

Hong, E-G EP1421

Hacques, E EP966

Hanzu, FA GP24

Hernández, TM EP569

& EP517

Haddad, M EP629

Haouchine, Z EP1182

Hernández-Barrera, V

Hong, S EP517

Hadj-Bekkouche, F

Hara, L EP16

EP431

Hong, SM EP1421

EP1234 & EP6

Harbeck, B EP800

Hernández-García, C

Hoon Chung, J GP219

Hadjkacem, F EP1349,

Harlamov, A EP415

EP1462, EP614

Hoorens, A EP1191

EP1361, EP66, EP667

Harris, NI EP1263

& GP71

Hopurcuog˘lu, D EP101

& EP770

Hartikainen, A-L EP1285

Hernando, ME EP681

Horányi, J EP1384

Hadoke, PWF EP802

Hasanbegovic, M EP1283

Hernik, A EP388

& EP1434

Hadoux, J EP179

Hasenmajer, V GP16

Herraiz, L EP184 & EP185

Horchani, I EP482

Haenelt, M EP639

Hashimoto, A EP1242

Herrera, EP EP107

Hormaechea-Agulla, D

& GP196

Hassan-Smith, Z OC3.5

Herrera-Martínez, A-D

EP790

Haffaf, E EP219

Hassiba, K EP138

EP159, EP776

Hornby, C EP798

Haffaf, L EP1386

Hatem, G EP616

& EP907

Hortopan, D EP1063

Hafiane, A EP661

Hatipogulu, B EP1015

Herrera-Martínez, AD

& EP16

Hafsa, SY EP1447

Hatri, S EP219

EP178 & EP182

Horváth, P GP37

Hagel, C EP932

Hatton, S EP430

Herrmann, E EP5

Horzelski, W GP183

Hahner, S EP52 & GP123

Hatzibougias, D EP1471

Herscovitch, P OC7.3

Hosoi, M EP27

Haj Kacem, F EP135

Hatzitolios, AI EP588

Herterich, S EP161

Hospers, G EP1045

Hajdukovic, Z EP787

Hauschild, M GP153

& EP932

Hotaran, G EP945

Hajjar, Y EP657

Hawari, R EP1192

Hescot, S EP179

Houang, M GP120

Hakaste, L GP76

Hawkins, A EP58 & GP115

Heshe, S EP70

Houari, S GP142

Hakkarainen, J EP364

Hayashi, S EP1029

Hespanhol, V EP773

Houchard, A GP191

& OC13.3

Haydar, S GP137

Hetland, ML EP40

Houlihan, D EP259

Halawa, MR EP1363

Haydardedeoglu, FE

Heuer, H S26.1

Houtman, R EP802

& EP513

EP963 & EP969

Hey-Hadavi, J EP1010,

Hoxha, V EP495 & EP765

Halder, L EP668

Haymana, C EP1165

EP1046, EP748,

Hoyos, EG GP179

Haldimann, M OC13.5

& EP362

EP884 & GP192

Hristozov, K EP1271

Halhalli, GSK EP1066

Hayon, M GP111

Heye, T GP185

Hrncic, D EP1184

Haliti, E EP585

Hazlehurst, J EP728,

Hiam, D EP1115

Hryniewicka, J EP1104

Halperin, I GP153 & GP24

EP730 & GP70

Hibbert, E EP1265

Hsiang, J OC11.4

Ham, HJ EP506

Healy, ML EP339

& EP592

Hsu, Y-C OC14.2

Hamad, F EP631 & EP649

Heaney, A GS2.5

Hidalgo, MD EP1331

Htay, T EP1458

Hamamatsu, K EP273

Heath, K EP904

Hilding, A EP557

Htet, TD EP426 & EP747

Hameg, F EP1386

Heaton, D EP386

Hill, JW EP1125

Hu, M EP1096

Hames, KY EP1385

Hebenstreit, D OC3.3

Hill, M EP1170

Hu, X EP754

Hammami, A EP355

Heck, A GP181

& EP208

Huang, C GP153

& EP762

Hedayati, M EP1406,

Hilsted, L EP40

Huang, H GP171

Hammond, G EP753

EP642, EP662 & OC5.2

Hiltermann, J EP1045

Huang, Z EP754

Hammouda, HB EP1236

Heikela, H EP692

Hirsch, D EP1374

Hubalewska-Dydejczyk, A

& EP1238

Helkkula, T GP76

& EP1391

EP1026, EP1297,

Hamouli-Said, Z EP1234

Hellstrom, A EP949

Hlavácˇková, M EP1438

EP1445, EP283,

& EP6

Helvaci, N GP212

Ho, B EP754

EP284, MTE8 & OC9.3

Han, J-H EP690

Hendawy, LM EP425

Hodes, A EP13

Huerta, ÁS EP183

Han, K EP690

& EP497

Hodson, L EP682, EP728,

Huerta, YZ EP862

Han, M EP1421

Hendra, H EP575

GP69 & GP70

& GP240

Handkiewicz-Junak, D

Henrik Nielsen, C OC13.2

Hodzic, M EP325

Huertas, RL EP882

EP1440

Henrion, D GP143

Hofland, H S30.1

Hughes, B OC3.5

Hanen, J EP762

Henrique, R EP146

Hofland, L EP182 & EP933

Hughes, BA OC1.3

Hankus, M GP67

Henry, B GP135

Hofland, LJ EP196

Hughes, D EP1192 & EP97

Hanley, B EP259

Hepsen, S EP1097

& EP197

Hughet, I EP1072

Hanna, P GP45

Herberg, F GP28

Hogan, A EP696

Huguet, I EP180 & OC10.2

Hannan, F S1.2

Hermann, P GP59

Hogea, MD EP774

Huh, JH EP236

Hannan, FM OC10.5

Hermann, W GP123

Holien, J EP1190

Huhtaniemi, I GP118

Hannon, Am EP1041

Hermosilla, AMG EP569

Hollenberg, A S6.3

& OC7.1

Hans, D EP243

Hermus, AR GP160

Holst, J S9.1

Hui, Z GP166

Hansen, A EP40

Hernández, IC GP179

Homorodean, C EP399

Hulsbergen-van de Kaa, C

Hanson, J EP928

Hernández, J EP984

Homuth, G OC3.4

GP10

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Humphriss, E GP65

Iglesias, P EP784, EP88,

Isabel Oliveira, A EP194,

Jain, A EP1052

& GP66

EP891, EP94 & GP241

EP195 & GP217

Jako, M EP731

Hunter, M GP131

Iglesias, SG EP8

Isailovic, T EP1114,

Jakob, F MTE9

Hunter, S EP1041

Igna, CP EP1364

EP166, EP177, EP191,

Jakobi, M OC7.1

Hunyady, L EP804

Ihtiyar, E EP110

EP75, EP80 & GP139

Jakuboniene, N EP1437

Huo, Y GP129

Ikonomi, M EP1370

Isenović, ER EP1245

& EP479

Hurej, S EP1382

Il’in, A EP1036

& EP356

James, A EP1306

Hurme, S GP50

Ilhéu, O EP1459

Ishimwe, J EP37

Jan vanderLely, A EP1010

Husebye, E EP49

Ilhan, TT EP1101

Isidori, AM EP1050,

Jana, J EP553

Husebye, ES EP33

Ilias, I EP793

EP1054, EP537,

Jandíková, H EP14

& EP59

Ilic, D EP1114, EP166,

GP149, GP16 & OC9.5

Janezˇ, A EP1105

Husi, G EP495

EP177, EP191, EP75,

Isidoro, J EP1461

Janeski, H EP367, EP677

Huson, L GP131

EP80, GP139 & GP140

Isik, S EP56

& EP678

Huten, N OC11.2

Ilic, I EP64

Islam, N EP1016

Janeski, N EP367

Hutter, N OC9.2

Ilie, MD EP830

Ismail, M EP205

Janez, A GP136

Huzmeli, C EP675

Illes, P EP803

Ismailov, S EP1186,

Jang, HW OC9.4

Hwang, K-A EP739

Ilovayskaya, I EP1141,

EP1187 & EP686

Jang, J-Y EP438

& GP144

EP905 & GP193

Isomaa, B GP76

Janicki, A EP1433

Hyuk Kim, T GP219

Ilsley, D EP409

Istók, R EP1384

& EP1474

Ilyin, A EP521, EP568

Ito, K EP1385

Janković, S EP359

Iacovazzo, D EP991

& EP881

Ito, S GP14

Jankovic, A EP693

Iacoviello, M GP214,

Imen, A EP780

Itoh, Y EP273

Jankovic, D GP197

GP215 & GP216

Imga, NN EP1035

Ittmann, M OC7.5

Jannini, EA EP370

Iacuaniello, D EP1056,

İmga, NN EP1453

Iushko, K EP458

Janssen, J GP174

EP34 & EP927

Imhof, R EP782

Ivan, M EP240

Janssen, JAMJL GP116

Iancu, EM EP307

Imre, E EP47

Ivanova, A GP92

Jansson, M GP182

Iancu, S EP560

In Kim, H GP219

Ivashenko, O GP157

Jarek-Martynowa, IR EP561

Ianevskaia, L EP200

Inácio, A EP267

Ivovic, M EP127 & EP42

Jarić, I EP212 & EP359

Ibán˜ez-Costa, A EP698

Inácio, I EP106

Iwakura, Y GP14

Jaric, I EP779

& EP929

Ing, S EP291

Iwasa, T EP1156

Jarvis, S OC3.2

Iban˜ez-Costa, A EP941

Iniesta, J EP681

Iyidir, OT EP39

Jarzab, B EP1420, EP1440

Ino, R EP840

Izumi, Y EP1270

& EP349

Ibadula, S EP1301,

Inostroza-Nieves, Y OC6.5

Izuzquiza, A EP1040

Javier Martinez-Martin, F

EP1302 & EP1304

Ibarra-Reynoso, L-d-R

Ioachim, D EP1216,

EP193

EP666

EP1221 & EP1466

Járay, B EP1384 & EP1434

Jayanthy, R EP1140

Ibarra-Reynoso, LdR

Ioana, AA EP587

Jannari, M OC4.2

& EP475

EP437

Ioana, IA EP720

Jarvelin, M-R EP1110

Jayasena, C GP131

Ibragimova, N EP736

Ioannidis, D EP1139

Jørgensen, JOL GP17,

Jayaweera, J EP124

Ibraheem, N EP97

Ioannidis, J EP744

GP181, EP63, GP190

Jazbec, A EP508

Ibrahim, A EP1240

Ion, O EP1371

& EP654

Jaziri, H EP355

& EP649

Iordachescu, C EP1063

Jørgensen, N GP150

Jeandidier, N EP1352

Ibrahim, NA EP1299

& EP16

Jabrocka-Hybel, A OC9.3

Jeanneret, F EP782

Ibrahim, RH EP497

Iorgi, ND EP922

Jacewicz, M EP1104

Jedeon, K GP142

Ibrahim, WA EP425

Iozzo, P MTBS2

Jach, R EP141

Jedrzejuk, D EP1135

Ichihara, A EP1014

Ipekci, S EP1214, EP256,

Jackuliak, P GP38

Jemuovic, Z EP956, GP188

Icin, T EP1024, EP1089,

EP419 & EP421

Jacob, J EP1249 & EP1296

& GP197

EP116, EP245

Ipekci, SH EP1101,

Jacob, S EP597

Jendrzejewski, J EP396

& EP709

EP1167 & GP96

Jacyna, A EP577

Jenkinson, C EP798

Iconaru, L EP225

Ippolito, S EP688

Jae Chung, Y GP219

Jenny-Burri, J OC13.5

Ida Maiorino, M EP1293

%& EP691

Jaeschke, H OC4.2

Jensen, B EP40

Ientile, R GP175

Iqbal, Z EP1092, EP1225,

Jaffe, A EP735

Jensterle Sever, M GP39

Ifteni, PI EP774

EP205 & EP761

Jaganmohan, B EP552

Jensterle, M EP1105

Igarashi, Y GP14

Irahara, M EP1156

& EP553

& GP136

Igaz, P GP3

Iregui, IO EP1023

Jagucianskaite, G EP171

Jeon, MJ EP1366, EP1367

Iglesias, MMG EP1023

Irfan, M EP1262

& GP211

& EP1421

Iglesias, N EP1040

Irigoyen, L EP1332

Jahan, S EP1092, EP1225,

Jeon, S-Y EP1189 & EP151

& EP112

Irwin, S EP501, EP558

EP205 & EP761

Jeon, Y EP231, EP233

Iglesias, NC EP1217

& EP584

Jahromi, MS EP1125

& EP697

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Jeong, JS EP554

Joshi, S EP555

Kalthoum, M EP1128,

Karamagiolis, S EP559

Jeong, YA EP987

Joshi, SR EP553

EP189, EP77 & EP770

Karanikas, MA EP1378

Jercalau, S EP108,

Jouinot, A OC7.2

Kaltsas, G EP1253, EP176

Karapanagioti, A EP67

EP1395 & GP21

Jozkow, P EP1160

& EP67

Karapanou, O EP1047

Jeremic, D EP694

Jublanc, C GP189

Kaltzidou, V EP217

Karathanassi, I EP483

Jeremic, R EP470

Jueppner, H GP45

Kamada, T EP643

Karavanaki, K GP99

Jervis, N EP192 & EP746

Jung, GS EP506 & GP56

Kamalov, T EP736

Karavitaki, N EP1051,

Jesús, C EP641

Jung, KY EP1451

Kamaruddin, S EP25

GP114, GP180 & S13.1

Jessen, N EP654

Jung, SJ EP590

Kamenicky, P GP19

Karayel, T EP679

Jesus Obregon, M GP217

Junquera, F EP165

Kamenov, Z EP699

Karbownik-Lewinska, M

Jesus, C EP1323 & EP32

Jurecka-Lubieniecka, B

& GP82

EP1325

Jesus, DFM EP74

EP349

Kamilla, I EP1124

Karefylakis, C EP680

Jeunemaitre, X GP15

Jurek, A OC12.4

Kaminskyi, O GP86

Kareva, M EP1025

Jeung, E-B EP1100, EP248,

Juskiene, R EP171

Kamp, K S14.3

& EP345

EP727, EP738 & GP42

Juszczak, M EP682

Kamyshna, V EP454

Karim, R EP190 & EP316

Jevtic´, JT EP1245 & EP356

Juul, A GP150

& EP455

Karimova, M EP314

Jguirim, A EP833

Juul, R GP152

Kamyshny, A EP454

& EP324

Jhamb, R EP408

& EP455

Karlovich, N EP242

Ji Jeon, M OC14.5

Kósa, J EP1434 & GP37

Kanamoto, N EP27

& EP527

Jiang, M EP1

Kohrle, J OC3.4

Kandaraki, E EP1098

Karmali, R EP225

Jiménez, CM EP882

Komoglu, S EP565

Kang, H-C EP987

Karonova, T EP200

Jiménez, IA EP294

Kovesdi, A EP1434

Kang, HY EP727

Karsenty, G S7.2

Jiménez, MJJ EP581

Kugler, A EP91

Kang, R EP494

Kartal, I EP1243 & EP447

Jiménez, T EP1284

Kuhnen, P S24.1

Kang, S EP316

Karwowski, B EP1435

& GP210

Kusters, B GP160

Kang, SA GP42

Kasamaki, Y EP1270

Jiménez-García, R EP431

Kałuz˙na, M EP1074,

Kania, L EP577

Kasifoglu, N EP1294

Jiménez-Vacas, JM EP790

EP1433 & EP1474

Kanouta, F EP217

& EP467

Jiménez-Varas, I EP185

Kabacam, S GP212

Kaoustou, S EP239

Kasparova, P EP837

Jimenez, F OC8.5

Kablia Samia, O EP138

Kaplieva, M EP556

Kassi, E EP67 & GP236

Jimenez-Varas, I EP184

Kacem, FH EP1128,

Kapliyeva, M EP515

Kassi, G EP1008, EP1098

Jmaa, A EP355

EP167 & GP113

Kappeler, L OC5.5

& EP38

Joa˜o Bugalho, M EP1049,

Kapsalaki, E EP861

Kassir, N GP110

Kacem, M EP1389

EP1055, EP329

Kapusta, P OC9.3

Kastanakis, S EP625

& EP441

& EP791

Kara, M EP620

Kastelan, D EP71, EP81

Kadioglu, P GP187

Joa˜o Oliveira, M EP1155

Kadrina, N EP1036

Karabid, NM EP926

& GP122

& EP818

Kafetzi, M EP62 & EP885

Karabulut, E GP212

Kastelan, M EP71

Joao Martins, M OC14.3

Kaftanovskaya, E EP754

Karaburgu, S EP1129

Katalinic, D EP209

Joaquim, S EP1133

Kahraman, S EP1144

Karaca, A EP1175,

& GP232

Jodkowska, A EP187

Kahramanca, FD EP1429

EP317, EP344, EP384

Katamadze, N EP504,

& EP78

Kaikkonen, K EP1110

& EP854

EP650 & EP797

Johannsson, G EP55

Kaindl, G EP1087

Karaca, Z EP1129

Kats-Urgurlu, G EP155

& GP9

Kaiser, U EP1342

& EP968

Katsamakas, M EP1473

Johansson, A GP182

Kajdaniuk, D EP349

Karachaliou, F EP62

Katsavouni, C EP366

Jokela, H EP364 & OC13.3

Kajor, M EP1382

& EP885

Kaufman, J-M EP1191

Jona, E EP1115, GP135

Kakarigi, L EP71

Karachentsev, I EP982

Kaufmann, ML EP1087

& GP141

Kalaitzidis, R EP299

& EP983

Kaur, G EP558

Jonas, N EP13

Kalaitzidou, S EP217

Karaduman, T EP815

Kaur, H EP1249

Jonas, W OC3.4

Kalan Sarı, I EP1053

& GP74

Kawaguchi, S EP1242

Jones, G GP104

Kalantaryan, LG EP422

Karagoz, H EP644 & GP95

Kawamura, H EP1270

Jonsdottir, G EP19

Kalere, I GP209

Karahan, I EP604

Kawashima, A EP273

Jonsson, P EP1010, EP884

Kalhan, A EP303 & GP114

& EP683

Kaya, A EP1305, EP1416

& GP192

Kalikakis, G EP1418

Karakaya, P EP1235,

& EP545

Jordan-Perez, B EP666

Kalinin, A EP1025

EP644 & GP95

Kayas, D EP86

Jordana, L EP247

Kalinin, P EP799 & EP895

Karakaya, S EP1343

Kayatas, M EP675

Jorgensen, J MTE2

Kalisz, M EP908

Karakose, M EP1097,

Kazakou, P EP202

José Requena-Tapia, M

Kalnina, I OC6.3

EP1368, EP327

Kazaryan, A EP1457

EP790

Kalogeris, N EP239

& EP999

Kazmi, SAR EP761

Joshi, A EP844

Kalter-Leibovici, O EP735

Karakurt, F EP1416

Kearney, T EP1022

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Kearns, S EP430

Khan, I EP85

Kim, JH EP452, EP531,

Klimaite, R EP1321,

Kebapci, M EP1444

Khan, R EP498

GP162, GP54 & GP87

EP1436 & EP164

& EP69

Khasanova, K EP464,

Kim, K-S EP516

Kljajic Babic, K EP1151

Kebapci, MN EP110

EP465, EP617

Kim, M EP1366 & EP1367

Klocek, M EP357

& EP1444

& GP170

Kim, MJ GP56

Kloos, C EP528

Kebapci, N EP69

Khasawneh, A EP424

Kim, MK EP554

Klose, M EP40 & GP181

Kebapcilar, A EP1167

Khatib, M EP867

Kim, NH GP91

Klovins, J EP931 & OC6.3

Kebapcilar, AG EP1101

Khattak, A EP1339

Kim, S-M EP516, EP950 &

Kluczynski, L EP1026

Kebapcilar, L EP1101,

Khessairi, N EP1193,

EP1189

Kluk, A EP1450

EP1167, EP1214,

EP1208 & EP1212

Kim, SG EP1451 & GP91

Klusonova, P EP730

EP256, EP419, EP421

Khiari, K EP1232,

Kim, SK EP438

Kluth, O OC2.3

& GP96

EP1233, EP147,

Kim, SR EP590

Klyushina, A GP78

Kebebew, E GP124,

EP482, EP832

Kim, SW EP1424 & OC9.4

Knape, M GP28

GP186, OC7.3 & S19.2

& EP87

Kim, SY GP162

Knappe, U GP176

Kedad, L EP718

Khodgaeva, F EP1106

Kim, TH OC9.4

Knezevic, N EP71

Kee Shong, Y OC14.5

Khoo, B EP985

Kim, TY EP1366, EP1367

Knigge, U D2.1

Keerthi, AvB EP555

Khoo, J EP24 & OC11.4

& EP1421

Knip, M S29.1

Keevil, B EP1169

Khovidhunkit, W EP1288

Kim, WB EP1366, EP1367

Knispelis, R EP839

Kefeli, M GP243

Khripun, I EP1164

& EP1421

Knobloch, L EP932

Kehinde, A EP1095

& EP695

Kim, WG EP1366, EP1367

Kołodziej-Kłe˛k, A EP1338

Keil, M GP68

Khroyan, A EP304

& EP1421

Kołodziejczak, R EP1205

Keinanen-Kiukaanniemi, S

Khusniyarova, K EP1141

Kim, Y EP1256, EP452,

& EP1336

EP1110

Khyzhnyak, O EP982

EP531, GP54 & GP87

Kobyliak, N EP1146,

Keithellakpam, K EP408

& EP983

Kim, YB GP145

EP622, GP60 & OC2.4

Kek, PC EP29 & EP46

Kialka, M EP1111,

Kim, YM EP700

Koca, C EP1108

Kekstas, G GP31

EP1148, EP141,

Kim, YN OC9.4

Koca, N EP759

Kelepouris, N EP748

EP357, EP371

Kineman, RD EP698

Koca, TG EP759

Kelestimur, F EP1129,

& EP890

Kinikoglu, O EP834

Koch, M EP5

EP968 & S18.2

Kiamanesh, R D2.2

Kinlen, D EP696

Kochanowski, J EP908

Kelly, N EP1309

Kiec-Klimczak, M EP284

Kiokas, S EP423

Kocjan, T EP36, GP39

Kemali, Z EP219

Kilbane, M EP259

Kirac, CO EP1101,

& OC10.4

Kempegowda, P EP1052

Kilic, AU EP968

EP1214, EP256

Kocsis-Deák, B EP1434

& OC3.3

Kilic, I EP237

& GP96

Koetsveld, Pv EP182

Kendereski, A EP127

Kilic, M EP1377, EP1429,

Kirchner, J N2.2

Kogan, M EP1164

& EP42

EP237 & GP233

Kirchner, T EP52

Koh, SB EP236

Kendir, IC EP421

Kilicarslan, A EP1429

Kiremitci, S EP967

Kohler, F EP1369

Kenyeres, P EP1410

& GP233

Kiric, MM EP491

Kok, I EP332

Kermaj, M EP495, EP634

Kilicli, F EP834

Kirnap, NG EP1431

Kokareva, L EP736

& EP765

Kilit, TP EP1380

& EP39

Kokkinos, M EP67

Kero, J OC4.2

Kilkelly, K EP720

Kirschner, G GP37

Koksharova, E EP561

Kerstens, MN EP155

Killinger, Z GP38

Kiseleva, T GP170

Kolátorová, L EP14

& N1.3

Kim, A EP1141

Kiselova, I GP86

Kolag˘ası, O EP1053

Keskin, C¸ EP277

Kim, B EP233 & EP697

Kistorp, C EP63 & GP181

Kolackov, K GP165

Keskin, C EP1059, EP967

Kim, C-W EP1109

Kita, M EP1303, EP1307,

Kolenc-Peitl, P EP1445

& EP988

Kim, CH EP590

EP1417, EP1471,

Kolesnicova, G EP917

Keun, H NSA1

Kim, D-M EP438, EP605

EP223, EP68, EP771,

Kolici, E EP2

Keutgen, XM GP124

& EP729

EP828 & GP40

Koller, T EP1173

& OC7.3

Kim, DS EP1116 & EP925

Kitagawa, W EP1385

Kollerova, J EP1046

Khabeishvili, N EP658

Kim, G-S EP151

Kitajima, N EP4

Kollipara, P EP1354

Khachatryan, M EP304

Kim, H EP506, GP219

Kitsos, A EP299

Kolodkina, A EP1025

Khacimova, L EP200

& OC9.4

Kiyici, S EP322, GP112

Kolodziej, M EP1477

Khajavi, N EP806 & OC2.3

Kim, HI EP1424 & OC9.4

& GP161

Kolomiets, N EP749

Khalaj, A EP662 & OC5.2

Kim, HJ EP729

Kleber, ME GP107

Kolosszar, S EP731

Khalfallah, Y EP1126

Kim, HK EP987

Klein, J-P EP1126

Kolouri, O EP877

Khalid, M EP631 & EP649

Kim, HS GP145 & GP91

Kleinau, G OC2.3

Kolsi, B GP113

Khalimova, Z EP314,

Kim, HY EP1451

Kleine, MT EP385

Kolukula, VK EP552,

EP324 & EP901

Kim, I EP233 & EP697

Klephortova, I EP521

EP553 & EP555

Khan, A EP291

Kim, J-H EP729 & GP169

Klett, D EP1123

Komarowska, H EP388

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Komerdus, I EP1069

Kotaja, N OC13.3

GP22, GP119, GP121,

EP1366, EP1367 &

& EP50

Kotis, M EP217

& EP161

EP1421

Kometani, M OC3.1

Koukkou, E EP793

Krompa, K EP1472

Kyle, C EP1314

Kondracka, A EP48

Koukoulioti, E GP80

Krssak, M EP638

Kyoung Kim, M EP690

Kondratiuk, K EP1146,

& EP176

Krstevska, M EP499

Kyriacou, A EP481

EP622 & OC2.4

Koukoulis, G EP483

Krude, H MTE4 & OC2.3

Kyriienko, D OC2.4

Kondratiuk, V EP1146

Koukoulis, GN EP559

Kruljac, I EP43, EP172,

Kyrimis, T EP217

& EP622

& EP618

EP463 & EP549

Kondrotiene, A EP434,

Kouraklis, G EP1253

Krupinova, J EP257,

La Sala, D EP1064

EP839

Koussay, A EP646, EP780

EP318, EP323 & EP347

La Vignera, S OC13.4

& GP244

& EP1229

Krylov, V EP651

& EP35

Konijnenberg, M EP1445

Koutsilieris, M EP275

Krzesinski, P OC12.4

Lacˇković, M EP1245

Konishi, S OC3.1

Kovács, L GP44

Ksela, U EP204

Labashova, V EP480

Konrade, I EP931, GP209

Koval, S EP458

Ksiaa, M EP355 & EP762

Lacka, K EP721

& OC6.3

Kovaleva, E EP257

Kuzˇma, M GP38 & EP1173

& EP1348

Konstantinova, E EP663

Kovo, M EP1185

Kucharczyk, M GP154

Lacquement, E EP616

Konstantopoulos, K

Kowal-Bielecka, O EP466

Kudo, M GP14

Lacramioara Serban, I

EP417, EP442

Kowalczyk, M EP1348

Kudou, K GP134

EP809

& EP509

Kowalik, A EP1382

Kukulska, A EP1420

Lacroix, A P3 & EP1039

Kopchick, J S3.2

Kowalska, A EP1274,

& EP1440

Lacroix, D OC5.3

Kopczynski, J EP1382,

EP1297, EP1382,

Kulaksizoglu, M EP545,

Lacy, C EP558

EP1409 & EP1442

EP1305 & EP1416

Laczmanski, L EP1135

Kopilova, O GP86

Kowalska, I EP466

Kulcsár, I GP44

Lafoyianni, S EP1139

Kor, A GP96

& EP1104

Kulczynski, L EP283

Lages, A GP35, EP44,

Korac, A EP693

Kozan, P EP592

Kuliczkowska-Plaksej, J

EP45, EP61 EP203,

Korac, A EP693

Koziara, M EP1477

EP1135

EP392, EP394, EP444,

Korac, B EP693

Koziolek, M EP229

Kumar Ch, S EP552

EP445, EP1009,

Korbonits, M GP160,

Kozloviene, D EP1437

Kumar, A GP195

EP1049, EP1195 &

GP195 & EP954

Kramer, U EP800

Kumar, H GP167

EP1475

Koreiviene, R EP164

Krajewska, J EP1420,

Kumar, J EP134

Laguna, MdCS EP581

Koren, R EP1313

EP1440 & EP1441

Kumar, M EP1210

Lahesmaa-Korpinen, A-M

Koren, S EP199 & EP1313

Krajnc, M EP204

Kumbasar, A EP1327

EP1285

Korevaar, T S5.1

Kraljevic, I EP71

Kummer, E EP199

lahner, H GP177

Korkmaz, HA EP410

& EP81

Kumru, H OC12.3

Lai, A EP688 & EP691

& EP413

Krasilnikova, V EP1308

Kundzina, L EP342

Lai, J EP321

Korolenko, H EP1308

Krasner, A GP47

Kunori, T EP1242

Lainetti, KR EP380

Korpershoek, E OC7.2

Krass, M EP607

Kunzke, T OC1.1 & EP52

Lainez, M EP1001

& EP155

Kratschmar, D EP781,

Kuppusamy, M EP37

Laiz, B EP99

Korzynska, W EP78

EP782 & EP822

Kuprionis, G EP1437

Lakatos, G GP37

Kósa, JP EP1384

Kraus, J EP1441

Kurek, A GP154 & GP158

Lakatos, P GP37, EP1384

Kosák, M EP14 & EP208

Krawczuk-Rybak, M

Kurowska, M EP831

& EP1434

Koschka, K EP1188

EP1226

& EP850

Lakis, Me GP124

Koseoglu, D EP287

Krawczyk, M EP775

Kursat, FM EP1235

Lal, V EP1239

& EP1329

Krcma, M EP293

Kurt, CC EP1379

Lalli, E EP91 & GP2

Kosilek, RP EP1027

Krebs, M EP638

Kurt, K EP1101

Laloglu, E EP1108

Kossiva, L GP99

Kreivaitiene, E EP543

Kuru, B GP243

Lalonde, MN EP1373

Kostareva, A GP78

Krentowska, A EP466

Kust, D EP172

Lam, A EP426

Kostic, S EP64

& EP1104

Kusumoto, T GP134

Lam, L EP1314

Kostin, G EP269 & EP286

Kriksciuniene, R EP543

Kut, A EP39

Lamaziere, A GP19

Kostitska, I EP628

& EP1102

Kutbay, NO EP1194 & EP1379

Lambert, E GP135

Kostoglou-Athanassiou, I

Krivonosov, N EP760

Kutin, M EP799 & EP895

& GP141

EP136, EP221, EP222,

Krivosheev, A EP126

Kuzior, A EP105, EP107,

Lambert, G GP135, GP141

EP275, EP276, EP366,

& EP1457

EP170, EP193, EP390,

& EP1115

EP368, EP1300 &

Krivosheeva, Y GP193

EP530, EP621 & EP757

Lambert, P EP295

EP1460

& EP905

Kuzmenko, N EP695

Lambrescu, IM EP763

Kostopoulos, M EP366

Krogh-Rasmussen, A

Kwapich, M OC5.3

Lambrinoudaki, I EP1084

Kostova, M EP1271

OC13.2

Kwon, H-S OC14.5,

& EP214

Kostovska, KB EP499

Kroiss, M OC1.1, OC7.2,

EP554, EP690,

Lameirao, C EP468

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Lamia, K EP279

León, MVC EP563, EP769,

EP713, EP1050 &

Limem, K EP1290

Lamy, C EP179

EP1331 & EP1467

EP1054

& EP1430

Landin, A OC3.4

Lean, M S24.3

Lenzi, P GP223

Lin, H EP1

Lanne, T OC6.4

Lebkowska, A EP466

Leo, M OC4.4

Lin, K-H GP64

Lang, F OC11.5

& EP1104

Leo, MD EP927

Lin, W GP171

Lang, K GP122

Leboulleux, S D5.2

Leon, MVC EP270

Lin, Y EP1

Langdahl, B D3.1

Leca, B EP855

Leopizzi, T GP214, GP215

Linardi, A EP793

Langova, D EP1272

Leca, BM EP143

& GP216

Linares, JLC EP406

Lania, A OC7.4

Lechner, A GP196

Lerchbaum, E S27.2

& EP407

Lania, AG EP924

& EP639

Lessi, F EP348

Lindgren, M GP117

lanschakov, K EP323

Lecumberri, B EP904

Leszczynska, E EP1226

Linglart, A S1.1 & GP45

Lanz, C EP609

Leczycka, M EP396

Leteurtre, E EP1369

Links, TP OC9.1 & EP155

Lapauw, B EP1019

Leczycka, ME EP766

Letra, L EP704

Lio, S EP1215

& EP1191

Ledwon, A EP1440

Leushev, B EP749

Lioni, A EP239

Lapshina, A EP917

Lee, C EP231

Leustean, L EP188

Lipinska, D EP466

Lara, A EP641

Lee, EJ EP960

& EP961

Lippert, J GP119

& EP1278

Lee, H-M GP47 & EP1109

Leví, AR EP1072

Lira, A EP1356

Lardiés-Sánchez, B EP461

Lee, HJ EP700

Levina, K EP142

LIRA, D EP490 & EP492

Laroche, S GP189

Lee, Hm EP729

Levine, F OC6.1

Litwiniuk, A EP908

Larrán, L EP1278

Lee, J-H OC14.2, GP91

Levine, MA GP47

Litwinowicz, M EP721

Larrauri, MZ EP125

& EP248

Levterov, G EP600

Liu, C-L OC14.2

Larsen, TH EP33

Lee, JH EP727 & EP1100

Levterova, B EP600

Liu, Q EP801

Larumbe, T EP3, EP9

Lee, K EP231

Levy, S EP1374

Livadas, S OC4.5 & EP588

& EP952

& EP959

Lewandowski, K GP183

Livingstone, DEW EP802

Laschet, C EP928

Lee, KY EP590

Lewicki, M EP144, EP338

Liyanarachchi, KD EP879

Lason, W GP154

Lee, M EP605

& EP865

Lizama, J OC5.1

Lassoued, N EP833,

Lee, MY EP236

Lewinski, A GP183,

Lizarraga, A EP1040

EP1236 & EP1238

Lee, S-H GP145, EP531

EP1325

& EP1217

Laszlo, A EP742

& EP690

& EP1435

Lizis, P EP1297

Lattarulo, MS GP214

Lee, SB GP54, GP87 &

Lezaic, L EP1445

Lizis-Kolus, K EP1297

& GP216

EP452

Lhadj, C OC5.5

& EP1382

Latt, J GP182

Lee, W GP129

Li, G EP551

Ljubic, S EP508

& EP1070

Leenhardt, L GP148

Li, L GP171

Ljubojevic, N EP806

Lau, E EP195

Lefebvre, H GP12 & GP120

Li, Q OC1.5

Llahana, S N2.4

Lau, N EP321

Lefter, A EP1067

Liang, J GP171

Llamazares-Iglesias, O

Laukiene, R EP1412

Leighton, E GP104

Liang, R GP119

EP866

Laura Tanda, M EP691

Leijon, H EP163

Liarigkovinos, T GP32

Llavero, M GP198

Laura, I EP939

Leita˜ o, C EP919

& EP1418

& EP227

Laura, MM EP74

Leita˜ o, F EP44

Libé, R OC7.2

Llevy, S EP1391

Lauretta, R GP149

Leita˜ o, P EP872

Libè, R GP123

Lloclla, EAC EP270,

Lauretti, L EP997

Leitao, C EP648

Libeert, D EP812

EP563 & EP1467

Laursen, T EP40

Leite, V MTE14, OC14.3,

Licchelli, B GP214, GP215

Lobo, C OC14.3

Lautier, C GP137

GP23, GP126, EP258,

& GP216

Lobo, J EP82

Lavenberg, J GP192

EP297, EP1219 &

Lichiardopol, C EP1364

Lobstein, T S4.3

Lavy, R EP199

EP1454

Lichtenegger, K EP609

Locatelli, M EP924

Law, N-M OC11.4

Leite-Moreira, A GP217

Lidiya, B EP989

Locht, H EP40

Lazúrová, I EP1127

Leiva, Ad EP681

Lienhardt, A GP120

Locsei, Z GP44

Lazúrová, Z EP1127

Leka-Emiris, S EP62

Lietzow, J OC3.4

Lodish, M GP68 & EP13

Lazanas, M EP239

Lemme, R EP152

Lila, B EP120 & EP138

Loeliger, R OC9.2

Lazaris, E EP423

Lemos, E EP51

Lim, HJ EP700

Lof, C OC4.2

Lazarou, L EP1417

Lemos, N GP79

Lim, J EP1314

Lofrano-Porto, A OC4.3,

Lazo-de-la-Vega-Monroy,

Lemos, R EP704

Lim, JS EP236

GP26, EP84 & EP807

M-L EP666

Lenarcik-Kabzda, A

Lim, SL EP115

Loh, LM EP29 & EP46

Lazo-de-la-Vega-Monroy,

EP1135

Lima, C OC4.3

Lohse, K EP806

ML EP437

Lenart-Lipinska, M EP144

Lima, LM GP234

Loiodice, S GP142

Lazovic, R EP1283

& EP338

Limam, K EP1427 & EP1428

Loktionova, A EP1141

Lea˜ o, M EP305 & EP807

Lenzi, A OC9.5, GP16,

Limbert, C GP222,

Lombès, M OC5.5

León, CA EP107

GP149, GP168, EP537,

EP1207 & EP1486

Lombardi, G EP777

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Lombes, M GP7

Ludecke, DK GP176

Maaroufi, A EP441

Maisnam, I EP343

Lomtatidze, G EP647

Ludgate, M EP1342

& EP1389

Maitre, SC GP19

Londero, T EP919

Ludwig, P EP52

Macário, F EP175

Majeed, M EP572

Longhurst, A EP280

Ludwig-Gałęzowska, A

Macário, MC EP394

Majewska, R EP890

Lopes, A EP567

OC9.3

Macazaga, VP EP294

Majewska, U EP1274

López, AA EP948

Luger, A EP638 & EP1010

Macedo, D EP297

Majic Milotic, D EP1151

Lopes, AM EP824

Luisi, F GP168

Macena, LB GP178

Majos, A GP173

López, AV EP878

Luiz, HV EP1298

MacFarlane, H EP1306

Majstorović, T EP1469

López, IF EP563

Lumi, E EP2, EP546,

Machado, C EP51, EP145,

Mak, G EP1339

López, J EP973

EP1370

EP1155, EP1211,

Mak, OK EP894

López-Fernández, J EP906,

& EP1470

EP1351 & EP1356

Makarchuk, N EP420

EP909 & EP910

Lungu, I EP114 & EP158

Machenahalli, P GP29

Makay, O EP1194

Lopes, JM EP174

Lunn, M EP1075

& GP30

Makhlina, A EP556

Lopes, L EP139, EP887 &

Luo, C-W EP1103

Machlowska, J OC9.3

Makhlina, E EP515

EP1359

Lupian˜ez, A EP681

Maciejewski, A EP721

Makhonin, A EP1286

López-Iglesias, M EP11

Luque, PS EP708 & EP717

& EP1348

Makitie, O OC10.5

& EP955

Luque, R-M EP819

Maciejewski, M EP1372

Maksoud, H EP766

Lopes, N EP468

Luque, RM GP128, EP178,

Maciel, A OC4.3

Makstiene, J EP1437

Lopes-Ventura, S GP126

EP472, EP698, EP790

Mackay, D GP45

Malagnino, V EP782

Lopez, FJV EP544

& EP929

MacKenzie, SM GP58

Malaktari- Skarantavou, S

Lopez, IF EP270

Luque-Fernández, I EP866

Macut, D GP139, GP140,

EP1202

Lopez, M GP111 & EJE1

Luque-Huertas, RM EP941

EP75, EP80, EP166,

Malaktari-Skarantavou, S

Lopez, MJ EP1001

Luster, M D5.1

EP177, EP191, EP484,

EP859

Lopez, MLA EP1023

Lutjohann, D EP359

EP1114 & EP1184

Malchiodi, E EP1043

Lopez, N EP944

Lutsenko, A EP1028

Madeo, B GP33 & GP51 &

Maldonado, G EP1332

López-Miranda, J EP472

Luzi, L OC6.2 & EP653

EP1383

Malecka-Tendera, E GP67

López-Presa, D EP1021

Lwow, F EP1135

Mader, JK EP609

& EP726

López-Tinoco, C EP1278

& EP1160

Maduen˜ o, FJT EP627

Malek, I EP120

López-Valasco, R EP858

Lyga, S OC4.4

Maduen˜ o, FT EP998

Males, D GP73 & EP1044

López-Velasco, R EP915

Lyhne, J GP17

Madureira, D EP1330

Maletkovic, J EP361

& EP1203

Lyra, R EP841, EP899

Maecke, H EP1445

Malhotra, N EP1249

Lopez-Tinoco, C EP544

& EP975

Maeda, T EP1385

Malicka, J EP831 & EP850

Lopez-Velasco, R EP535,

Lyratzopoulos, N EP1378

Maffei, M EP397

Malicka, K GP183

EP1174, EP1200

Lysianyi, M EP622

Maffezzoni, F OC10.3

Malik, R EP453

& EP1287

Lyssenko, V S29.2

Maffi, P OC6.2

Maliqueo, M EP1120

Lorena, DF EP74

Lyssikatos, C GP68,

Mafra, M EP1000

Mallo, F GP52, GP75

Lorena, SG EP74

GP236 & EP13

Magalha˜ es, D EP140,

& GP156

Losada, E GP84

Lyubov, M EP989

EP477, EP564, EP630,

Malm, J EP1246

Losito, S EP1407

EP719, EP871 & EP872

Malouf, J GP36

Lotfi, C GP6

Magas, S EP1161

Mamdouh, M EP1154

Lotfi, L EP149

Márquez, PO GP240

Maggi, M GP147, EP370

Mamedova, E EP345

Louiset, E GP12

& EP862

& EP377

& EP346

Lourenc¸o, A GP217

Márquez-Pardo, R EP858,

Maggioni, A EP922

Mami, FB EP502

Louro, P EP394

EP915 & EP1203

Magno, S EP397

Mammadova, A EP378

Louvigné, M GP143

Makela, S GP167

Magro, G EP268

Manani, C EP827

Løva˚s, K EP33, EP49 & EP59

Maki-Jouppila, J EP692

Maha, K EP646 & EP1229

& EP828

Ltaeif, B EP1290, EP1427,

Mannisto, T EP1285

Mahdi, A EP741

Mancha-Doblas, I GP71

EP1428 & EP1430

Marz, W GP107

Maher, E GP27

& EP614

Łuczyn˜ ska-Kotodziejczak, A

Méndez-Bailón, M EP431

Maher, M EP1299

Manchenko, O EP521

EP1336

Møller, N EP654

Maher, MM EP497

Mancini, A EP1260

Luís Medina, J EP1289

Muller, B EP18

Mahlina, E EP523

Mancini, C EP713

Luís, R GP226

Muller, N EP528

Mahmoodi, B OC5.2

Manda, D EP1063,

Lu, B EP934

Muller, T OC2.3

& EP642

EP1094, EP1176,

Lubrano, C GP168,

Muller, U EP528

Mahomed, F EP28

EP1180, EP1216

EP702, EP713

Muller-Reible, C GP119

Maia, JC GP234 & EP140

& EP1466

& EP1054

Munzker, J EP1188

Maillo-Nieto, A EP180

Mandache, E EP16

Luconi, M OC7.2, GP3 &

Mašlanková, J EP1127

Maina-Nock, T EP1445

Mangafas, N EP239

GP8

Ma, D EP1

Maiorino, MI EP1121

Mangelsdorf, D P2

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Maniatis, A GP66

Marconcini, G EP970

Marquez-Pardo, R EP535,

Martins, AC EP10, EP181

Manita, I EP486

Marcondes, J GP178

EP1174, EP1200

& EP599

Manjer, J EP1246

Marczewski, K EP826,

& EP1287

Martins, AF EP41, EP96,

Mannelli, M OC7.2, GP3,

EP1282 & EP1372

Marre, M EP1310

EP281, EP853, EP897,

GP8, GP25, GP123,

Marek, B EP349

Marshania, Z EP797

EP898, EP1012,

EP92 & EP93

Marelli, F OC8.2 & EP1222

Marszałek, A EP1474

EP1021 & EP1269

Mannfolk, P GP182

Marengo, AP EP88 & EP94

Martín, AA EP574

Martins, C EP923

& EP1070

Margarida Póvoa, A

Martín, AG GP89

Martins, D GP35, EP44,

Mannina, C GP108

EP1155

Martín, DRdA EP717

EP45, EP61, EP175,

Mannstadt, M GP47

Maria Aragués, J EP791

Martín, E EP180

EP203, EP392, EP394,

& EP291

& EP1055

Martín, FJM EP107

EP444, EP445,

Mannucci, E EP370

Maria Mongioı`, L OC13.4

Martín, LS GP241

EP1009, EP1195,

Manojlović-Stojanoski, M

Maria, RG EP74

& EP150

EP1475,

EP212

Mariani, L EP986

Martín, RDlV EP544

Martins, H EP1461

Manojlovic-Gacic, E EP954

Mariani, S GP168, EP702

Martín-Iglesias, D EP443,

Martins, JM EP281, EP41,

Manojlovic-Stojanoski, M

& EP713

EP524 & EP593

EP853 & EP96

GP62

Maric, A EP491

Martín-Portugués, AB

Martins, LS EP460

Manolachie, A EP188

Marie Kolte, A OC13.2

EP183

& EP462

& EP1360

Marijnissen-van Zanten, M

Martínez, A EP973

Martins, MJ EP1475

Manolopoulos, K OC3.3

GP10

Martínez, AH EP708

Martins, PC EP1465, EP82

Manosso, K EP1013

Marinò, M EP1247

& EP717

& EP98

Manskaya, K EP983

Marin, CC EP270

Martínez, C EP681

Martins, R EP1459

Manso, F EP706

Marin, M EP693

Martins, AD EP1179

& EP1463

& EP707

Marin, MG EP755

Martínez, CM GP238

Martins, S EP567

Mansoor, Q EP205

Marina, L EP42 & EP127

Martínez, MJ EP681

& GP205

Mansoor, R EP1262

Marinis, LD S13.2

Martínez-Aguayo, A

Martins, T EP1049,

Mantachik, M EP737

Marino, L GP153

OC5.1

EP1459 & EP1463

Mantel, A GP45

Marino, M GP245

Martínez-Chacón, G GP167

Martins-Costa, S EP457

Mantovani, A EP743

& EP1131

Marta, H EP641

Martynov, S EP521

Mantovani, G OC9.5,

Mariot, J EP1123

Marti, J EP247

Martynska, L EP908

GP43, EP924 &

Mariotti, M EP653

Marti-Ayerdi, J EP247

Martynyuk, L EP420

EP1043

Marjot, T GP70

Martin, L EP1190

Marugan, J EP754

Mantovani, G EP20

Markelic, M EP693

Martin, M EP1415

Marx, SJ OC7.3

Mantripp, D EP728

Marker, A GP27

& EP1476

Masaki, C EP1385

Manuel Cameselle-Teijeiro,

Markey, K EP798

Martin, P-Y OC13.5 & EP820

Masana, L MTE16

J OC14.3

Markosyan, RL EP422

Martin, S EP143, EP943,

Mascaren˜ o, I EP906,

Marc¸alo, J , EP157, EP300,

Markovic, I GP225

EP1263 & EP1371

EP909 & EP910

EP1255 & EP1340

& EP1480

Martin, SC EP947

Mascarenhas, M EP234,

Marín, CC EP563, EP1331

Markozannes, G EP1172

Martin-Grace, J EP430

EP897 & EP898

& EP1467

Marmarinos, A GP99

Martin-Perez, M EP193

Mascarenhas, MR EP1083

Marín, T EP603

Maroldi, R OC10.3

Martinelli, C EP7

& EP243

Marakoglu, K GP96

Marote, S EP133

Martinelli, S GP25, EP92

Mascarenhas, R EP232

Maranghi, M EP397

Marotta, V EP1407

& EP93

Maseroli, E EP370

Maraver, S GP111

Marouani, N OC11.5

Martinerie, L OC5.5

Masetti, G EP1342

& EP868

Marova, E EP917

Martinez, A OC1.2

Mashahit, M EP412

Marawan, D EP1299

Marques, A EP1206

Martinez, G GP73

Masiello, E EP688

Marazuela, M OC10.2

Marques, AP EP129

& EP459

& EP691

& EP180

& EP174

Martinez-Laguna, D GP84

Maslova, N EP760

Marc, J OC10.4 & GP39

Marques, B EP1459

Martinez-Martin, FJ

Mason, I GP4

Marcelino, M EP139

& EP1463

EP105, EP170, EP390,

Masood, Q EP606

& EP1359

Marques, C EP1049

EP530, EP621

Masovic, S EP693

Marcheggiani, F EP1260

Marques, H GP242

& EP757

Mastorakos, G EP1172,

Marcinkowska, E EP721

Marques, O EP706,

Martinez-Triguero, ML

EP588 & S25.2

Marcocci, C GP33, EP238,

EP707, EP1049,

EP99

Matías, LG EP365

EP274, EP278, EP288,

EP1071 & EP1080

Martino, G EP1260

Mat, A EP696

EP348, EP970 &

Marques, P GP195

Martino, MCD EP786

Matafome, P EP704

EP1247

Marques, PV EP468

Martins, A GP242, EP57,

Matchekhina, L S5.3

Marcon, L EP20

Marques, R GP222

EP599 & EP1058

Matei, L EP838

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Matens, H EP883

McCormack, A OC12.2

Mercadante, R EP1043

EP897, EP898

Mateo-Gavira, I EP714

McDermott, M EP291

Mercedes, R EP641

& EP974

& EP715

McDonnell, DP GP63

Mercier, L EP179

Miguel, Pd EP184

Mateos, CG-F EP290,

Mcgrath, R EP720

Mergen, H EP815 & GP74

& EP185

EP372, EP374, EP610,

Mchirgui, N EP1232,

Mergler, S EP806 & OC2.3

Miguel-Novoa, Pd EP900

EP611 & EP612

EP1233, EP147

Meric, C EP1165

Mihai, A-C EP1419

Materazzi, G EP278

& EP832

Meriem, B EP120 & EP138

Mihai, D EP1395

Mathieu, M OC1.2

McInnes, KJ EP802

Merino, JF EP99

Mihajlovska, M EP1355

Matias, A GP126

Mckone, E EP430

Merino-Torres, JF EP681

& EP1478

Matias, JS GP133

McLean, M GP27

Merkle, E GP185

Mihajlovska, S EP1355

Matias, R GP222

McNeil, C GP69

Mermejo, L EP7

& EP1478

Matos de Figueiredo, C

McQuaid, S EP1318

Mert, EO EP856

Mihu, D EP1364

EP818

Meatchi, T GP15

Mert, M EP1235, EP644

Mijares, AH EP1178

Matos, A EP632 & OC5.4

Med, MS EP149

& GP95

Mikšík, I EP1082

Matos, AC EP1422, EP226

Medeiros, S GP110

Meryam, E EP387

Mikadze, K EP658

& EP486

Medic-Stojanoska, M

& EP845

Mikalauskaite, R EP1436

Matos, L EP1446 & EP887

EP1089, EP116

Mesa, C EP1244

& EP479

Matos, LG EP519

& EP709

Mesa, EM EP862

Mikelaityte, G EP1321

Matos, MJ EP100 & EP82

Medina, D EP1278

& GP240

Mikhaleva, O EP568

Matos, P EP1448

Medina, JL GP199

Mesa, J EP944

Mikhaylova, D GP157

Matrone, A EP288

Medina-Rivero, D EP714

Mesenka, D EP1020

Mikhno, H EP351

Matsiushava, J EP286

& EP715

Meskine, D EP246, EP65

Mikina, E EP1274

Matsuzaka, T GP166

Mednieks, J EP142

& EP718

& EP1382

McEwan, B IPSEN1

Medras, M EP1160

Mesquita, A EP82

Mikolajczak, R EP1445

Matsuzaki, T EP1156

Megerle, F GP123

Messina, E EP1056

Mikulecka, A EP1082

Matsuzu, K EP1385

Mehmood, A EP692

Mestre, JL GP12

Milankov, A EP1024

Matta-Coelho, C EP1071,

Meienberg, F EP889

Methlie, P EP49

Miler, M EP359, EP779,

EP1080 & EP1091

Meijer, OC EP802

Meyer, A EP822

GP202 & GP62

Mattheisson, K EP426

Meireles, C GP26

Meyer, G EP5

Miletic, M EP111

Mattsson, A OC8.4

Mel’nichenko, G EP881

Meyer, J EP13

Milewicz, A EP1135

Matucha, P EP1143

Melchars, D EP802

Mezghani, I EP1324

Milewicz, T EP1111,

Matulevicius, V EP173

Mellado-Soria, J EP1462

Mezosi, E EP1410

EP1148, EP141,

Matusik, P EP726

Mellidez, J EP174

Mezoued, M EP65

EP357, EP371

Matuszewski, W EP17

Melmed, S S23.2

Mezyk, R EP1274

& EP890

Matyjaszek-Matuszek, B

Melnic, E EP935

& EP1409

Milheiro, A EP519

EP547 & EP865

Melnichenko, G EP220

Mezzullo, M EP1166,

Milic, N EP709

Maurer, J EP154

Melo, D EP53

EP669 & EP671

Milicevic, I EP177

Mauricio, D D6.2 & GP84

Melo, EG EP862 & GP240

Mghari Ghizlane, E EP309

Milin-Lazovic, J EP42

Maushart, C OC9.2

Melo, GB EP949

Mghari, GE EP1334

Milionis, C EP793

Mavragani, C EP275

Melo, M EP1449, EP1475,

& EP476

Miljic, D EP779, EP892,

Mavroeidi, V EP176

EP45, EP899, GP35,

Mhidhi, S EP502

EP953, EP954, EP956,

& EP67

OC14.3 & S19.3

Mhiri, A EP1290, EP1427,

GP188, GP197, GP202

Mayila, Y EP1156

Melo, P EP337

EP1428 & EP1430

& GP62

Mayoni, S EP1237

Melus, V EP1344

Min˜ ambres, I EP586

Miller, BS GP65 & GP66

Mazarico, I EP165

Memo, M OC10.3

Micali, G EP1163

Millo, C OC7.3

& GP238

Menéndez, E EP1332

Michalakos, S EP62

Mills, E EP1196, EP123,

Mazeh, H EP1374

Mena, SC EP1481

Michalik, B EP1440

GP29 & GP30

Mazerkina, N EP1025

Mendes de Almeida, M

& EP349

Milošević, V EP212

& EP1057

GP213

Michelli, A GP204

& EP359

Mazic, S EP470

Mendes, P EP1291

Micheu, A EP1134

Milos, I EP1068

Mazilu, A EP1254

& EP1292

Micic, D EP42, EP470

Milosevic, V EP779,

Mazur, G EP187 & EP78

Mendonça, E GP242

& EP694

GP202 & GP62

Mazzanti, C EP348

Menendez-Torre, E

Mickuviene, N EP1346

Milotic, DM EP1161

mazzeu, J OC4.3

EP1484

Middleditch, M EP1314

Mimita, W EP1232,

Mazziotti, G GP231,

Menor-Almagro, R EP374

Mieszkowska, A EP547

EP1233, EP147

MTE11, OC10.3

Meola, A EP288

Miftaraj, M EP55

& EP87

& OC12.5

Meoro, A EP1415

Miguéns, J EP1021,

Mimouni, S EP994

McAdams, B EP958

& EP1476

EP1049, EP896,

Minallah, S EP205

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Mineesk, D EP381

Mohamed, K EP160

Moolla, A EP730, GP138

Moskvicheva, T EP556

Mingrone, G S15.1

Mohamed, MS EP497

& OC3.5

Mosorin, M-E GP55

Minisola, S GP33

Mohamed, RB EP502

Moore, K EP1150, EP1153

Mostafa, BM EP1363

Minnetti, M GP16

Mohammed, A EP25

& EP487

Motomura, k GP166

Mintziori, G EP214, EP68

Mohammed, FR EP720

Moore, WV GP65

Mourad, B EP1154

& EP771

Mohammed, K EP190

Mora, M GP24 & GP57

Mouslech, Z EP588

Miranda, A EP1227

& EP395

Mora, PL EP406 & EP407

Moustou, H EP1418

Miranda, E EP341

Mohaupt, M OC13.5

Mora-Navas, L GP71

Moutschen, M EP883

Mirante, A EP1227,

Mohd Ali, N EP874

Moradgholi, S GP164

Moya, VA EP1178

EP887 & GP109

Mohd, A EP408

Morais, O EP84

Moyson, C EP1393

Mirica, A EP122

Mohideen, P GP131

Moran, L EP1115 & EP747

Mrabet, H EP1349,

Mirica, R EP122

Mohort, T EP523

Moran, M EP211

EP135, EP189

Mirmiran, P EP642,

Moilanen, L GP50

Morar, A EP846

& EP335

EP662 & OC5.2

Mokhort, A EP527

Moreira, Â GP18

Mrabet, HE EP1361

Mirnaya, S EP257, EP318

Mokhort, E EP749

Moreira, A EP1465, EP7

Mrabet, S EP355 & EP762

& EP347

Mokhort, T EP511, EP515,

& EP82

Mrad, M EP482

Mirošević, G EP172,

EP527, EP536, EP540,

Moreira, AM EP919

Mrdovic, I EP367

EP463 & EP549

EP663, EP664

Moreira, BM EP1179

Mrozinska, S EP1111,

Miron, A EP1371

& EP749

Moreira, C EP235

EP1148, EP141

Mirosevic, G EP43

Mokrysheva, N EP257,

Moreira, H EP203

& EP371

Mishevska, SJ EP875

EP318, EP323, EP345,

Moreira, S EP392

Msika, S OC11.2

Mishra, B EP408

EP346 & EP347

Morelli, A EP377

Mun˜oz de Nova, JL EP180

Missiroli, S EP789

Moleiro, F EP1323 & EP32

Morelli, S GP16

& OC10.2

Mitchell, C EP802

Molero, IG EP998

Morelli, V EP1043 & EP20

Mun˜oz, A EP9

Mitchell, R GP10, GP180

Molina-Vega, M EP614

Moreno Ortega, E EP1392

Mun˜oz, JMGdQ EP563

& GP4

& GP71

Moreno, Ó EP904

Mun˜oz, MR EP705

Mithieux, G S15.2

Molinaro, E EP1414

Moreno, B EP973

Mun˜oz-Garach, A

Mitrović, B EP356

& EP238

Moreno, C EP112 & EP1040

EP1462, EP224,

Mitrovic, M EP1089

Molitch, ME EP1015

Moreno, IH EP574

EP614 & GP71

Mittica, M OC14.1

Molka, C EP1229

Moreno, LM EP948

Mun˜oz-Jiménez, C EP1159

Mizamtzidi, M EP1139

& EP646

Moreno, MÁG EP474,

& EP941

Mladenović, V EP1245

Mollejo, M EP973

EP602, EP882

Mun˜oz-Jimenez, C EP500

Mladenovic, V EP484

Molnar, D EP491

& EP1932

Mun˜oz-Rivas, N EP431

Mnif, F EP1349, EP1361,

Molnar, Z EP742

Moreno, MÁG EP1932

Muco, E EP765

EP189, EP335, EP66,

Monaghan, P EP1169

Moreno, NA EP1072,

Mudenha, ET EP1192

EP77 & GP113

Monari, F EP1381

EP1481 & EP574

Mudiganti, NSV EP475

Mnif, M EP1128, EP1361,

Mondal, D EP1020

Moreno, PM EP474,

Muela, IS EP76

EP167, EP189, EP335,

Monereo, S EP1030

EP602 & EP882

Mueller, B EP687 & EP942

EP66, EP77 & EP770

Mongioı`, LM EP1163

Moreno, RMG EP574

Muhammad, A GP174

Moc¸o, R EP337

& EP35

Moreno-Moreno, P

Mujica-Mota, M GP100

Moata, H EP476

Moniz, AP EP1459

EP1159, EP159,

Mukherjee, AK EP343

Moazam, SG EP553

Moniz, C EP596

EP500, EP776, EP819,

Mukhopadhyay, S EP409

& EP555

Moniz, L GP222

EP907 & EP941

Mukhtar, R EP1230

Mocan, M EP398

Monoranu, CM EP932

Moresi, V EP825 & GP221

Mulatero, P EP37

& EP400

Monreal, IA EP920

Moretti, C OC9.5

Munichoodappa, K EP409

Mochort, T EP541

Montalto, G GP108

Morgado, P EP872

Munier, M GP143

Moehlecke, M EP648

Monteiro, J EP1362

Morgan, H EP303

Munkhzaya, M EP1156

Mofokeng, TRP EP28

& EP243

Morgan, RA EP802

Munteanu, V EP252

Moga, MA EP774

Monteiro, K OC2.5

Morganstein, D EP1458

Munter, G EP228 & OC4.1

Mogos, S EP213, EP252,

Monteiro, M GP18

Morgia, G GP127

Munukka, E GP167

EP260, EP838

Monteiro, MP EP1179

Morillas, V EP755

Murabe, H EP273

& EP961

& EP146

Morin-Papunen, L EP1110

Muratani, M GP166

Mogos, V EP1076,

Monteiro, N EP1323

& GP55

Muravyova, I GP86

EP1209, EP213,

& EP32

Mormando, M OC12.5

Mures, P EP3

EP252, EP260

Monteiro, S EP1211,

Morotti, A GP130

Murillo, FH EP1178

& EP961

EP1351, EP1356,

Morsi, H EP83

Muros, MM EP569

Mohamed Abdelsalam, M

EP145 & EP51

Mosbah, R EP743

Muros, T GP111

EP1154

Moola, A GP70

Moschouris, P EP67

Murphy, C EP720

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Murray, R EP912

Natalya, G EP989

Neves, C EP1006, EP1081,

EP1485, EP308, EP58

Murray, RD EP22, GP11

Natchev Natchev, E

EP1289, EP1357,

& GP115

& GP20

EP1046

EP140, EP1446,

Nikookam, Y EP103

Musat, M EP1063

Nathalie, E OC14.4

EP169, EP181, EP194,

Nikopoulou, S EP793

Mussap, M OC14.1

Nathanson, L OC7.5

EP195, EP493, EP53,

Niles, N EP321

Musson, P N3.1

Naumenko, E EP511

EP54, EP576, EP613

Nilubol, N GP124, GP186

Mustafa, A GP88

Naumova, L EP358,

& GP199

& OC7.3

Mutlu, HH EP447

EP507 & EP510

Neves, F EP807

Nimalasena, S EP1458

Mutluay, R EP1375

Naumova, M EP358,

& GP26

Nishi, M GP6

Muzza, M EP1432

EP507 & EP510

Neves, J EP567

Nishiyama, A OC6.5

Myhr, C EP754

Navalón, CI EP432, EP433

Neves, JS EP1081, EP140,

Nisic, T EP111 & EP1261

Mykhailiv, L EP420

& EP705

EP169, EP493, EP53,

Nistal, M EP904

Mykhalchyshyn, G OC2.4

Navaratnam, J EP134

EP54, EP576, EP719

Nivelo-Rivadaneira, M

Mykytyk, M EP982

Navasardyan, LV EP422

& GP199

EP390

& EP983

Navmenova, Y EP515,

Newbold, K EP1458

Nivelo-Rivadeneira, M

Myrzabaeva, A EP532

EP523 & EP556

Newell-Price, JDC EP879

EP105, EP107, EP170,

Mysliwiec, J EP31

Navrozidou, P EP483

Newsome, P OC3.5

EP193, EP530, EP621

Myszka, R EP592

& EP559

Nezi, M EP239

& EP757

Myszka-Podgórska, K

Nawal, E EP845

Nezos, A EP275

Nizam, N OC12.1

EP17

Nawal, EA EP1337,

Nezu, M GP14

Nobre, E EP1037, EP1085,

EP379, EP387, EP488,

Ng, D GP65

EP1269, EP1340,

Nadal, E GP241

EP640 & EP888

Nicolae, AC EP1137

EP320, EP897, EP898,

Nadin, K EP1468

Nazarovs, J EP931

& EP376

EP95, GP237 & GP239

Nadira, F EP279

Nazir, S EP761

Nicolaescu, I EP1138,

Nock, BA EP1445

Naem, E EP160

Nechaeva, O EP1457

EP1147 & EP307

Nockel, P GP124 & OC7.3

Nag, S EP1358, EP1398

Nechayeva, V EP539

Nicolas, G GP185

Noczynska, A EP775

& EP89

Necib, B EP149

Nicolay, SS GP196

Nodari, M GP231

Nagahama, M EP1385

Nedelcu, I EP1216

Nicoli, A EP1123

Nogués, X GP84

Nagaiceva, J EP142

Nedeljkovic-Beleslin, B

Niconova, L EP541

Nogueira, C EP1081

Nagatsuji, M EP27

EP111 & EP1261

Niculescu, A-M EP1216

& EP630

Nagtegaal, AP GP116

Nedergaard, J P5

Niculescu, D EP980

Noh, JH GP91

Nagy, EV EP1410

Nefedova, L EP1141

Niculescu, DA EP1018

Nolasco, F EP599

Nagy, Z GP3

Neggers, S EP1010

Niederlander, N GP153

Nolting, S EP154

Naik, M EP1277 & EP526

& GP174

Niedziela, M GP220

Noordzij, W EP155

Nakagawa, Y GP166

Neggers, SJCMM GP116

Nielsen, EH GP181

Norberto, S EP403

Naliato, E EP152

Negri, M EP34, EP786,

Nielsen, TL GP59

Nordstrom, C-H EP1070

Nam Kim, Y GP219

EP927 & GP184

Niemyska, K EP1442

& GP182

Nam, JS EP452, EP531,

Negru, M EP1345

Nieto, ÁM EP1072

Normann, KR OC8.3

GP54 & GP87

Nehlich, M OC5.5

Nieto-Gonzalez, A EP224

Noroozzadeh, M EP1183

Nam, JY EP960

Nejatian, N GP83

Nigro, N EP918 & EP942

Norris, J GP203, GP206

Nampoothiri, L EP1117

Nelimarkka, L GP50

Nikanava, L EP540

& GP63

Nana, M EP303

Nelson, L EP1263

Nikankina, L EP685

Norton-Branda˜ o, F

Napoli, F EP922

Nemes, O EP1410

& EP881

EP1454

Naqvi, A EP1196, EP123

Nemeth, A GP153

Nikitin, A EP220

Noruegas, MJ EP1227

& GP29

Németh, R GP44

Nikitina, I EP1146

Nota, N EP1032

Nar, A EP1431 & EP39

Nemoto, N EP1242

Nikolac, N EP209

Nour, E EP762

Narayanan, N EP555

Nermoen, I EP59

& GP232

Nourbakhsh, M GP164

Nardi, M EP1247

Neselioglu, S EP1347

Nikolaeva, N EP594

Novak, S EP491

Narimova, G EP15

Nesi, G GP223 & GP8

Nikolaidou, A EP1473

Novakovic Paro, J EP1024

Naseem, AA EP1092,

Nesic, J EP484

Nikolaou, N EP730

Novakovic-Paro, J EP116

EP1225, EP205

Nesovic, N EP677

& GP69

& EP709

& EP761

Nesovska, R EP285

Nikolic, D GP108

Novalbos-Ruiz, JP EP714

Naser, RA EP424

Nestorović, N EP212

Nikolic-Djurovic, M

& EP715

Nash, Z GP131

Nestorovic, N GP62

EP953, EP954

Nowak, K EP469

Nasiri-Ansari, N GP236

Neto, LL EP896 & EP974

& GP197

Ntali, G EP202 & GP180

Nasiroglu Imga, N EP56

Neumann, S NSA5.2

Nikolopoulos, G EP67

Ntova, V EP1008 & EP38

& EP589

Neuroendócrinos, GET

Nikookam, K EP103,

Nun˜ez, MS EP1072

Nasr, MS EP425

EP174

EP1213, EP1354,

& EP574

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Nunes, A EP389

Okamoto, K EP273

Ollila, M-M EP1110

Oruk, GG EP964

Nunes, J EP1133 & GP133

Okazaki, K EP273

Olmedilla, YL EP1030

Osório, AS EP1037,

Nunes, JS EP181

Oki, M EP4

Olmedo, C EP3, EP9

EP1083, EP1085,

Nunes, M-L GP120

Øksnes, M EP49

& EP952

EP1269, EP243,

Nunes, MT EP716, GP163

Oktas, B EP604

Olmezoglu, A EP964

EP320, EP897, EP898,

& GP224

Okurog˘lu, N EP266

Olofsson, C EP557

EP95, GP237

Nunes, T EP255

& EP440

Olsson, DS GP9

& GP239

Nur Firat, S EP317

Okuroglu, N EP565

Olsson, H GP177

Osaku, T EP1385

Nuria, AG EP74

Okuturlar, Y EP1235

Olsson, T GP9

Osowicz-Korolonek, L

Nurrulina, G EP464

& EP644

Olteanu, M EP1419

EP229

& EP465

Olaizola, I EP869

Olveira, G EP755, EP756,

Ostanek, B GP39 & OC10.4

Nuutila, P GP50

Olarescu, NC OC8.3

EP808 & EP868

Osuga, Y GP134

Nuzzo, F GP245

Olczyk, T EP1440

Omata, K GP14

Ostgren, CJ OC6.4

Nvokov, I EP735

Oleaga, A EP112

Omelchenko, E EP580

Otasevic, V EP693

Nye, E EP426

Oleg, K EP73

Omer Yazicioglu, M

Otero, J GP241

Nystrom, F OC6.4

Olga, G-P EP641

EP1413

Othonos, N GP70

Olivar, M EP973

Omer, T EP877

Ouali, S EP1322

O’Donovan, C EP505

Olivar-Azuara, M EP866

Omma, T EP1175, EP384

Ouannes, S EP1236,

O’Donovan, O EP505

Oliveira, A EP451, EP477,

& EP854

EP1238 & EP833

O’Hara, L GP159 & GP4

EP564 & GP200

Omri, M EP502

Oudjit, B EP219, EP450

O’Hare, JA EP1339

Oliveira, AI EP1079, EP53

Onbasi, K EP1294,

& EP633

O’Reilly, MM EP1150,

& EP54

EP1380 & EP467

Ouerdani, S EP1389

EP1153, EP798,

Oliveira, B EP313

Oncul, S EP821

Oueslati, H EP1322

GP180 & OC3.3

Oliveira, C EP1422

Ono, Y GP14

Oueslati, I EP1193,

O’Shea, D EP696

Oliveira, CRP EP949

Onofriichuk, I EP358,

EP1201, EP1208,

O’Shea, P EP720

& GP178

EP507 & EP510

EP1232, EP1233,

O’Sullivan, N EP259

Oliveira, D EP1009,

Oprea, L EP1063

EP1328, EP147,

Obel, E EP865

EP1195, EP1475,

Oprea, T-E EP215

EP207, EP340, EP482,

Obermayer-Pietsch, B

EP203, EP392, EP394,

Oprisor, I EP846

EP570, EP832

EP1188 & GP107

EP44, EP444, EP445,

Orłowski, M EP1450

& EP87

Obiols, G EP944

EP45, EP57, EP61,

Or, K EP1313 & EP199

Oukit, L EP1334 & EP476

EP922 & GP35

Orbetzova, M EP600

Ould-Kablia, S EP1182

Obolonczyk, L EP396

Oliveira, E EP382

Orchard, E EP1145

Ouldkablia, S EP1386

Obradović, M EP1245

Ocieczek, M EP1441

Oliveira, FT EP949

Ordo

˜ez-Can˜ izares, MC

& EP450

Odermatt, A EP730,

& GP178

EP224

Ounaslehto, A GP50

EP781, EP782, EP802

Oliveira, J EP1058, EP512,

Orehek, N GP39 & OC10.4

Overgaard, R GP152

& EP822

EP548, EP573

Orhan, B EP249

Øystese, KAB OC8.3

Oei, E EP744

& EP773

Oriola, J EP868

Oz, A EP842

Oei, L EP744

Oliveira, JM EP1351

Orlando, P EP1260

Oz Gul, O EP131, EP132,

Ogando, H GP52 & GP75

Oliveira, L EP1422

Orlov, A EP1286

EP601, EP608, EP72

Ogilvie, A GP195

Oliveira, MJ EP1211,

Orlova, E EP345

& EP751

Ogimi, Y EP1385

EP1351, EP1356,

Orlova, M EP1266

Ozawa, Y EP1270

Ogle, G EP428

EP145, EP51 & EP923

& EP1316

Ozbek, M EP1097,

Ogmen, B EP1377

Oliveira, P EP1009, EP203

Oros, S EP1094, EP1176

EP1368, EP327

& GP233

& EP44

& EP1180

& EP999

Ogmen, BE EP1429

Oliveira, PF EP1179

Orosia, M EP1332

Ozcan, M EP815 & GP74

Ognjanovic, S EP1114,

Oliveira, S EP613

Orsini, N EP557

Ozcelik, O EP1368

EP166, EP177, EP191,

Oliveira, SC EP1081,

Ortega, JV EP76

Ozdemir, A EP266, EP440

EP75, EP80 & GP139

EP169, EP493, EP53,

Ortega, N EP1130

& EP565

Oguz, S GP212

EP54, EP576, EP719

Ortega-Salas, R EP178

Ozdemir, B EP1235

Oh, H-S EP1366, EP1367

& GP199

Ortiz, A EP88 & EP94

& GP95

& OC14.5

Oliveira-Filho, AF EP389

Ortiz, AM EP769

Ozdemir, D EP1258,

Oh, S EP950

Oliveira-Neto, LA EP949

Ortiz, D OC5.1

EP1264, EP1377,

Ohkuwa, K EP1385

Oliveira-Santos, AA EP949

Ortiz, R OC6.5

EP331, EP843, EP856

Ohlsson, C OC3.4

& GP178

Ortolá, A EP184 & EP185

& GP233

Oliviero, S NSA3

Ortola-Buigues, A EP900

Ozdemir, K EP683

Ohno, H GP166

Olldashi, B EP1470

Oruc, A EP751

Ozderya, A EP289

Ohrman, T EP766

Ojo, A EP1485 & EP308

Olldashi, T EP2 & EP1370

Oruc, C EP821

Ozgen, G EP1194

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Ozgurtas, T EP362

Palazzo, F EP123

Papi, G EP1341 & EP1426

Patino, H GP187

Ozisik, H EP1194

Palermo, A GP33

Papierska, L EP469

Patocs, A GP3

Ozkan, C¸ EP1144

Palha, A EP1049, EP1062

Papoutsis, I GP80

Patrício, M EP704, EP887

Ozkan-Gurdal, S EP265

& EP1446

Pappa, D EP861 & EP864

& GP109

Ozkaya, M EP1003

Palha, AM EP1006

Pappalardo, MA EP1118

Patrascioiu, I OC12.3

Ozkul, Y EP1129

Paliczka-Cieslik, E EP1440

Paragliola, RM EP1341

Patt, M EP782

Ozmen, S GP161

Pallone, S EP1013

& EP1426

Patti, AM GP108

Ozturk, B GP96

Palma, I EP350, EP824

Pardi, E EP278 & EP348

Patyra, K OC4.2

Ozturk, FY EP109

& EP921

Pardo, JA EP948

Paul, BN EP701

& EP836

Palmieri, S EP1043

Paredes, I EP1044

Paula Moreira, A EP198

Ozturk, L GP49

& GP33

Paredes, S EP706 & EP707

Paula, G EP723

Ozturk, O EP362

Palomares-Ortega, R

Parente, R EP7

Paulino, J EP599

Ozugur, S EP289

EP500

Park, BY EP506

Pauliukiene, B EP1276

Palomera, E GP57

Park, JH EP925

Pauliukiene, R EP164

Pávai, D EP1086

Paluzzi, A GP180

Park, JS EP452, EP531,

Paun, D EP1176, EP1180

Pa˚lsson, A EP1070

Palyga, I EP1274, EP1382

GP54 & GP87

& EP240

Péchère-Bertschi, A

& EP1409

Park, K EP452, EP531,

Paun, DL EP122

OC13.5

Pamedytyte, D GP244

EP592, EP960, GP54

Paun, S EP122

Pérez, FG EP1467, EP563

Pampaloni, F EP370

& GP87

Pavai, D GP38

& EP769

Pan, k GP192

Park, KG EP383, EP506

Pavel, M GP177

Pérez, M EP938

Panagiotou, A EP1303,

& GP56

Pavlova, M EP1057

Pérez, MDA GP89

EP1307, EP1417,

Park, KH EP700 & GP169

Pavlovic, D GP197

Pérez, MSG EP294

EP1471, EP223, EP68

Park, S EP1366, EP1367,

Pawlak, D EP1445

Pérez-Fernández, L EP461

& GP40

EP605 & OC14.5

Payer, J EP1173 & GP38

& EP619

Panarotto, MB GP231

Park, SH EP960

Payumo, E EP216

Pérez-Luis, J EP906,

Panay, N GP131

Park, SI EP700

Pazaitou-Panayiotou, K

EP909 & EP910

Pancic, JM EP168

Park, SW EP516

EP1473

Pérez-Rodríguez, J EP443,

& EP767

Park, SY EP1100, EP248,

Pazanin, L EP43

EP524 & EP593

Pande, DG EP1277

EP738, GP42 & OC9.4

Pazderska, A EP1150,

Pérez-Villa, L EP1462

& EP526

Park, Y-M EP690

EP1153 & EP487

Pacak, K EP92, EP93,

Pandurevic, S EP42

Parker, M EP1190

Pchelin, I EP518 & GP92

GP25 & OC7.3

Pane, A GP24

Paro, JN EP245

Pen˜ a, A EP938

Paccapelo, A EP1381

Panebianco, MV EP1251

Partha, P EP25

Pen˜ a, IF EP563

Paccaud, F EP820 & OC13.5

Panocchia, N EP1260

Parv, F GP53

Pen˜ a, JIF EP270 & EP769

Pace, L GP231

Panousis, P EP1473

Parveen, N EP205

Peacey, S EP1259

Pach, D EP1026 & OC9.3

Pantazi, E EP1300,

Parvu, L EP1466

Peacock, M GP47

Pacha, J EP1082

EP1460, EP221,

Pascal-Vigneron, V EP966

Pechére-Bertschi, A EP820

Pacheco, LV EP432,

EP222 & EP276

Pascanu, I EP1364 & EP16

Pechuan, J GP111

EP433 & EP705

Panteleeva, E EP905

Paschke, R OC4.2

Peculis, R EP931 & OC6.3

Paci, A EP179

Pantelidis, D EP366

Paschou, S EP1139

Pedersen, B GP190

Pacini, F EP1295 & EP60

Panthagani, AP EP1192

& EP214

Pedersen, MH EP654

Padlipskaite, A EP1412

Pantoflinski, J EP1026

Paschou, SA EP423

Pedersen, SB EP654

Padure, A EP1466

Panveloski-Costa, AC

Pascu, AM EP774

Pedicelli, A EP997

Padzik, A GP118

EP716

Pascual, C EP3

Pedraza-Arévalo, S EP178,

Pagotto, U EP1166,

Papadakis, G EP1098,

Pasqualetti, P EP1050

EP472, EP698

EP1381, EP669

EP1373, EP217,

Pasquali, R EP1135,

& EP790

& EP671

EP417, EP442, EP509,

EP669, EP671 & CET1

Pedro, J EP719

Paiva, I EP1009, EP1049,

GP153 & N3.2

Passos, D EP1359

Pedroncelli, A GP187

EP44, EP57 & EP61

Papadakis, GZ OC7.3

& EP139

Pedroso de Lima, J EP198

Paiva, S EP392, EP394,

Papadopoulou, D GP131

Pastor, F EP1415

Pedroso, JC EP1356

EP61 & EP922

Papaevangelou, V EP885

Patakov, M MTE15

Peene, B EP1393

Paixa˜ o, R EP1083

Papagianni, M EP588

Patalano, R EP927

Pehlevan, E EP47

& EP243

Papakokkinou, E GP9

Patalong-Nowak, M

Pehlivan, B EP644

Paixao, AL EP468

Papanikolaou, I EP176

EP229

Peiró, I EP150, EP88,

Paja, M EP1040, EP112,

Papastathi-Boureau, C

Patel, C EP744

EP94 & GP241

EP1217 & EP128

EP1126

Patel, D GP124, GP186

Pejin, R EP245

Pajovic, M EP678

Papavasiliou, S EP1418

& OC7.3

Pekgoz, M EP1017

Pakarinen, P EP364

& GP32

Patel, N GP100

Pekic, S EP892, EP953,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP954, GP188

Peros, K EP1151

Phelan, N EP1150,

Pitchaiprasert, S EP1288

& GP197

& EP1161

EP1153 & EP487

Pittathankal, A EP103,

Peláez, N EP150

Perotti, P EP26 & GP123

Phillips, S GP135

EP1213, EP1485

Pellegata, N EP91 & EP926

Perreira, C EP1032

Pián, H EP94

& EP58

Pellegata, NS OC8.1

Perrino, M EP1408

Piętkowski, J OC9.3

Pitteloud, N GP153

Pellegrino, M EP268

& EP1432

Piantanida, E EP1451,

& S10.3

Pellegrino, T GP231

Perros, P EP1342 & S12.3

EP688 & EP691

Pivac, N EP595

Pelosini, C EP397

Perrotta, R EP794

Piasecka, B EP466

Pivonello, C EP34, EP786,

Pemovska, G EP285

Persani, L EP1222

Picado, B EP548 & EP573

EP927 & GP184

& EP875

& OC8.2

Picallo, M EP1030

Pivonello, R EP1015,

Pendovski, L GP62

Persson, A EP55

Piccinini, S OC7.4

EP1039, EP1056,

Penna-Martinez, M GP83

Pesic, M EP64

Piccolo, R EP291

EP34, EP786, EP927,

Penning, T EP730

Peso, CD EP1476

Picerno, IAM GP175

GP177, GP184

Penso, R EP184 & EP185

Pestana, A EP1357

Pichl, C EP1027

& GP187

Perazo, C EP794

& EP1449

Picon, N EP385

Piwowar, M EP1274

Percinic-Popovska, F

Petakov, M EP177, EP191,

Picu, C EP1094, EP1216

Planas, A EP150

EP779

EP80, EP892, EP953,

& EP1466

Planck, T EP1246

Perdigones, CD EP406,

EP954, EP956, GP188

Pieber, TR EP609 & GP107

Planella, JRU EP294

EP407 & EP627

& GP197

Piedade, C EP1227

Plank, J EP609

Perdomo, C EP227

Peter, P EP25

Piedrola, G GP111

Plaseski, T EP285

& GP198

Peterkova, V EP1025

Piemonti, L OC11.1

Platokouki, H EP885

Perego, S EP777

Petersén,

˚ EP1070

& OC6.2

Platonova, A EP126

Pereira, A GP197

& GP182

Pieruzzi, L EP1414

Platonova, N EP323

Pereira, B EP174

Petersen, S GS2.4

Pietila, S GP167

Platonova, O EP736

Pereira, BD EP596

Petersenn, S EP1039,

Pietri, L GP19

Plesoianu, C EP1345

Pereira, C EP1142, EP310,

GP191, OC12.2

Pigarova, E EP1028,

Poblocki, J EP229

EP783, EP788

& S14.1

EP1034, EP1036,

Pofi, R EP537 & GP149

& EP887

Petkovic, MM EP369

EP323, EP347, EP913,

Poggiogalle, E EP702,

Pereira, FA EP949

Petrangeli, E EP702

EP914 & GP157

EP713 & GP168

Pereira, H EP98

Petraviciute, M EP1276

Pignata, SA EP1443

Poglitsch, M GP2

Pereira, J EP1077,

Petre, O EP1147

Pignatelli, D EP1181,

Poiana, C EP1007,

EP1078, EP788,

Petre, OA EP1138

GP153 & GP18

EP1018, EP1067,

EP870 & GP200

Petrenaite, A EP171

Pignatti, E EP1123

EP1353, EP137,

Pereira, L EP1449

& GP211

Pigny, P OC5.3

EP1419, EP911,

Pereira, M EP1289, EP613

Petrenko, S EP749

Pilli, T EP1295 & EP60

EP980 & GP137

& GP199

Petrescu, D EP114

Piltonen, T EP1110

Pojo, M GP126

Pereira, ML EP57, EP706

& EP158

& GP55

Polat, S EP1129

& EP707

Petrescu, S EP148

Pimenta, J EP380

Polat, SB EP1002,

Pereira, SS GP18

Petris, R EP122

Pinhal, F EP1362

EP1320, EP1377,

Pereira, T EP1279,

Petrone, L OC9.5

Pinheiro, MI EP512

EP1429, EP237

EP1362 & EP267

Petrot-Keller, I GP148

Pinto, A GP23

& EP331

Pereira, TA EP350, EP824,

Petrov, V EP1025

Pinto, M EP578 & EP626

Polesel, DL EP385

GP228 & GP229

& EP346

Pinton, P EP789

Poli, G GP8

Pereira-Gurgel, VM EP949

Petrova, E EP117

Pinzani, P GP8

Pollak, M S23.3

Perera, S EP134

Petrovic, D OC13.5

Pipero, P EP571

Polledri, E EP1043

Peretianu, D EP1157

Petrovskaya, E EP695

Pirags, V EP142, EP931

Polovina, S EP694

Perez, FG EP270

Petychaki, F EP67

& OC6.3

Polovina, TS EP71 & EP81

Perez-Bravo, F EP1120

Peverelli, E EP20 & EP924

Piran, R OC6.1

Polychronidis, A EP1378

Perez-Fuentes, R OC6.5

Peynirci, H EP608

Pirelli, A GP43

Polymeris, A EP202

Perez-Olivares, L EP1044

Peyroteo, M EP1465, EP82

Pires, M EP1362

Ponce, MH EP581

Perez-Rivas, LG GP160

& EP98

Pires, S EP1227

Ponikwicka-Tyszko, D

Pergadou, H EP885

Pezzani, R GP3

Pires, V EP1359

OC7.1

Perge, P GP3

Pezzullo, L EP1407

Pirotte, B EP928

Ponirakis, G EP453

Perić, B EP172, EP463

Pfeifer, M EP1046, EP36,

Pisco, J GP90

Pontén, F GP155 & GP194

& EP549

GP39, OC10.4 & S18.3

Piskinpasa, H EP1235

Ponte, B EP820

Peric, B EP43

Pfeilsticker, A EP84

Pisoschi, M EP1157

& OC13.5

Peris, BP EP1072

Pfenninger, A GP105

& EP1158

Pontecorvi, A EP1260,

Perkovic, MN EP595

Pfleger, L EP638

Pistja, E EP645

EP1341, EP1426,

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

EP161, EP997

Prague, J GP131

Punales, M GP93 & OC2.1

Ragonese, M GP175

& OC12.5

Prakapiene, E EP164,

Punda, A EP1469

Rahman, H GP125

Pontinha, CM EP1000

EP542 & EP637

Purice, M EP1221,

Rahman, N GP118

Pontremolli, C GP77

Prakash, S GP105

EP1353, EP1364

& OC7.1

Pop, DD EP846

Prassad, V S2.3

& EP1419

Rahmayani, F EP363

Pop-Radu, CC EP241

Pratas, S EP660

Puspanathan, P EP115

Raica, M EP935

Popa, C EP1353

Prazeres, S EP1330,

Putilin, D EP455

Raileanu, C EP1345

Popa, DE EP376

EP258 & EP486

Puttanna, A EP409

Raimundo, L EP887

Popa, O EP1216

Preciado-Puga, M-d-C

Puukka, K EP1110

Rajendiran, N EP555

Popa, SVO EP206

EP666

Puzianowska-Kuznicka, M

Rajic, AS EP36, GP39

Popescu, D EP1364

Preda, A EP1094

EP577

& OC10.4

Popescu, N EP1018

Preda, C EP1073, EP213,

Rajicic, N EP884

Popik, E EP818

EP252, EP260, EP813

Qasim, B EP940

Rakovic, D EP42

Popova, D GP82

& EP961

Qayyum, M EP1092,

Ramalho, A EP1465

Popova, N EP1036

Premoli, P EP688 & EP691

EP1225, EP205

Ramazanova, L EP39

Popova, P GP78

Premosa, T EP491

& EP761

Ramishvili, L EP315

Popović-Radinović, V

Prete, A GP122

Queirós, DaPSGPSoD

Ramos, EG GP198

EP1245 & EP356

Preto, J EP174

EP477

Ramos, M EP1227

Popovic, B EP1114,

Prichystalova, H EP803

Queirós, J EP477, EP564,

Ramos-Leví, A EP574

EP166, EP168, EP177,

Prieto, A EP863

EP576, EP630, EP719

Ramos-Leví, AM EP180

EP191, EP75, EP80

Prieto-Alhambra, D GP84

& EP773

Ramos-Levi, A OC10.2

& GP139

Prior-Sánchez, I EP1392

Queiros, R EP468

Rance, B GP15

Popovic, D EP1089

& EP159

Quesada, M GP111

Randeva, H D4.1

& EP245

Procopiuc, C EP1221,

Quezado, MM GP236

Ranetti, A-E EP1132

Popovic, V EP953, EP954,

EP206, EP352 & EP817

Quinkler, M EP22, GP11,

Ranetti, AE EP1254

EP956, GP188, GS2.3

Prodanovic, J EP1024,

GP122, GP123, GP20

Rangger, C EP1445

& OC12.2

EP116 & EP709

& OC7.2

Rankov-Petrovic, B

Popovic-Brkic, V GP190

Proença, H EP1387

Quinn, L EP1052

EP1184

Popovic-Pejicic, S EP712

Prokop, J EP1226, EP133,

Quintana-Arroyo, S

Raoul, M EP939

Porcel, JÁR EP1331,

EP1446 & EP181

EP105, EP170, EP193,

Rapizzi, E EP92, EP93

EP1467 & EP563

Pronin, O GP86

EP390, EP530, EP621

& GP25

Porcel, JAR EP270

Proseva, T EP875

& EP757

Raposo, J EP562

Porksheyan, M EP415

Proverbio, MC EP1432

Quinton, R EP1239

Raposo, L EP146 & GP205

& EP73

Provvisiero, DP EP786

& GP153

Raposo, NC EP660

Portal, JJ OC11.2

& EP927

Rapposelli, S GP223

Portilla, AJ EP294

Prozorova, T EP454

Ra˘di, RA EP328

Raquel, C EP641

Portillo, CM EP569

Pruijm, M EP820

Río-Moreno, Md EP472

Rasic-Markovic, A EP1184

Portius, D EP692

& OC13.5

Ríos, MHC EP374

Rask, E EP680

Portugal, J EP1298,

Prystupiuk, L EP358,

Rıza Uysal, A EP1273

Rask, P EP680

EP1422, EP226,

EP507 & EP510

Runkorg, K EP607

Rasmussen,

˚K EP40

EP486 & EP996

Prystupiuk, M EP358,

Rached, A EP1212

Rasmussen, M GP152

Pospíšilová, H EP1170

EP507 & EP510

Radacs, M EP742

Rata˜ o, P EP1454

& EP14

Przeorska, D EP1074

Radenković, S EP1245

Rathnayake, T EP272

Potì, F EP1112

Przhiyalkovskaya, E

Radian, S EP1067

Rausei, S EP1451

Potier, L EP1310

EP1028

& GP137

Raverot, G GP120

Poulsen, PL GP17 & OC1.4

Przybylik-Mazurek, E

Radojkovic, D EP64

& OC12.2

Poupino, J EP243

EP1445

Radojkovic, M EP64

Ray, A EP343

Pournara, E GP190

Puar, T EP24

Radulescu, M EP1419

Raynor, H S4.1

Poutanen, M EP364,

Puar, TH GP160

Radzeviciene, L EP542

Raza, A EP761

EP692, OC13.3

Puca, E EP1370, EP1470,

& EP637

Razanskaite-Virbickiene, D

& OC3.4

EP2 & EP571

Rafael, A EP468 & GP222

EP550

Powell, M GP195

Pugeat, M GP137 & S18.1

Rafailidis, S GP40

Razavi, SA EP1406

Poyares, L EP716

Puglisi, S EP26 & GP175

Raffin-Sanson, ML GP19

Razzaghy-Azar, M GP164

Pozza, C GP149

Puig-Domingo, M GP57

Rafik, K EP939

Rebai, M EP667

Prada, ETA EP154

& GP84

Rafiq, B EP311

Rebelo, AF EP468

Prados-Gonzalez, ME

Puliani, G EP1050

Ragazzon, B GP13

Rebelo-Marques, A EP44

GP128

& EP1054

Raghavan, V OC11.2

Rebollo Román, EP1392

Praet, M EP1191

Pulido, P OC6.5

Ragnarsson, O GP9

Rebollo, I EP1001

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Rebollo-Román, Á EP159,

Rickard, AJ GP2

Rodríguez, CN GP89

EP1295, EP1311,

EP500, EP776, EP819

Rickers, L EP682

Rodríguez, FJ EP904

EP1452 & EP414

& EP907

Ricordi, C OC6.2

Rodríguez, JCR EP8

Rosário, F GP242

Recabarren, MP EP636

Riesco-Eizaguirre, G

Rodríguez, PC EP725

Rosa Alhambra Expósito,

& GP132

GP235

Rodríguez-Martín, A

M EP1392

Recabarren, S EP1120

Rigla, M EP165 & GP238

EP714 & EP715

Rosa, SL EP1451

Recabarren, SE EP636

Rikhsieva, N EP1106

Rodríguez-Perálvarez, M

Rosca, R EP1094, EP1176

& GP132

& EP1257

EP698

& EP1180

Recamonde-Mendoza, M

Rio-Moreno, Md GP128

Rodrigo-Cano, S EP681

Rosenberg, K EP13

OC2.1

Rios, E EP140 & EP1449

Rodrigues, A EP79

Rosenwald, A GP119

Redondo, LR EP432,

Ristic, N EP779, GP202

Rodrigues, C GP133

& OC1.1

EP433 & EP705

& GP62

Rodrigues, D EP45

Rosetti, S EP688

Refardt, J EP889 & EP918

Riva, E EP196, EP197

Rodrigues, E EP1058,

& EP691

Rego, T EP1006, EP251

& EP789

EP1206, EP140,

Ross, IL EP28

& EP725

Riva, S GP77

EP305 & EP54

Ross, RJ GP61

Reichelt, AJ EP457

Rivadeneira, F EP744

Rodrigues, F EP1459,

Ross, RJM EP879

Reimondo, G EP26

Rivera, A OC6.5

EP1463

Rossi, G EP970

Reincke, M EP52 & GP160

Rivera, NG EP569

& EP174

Rossi, L GP223

Reis, D EP897 & EP898

Rivero-Muller, A GP118

Rodrigues, I EP1330,

Rossiter, P EP295

Reiter, E EP1123

Rizk-Rabin, M GP5 & GP13

EP750, EP795, EP796

Rost, S GP119

Rejaibi, S EP1322

Rizoulis, A EP861

& EP829

Rotariu, D EP1073

Rejeb, O EP1212, EP1322,

Rizvi, A EP958, GP106

Rodrigues, M GP94

Rothman, JG GP47

EP1324, EP1328,

& GP108

Rodrigues, P EP1356,

Roussel, O EP9

EP207 & EP570

Rizvi, SSR EP1092,

EP51, EP807 & EP871

Roussel, R EP1310

Rekik, N EP1128, EP1349,

EP1225, EP205

Rodrigues, T EP704

Rovite, V EP931

EP1361, EP189,

& EP761

& EP919

Roy, S EP343

EP335, EP66 & EP770

Rizza, L GP16

Rodriguez, EG EP1373

Rozanska, A EP1441

Rella, N EP1237, EP1251

Rizzo, C GP214, GP215

Rodriguez, JCR EP459

Rozhinskaya, L EP1028,

& EP211

& GP216

Rodriguez, P EP1001

EP345, EP346, EP881

Remédio, F EP599

Rizzo, M GP108

Rodriguez, S OC1.2

& GP157

Remolar, M^aÁB GP48

Rjeb, O EP1193, EP1201,

Rodriguez-Manas, L MTE1

Rubin, B GP5

Renard, C EP883

EP1208 & EP340

Rodriguez-Perez, A EP390

Rubin, C EP735

Rep, S EP1445

Rkik, N EP135

Rogatko, I EP890

Rubino, C GP148

Repaci, A EP1381

Robalo, B EP310

Rogowski, MP GP172

Ruchała, M EP1074,

Repetto, G OC5.1

Robenshtok, E EP1374

Rojas, C EP938

EP1433, EP1450

Requena, M EP1030

Roberts, R GP131

Rojek-Tre˛bicka, J EP48

& EP1474

Resende, E GP98

Robles-Cabeza, L EP1462

Roldan, E EP1001

Ruchala, M EP1252,

Resman, KG EP36

Rocío, P EP641

Romagnoli, P GP25

EP1275, EP388

Restituto, P EP227

Roca-Rodríguez, MM

Roman, DL EP952

& GP220

Reubi, JC GP185

GP71

Roman, G EP560

Rucz, K EP1410

Reyes, LM EP8

Rocha, A GP2

Román, ÁR EP1392

Rudaz, S EP782

Rezgani, I EP502

Rocha, G EP1155,

Romanelli, F GP33

Rudelle, H GP143

Reznik, Y GP12

EP1211, EP1351,

Romanowska-Prochnicka,

Rudovich, N EP1087

Rhayem, Y EP52

EP1356, EP145,

K EP469

Ruel, I EP661

Rheinheimer, J EP648

EP174 & EP51

Romeo, EL EP1118

Ruffinelli, JC GP241

Ribeiro, C EP1465,

Rocha, J EP320

Romeo, PD GP175

Ruggeri, RM EP1443

EP1475, EP82, EP98

Roche, D EP295

Romero, J OC6.5

& GP208

& OC14.3

Rochira, V EP1166,

Romero, JC GP73

Ruiz-Noa, Y EP437 & EP666

Ribeiro, I EP1049

EP1383, GP146

Romero, SG EP868

Rungby, J GP17

Ribeiro, J EP791

& GP51

Ronchi, C EP932, GP5

Runkle, I EP900

Ribeiro, K EP723

Rochtus, A GP45

& OC1.1

Ruohonen, S EP364

Ribeiro, L EP706 & EP707

Rodgers, R EP1190

Ronchi, CL EP161, EP20,

& OC4.2

Ribeiro-Oliveira, A

Rodic, G EP191

GP1, GP119, GP121

Ruohonen, ST EP692

EP1011

Rodien, P GP143

& GP22

Ruokonen, A EP1110

Riccetti, L EP1123

Rodionova, T EP1266

Ronchi, SSC OC7.2

Rurale, G EP1222

Richell, G EP1342

& EP1316

Roost, K EP104

Rusalenko, M EP556

Richter, S EP92, EP93

Rodríguez, A EP1284

Roque, C EP1088,

Russi, V EP825 & GP221

& GP25

& GP210

EP1177, EP1207,

Russo, GI GP127

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Russo, GT EP1118

Sagarribay, A EP1000

Sampaio, L EP310

Santos, J EP1459

Rusu, C EP813

& EP1062

& EP887

& EP1463

Rusu, S EP1419

Saglam, DA EP856

Sampedro-Nún˜ez, M

Santos, JG EP1422

Rutjowski, D EP577

Saglar, E EP815 & GP74

EP180 & OC10.2

Santos, K EP1029

Rutkowska, J EP17

Sahara, A EP273

Sampron, N EP1023

Santos, LR EP1357

Ruza, I EP342

Sahin, AB EP852

Samra, ABA EP160

Santos, R EP297

Ryan, J EP682

Sahin, D EP815 & GP74

& EP453

Santos, S EP1323 & EP32

Rybka, J GP72

Sahin, I EP330, EP620

Samson-Couterie, B GP15

Santos-Antunes, J EP576

Rylander, L EP1070

& EP703

& GP2

Santos-Silva, R EP1058

& GP182

Sahin, M EP1273, EP277

Samueloff, A OC4.1

Santrac, N EP1480

Ryo, M GP14

& EP967

Sana, R EP387 & EP845

& GP225

Ryu, J-S OC14.5

Sahiner, Z EP344

Sancak, S EP266

Sanxhaku, R EP765

Said, A EP1447

& EP440

Sanz-París, A EP461

Saida, F EP279

Sanches, AC EP174

& EP619

Sá, M GP98

Saidane, D EP667

Sanches, C EP82

Sapera, A EP217

Ságová, I EP1086

Saidnazirkhanova, M

Sanchez-Lechuga, B

Saponaro, F EP278,

& GP38

EP880

EP544

EP348 & GP33

Sáiz-Sátjes, M EP530

Saif, A EP1240

Sanchez-Ragnarsson, C

Saraiva, C EP1177,

Sánchez, CM EP1072

Saigí, I EP165

EP1484

EP1452 & GP222

Sánchez, EG EP569

Sailer, C EP942

Sandoval, D EP1120,

Saraiva, J EP1475 & EP45

Sánchez, IP EP474

Sainsbury, C GP104

EP636 & GP132

Sarak, T EP604

& EP602

Sainte-Catherine, D OC1.2

Sandu, K EP1373

Saranti, S EP1202

Sánchez, JRC EP708

Saiz-Satjes, M EP757

Sandu, R EP306

Sarantopoulou, V EP202

& EP717

Sajdak, D EP1119

Sane, T EP163

Sarauskas, V EP164,

Sánchez, M^aBG EP432

Sakali, A EP864

Sanli, C EP1223

EP839 & GP244

& EP433

Sakcı, E EP266

Sansoni, V EP777

Sarchielli, E EP377

Sánchez-Lechuga, B

Sakka, I EP1201, EP1212

Santacruz, E EP88 & EP94

Sardella, C EP970

EP1278

& EP340

Santaguida, MG GP221

Sardinha, LB EP632

Sánchez-Sánchez, R

Sakka, V EP239

Santana, I EP704

Sari, CI GP141

EP178

Sala, GBL EP1123

Santana-Suárez, AD

Sarkinaite, M EP173

Sarnblad, S EP680

Salem, A EP762

EP530

Sarkisova, K EP561

Sérgio Neves, J EP1289,

Salenave, S EP966

Santana-Suarez, AD

Sas, T GS1.2

EP194, EP195

& GP19

EP105, EP170, EP390,

Sasic, I EP369

& GP217

Salgado, D EP788

EP621 & EP757

Sass, S EP91

Sørensen, HT GP17

Salgado, L EP1454

Santarem, R EP84

Sassi, L EP688 & EP691

Saarinen, N GP167

Salici, AG EP679

Santharam, S EP1051

Sastre, J EP1218 & EP973

Saavedra, A EP1058,

Salituro, N EP1381

Santi, D EP1107, EP1166,

Satoh, F GP14

EP1206, EP305

Salminen, S GP167

GP146 & GP51

Satti, H EP597

& EP630

Salomon, CF OC5.1

Santi-Cano, MJ EP714

Saucedo-Toral, CA EP437

Saba, L EP26

Salsamendi, JL EP247

& EP715

Sauter, N EP1015

Sabater, EMR EP1178

Saltiki, K EP1411

Santiago, A GP179

Sava, E EP143 & EP855

Sabatini, M GP172

& GP230

Santiago, Md EP904

Savasteeva, I EP556

& GP223

Salvador, J EP906, EP909

Santiago, P EP1332

Savchanka, A EP664

Sabatino, J EP688

& EP910

Santiago-Perez, A EP900

Savic, S EP111 & EP1261

& EP691

Salvatori, M GP231

Santini, F EP397

Savopoulos, C EP588

Sabico, S GP46 & GP77

Salvatori, R EP883, EP949

Santos, AC EP146

Savosteeva, I EP515

Sabino, T EP133, EP1446

& GP178

& GP205

Savvidis, C EP1202

& EP181

Salvi, M EP1342

Santos, AI EP1298

& EP859

Sablon-Gonzalez, N EP621

Salvianti, F GP8

& EP1422

Sawamura, T OC3.1

Sadowski, SM GP124

Samardzˇić, V EP356

Santos, AP EP100, EP146

Sawicka, A EP1372

& OC7.3

Samardzić, V EP1245

& EP174

& EP826

Saeger, W EP932 & GP176

Sambo, M EP1030

Santos, C EP1446 & OC5.4

Sawicka-Gutaj, N EP1252

Saez-Lopez, C EP753

Samia, E EP1154

Santos, F EP1177

& EP1275

Safak, O EP1464

Samia, OK EP120

& EP1452

Saygili, ES EP109

Safarova, M EP901

Sampaio, F EP243

Santos, FS EP1088,

& EP836

Safi, AW EP534

Sampaio, IL EP100

EP1207, EP1311,

Sayilar, EI EP758

Safi, W EP335 & EP770

Sampaio, J EP1387

EP1486, EP414,

Sayiner, ZA EP1003

Sagar, R EP280 & EP334

& EP95

EP725 & EP951

Sazonava, A EP527

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Sbardella, E EP1050,

Seki, M EP4

Sever, MJ OC10.4

Shin, JY EP236

EP1054 & GP16

Seki, T EP4

Sevimli, H EP1108

Shin, M EP233 & EP697

Sbiera, I GP121 & GP22

Seki, Y GP134

Sezer, A EP1198, EP1396,

Shin, Y EP233 & EP697

Sbiera, S EP161, EP932,

Sekiya, M GP166

EP1397, EP1399,

Shinya, F EP1242

GP1, GP119, GP121,

Selfa, SMM EP998

EP1400, EP1401,

Shiraso, S EP1242

GP22, GP5 & OC1.1

Selkina, V EP556

EP1402, EP1403,

Shirin, H EP199

Scagliotti, V OC8.5

Selleva˚ g, K EP33

EP271 & EP981

Shishkin, A EP518

Scappaticcio, L EP1121

Selmi-Ruby, S EP1449

Sfar, MT EP1236, EP1238

Shkurta, A EP765

& EP1293

Selva, D EP753

& EP833

Shoback, DM GP47

Scaroni, C EP1042

Selvarajan, R EP553

Sgromo, B EP682

Shong, YK EP1366,

& EP1056

Sema, D EP1281

Shackleton, CHL OC1.3

EP1367 & EP1421

Scarpa, L EP1445

Sematonyte, J EP1102

Shah, S EP553

Shorakae, S EP1115,

Scavello, I EP370

Semple, R EP466 & OC3.3

Shah, T OC3.5

GP135 & GP141

Schofl, C EP1020

Sen, EC EP109 & EP836

Shah, U EP58

Shrikrishnapalasuriyar, N

Schurmann, A OC2.3

Sencar, E EP1368

Shah, V EP272

EP303

Schutz, P OC11.3

Sendur, SN GP61

Shahid, G EP205

Shteinshnaider, M EP1313

Schalin-Jantti, C EP163

Sennarog˘lu, E EP538

Shahida, B EP1246

Shukla, R EP1333

Schalin-Jantti, C OC10.5

Sentosun, U EP282

Shakirov, H EP736

Shvangiradze, T EP659

Schally, AV GP151

Senyurt, M EP1108

Shalimova, A OC2.2

& EP685

Scheerer, P NSA5.1

& EP429

Shamanadze, A EP504

Shved, M EP420

Schilbach, K EP1027,

Seo, hA EP506

& EP650

Shyman, Z EP436

EP639 & GP196

Seo, JA GP91

Shamkhalova, M EP521

Shyshko, V EP527

Schipor, S EP1094,

Seo, JB EP383, EP506

& EP568

& EP663

EP1216, EP137

& GP56

Shanik, MH EP291

Siamopoulos, C EP299

& EP1466

Seo, Y-G EP700

Shao, R EP1096

Siderova, M EP1271

Schlegel, N OC1.1

Seok, JW EP729

Sharabiani, MT EP1458

Sidneva, Y EP799

Schlosser, A EP932, GP1

Sepek, M EP187

Sharefi, AA EP1398

& EP895

& GP5

Seppanen, M GP50

Shargorodsky, M EP1185

Sidorin, A EP1394

Schmid, C EP104

Sepp, K EP1388, EP1410

& EP580

Sierra, M EP1044

Schmidt, E EP1410

& EP742

Sharipova, J EP617

& GP73

Schoenmakers, N S26.2

Septier, A OC1.2

Sharma, D EP1309

Siffroi, J-P GP148

Schopohl, J EP1027,

Sequeira Duarte, J EP1049

Sharma, P EP1333

Sigaud, T OC11.5

EP1039 & GP196

Sequeira, J EP1177

Sharma, R GP166

Siggelkow, H EP353

Schreiner, J GP121

Seraphim, P GP163

Shatalov, I GP92

& OC10.1

Schuetz, P EP687

Serez, B EP1404

Shatarnova, T EP670

Sigirli, D GP161

& EP942

Serfling, G EP800

Shauly-Aharonov, M

Sigurjonsdottir, H EP19

Schuster, D EP822

Sergey, D EP1248

EP624

& EP21

Schutter Harlinde, D

Serguey, D EP73

Shebl, T EP416

Silaghi, CA EP114, EP158,

OC14.4

Serra, F EP1088, EP1359

Shelestova, E N1.1

EP328, EP398, EP399

Schwaiger, R EP639

& EP139

Shell, J GP124 & OC7.3

& EP400

& GP196

Serra, FA EP951

Shepelkevich, A EP269,

Silaghi, H EP114, EP158,

Schwambach, F EP1013

Serra, L GP238

EP286, EP480

EP328, EP398, EP399

Schwarcz, E GP9

Serra-Caetano, J EP887

& EP737

& EP400

Schwarzmayr, T EP52

& GP109

Sheriba, N EP1154

Silamikelis, I OC8.3

Schweighofer, N GP107

Serra-Prat, M GP57

& EP1299

Silea, S EP1007 & EP980

Sciammarella, C EP1407

Serraclara, A EP1044

Sherlock, M EP1041,

Silva, AL EP1448

Scillitani, A GP130

Serrano, ACR EP76

EP1150, EP1153,

Silva, C EP451, EP807

& GP33

Serrano, RN GP89

EP339, EP487, EP572,

& GP73

Scinic, O EP1302

Serrano-Blanch, R EP178

EP70 & EP798

Silva, E EP133

Sclumberger, M GP148

Serrano-Nascimento, C

Sherman, M EP661

Silva, F EP1351, EP490

Scoazec, JY S17.3

EP716

Shestakova, M EP521,

& EP492

Scoscia, MF EP1251

Sert, C GP191

EP561, EP568, EP659

Silva, J EP1218, EP1359,

Scotté, M OC11.2

Sert, M EP1241

& EP685

EP139 & EP57

Secchi, A OC6.2

Sertba¸, Y EP440

Shestakova, T EP50

Silva, L GP94

Sedman, T EP607

Sertbas, M EP565

Shibina, L EP1036

Silva, LF EP267

Sefi, W EP167

Seshadri, KG EP552

Shimano, H GP166

Silva, R EP1461, EP468

Segerstedt, E GP9

Sesmero, A EP9

Shimon, I EP1046

& EP57

Seiça, R EP704

Setti, M GP51

Shin, D EP1256

Silva, RS EP512 & GP227

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Silva, S GP222

Sir-Petermann, T EP1120,

Smirnova, L EP540

Sordi, V S20.1

Silva, T EP57 & EP933

EP636 & GP132

Smit, J GP197

Sorin, I EP587

Silva, TNd EP1422

Sira, L EP1410

Smith, D EP1041

Sosic-Jurjevic, B GP202

Silva-Fernández, J EP11,

Siracusa, M EP1443

Smith, K GP104 & GP106

Sˇošic-Jurjević, B EP212

EP456 & EP955

Sirbu, A EP1371, EP855

Smith, L GP10, GP159,

Sˇošo, G EP1469

Silva-Nunes, J EP1446

& EP943

GP4 & S10.1

Soto, C EP3, EP9

& EP451

Sirbu, AE EP947

Smolen, A EP865

& EP952

Silveira, D EP807

Sironi, M GP77

Smolovic, B EP1283

Soto, CC EP603

Silveiro, SP EP457

Sisman, M EP1017

Snabboon, T EP1288

Soto-Moreno, A EP929

& OC2.5

Sisman, P EP1017, EP102,

Snyder, M EP744

Sottomayor, C EP129

Silvestre, C EP1083,

EP131, EP1335,

Soare, I EP943

Soua, H EP1236

EP119, EP1387,

EP333, EP336, EP608,

Soare, IS EP947

& EP1238

EP157, EP243, EP329,

EP679 & EP852

Soares, AA OC2.5

Soula, M EP754

EP897, EP898

Sitch, A GP122

Soares, P EP1357, EP1449

Soumaya, M EP780

& GP226

Sjoberg, S N1.4

& OC14.3

Sousa Santos, F EP1295

Silvestri, S EP1260

Sjogren, K S7.3

Soares, S EP1155

Sousa, A EP51

Silvius, B EP635

Sjostedt, E GP155

Sobhi, N EP219

Sousa, AM EP1356

Simó-Servat, A GP241

Skalniak, A EP1297,

Sobral, J EP51

Sousa, B EP722

Simo˜ es, H EP1219, EP57,

EP283, EP284 & OC9.3

Sobrinho-Simoes, M OC14.3

Sousa, I EP596

EP725 & EP772

Skorkiewicz, K EP1445

Sodikov, S EP1106

Sousa, L EP567

Simo˜ es, MS EP1357,

Skowronska-Jozwiak, E

Sodji, M OC11.2

Sousa, M EP1179

EP1449 & P6

GP183

Sohn, SY EP1424

Sousa, R EP1454

Simo˜ es, R EP232 & EP234

Skrobisz, J EP1252

Soidán, JLG EP365

Sousa, S EP1133, EP1155,

Simo˜ es-Pereira, J EP1142,

& EP1275

Soler, MG GP48

EP403, EP84

EP1454, EP772,

Skrobowski, A OC12.4

Sokhatska, O EP1289

& GP133

EP783, EP816

Skrodeniene, E EP550

& GP199

Souteiro, P EP1081,

& GP133

Skrzypulec-Plinta, V

Sokolowski, A EP1477

EP140, EP169, EP194,

Simaityte, P EP173

EP1119

Solak, M EP71 & EP81

EP195, EP477, EP493,

Simanaviciene, V GP244

Skuja, S GP209

Solari, D EP927

EP53, EP54, EP564,

Simeakis, G EP1411

Skuridina, D EP1034

Solari, S OC5.1

EP576, EP630

& GP230

Slagter, S EP672

Soldatovic, I EP367,

& EP719

Simeoli, C EP34 & EP786

& OC9.1

EP677 & EP678

Southall, N EP754

Simeoni, L EP807 & GP26

Slama, AB EP355

Soldevila, B GP84

Souto, SB EP1091

Simkovic, M EP837

Slavikova, E EP1344

Soler, GS EP294

Souto-Moura, C EP872

Simo, R EP753

Slezak, T GP118

Solntsava, A EP351,

Souza, B GP94

Simoes, H EP258 & GP23

Slim, I EP1428 & EP1430

EP670 & EP814

Souza, Bd EP648

Simon, T GP148

Slimane, H EP1193,

Solovov, V EP1286

Souza, L EP723

Simona, F EP587

EP1201, EP1208,

Soltész, P EP1384

Sowa-Staszczak, A

Simonds, S EP373

EP1212, EP1322,

Solter, M EP209

EP1297, EP1445

Simonelli, I EP1050

EP1324, EP1328,

& GP232

& EP283

Simoni, M EP1107,

EP207, EP340

Soltsava, A EP218

Sowinska-Przepiera, E

EP1112, EP1123,

& EP570

Soltysik, K GP67

EP229 & EP230

EP1131, EP1383,

Slimene, MFB EP1428

Somali, M EP588

Sowinski, J EP1275

GP245 & GP51

& EP1430

Someya, FN EP1447

Sˇošić-Jurjević, B EP359

Simoniene, D EP1321,

Sliwczynski, A EP577

Sondergaard, E OC1.4

Soysal-Atile, N EP446

EP1436 & EP479

Slomian, M EP1372

Song, E EP1366, EP1367

& EP842

Simpson, H GP27

Sloot, Avd GP153

& OC14.5

Sozen, M EP1167

Simsek, S EP912

Slowinska-Lisowska, M

Song, K-H EP438, EP514,

Spottl, G EP154

Simu˚ nková, K EP14

EP1160

EP554 & EP690

Spada, A EP20, EP924

Sinclair, A EP798

Slusarczyk, J GP154

Song, SO EP960

& OC7.4

Singh, AK EP701

& GP158

Song, Y OC1.5

Spagnolo, F GP175

Singh, R EP741

Sluszniak, A EP1409

Song, YD EP960

Span, P GP10

Singh, V EP1333

Smaili, M EP65

Sonmez, A EP1165

Spiroiu, C EP1254

Siolos, A EP1303, EP1307

Smajic, E EP609

& EP362

Spremovic-Radjenovic, S

& EP1417

Smajis, S EP638

Sonmez, C EP821

EP111

Siomkajło, M GP72

Smircic Duvnjak, L EP1151

Sonzogni, B EP1043

Spyropoulos, P EP136

Sipila, P OC13.3

Smircic-Duvnjak, L EP508

Soo, S-C EP272

Sˇrámková, M EP14

Sipkova, Z GP206

& EP595

Sook Kim, E EP690

Sˇrámková, M EP1143

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Sreckovic, B EP367,

Stikkelbroeck, N GP10

Suzaki, N EP1039

Tabor, VH EP1365

EP677 & EP678

Stobiecka, E EP1420

Suzuki, A EP1385

Tabur, S EP1003

Sri Venkata, M EP408

Stochholm, K OC1.4

Svard, D GP182

Tagliati, F EP789

Sriamareswaran, R EP426

Stoffel, M MTBS3

Svaikeviciene, K EP156

Tagliavini, S EP1123

Sroczynski, M EP187

Stojanoska, MM EP1024,

Svarre Nielsen, H OC13.2

& GP51

Stárka, L EP1143, EP1170

EP245 & EP956

Svensson, A-M EP55

Taha, MO EP425

& EP14

Stojanovic, M EP111,

Svilias, I EP1197

Tahir, F EP1092, EP1225,

Stępor, M EP48

EP678, EP892, EP953,

Swan, J EP13

EP205 & EP761

Stormann, S EP1027

EP954, EP956, GP188

Swarbrick, M EP1312

Taieb, A EP1229, EP646

& GP196

& GP197

Swee, DS EP29 & EP46

& EP780

Stan´ czyk, A EP48

Stojanovic, Z EP127

Sweep, F GP10

Takagi, A EP4

Stacey, H EP575

Stojkovic, M EP111

S´wider,G EP1338

Takao, T EP643

Stacul, F GP204

& EP1261

Swirska, J EP338

Takeda, Y OC3.1

Stakor, MS EP1161

Stokic, E EP1089 & EP245

Sworczak, K EP396

Takeuchi, Y GP166

Stalla, G EP912

Storey, C OC5.5

Syed, I EP1485

Takito, D EP1029

Stalla, GK GP160

Storr, H GP195

& EP58

Taliani, E EP1383

Stalvey, M GP66

Strajhar, P EP782

Sygut, J EP1474

Taliano, M GP151

Stamenkovic-Pejkovic, D

Strasburger, C GP190

Sykiotis, GP EP1373

Tallini, G EP1381

EP694

Strasburger, CJ GP192

Sykja, A EP1303 & EP223

Tam, AA EP1429

Stamm, B OC10.1

Stratakis, C EP13, GP28

Sylvetsky, N EP228

Tamatea, J EP1312

Stamm, N OC10.1

& GP68

Symington, E EP124

Tamer, G EP1243

Stancˇík, M EP1086

Stratakis, CA GP12

Syrenicz, A EP1205,

Tampouratzi, D EP217

Stancic, A EP693

& GP236

EP1336, EP229

Tampourlou, M EP1051

Stanciu, M EP1364

Strauss, L EP692 & GP167

& EP230

& GP180

& EP391

Strebkova, N EP1025

Syrenicz, M EP230

Tan, J OC11.4

Stancu, C EP1220

Strobel, R EP1244

Syska-Bielak, A EP1441

Tan, S EP724

Stanescu, B EP1220

Strom, T GP15

Székely, E EP1384

Tancic-Gajic, M EP127

Stankiewicz-Olczyk, J

Strom, TM EP52

Székely, T EP1384

& EP42

GP72

Stukens, J EP931

& EP1434

Tanda, ML EP1451 & EP688

Stanoevich, I EP1028

Suárez, ADS EP107

SzU˜cs,N EP1046

Tanday, R EP1213,

Stanojevic´, A EP356

Suarez, E OC7.5

Szabo, Z EP1410

EP1354, EP1485

Stanojlovic, O EP1114,

Subías, D EP165

Szakács, G GP44

& EP308

EP1184, GP139

Sucaliuc, A EP16 & EP240

Szanto, Z EP1134 & EP860

Tandircioglu, UA EP724

& GP140

Sucesso, MB GP227

Szczepanek-Parulska, E

Tang, J EP1

Stanworth, R EP1192

Sudar-Milovanović, E

EP1433, EP1450,

Tanimoto, M GP134

Starchenko, T EP458

EP1245

EP388 & GP220

Tanko, Z EP860

Starostina, E EP1069

Sugano, H EP840

Szekeres, S EP1410

Tanna, R EP525

Stashuk, G EP905

Sugino, K EP1385

Szeliga, K GP67

Tanrikulu, S EP1038

Stasiolek, M EP1435

Sukhanova, O EP1036

Sztefko, K EP890

& OC12.1

Stassen, L EP339

Suleiman, N EP160

Sztembis, J EP1338

Tanriverdi, F EP968

Stebbing, J EP386

Suligowska, A EP1442

Szujo, S EP1410

Tapanainen, J EP1110

Stefan, C EP262

Sumarac-Dumanovic, M

Szuman, G EP1251

& GP55

Stefanescu, AM GP21

EP367 & EP694

Szymonek, M EP1274,

Tapia, J EP681

Stefaroi, C EP838

Sun Jeong, J EP690

EP1382 & EP1409

Tapia-Castillo, A OC5.1

Steffensen, C EP63

Sun, N OC1.1

Szyska-Skrobot, D EP1382

Tapikara, Z EP362

& GP17

Sundaram, AY OC8.3

Tarach, J EP547, EP831,

Steinhauer, S GP119

Sundgren, PM EP1070

Távora, A EP51

EP850 & EP865

Steinschneider, M EP199

& GP182

T’Sjoen, G EP1019

Tarach, JS EP144 & EP338

Stejereanu, L EP763

Sung, Y-A EP925

Tóbiás, B EP1434

Tarasova, T EP913

Stelmachowska-Banas, M

Sung, YA EP1116

Tutuncu, NB EP1431

& EP914

GP173

Sunthornyothin, S

Tutuncu, Y EP538

Tarcin, OU EP47

Stelmaszewska, J GP118

EP1288

Ta¸çılar, ME EP673

Tardy, V GP19

Steponaviciute, R EP173

Susanti, VY EP363

Tabaei, K EP662

Tarigopula, G EP25

Stepto, N EP1115 & EP747

Suter-Widmer, I EP942

Tabarin, A GP120 & OC7.2

Tarsitano, MG GP149

Stettler, C EP1090

Sutulovic, N EP1184

Tabassum, S EP1016

Tartaglione, T EP991

Steven, N EP1052

Suvanto, E EP1285

& EP606

& EP997

Stevenson, J EP1084

Suwanwalaikorn, S

Tabbal, H OC1.2

Tas, B EP565

Stieg, MR GP160

EP1288

Tabor, MH EP1365

Tashmanova, A EP436

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Taskaldiran, A EP1175

Terrasi, A GP130

Tiulpakov, A EP1025,

Torres, I EP100 & EP146

Taskaldiran, I EP1175,

Terriou, L EP1369

EP345 & EP346

Torres, JFM EP183

EP384 & EP854

Terroba, C EP603

Tiwari, S EP701 & EP741

Torres, MM GP89

Taskinen, M-R GP76

Tertipi, A EP217

Tkachuk, A GP78

Torres, SG EP1178

Taskiran, B EP1375

Terzolo, M EP161, EP26,

Toba, L GP156, GP52

Torres-Arroyo, B EP11,

& EP244

GP122, GP123

& GP75

EP456 & EP955

Tassone, F EP268

& GP8

Tobiás, B EP1384

Torres-Barea, I EP1174,

Tastekin, E EP1198,

Tesic, D EP1089

Tobin, L EP696

EP1200, EP1203,

EP121, EP1396,

Tetiker, T EP1241

Tocino-Hernandez, AL

EP1287 & EP535

EP1397, EP1399,

Teulé, A EP150

EP105

Torres-Barea, IM EP858

EP1400, EP1401,

Tezuka, Y GP14

Todd, JF EP1196, GP29

& EP915

EP1402, EP1403,

Thé, AC EP841, EP899

& GP30

Torres-Rasgado, E OC6.5

EP271 & EP981

& EP975

Todorova, B EP285

Torres-Torrenteras, J

Tatli Dogan, H EP1413

Thakker, R S2.1

Tofan, M EP792 & EP809

EP753

Tauchmanova, L EP1039

Thakker, RV OC10.5

Toivanen, S EP163

Tortora, A EP1064

& GP177

Themeli, A EP645

Toivonen, R GP167

Tortosa, F EP896 & EP974

Tauni, R EP254, EP272,

Theodoropoulou, M

Tokac, M EP237

Torun, D EP1165

EP525, EP732

GP160

Tokunaga, S EP27

Torun-Jurkowska, A

& EP877

Theodorou, M EP1084

Toldy, E GP44

EP547

Tavares, C EP1449

Thoda, P EP861

Toledano-Delgado, Á

Toruner, FB EP1144

Tavares, L EP791

& EP864

EP819

Tosheva, G EP1271

Tavares, P EP1155,

Thomas, S EP1032

Tomé M EP298, EP302

Toth, M GP3

EP1211, EP1351,

Thomasius, F EP353

& EP341

Toubert, ME GP148

EP1356, EP145

Thomo, T EP495

Toma, GM EP1364

Touraine, P GP12

& EP51

Thompson, C EP1041

Tomczyk, R EP357

Tournis, S EP859

Tavares, T EP337

& EP768

Tome, M EP623

Tozzi, R EP702

Tay, WL EP29

Thordarson, H EP49

Tomic, D EP116

Trabado, S GP7

Taylor, AE EP1150,

Thordarson, HB EP33

Tomic, M EP508

Trainer, P EP1169

EP1153 & OC3.3

Thorsby, PM EP59

Tomic-Naglic, D EP1089

Tramontano, AL EP1064

Taylor, AE OC1.3

Tiaka, E EP1047

Tomlinson, J EP682,

Tran, DN EP1100, EP727

Tayyeb, S EP428

Tiano, L EP1260

EP728, EP730, EP798,

& EP738

Tazza, L EP1260

Tiberg, F GP177

GP69, GP70, OC3.3,

Tranfaglia, C GP231

Teede, H EP1115, GP135

Tiffreau, V EP1439

OC3.5 & S25.3

Tranti, T EP1123

& GP141

Tigas, S EP1172, EP299

Tomlinson, JW GP138

Trapella, C EP789

Tehrani, FR EP1125

& EP559

Tomoda, C EP1385

Trattnig, S EP638

& EP1183

Tigishvili, L EP315

Tomokuni, J EP273

Travlos, A EP1460,

Teixeira, G GP163

Timon, C EP339

Tomulescu, V GP21

EP202, EP221

Teixeira, JP EP1422

Timur, O EP1113

Tonoli, D EP782

& EP276

Teixeira, M EP100

Tinahones, F EP755,

Toogood, A EP1051,

Trenti, T GP51

& GP163

EP756, EP808

EP1052 & GP180

Treppiedi, D EP20

Teixeira, R EP1279

& EP868

Top

¸uog˘lu, C EP1453

& EP924

Teixeira, S EP496 & EP567

Tinahones-Maduen˜ o, F

Topaloglu, O EP1320,

Tresoldi, A OC7.4

Tekin, G EP421

EP1462

EP1326, EP1377,

Triana, P EP984

Tekin, S OC12.1

Tinahones-Maduen˜ o, FJ

EP1413, EP330,

Triantafillou, E EP217

Tekin, ZN EP1122

EP614 & GP71

EP620 & EP703

Trifanescu, R EP1353

Teles, L EP54 & EP169

Tino, P OC1.3

Topcuoglu, C EP1347

& EP137

Temessek, A EP502

Tinu, A-M GP21

Toporcerová, S EP1127

Trifunović, S EP212

Temizkan, S EP289

Tippisetty, S EP552

Toppari, J GP118, OC4.2,

Trifunovic, S GP62

Tenés, S EP681

& EP553

OC7.1 & S21.2

Triggiani, V GP214,

Tennagels, N GP105

Tirnovan, M EP1076,

Toprak, İD EP113

GP215 & GP216

Tenu, I EP560

EP1360 & EP188

Topsakal, S EP1405,

Trimarchi, F EP1443

Tepla, O GP86

Tirnoveanu, M EP1209

EP656, EP971

& GP208

Terakawa, N GP134

Tirosh, A EP13, GP124,

& EP972

Tripolski, M EP23

Teresa Gallego, M EP1415

GP186 & OC7.3

Torffvit, O EP557

Tripsianis, G EP1378

Terlizzese, P GP214,

Tishkovsky, S EP540

Toromanyan, E EP304

Trivin˜ o, V EP891

GP215 & GP216

& EP541

Torralvo, FS EP756

Trofimiuk-Muldner, M

Terol, E EP1415

Tissier, PL GP159

Torregrossa, L EP1414

EP1445

Terraris, D GP43

Tiszlavicz, L EP1388

& EP348

Trofimiuk-Muldner, M

Endocrine Abstracts (2017) Vol

19th European Congress of Endocrinology 2017

EP1026, EP283

GP138, GP203

Urbanavicius, V EP173

Vale, Sd EP1012, EP1021,

& EP284

& GP206

Urbanczuk, M EP144,

EP41, EP853 & EP897

Trojan, E GP158

Turpin-Nolan, S GP105

EP338 & EP865

Valea, A EP117, EP846

Trolle, C OC1.4

Turunen, S EP1285

Urbani, C EP970

& EP979

Troncone, G EP1407

Tutal, E EP1097, EP1368

Urboniene, J EP1276

Valeeva, E GP170

Troshina, E EP659

& EP327

Ureten, K EP684

Valeeva, F EP464, EP465,

& EP685

Tutuncu, N EP39

Urhan, M EP1455

EP617 & GP170

Trotti, E EP688 & EP691

Tutuncu, Y EP56

Urmanova, Y EP1106,

Valente, A EP562 & OC5.4

Trouillas, J EP954, GP194,

Tuzcu, AK EP937

EP880 & EP965

Valente, I EP997

GS2.6 & OC12.2

Tuzcu, S EP937

Urquhart, T MTNE1

Valente, V EP129, EP1479

Trova˜ o, E EP841, EP899

Twito, O EP1374

Ursu, HI EP1364

& EP1483

& EP975

& EP1391

Urun, V EP684

Valera, MAE EP432

Trummer, C EP1188

Twomey, P EP430

Uruno, T EP1385

& EP433

Trybek, T EP1274

Tymms, DJ EP1210

Urwyler, S OC11.3

Valero, MA EP1218

Tsagarakis, S D1.2

Tzamali, X EP202

Urwyler, SA EP687

Valickas, R EP1437

& EP1047

Tzanavari, A EP366

Uscebrka, G GP202

Valido, F EP1459

Tsakova, A GP82

Tzanela, M EP1047

Usta, R EP565

Valkusz, Z EP1388,

Tsamadias, V GP32

Tzelepi, K EP1471

Ustun, F EP118, EP1198,

EP1410 & EP742

Tsapaeva, N EP663

Tziomalos, K GP140

EP1396, EP1397,

Vallespin, E EP904

Tsatsoulis, A EP1172

Tzoulis, P EP386

EP1399, EP1400,

Valta, H OC10.5

Tschop, MH OC2.3

Tzvetkov, M EP353

EP1401, EP1402,

Valtere, A EP931

Tschiedel, B GP93 & OC2.1

EP1403, EP201,

Valtink, M EP806

Tschop, M GH1

Ušćebrka, G EP212

EP271, EP848

Valverde, M EP435

Tschopp, O EP104

Uc, ZA EP962

& EP981

van Beek, A EP402

Tselebis, A EP793

Ucan, B EP1368, EP327

Utku, OG EP684

& EP672

Tselovalnikova, T EP1057

& EP999

Utlu, M EP1113

van de Meerhaeghe, T

Tseng, C-H EP404 & GP97

Ucar, MG EP1101

Uygun, B EP322

GP41

Tseng, F-Y EP1319

Ucci, S EP825 & GP221

& GP161

Van de Velde, F EP1191

Tsentidis, C EP1008, EP38

Ucgun, AB EP1380

Uygur, M EP47

van den Broek, M EP402

& GP99

Ucgun, S EP1294

Uygur, MM EP665, EP676

Van den Bruel, A EP1393

Tsiberkin, A EP978

Uchigata, Y EP1014

& EP851

van der Horst-Schrivers,

Tsikarishvili, N EP315

Uchman, D EP908

Uysal, S EP282

ANA EP155

Tsirona, S EP1098

Ueland, G

˚ EP49

Uzieblo-Zyczkowska, B

van der Klauw, M EP672

Tsirou, E EP68

Ugalde, A EP1217

OC12.4

& OC9.1

Tsitlakidis, D EP528

Ugarte, E EP1040 & EP112

van der Lely, AJ GP116

Tsoli, M EP67

Ugolini, C EP1414

Vázquez-Borrego, M-C

& GP174

Tsoriev, T EP881

Ugur, K EP249

EP819

Van Doninck, N EP393

Tsourouflis, G EP1253

Uitterlinden, A EP744

Vázquez-Borrego, MC

van Eck, JP GP116

& GP80

Ujházi, S EP1127

EP929

van Etten, B EP155

Tsoy, U EP200 & EP978

Ulianova, I EP521

Vaarasmaki, M EP1285

Van Gaal, L OC3.5

Tuchiyama, Y EP840

Ulkar, SE EP1144

Vcˇelák, J EP1143

van Herwaarden, T GP10

Tudorache, S EP1364

Ulyana, T EP989

Vítku˚, J EP1143 & EP14

Van Koetsveld, P EP933

Tukiendorf, A EP349

Unal, B EP330

Vanˇuga, A EP1086

van Kralingen, J GP58

Tulpakov, A EP913

Unal, M EP56

& GP38

Van Meter, QL GP65

& EP914

Unay, B EP673

Vanˇuga, P EP1086

van Niel, J EP635

Tuna, MM EP1453 & EP56

Undeutsch, H OC4.2

& GP38

Van Nieuwenhove, Y

Tuncez, OE EP362

Ungureanu, M-C EP1209,

Vaca, CS EP459 & EP8

EP1191

Tungalagsuvd, A EP1156

EP961 & GP34

Vagnerova, K EP1082

Van Ooswaard, M N3.3

Tuomi, T GP76

Unlu, A EP1167, EP419,

Vainikonyte-Kristapone, J

van Pelt, A S10.2

Tupea, C EP1063

EP421 & GP96

EP1437

van Vliet-Ostaptchouk, J

Tupikowska-Marzec, M

Unluhizarci, K EP968

Vaira, V GP130

EP672 & OC9.1

GP165

Unluhizarci, K E1129

Vajauskas, D GP31

van Waateringe, R EP672

Tupikowski, K EP187

Unsal, İO EP327 & EP999

Val-Zaballos, FD EP11

& OC9.1

Turatti, W EP7

Unsal, I EP1097 & EP1368

Valadares, L EP84

vanderLely, AJ GP192

Turek-Jabrocka, R EP1026

Unsal, YA EP186

Valadas, C EP660

Vandewalle, S EP393

& OC9.3

Unuane, D GP41

Valassi, E GP36

Vanka, R EP89

Turkon, H EP1099

Unverdi, H EP317

Valdivia, C OC5.1

Vanselow, JT EP932, GP1

Turner, H EP1145,

& GP5

Urbánková, H EP1086

Vale, C GP217

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Vantyghem, M-C EP1369,

Velickiene, D EP448

Victor, M EP1298

Vita, R EP1118 & EP1171

GP120 & OC5.3

& EP449

Vidal, J OC12.3 & S15.3

Vitale, M EP1064

Vantyghem, MC EP1439

Velija-Asimi, Z EP976

Vidal-Ríos, P EP1284

Vitali, E OC7.4

Vanya, M EP731

Velikova, T GP82

& GP210

Vitellius, G GP7

Vaquero-Barrios, J-M

Velkeniers, B GP41

Vidal-Ríos, S EP1284

Vitkauskiene, A EP173

EP776

Velloso, RN EP389

& GP210

Vitorino, H EP1323

Varani, M EP1123 & GP51

Venaki, E EP793

Vidmar, G GP39 & OC10.4

& EP32

Varela, A EP719

Vendramini, MF EP380

Vidovic, J EP491

Vitti, P EP1247, EP1414,

Vargas, ML EP1481

Vendrell, CS EP1178

Vieira, A EP1362 & EP267

EP238, EP397 & S19.1

Varo, N EP227

Venegas-Moreno, E EP929

Vieira, J EP1356

Vitulli, F EP927

Varthakavi, P EP844

Venkataraman, S EP555

Viengchareun, S GP7

Vlachopapadopoulou, E

Vasar, E EP607

Venneri, MA EP537

& OC5.5

EP62

Vaschenko, E EP536

Vensa˜ o, L EP79

Vignali, E EP238, EP274

Vlad, M EP1068, EP1364,

& EP556

Ventosa, M EP603

& EP288

EP153, EP306 & GP53

Vasconcelos, C EP1088,

Ventura, M EP1009,

Vignera, SL EP1163

Vladimir, M EP1248

EP1177, EP1207,

EP1195, EP1475,

& GP127

Vladislav, C EP989

EP1311, EP1452,

EP203, EP392, EP394,

Vignozzi, L EP370, EP377

Vladoiu, S EP1094,

EP1486, EP414,

EP44, EP444, EP445,

& GP147

EP1176 & EP1180

EP887 & EP951

EP45, EP61 & GP35

Vigouroux, C OC5.3

Vlaski, J EP1089

Vasile, M EP1364

Veríssimo, D EP1359

Vijayan Melapatte, A

Vlychou, M EP483

Vasileiadou, S EP1473

& EP139

EP1052

& EP559

Vasileiou, A EP483

Vera, L EP1415 & EP1476

Vikentieva, E GP82

Vogiatzi, E EP1460,

Vasileiou, E EP1008

Vera-Llonch, M EP1263

Vikulova, O EP568

EP202, EP221

Vasileiou, V EP1411

Verdelli, C GP130

Vilaça, J EP1291

& EP276

Vasilescu, F EP16

Verdes-Sanz, G EP461

& EP1292

Vogt, B EP820 & OC13.5

Vasiliev, E EP1025

Verdi, H EP1431

Vila, G EP1010

Vogt, D EP889

Vasilieva, N EP351

Veresiu, I EP560

Vila, L EP1332

Vohra, G EP1333

Vasiliu, I EP809

Veresiu, IA EP398, EP399

Vilar, C EP841, EP899

Voicu, G EP1221

Vasiljevic, A EP954

& EP400

& EP975

Voicu, O EP1007

Vasilkova, V EP511

Vergara, A EP938

Vilar, L EP841, EP899

Vojnovic-Milutinovic, D

Vasilyev, E EP345

Verkauskiene, R EP1102,

& EP975

EP1114, GP139

& EP346

EP434, EP542

Vilardell, C EP165

& GP140

Vasovic, O GP197

& EP839

Vilas, AP GP237

Vokes, TJ EP291 & GP47

Vasoya, S EP1117

Verma, N EP741

Vilaverde, J EP496

Volante, M EP161

Vasques, M EP519

Veronesi, G EP688

& EP921

Volk, J EP814

& EP599

& EP691

Villabona, C EP150, EP88,

Volke, V EP607

Vass, A EP731

Verrijken, A OC3.5

EP891, EP94 & GP241

Volkova, N EP218, EP415,

Vassilatou, E EP1139

Verroken, C EP1019

Villanova, T GP151

EP539, EP73 & EP760

Vassiliadi, D-A EP1139

Verrua, E EP1043

Villanueva-Herraiz, SI

Volle, D S11.1

& GP122

Versari, A GP231

EP769

Volovat, C EP792 & EP809

Vasyliene, G GP31

Vershinina, M EP1036

Villas, L EP1284 & GP210

Volzke, H S21.3

Vaz de Castro, R EP1055

Vezbaviciene, V EP550

Villette, B EP966

Vorobiev, S EP695

& EP791

Vezzoli, V OC8.2

Viloria, MdM EP1331

Vorobyev, S EP1164

Vecchiola, A OC5.1

Vin˜ a, V EP3, EP9 & EP952

Vinagre, J OC14.3

Voronkova, I EP126,

Veeger, N EP402

Vin˜ uela-González, L GP71

Vinaixa, M EP435

EP318, EP323 & EP345

Vega, MM EP406, EP407,

Viana, GS EP716

Vincentis, SD EP1166

Vorotnikova, S EP1034

EP627 & EP998

Viana, J EP1330

& GP51

& EP1036

Veiga, L EP451

Vicari, ES EP1163

Vinha, E EP1077, EP1078

Vosjan-Noeverman, M

Veiga, R GP242

Vicaut, E OC11.2

& EP140

EP1045

Vela, ET GP89

Vicchio, TM EP1443

Vinogradova, A EP936

Vozdvizhenskiy, M EP1286

Velarde, AP EP878

& GP208

Vinson, G GP18

Vrkljan, M EP172, EP43,

Velasco, M EP984

Vicennati, V EP1381,

Vintila, M EP206 & EP352

EP463 & EP549

Velden, JAd GS1.3

EP669 & EP671

Violante, A EP152

Vryonidou, A EP1139,

Veldhuis, J GP131

Vicente, A EP866 & EP973

Virgolini, I EP1445

EP239 & EP423

Velez, A EP175

Vicente, N EP392

Virili, C EP825

Vujović, M EP1245

Velez, MA EP1030

Vicentini, L EP1408,

Visalli, G GP175

& EP356

Velicescu, C EP213, EP252

EP1432 & GP130

Visockiene, Z EP156,

Vujovic, A EP470

& EP260

Vicic, I EP43

EP171, GP211 & GP31

Vujovic, M EP677

Endocrine Abstracts (2017) Vol 49

19th European Congress of Endocrinology 2017

Vujovic, S EP127 & EP42

Werner, U GP105

Yahi, A EP1182

Yildiz, OB EP378

Vukovic, B EP1024,

Wernig, F EP123

Yakout, S EP263

Yildiz, SO EP821

EP116, EP245

Wessling, A EP1055,

Yakut, F EP937

Yildiz, SS EP1228

& EP709

EP1204, EP1255,

Yalcin, MM EP1144

Yilmaz Bulbul, B EP1396

Vuksanovic, M EP369

EP1340, EP243,

Yalcin, S EP1280, EP529

& EP1397

Vulpoi, C EP1073,

EP300, EP791, EP897

& EP683

Yilmaz, BA EP1144

EP1076, EP1209,

& EP898

Yalcin, Y EP1431

Yilmaz, E EP110

EP1345, EP1360,

Westen, DV GP182

Yalin, GY EP1038,

Yilmaz, FM EP1347

EP188, EP213, EP252,

Westgate, C EP798

EP1327 & OC12.1

Yilmaz, N EP1061

EP260, EP792, EP809

Wiersinga, W S6.2

Yamagami, K EP27

Ylli, A EP1470, EP495,

& EP961

Wik, H GP117

Yaman, S EP856

EP546, EP571

Vurnek, I EP172

Wikiera, B EP775

Yamanaka, Y EP643

& EP765

Wikstrom, J GP194

Yamina, A EP120

Ylli, D EP1370, EP1470,

Warn, M GP117

Wild, D GP185

& EP138

EP2, EP495, EP546

Wagner, C EP1352

Wild, V GP5 & OC1.1

Yanes, EP435

& EP765

Wahlberg, J GP9

Wilieman, M EP723

Yang, L OC7.3

Yokota, T EP273

Wajda, A EP1148

Wilkinson, IR GP61

Yang, M EP801

Yoldi, A EP869

& EP371

William, A EP1213

Yang, P-S OC14.2

Yologlu, S EP703

Wajdi, S EP77

Williams, T EP37

Yang, S OC1.5

Yoneda, T OC3.1

Walch, A EP52, GP22

Williamson, C MTE3 & OC3.2

Yang, TY GP162

Yong Kim, T OC14.5

& OC1.1

Wilusz, M EP1026

Yang, W-S EP1319

Yoo, HJ GP91

Walczyk, A EP1274,

Winhofer, Y EP638

Yano, K EP1156

Yoo, WS GP207

EP1382 & EP1409

Winston, LR OC3.2

Yarets, Y EP556

Yoon, Bk EP729

Waldmann, J OC7.2

Winzeler, B EP889, EP918

Yarman, S EP1038

Yoon, JH EP987

Walenkamp, AME EP155

& EP942

& OC12.1

Yoon, K EP605

Walicka, M EP577

Witek, P OC12.4

Yarom, N EP199

Yorulmaz, G EP1033,

Waligórska-Stachura, J

Witte, K S27.1

Yasuda, A EP4

EP110, EP12, EP1375,

EP1252

Wołkow, P OC9.3

Yatabe, J EP1014

EP1444, EP244,

Waligorska-Stachura, J

Woischke, C EP52

Yatabe, M EP1014

EP264, EP418, EP427,

EP1275

Wojtyna, E EP1441

Yavuz, DG EP47, EP665,

EP69 & EP90

Walker, BR EP802

Wojtysiak-Duma, B EP547

EP676, EP851

Yoshida, H EP1242

Wall, J EP1265

Wolczynski, S EP1104,

& GP187

Yoshimoto, R EP273

Walsh, M OC3.3

GP118 & OC7.1

Yavuz, ST EP673

Yosra, H EP1229 & EP646

Wang, H-C EP1093

Wolf, P EP638

Yaylalı, GF EP1405,

You, J GP54

Wang, L EP916

Wolffenbuttel, B EP672

EP656, EP971

You, JH EP452, EP531

Wargny, A EP1126

& OC9.1

& EP972

& GP87

Warren, ML GP47

Wong, E EP1339

Yazicioglu, O EP1326

Youcef, HS EP1315

Wasoori, SC EP526

Woods, C GP70

Yazidi, M EP1193,

Young Kim, E OC14.5

Wass, J GP180 & P1

Wook Kim, S GP219

EP1201, EP1208,

Young Park, S GP219

Watson, M EP682

Wouters, H OC9.1

EP1212, EP1322,

Young, J EP1015, GP12

Watts, NB GP47

Wright, N GP66

EP1324, EP1328,

& GP19

Wawak, E EP1282

Wu, F-J EP1103

EP207, EP340

Young, P EP211

Wawrusiewicz-Kurylonek,

Wu, J EP744

& EP570

Yu, SH EP959

N EP31

Wu, S EP426

Yedinak, C N2.1

Yuce, ZT EP968

Webb, S EP1010 & GP192

Wygoda, Z EP1420

Yeh, S GP129

Yucel, S EP620

Webb, SM GP36

Yemelyantsava, T EP670

Yudina, A EP1057

Webber, L GP131

Xanthakou, E EP136

Yenigun, M EP86

Yurekli, BS EP1194

Weber, B EP1030

Xiao, J EP754

Yeoh, P EP985

& EP1379

Webster, R EP1051

Xifra, G GP24

Yerdesova, K EP532

Yurkovets, V EP737

Weigand, I EP932, GP1

Xilola, G EP1124

Yesildal, F EP1165

Yusupovna, Z EP15

& GP5

Xu, C GP153

Yeudachkova, T EP556

Yuzbashian, E EP642,

Weigel, N OC7.5

Xydiari, K EP1202

Yi, N EP934

EP662 & OC5.2

Weinert, LS EP457

& EP859

Yigitbasi, A EP1403

Weinstein, LS OC4.2

Yildirim, A EP937

Zabalegui, A EP112,

Wejman-Matela, A EP388

Yadagiri, M EP409

Yildirim, AE EP1035

EP1217 & EP128

Wen, J GP171

Yaghmaei, F GP164

Yildiz, F EP429

Zabeen, B EP428

Wen, L GP171

Yagiz, B EP12

Yildiz, K EP478, EP566

Zabransky, M EP912

Wengrowicz, S EP1332

Yahagi, N GP166

& EP710

Zabuliene, L EP1276

Endocrine Abstracts (2017) Vol 49